Foods to help if you have High Blood Pressure

High Blood Pressure Exercise Program

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Multicentre Hypertension Trial

The trial was a randomised double blind comparison of three treatments for hypertension and has been reported by Hall etal. (1991). One treatment was a new drug (A) and the other two (B and C) were standard drugs for controlling hypertension (A Carvedilol, B Nifedipine, C Atenolol). Twenty-nine centres participated in the trial and patients were randomised in order of entry. Two pre-treatment and four post-treatment visits were made as follows

Arterial Changes in Aging and Hypertension

Arteriosclerosis is the process of age-related large artery stiffening usually found in individuals with wide PP or systolic hypertension. This adventi-tial and medial process must be differentiated from atherosclerosis, the occlusive low-grade endovascular inflammatory process that results from endothe-lial dysfunction and lipid oxidation. Arteriosclerosis often coexists with atherosclerosis but is worth differentiating from the former because prevention and treatment of the two conditions probably differ significantly. Histo-pathologically, arteriosclerosis is a diffuse non-inflammatory fibrotic process affecting primarily the adventitia and media, with breakdown of elastin, increased collagen and matrix deposition, and VSM hypertrophy 23 . Changes in other arterial wall components such as the vasa vasora may contribute to arteriosclerosis because occlusion of these adventitial vessels tends to increase the collagen elastin ratio and arterial stiffness 26 .

Physiology Of Portal Hypertension

Portal hypertension is defined as an elevation of the hepatic venous to systemic pressure gradient over the normal value of 3-6 mmHg. Portal hypertension arises as a consequence of either hepatobiliary or perihepatic vascular disease, which leads to increased resistance to flow in the portal vein. Secondary changes in vascular tone within the splanchnic and systemic circulations lead to increased blood volume and potentiate the portal hypertension. Prehepatic, intrahepatic, and posthepatic diseases can give rise to portal hypertension. The initial increase in pressure is thought to develop as a result of sinusoidal compression by regenerative nodules and collagen deposition by fibroblasts (4). Mechanical compression is potentiated by changes in vascular tone within the liver sinusoids. Increased collagen deposition in the space of Disse impairs oxygen delivery to hepatocytes, increases sinusoidal vascular resistance, and correlates with the degree of portal hypertension (5). These...

Diagnosis Of Portal Hypertension

The diagnosis of portal hypertension can usually be made based on a carefully performed history and physical examination in conjunction with appropriate laboratory studies. Measurement of the hepatic venous Some authors have advocated measurement of the hepatic venous pressure gradient to assess adequacy of pharmacologic therapy for portal hypertension (8). As most cirrhotic patients are at significant risk for complications from angiographic procedures, this practice has not been widely adopted.

Identify current drug therapies for hypertensive patients

Single-agent therapy is usually initiated if this is ineffective, multiple agents may be prescribed. Multiple factors determine which agents are used, including race, gender, age, and comorbidities. For instance, black patients respond better to calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and p-blockers. p-Blockers are relatively contraindicated in patients with reactive airway disease, and patients with renal artery stenosis should not receive ACE inhibitors. Diuretics produce hypokalemia and hyperglycemia. p-Blockers are not particularly effective in elderly patients. Table 28-1 reviews commonly prescribed antihypertensive medications. TABLE 28-1. COMMONLY PRESCRIBED ANTIHYPERTENSIVE MEDICATIONS rebound hypertension, decreases

How should intraoperative and postoperative hypertension be managed

Pain is the most common cause of postoperative hypertension, but other causes should always be considered. Intraoperatively consider increasing the delivered concentration of volatile anesthetic or administering additional opioids. Consider the usual hourly doses of common opioids and determine whether the maximum limit has been reached. The usual guidelines for opioid administration may not apply to patients receiving opioids chronically. If administration of volatile agents and opioids does not address HTN sufficiently, consider primary antihypertensive agents. After surgery opioid therapy should be titrated to respiratory rate and the patient's interpretation of the severity of pain. Nerve blocks and analgesic adjuvants such as ketorolac should be considered. Frequently used antihypertensive agents in the perioperative period are discussed in Table 28-3.

Oxidative stress and Hypertension

Abstract Oxidative stress is defined as the imbalance between the formation of ROS and antioxidant defense mechanisms. The vasculature is a rich source of ROS, which under pathological conditions, plays an important role in vascular damage. There is growing evidence that increased oxidative stress and associated oxidative damage are mediators of vascular injury in cardiovascular pathologies, including hypertension, atherosclerosis, and ischemia-reperfusion. Increased production of superoxide anion and hydrogen peroxide has been demonstrated in experimental and human hypertension. This development has evoked considerable interest because of the possibilities that therapies targeted against reactive oxygen intermediates by decreasing generation of ROS and or by increasing availability of antioxidants, may be useful in minimizing vascular injury and hypertensive end organ damage. This chapter focuses on vascular actions of ROS, the role of oxidative stress in vascular damage in...

Are hypertensive patients undergoing general anesthesia at increased risk for perioperative cardiac morbidity

Although numerous studies have demonstrated that increased preoperative systolic BP is a significant predictor of postoperative morbidity, there are no data that establish definitively whether the preoperative treatment of hypertension reduces perioperative risk. However, poorly treated hypertensive patients have increased intraoperative BP lability, and hemodynamic fluctuations do have some relationship to postoperative complications. In addition, some patients with hypertension will have end-organ damage. It seems reasonable that for nonemergent surgical procedures hypertension should be treated before surgery.

Describe an approach to the evaluation of postoperative hypertension and tachycardia

A hyperdynamic postoperative phase is not an uncommon event. Frequently observed and readily treatable causes include pain, hypoventilation, hypercarbia, hypothermia with shivering, bladder distention, and essential hypertension. Also consider hypoxemia, hyperthermia and its causes, anemia, hypoglycemia, tachydysrhythmias, withdrawal (e.g., drug and alcohol), myocardial ischemia, prior medications administered, and coexisting disease. Rarely the hyperdynamic state may reflect hyperthyroidism, pheochromocytoma, or malignant hyperthermia.

Chronic hypertension and gestational hypertension

Chronic hypertension occurs in 3-5 of pregnancies, although the incidence is increasing in the UK as maternal age increases. It is diagnosed by pre-existing hypertension or hypertension that occurs before 20 weeks' gestation, although the diagnosis may be masked by the normal slight fall in blood pressure that occurs in early pregnancy, and pre-eclampsia may rarely present earlier than 20 weeks. The risk of pre-eclampsia is approximately doubled, and there is also a greater risk of abruption and fetal growth restriction, but if the blood pressure is controlled women with chronic hypertension would be expected to have good outcomes. Gestational hypertension describes hypertension after 20 weeks' gestation without any features of pre-eclampsia, and occurs in 6-7 of pregnancies. The risk of pre-eclampsia is increased slightly, this risk increasing the earlier the hypertension develops. Blood pressure usually returns to normal within 1-2 months of delivery.

Oxidative Stress in Experimental Models of Hypertension

Oxidative stress in the vasculature has been associated with genetic and experimental hypertension. Spontaneously hypertensive rats (SHR)122, and stroke prone SHR (SHRSP)13, genetic models of hypertension, exhibit increased NAD(P)H-driven generation of *O2- in resistance (mesenteric) and conduit (aortic) vessels. These processes are associated with overexpression of NAD(P)H oxidase subunits, particularly p22phox, and enhanced activity of the oxidase.123 Several polymorphisms in the promoter region of the p22phox gene have been identified in SHR, which could contribute to enhanced NAD(P)H oxidase activity in these rats.124 These findings may have clinical relevance since an association between a p22phox gene polymorphism and NAD(P)H oxi-dase-mediated *O2- production in the vascular wall of patients with atherosclerosis has been described.125 Increased expression of p47phox has been demonstrated in the renal vasculature, macula densa, and distal nephron from young SHR, suggesting that...

List conditions that produce pulmonary hypertension

PH is said to be idiopathic if it is found in the absence of secondary causes such as pulmonary disease (congenital or parenchymal), cardiac disease (e.g., shunts, mitral stenosis, left ventricular failure), thromboembolic or obliterative pulmonary vascular disease, connective tissue disease (especially the scleroderma family), exogenous vasoconstrictive substances (e.g., the appetite suppressant flufenamine), or portal hypertension. Although rare in the general population, at-risk populations include those with connective tissue disease and human immunodeficiency virus. Idiopathic PH was formally called primary PH, is a diagnosis of exclusion, affects one to two per million populations, sometimes has a familial link, and is found more in women than in men. PAPs tend to be higher in idiopathic PH when compared to secondary causes of PH.

Oxidative Stress in Human Hypertension

Clinical studies have demonstrated increased ROS production in patients with essential hypertension,144-146 malignant hypertension,147 and pre-eclampsia.148 These findings are based, in large part, on increased levels of plasma and urine TBARS and 8-epi-isoprostanes, systemic markers of lipid peroxidation, and oxidative stress.144-146 However in never-treated mild-to-moderate hypertension lipid peroxidation is not increased,149 suggesting that oxidative stress is not implicated in the early stages of human essential hypertension, but may be more important in severe hypertension, such as malignant hypertension and pre-eclampsia.147 148 Decreased antioxidant activity and reduced levels of ROS scavengers such as vitamin E, glutathione, and SOD,145 and increased activation of vascular NAD(P)H oxidase may contribute to increased oxidative stress in hypertensive patients.20 150 Activation of the renin-angiotensin system has been proposed as a major mediator of NAD(P)H oxidase activation and...

Discuss the therapeutic usefulness and limitations of nitric oxide in pulmonary hypertension

Portal pulmonary hypertension (PPHTN) is a complication of cirrhosis and portal hypertension and has previously been considered a contraindication to liver transplantation. Epoprostenol has demonstrated some benefit in PPHTN the benefit of NO has been less convincing. KEY POINTS PULMONARY HYPERTENSION

Pulmonary Hypertension

Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure greater than 25 mmHg, and can be caused by several disorders (Table 7.18). The prevalence of PH has been estimated in 1.8-2 SLE-related APS and in 3.5-5 PAPS. Within APS, PH may result from various causes listed in Table 7.19. Table 7.18. Conditions associated with pulmonary hypertension. Arterial pulmonary hypertension (changes in precapillary arteries) Primary arterial PH Secondary arterial PH (scleroderma, MCTD and other CTD, congenital heart disease, portal hypertension, HIV, anorectic agents, cocaine, etc.) Postcapillary pulmonary hypertension (changes in pulmonary veins) Table 7.19. Pulmonary hypertension in APS. Pulmonary embolism (acute chronic) Left-sided heart failure Heart valve dysfunction Myocardial infarction Myocardiopathy Portal hypertension Pulmonary veno-occlusive disease Not directly APS-related

What causes pulmonary hypertension in association with congenital heart disease

Pulmonary artery hypertension (PAH) is associated with a variety of disease states and can also be idiopathic. When associated with congenital heart disease, PAH is usually the result of high blood flow and pressure in the pulmonary vasculature caused by left-to-right intracardiac shunting at the ventricular level. This situation is typically present with ventricular or atrioventricular septal defects, in which blood flows along a pressure gradient from the high-pressure left ventricle to the lower-pressure right ventricle.

Effects in Hypertension

Isolated systolic hypertension in the elderly has been related to the age-induced increase in aortic stiffness. Although the benefits of calcium channel blockers and diuretics have been demonstrated in this disease 28, 29 , clinical experience has shown that it is often difficult to lower the brachial artery SBP to the therapeutic target without using uncomfortably large doses. These doses may also induce excessive reductions in diastolic pressures that relate to total and cardiovascular mortality 30 . Greater decreases in diastolic blood pressure than in SBP stress the importance of pulse pressure during therapy as a risk factor. Although organic nitrates may not be able to combat the aortic stiffness of aging, they have a vasorelaxing effect on the peripheral arteries and ameliorate the deleterious effects of strong reflected waves into the aorta. Several small observational studies support this possibility as clinically useful 3133 . Although the use of nitrates in patients with...

Aliskiren Antihypertensive [38

Aliskiren is a first-in-class antihypertensive drug that acts by direct inhibition of renin. It is indicated for oral administration either as monotherapy or in combination with other antihypertensive agents. Renin catalyzes the cleavage of angiotensin to form angiotensin I, the first and the rate-limiting step of the RAAS. The inhibition of renin by aliskiren results in reduced levels of angiotensin I, angiotensin II, and aldosterone, all of which contribute to the antihypertensive effect. RAAS modulators are among some of the most commonly prescribed antihypertensive agents to date. Previously marketed drugs with this general mechanism include ACE inhibitors and ARBs, both of which act on steps downstream from renin. All inhibitors of RAAS, including aliskiren, can cause a compensatory rise in plasma renin concentration by suppressing the negative feedback loop. When this rise occurs during treatment with ACE inhibitors and ARBs, the result is increased levels of plasma renin

Interaction Between Venous Sinus Hypertension and CSF Pressure

Clinically, venous sinus hypertension due to obstruction is known to result in PTS. The most common clinical example of this is the venous obstruction of the cerebral sinuses that occurs in cerebral venous sinus thrombosis (CVT). Cerebral venous thrombosis is the most well recognized cause of venous sinus hypertension and when venous sinus thrombosis is limited to the lumen of the sinus and does not involve cortical veins the clinical picture may be identical to PTS 18, 147 . The acknowledgement of venous sinus thrombosis as a cause of PTS syndrome is evident in the need to exclude venous sinus thrombosis in cases of PTS 98 . This distinction between CVT and PTS is justified by the differences in management and prognosis of the two conditions 99 . These issues aside CVT does demonstrate the clinical effects of venous sinus obstruction on CSF and intracra-nial pressures. Venous sinus obstruction causes an increase in venous sinus pressure proximally. The effects of this raised cranial...

What is the significance of portal pulmonary hypertension How are these patients managed in the pretransplant period

In contrast to mosttransplant recipients, portal pulmonary hypertension (PPHTN) patients have an increased risk of death because of right ventricular failure in the peritransplantation period. Physicians are uncertain which PPHTN patients may undergo transplantation because there are no patient characteristics that clearly predict outcome. Patients with moderate to severe PPHTN should not be considered candidates until they undergo a trial of vasodilator therapy. The cause of pulmonary hypertension in liver failure patients is unknown, but the disease shares many similarities with primary pulmonary hypertension. Tissue hypoxia likely plays a role. The pulmonary circulation has increased vascular resistance that is transmitted back to the right heart and liver. The pulmonary vessels of patients with PPHTN are unable to accommodate increased blood flow during periods of aggressive blood transfusion and during the hyperdynamic postreperfusion phase, potentially resulting in acute right...

Atherosclerosis Arterial Stiffness and Antihypertensive Therapy

As shown earlier in this book, the links between atherosclerosis, arterial stiffness, age and high BP are often difficult to establish, particularly according to age. Many atherosclerotic alterations (AA) are subclinical and difficult to define in routine clinical investigations. On the other hand, many markers have been proposed, such as defects in vascular relaxation, alterations in endotheli-um-dependent flow dilatation and or presence of atherosclerotic plaques (see chapter by Baldewsing et al., pp 35-61, and chapter by Hayoz and Mazzolai, pp 62-75). Within the framework of antihypertensive drug therapy, it seems likely that the links between atherosclerosis and arterial stiffness should primarily be explored through a simple clinical description of CV events clearly related to AA. The principal AA are those responsible for peripheral arterial disease (see chapter by Safar, pp 199-211), coronary ischemic disease (see chapter by Kingwell and Ahimastos, pp 125-138) and carotid...

NADPH Oxidases in Hypertension

Maintenance of blood pressure is essential to health, and any gross deviations of blood pressure from normal can be life-threatening. The various mechanisms by which NADP(H) oxidases may lead to hypertension are discussed in the following subsections. 6.1. Angiotensin II-Related Hypertension Although the relationship between AT1 receptor and NAD(P)H oxidase activity is fascinating, several studies do not show a beneficial effect of ACE inhibitors and AT1 antagonists on endothelial function in patients with essential hypertension 48, 49 . However, these drugs have shown positive results in patients with CAD 50 . Thus, there is a possibility that NAD(P)H oxidases would modulate cardiovascular function. 6.2. NAD(P)H Oxidase-Derived Oxidative Stress in Hypertension Clinical studies have shown the occurrence of increased ROS production in humans with essential hypertension 51, 52 . Compelling evidence has accumulated to support a role for O2* in various forms of hypertension. Berry et al....

Systemic Hypertension

The prevalence of hypertension in APS has been described in 30-50 of the patients, depending on the cohort, and seems to be more prevalent in PAPS than in secondary APS. Etipathogenesis is summarized in Table 7.20. Livedo reticularis is a frequent accompanying sign, and has been found in up to 80 of the hypertensive APS patients. The severity of hypertension varies from mild labile to severe accelerated hypertension. In case of APS patients with poorly controlled hypertension with antihypertensive drugs, renal artery MRI should be considered to rule out renal artery stenosis.

Azelnidipine Antihypertensive [2931

Azelnidipine, a member of the 1,4-dihydropyridine class of L-type calcium channel blockers with a slow onset profile, was marketed in Japan for the treatment of hypertension. Azelnidipine is synthesized via the condensation of iso-propyl 2-(3-nitrobenzylidene)acetoacetate with acry-late. The diamino acrylate intermediate is prepared from the cyanoacetic ester by sequential treatment with HCl and ammonia. In receptor binding studies using porcine heart membrane fractions, azelnidipine exhibits an IC50 of 3.1 nM and an apparent Ki of 2.1 nM. Its tight binding and slow onset are correlated with its high lipophilicity. A slow onset is also noted in vitro in a rat aortic strip contraction assay, and this effect continues after removal of the drug from the bath solution. In the conscious spontaneously hypertensive rat (SHR) model of hypertension, it was more potent that nicardipine and also had a more gradual onset and long-lasting effect. This effect was noted both when dosed orally or...

Hypertension

Studies support a correlation between systemic hypertension and intracranial aneurysms. In a review of 16 clinical and 8 autopsy studies of 26,125 patients with intracranial aneurysms, 43.5 had a history of hypertension (109). Currently, an estimated 30 of the US population has hypertension (110). Data also suggest that hypertension is a risk factor for aneurysmal rupture. In a review of 20,767 Medicare patients with unruptured aneurysms, not only was the prevalence of hypertension significantly higher in the aneurysm group (43.2 vs. 34.4 ), but follow-up data showed that hypertension was a significant risk factor for subsequent SAH (111). In a review of the literature for longitudinal and case-control studies that evaluated risk factors for SAH, in addition to smoking and alcohol consumption, hypertension was found to be a significant risk factor (112 ). Hypertension has also been associated with multiple aneurysms (7,113,114). One study showed that a higher systolic pressure was...

High Blood Pressure

High blood pressure, or hypertension, increases your chances of developing heart disease or kidney disease and of having a stroke. About one in every four American adults has high blood pressure but may not be aware of it. It is often called the silent killer because it usually causes no symptoms. However, high blood pressure is easy to diagnose, and there are practical steps you can take to bring your blood pressure under control. Different activities make your blood pressure rise or fall. For example, normally, blood pressure rises when you are exercising and falls when you are resting. A blood pressure reading of 140 90 mm Hg or lower is generally considered normal. High blood pressure is classified according to guidelines that reflect the levels at which blood pressure begins to pose significant health risks. Normal blood pressure Lower than 130 mm Hg High-normal blood pressure 130 to 139 mm Hg High blood pressure A diagnosis of high blood pressure is based on two or more blood...

Induced Hypertension

The phenomenon of cerebral autoregulation in the healthy brain maintains constant cerebral blood flow the face of wide fluctuations in arterial blood pressure. However, the ischemic brain loses its capacity to autoregulate and becomes sensitive to blood pressure manipulation. This is most relevant in the ischemic penumbra, where raising mean arterial pressure has been shown to improve cerebral perfusion, with a concomitant return of electrical activity. In animal models of focal cerebral ischemia, induced hypertension therapy augmented cerebral blood flow, attenuated brain injury, and improved neurological function. , In humans, spontaneous hypertension is commonly observed in the setting of critical carotid artery stenosis, and lowering blood pressure can result in infarct extension and neurological deterioration.130 Induced hypertension is commonly used to improve perfusion in Based upon this rationale, the effect of pharmacologically induced hypertension on clinical and imaging...

Antihypertensives

Clonidine and guanfacine, marketed as Catapres and Tenex, respectively, were originally developed as medications to reduce high blood pressure. They have been found helpful for reducing excessive hyperactivity and impulsivity in children with ADHD, but there is currently no evidence that these agents improve the cognitive impairments of ADHD. The effects for clonidine usually persist for about six hours, while guanfacine usually lasts a bit longer. Usual daily doses reported by the group led by Wilens (2002) are 0.05 to 0.4 mg for clonidine and 0.5 mg to 3 mg for guanfacine. Many physicians using these medications do a baseline ECG and monitor the patient's vital signs during treatment. The most common side effect of these antihypertensives is drowsiness, although they can also cause depression or rebound hypertension as they wear off. Treatment with combinations of medications for ADHD and various comorbid disorders is now relatively common and apparently is becoming more widespread....

Key Points Autonomic Nervous System

Patients should take p-blockers on the day of surgery and continue them perioperatively. Because the receptors are up-regulated, withdrawal may precipitate hypertension, tachycardia, and myocardial ischemia. 2. Clonidine should also be continued perioperatively because of concerns for rebound hypertension.

Discuss the effects of ephedrine and review common doses of this medication Give some examples of medications that

Ephedrine produces norepinephrine release, stimulating mostly A1 and B1 receptors the effects resemble those of epinephrine although they are less intense. Increases in systolic blood pressure, diastolic blood pressure, heart rate, and cardiac output are noted. Usual intravenous doses of ephedrine are between 5 and 25 mg. Repeated doses demonstrate diminishing response known as tachyphylaxis, possibly because of exhaustion of norepinephrine supplies or receptor blockade. Similarly, an inadequate response to ephedrine may be the result of already depleted norepinephrine stores. Ephedrine should not be used when the patient is taking drugs that prevent reuptake of norepinephrine because of the risk of severe hypertension. Examples include tricyclic antidepressants, monoamine oxidase inhibitors, and acute cocaine intoxication. Chronic cocaine users may be catecholamine depleted and may not respond to ephedrine.

Review the mechanism of action for antagonists and side effects

P1-Blockade produces negative inotropic and chronotropic effects, decreasing cardiac output and myocardial oxygen requirements. p-Blockers also inhibit renin secretion and lipolysis. Since volatile anesthetics also depress contractility, intraoperative hypotension is a risk. p-Blockers can produce atrioventricular block. Abrupt withdrawal of these medications is not recommended because of up-regulation of the receptors myocardial ischemia and hypertension may occur. p-Blockade decreases the signs of hypoglycemia thus it must be used with caution in insulin-dependent patients with diabetes. p-Blockers may be cardioselective, with relatively selective B1 antagonist properties, or noncardioselective. Some p-Blockers have membrane-stabilizing (antiarrhythmic effects) some have sympathomimetic effects and are the drugs of choice in patients with left ventricular failure or bradycardia. p-Blockers interfere with the transmembrane movement of potassium thus potassium should be infused with...

Describe the pharmacology of aadrenergic antagonists

A1-Blockade results in vasodilation therefore a-blockers are used in the treatment of hypertension. However, nonselective a-blockers may be associated with reflex tachycardia. Thus, selective a1-blockers are primarily used as antihypertensives. Prazosin is the prototypical selective a1-blocker, whereas phentolamine and phenoxybenzamine are examples of nonselective a-blockers. Interestingly, labetalol, a nonselective p-blocker, also has selective a1-blocking properties and is a potent antihypertensive.

Review the preanesthetic and intraoperative management of pheochromocytoma patients

These patients are markedly volume depleted and at risk for severe hypertensive crises. It is absolutely essential that before surgery, a-blockade and rehydration should first be instituted. The ai-antagonist phenoxybenzamine is commonly administered orally. p-Blockers are often administered once a-blockade is achieved and should never be given first because unopposed arvasoconstriction results in severe, refractory hypertension. Labetalol may be the p-blocker of choice since it also has a-blocking properties. Intraoperatively intra-arterial monitoring is required since fluctuations in blood pressure may be extreme. Manipulation of the tumor may result in hypertension. Intraoperative hypertension is managed by infusing the a-blocker phentolamine or vasodilator nitroprusside. Once the tumor is removed, hypotension is a risk, and fluid administration and administration of the a-agonist phenylephrine may be necessary. Central venous pressure monitoring will assist with volume management.

Phillip Chung md and Karen E Kim ms md

The overall incidence of upper GI bleeding is approximately 100 cases per 100,000 population (4,5). Acid peptic disease (e.g., gastric and duodenal ulcers as well as gastritis) is the most common cause of upper GI bleeding, accounting for 50-75 of all cases (6-8), even among patients with chronic alcohol use, portal hypertension, and varices (9). Furthermore, the predominance of peptic ulcer bleeding has not been affected by the advent of improved acid suppression with medical therapy (6). Acid peptic disease is followed by variceal bleeding, gastric and duodenal erosive disease, and Mallory-Weiss tears in prevalence, each accounting for approximately 15 of the overall incidence (8,10). The elderly appear to be at particular risk, as the proportion of elderly patients who present with upper GI bleeding has steadily increased, with persons older than age 60 years accounting for 35-45 of all cases (11). This increase cannot be explained by demographics alone, as increasing age directly...

Vessel Wall Homeostasis And Aneurysmal Formation

Changes in the normal flow of blood through cerebral arteries, as in hypertension or increased efferent flow to an arteriovenous malformation, might initiate a cascade of molecular events designed to maintain cellular homeostasis of the vessel wall during regulation of cerebrovas-cular tone and repair of vasculature microinjury. It has been suggested that alterations in the ability to regulate this homeostasis might predispose some individuals to aneurysmal formation (125,126). For example, the regulation of Type IV collagen could possibly be impaired in certain individuals due to an overactivity of Type IV collagenase also known as matrix metal-loproteinase 9 (MMP-9) . It has been demonstrated that a polymorphism of the promoter for MMP-9 might be associated with the development of aneurysms (127). Thus, under situations that challenge normal cerebrovascular wall homeostasis, dysregulation of normal molecular responses that lead to enzymatic destruction of Type IV collagen by Type IV...

Ascending Cholangitis Following Portoenterostomy

Extrahepatic biliary atresia is an obliterative cholangiopathy that involves all or part of the extrahepatic biliary tree and, in many instances, the intrahepatic bile ducts. In the U.S.A., from 400 to 600 new cases of biliary atresia are encountered annually (46). The diagnosis is usually suggested by the persistence of jaundice for six weeks or more after birth. Several factors have been considered for the pathogenesis of extrahepatic biliary atresia, including viral infection (e.g., cytomegalovirus) (47), metabolic insults, and abnormalities in bile duct morphogenesis. Although selected patients benefit from prompt diagnosis and Kasai portoenterostomy surgical intervention (48,49) within the first 60 days of life, many ultimately require liver transplantation because of portal hypertension, recurrent cholangitis, and cirrhosis (50).

Animal Models Transgenic Mice And Mutated Flies

Animal models of CNS diseases, like those of other human diseases (e.g. hypertension, cancer) are surrogates rather than models of the human disease state. The spontaneously hypertensive rat (SHR), a model of hypertension has added little to the understanding of the molecular lesions in this cardiac disorder. Similarly, use of ocular angiogenesis models has only a theoretical relationship with the ability of compounds to inhibit or reverse the growth of cancer metastases. Nonetheless, animal models remain a critical link between in vitro, mechanistic compound characterization and transition to the clinic. The majority of currently used animal models of CNS disorders were developed using drugs, the therapeutic utility of which was determined in the clinic and were invariably mechanism drug rather than disease specific. Even with the many refinements introduced over the past three decades (54), the models available often result in the identification of newer compounds acting via the...

Modelling centre effects Model C

So far, the model has taken no account of the fact that the data are recorded at different centres. It is possible that values in some centres may tend to be higher than those in other centres. Such differences could be due, for example, to differences in the techniques of personnel across centres. It is also possible that some centres clinics may recruit patients with differing degrees of severity of hypertension (within the bounds of the study entry criteria) who could, on average, have higher or lower values of DBP. We can allow for these possibilities by adding centre effects to Model B

Discuss issues associated with estimating volume status in outpatients

For most outpatients the period of fasting would provide a rough estimate of volume deficit. A patient's hourly metabolic requirement is roughly 4 ml kg for the first 10 kg, 2 ml kg for the second 10 kg, and 1 ml kg for the remainder of his or her weight. The actual deficit may be less than calculated because of renal conservation of fluids. Factors that may result in volume depletion include chronic hypertension, diuretic use, diabetes mellitus, alcohol ingestion, and bowel preparations (2 to 4 L may be lost).

Repeated Measures Data

There were four post-treatment visits in the multi-centre hypertension trial introduced in the previous section. However, so far in this chapter we have chosen only to model measurements made at the final visit, which were of primary interest. An alternative strategy would be to include measurements from all four post-treatment visits in the model. Since measurements are made repeatedly on the same patients, we can describe these types of data as repeated measures data. For illustrative purposes we now assume that the centre has no effect at all on

How should acute hyponatremia be treated

The rate at which hyponatremia develops and the presence of symptoms determine the aggressiveness of treatment. If hyponatremia has developed quickly, the patient may develop nausea, vomiting, visual disturbances, muscle cramps, weakness, hypertension, bradycardia, confusion, apprehension, agitation, obtundation, or seizures usually the sodium content is found to be less than 125 mEq L. The aggressiveness of treatment depends on the extent of symptoms.

What is a mixed model

In random coefficients models a covariate effect is allowed to vary randomly. For example, in the repeated measures hypertension data considered in Section 1.4, interest might centre on the rate of change of DBP measured over the four treatment visits in the three arms of the trial. The random coefficients model allows this rate of change (or slope) to vary randomly between patients. This is achieved technically by fitting patients and the patient-slope interaction as random and these effects are referred to as random coefficients.

Future Needs and Unanswered Questions

Future studies that are needed for the evolution of this new assay include normal population distributions by gender and ethnicity an optimum cut-off value for a high versus normal concentration in ACS patients, comparing IMA levels in common disease states both with or without accompanying cardiac disease and added information in common diseases that coexist with cardiac ischemia, such as congestive heart failure, diabetes mellitus, chronic renal disease, hypertension (18). A better understanding of IMA kinetics over the early hours after the onset of an ACS is essential to understanding the interpretative value, if any, of serial monitoring of IMA after presentation.

Regulatory Impediments

In addition to commercial and technical issues, it is clear that ever-changing regulatory hurdles pose significant challenges to new antibiotic development. Because antibiotics can be used to treat more than one infection caused by a specific bacterial species, it is mandated that each infective indication due to S. pneumoniae or any other common pathogen to be treated must be studied in at least two clinical trials with a minimum number of isolates of intended species in each indication (often 10-25 strains per indication, with resistant phenotypes being considered a separate group). Yet despite the apparent prevalence of resistance, it can prove difficult to enroll enough valid patients in each indication to satisfy the needs of the regulatory authorities. This contradictory situation is due to the strict inclusion exclusion criteria, which can markedly reduce the number of evaluable patients. Additionally, in many other diseases that are preferred by the pharmaceutical industry,...

Adiponectin Deficiency and Cardiovascular Diseases

Adiponectin is inversely correlated with a panel of traditional cardiovascular risk factors, including blood pressure, heart rate, and total and low-density lipoprotein (LDL) cholesterol and triglyceride levels, and is positively related to high-density lipoprotein (HDL) cholesterol levels (80,81). Hypoadiponectinemia has been shown to be an independent risk factor for endothelial dysfunction and hypertension, regardless of insulin resistance (82,83). In addition, the association of hypoadiponectinemia with coronary heart disease (84), ischemic cerebrovascular disease (85), and coronary artery calcification (86) was also reported to be independent of classical cardiovascular risk factors, such as diabetes, dyslipidemia, and hypertension. A recent report by Kumada et al. showed that the prevalence of coronary artery disease in male subjects with hypoadiponectinemia (< 4 pg mL) was 2.05-fold higher than those with adiponectin concentrations of more than 7.0 pg mL, after adjustment for...

Classification and evolution of increased cardiometabolic risk states

It has been accurately observed that certain risk factors in humans appear to 'cluster' with clinical states such as obesity and type 2 diabetes. Specifically, this risk factor clustering, and the association with insulin resistance, led investigators to propose the existence of a unique pathophysiological condition1. Many names have been provided to describe this clinical state including 'metabolic syndrome', 'syndrome X', and 'insulin resistance syndrome'1. The particular names that refer to this risk factor clustering describe the human condition characterized by the presence of co-existing traditional risk factors for cardiovascular disease (CVD), such as hypertension, dyslipidemia, glucose intolerance, obesity, and insulin resistance, in addition to non-traditional CVD risk factors, such as inflammatory processes and abnormalities of the blood coagulation system2-6. Table 1.1 lists conditions and components associated with the clustering of risk factors. As seen, the components...

Maintaining a Healthy Weight

Being overweight is a major health problem in the United States, and there are many good reasons to keep your weight within a healthy range. You will feel better, look better, and have more energy than men who are overweight. Having more energy makes you more likely to exercise, which can help you fall asleep faster and sleep more restfully. But the most important reason to keep your weight within a healthy range is that you will lower your risk for certain chronic diseases, including heart disease, high blood pressure, diabetes, and certain forms of cancer. Doctors no longer believe that it is acceptable to gain a few pounds as you age. Maintaining your weight at a reasonable level throughout your life is key when it comes to reducing your risk for disease. Maintaining a healthy weight is one of the most beneficial, although most difficult, things you can do.A healthy weight not only boosts your confidence, but also minimizes your risk for major disorders such as diabetes, heart...

Potential Clinical Applications

Fenfluramine, at least partly, owes its anorectic actions (via 5-HT release and blockade of 5-HT re-uptake) to stimulation of 5-HT2c receptors, whereas its major metabolite norfenfluramine is a potent 5-HT2C agonist (41,42). Fenfluramine was removed from the U.S. market in 1997 because of its association with an increased incidence of valvular heart disease (VHD). It had been also associated with an increased risk for developing primary pulmonary hypertension (PPH). Because of

Arterial Stiffness Aging Arteriosclerosis and Atherosclerosis

Central artery elasticity is critically dependent on normal content and function of the matrix protein elastin, which with a half-life of 40 years, is one of the most stable proteins in the body. Despite this stability, fatigue of elastin fibers and lamellae can occur by the sixth decade of life from the accumulated cyclic stress of more than 2 billion aorta expansions during ventricular contraction. Long-standing cyclic stress in the media of elastic-containing arteries produces fatigue and eventual fracturing of elastin along with structural changes of the ECM that include proliferation of collagen and deposition of calcium 2 . Humoral factors, cytokines, and oxidative metabolites may also play a role. This degenerative process, classically termed arteriosclerosis, is the pathologic process that results in increased central arterial stiffness. In untreated, and even long-term treated hypertensive subjects, an acceleration of the rate of development of conduit artery stiffness is...

Some statistical issues

In the study of the alcohol-health relationship, it is sometimes difficult to differentiate a potential confounder from a mediator of a causal outcome. Examples of these factors are blood pressure, lipoproteins, hemostasis, perceived health status, and other indicators of current health. Control strategies in a data analysis initially should not include risk factors that might serve as potential mediators lying in the pathway between alcohol intake and outcome. Failing to control for confounders may inflate the potential benefit of alcohol intake. On the other hand, improper control for mediators may spuriously deflate the potential benefit of alcohol intake. If, for example, alcohol use increases hemorrhagic stroke risk through alcohol-induced hypertension alone, then control for blood pressure would produce a non-significant association between alcohol consumption and stroke.

Periodic Health Checkups for

Those at risk Men who have diabetes, high blood pressure, or a family history of glaucoma. To detect high blood pressure early, before it leads Those at risk Men with a family history of high blood pressure, heart disease, kidney disease, or stroke men who are overweight or have diabetes men who smoke or use tobacco products.

New Aneurysms And The Need For Followup

After adjustment for age and hypertension, female sex and cigarette smoking have been found to be independent risk factors for aneurysmal formation and growth (130). New formation of aneurysms at different sites have been reported up to 17 years after initial treatment for aneurysmal occlusion, implying a need for long-term follow-up by periodical cerebral angiography (58). In addition, 2 cases have been reported of de novo intracranial aneurysmal formation that developed quickly (131). One patient developed 2 new aneurysms within a 6-month period, whereas the other developed 2 new aneurysms within a 22-month period. Short screening intervals might be necessary in patients at high risk for new aneurysmal formation, including patients who are young, are female, are cigarette smokers, have a history of arterial hypertension, have first-degree relatives with intracranial aneurysms, or who have been previously treated for an intracranial aneurysm.

Acute Vs Chronic Aneurysms Cocainerelated Bleed Sites

The exact mechanism by which berry aneurysms form remains undetermined, but research indicates that propagation and rupture of the aneurysm are aggravated by hypertension and tachycardia (132). The drug most often associated with acute cerebrovascular events is cocaine. Intracerebral hemorrhages or SAHs are the most frequently observed cerebrovascular complications of this drug (123). Several mechanisms might be responsible for the cerebrovascular complications. Traditional teaching is that hypertension is the likely precursive factor in cocaine-induced aneurysmal rupture, and a sudden rise in systemic arterial pressure might cause hemorrhages, frequently in association with an underlying aneurysm or AVM. Recent reports have indicated that these patients might have underlying vascular malformations (133,134). Rupture of aneurysms and AVMs has been detected in up to half of the patients with hemorrhagic stroke due to cocaine abuse. In addition to stroke, cocaine seems to provoke...

Aging and Blood Pressure

Systolic hypertension is an acquired, age-related characteristic that has moderate and variable genetic contribution 11-15 but aging is not inexorably associated with systolic hypertension. In primitive or cloistered societies, there are no relations between age and BP and the incidence of hypertension at any age is very low 16, 17 . In industrialized societies, complex relations between age and BP are found (fig. 1) 6, 18 , where systolic BP increases linearly with age, while diastolic BP increases until about age 50 then declines. Mean arterial pressure (MAP) increases until about age 50 then plateaus, while PP is constant until age 50 then increases. In adults, systolic hypertension is thus the predominant form of the condition and the percent with diastolic hypertension rapidly dwindles with aging. Furthermore, systolic hypertension is not a consequence of longstanding diastolic hypertension, as once thought. Systolic hypertension arises de novo at any age, and often preceding...

Premedication and Preparation

Anxiety-related arterial hypertension, which could lead to aneurysmal rebleeding, must be balanced against the risk of oversedation, which prevents appropriate preoperative neurologic assessment and depresses ventilation. The latter could also result in hypercarbia and subsequent increase in CBF and intracranial pressure (ICP). Patients who present with Hunt and Hess (H& H) (6) or World Federation of Neurological Surgeons (WFNS) (7) Grades I and II benefit from a reassuring preoperative visit by the anesthesiologist. A patient who appears anxious might benefit from a small intravenous (IV) dose of a benzodiazepine and or opioids (midazolam 1-2 mg fentanyl 50-100 mcg) administered. In contrast, patients with a decreased level of consciousness (clinical Grades III and IV) are unlikely to suffer from significant anxiety. In fact, many patients with higher grades are intubated and mechanically ventilated and might need higher doses of benzodiazepines and opioids (IV administration of...

BP Components and Risk

To make matters more confusing, higher MAP and higher PP are each independently associated with increased cardiovascular disease risk. The contrasting effects of MAP and PP on diastolic DBP contribute to the frequently described and often misunderstood non-linear (U- or J-shaped) relation between diastolic BP and cardiovascular events. For example, low diastolic BP and wide PP are associated with increased risk of mortality 21 yet high diastolic BP independently increases risk 22 . The problem is in the confounding caused by the use of diastolic BP as a risk surrogate. The situation becomes much clearer if risk is attributed to either elevated MAP or elevated PP. Hypertension as a clinical condition is thus intrinsically heterogeneous, and is perhaps best considered as an admixture of disordered large artery function (generating systolic hypertension) and disordered microcirculatory function (generating diastolic hypertension). Understanding which form of hypertension to treat and how...

Induction of Anesthesia

Loss of consciousness is usually induced with thiopental (3-5 mg kg), propofol (1.5-2.5 mg kg), or etomidate (0.1-0.2 mg kg), all of which reduce cerebral metabolism and TMP. However, extra precautions are warranted in patients with high clinical grades (III and IV), who are exceptionally vulnerable to developing cerebral ischemia following a reduction in MABP during induction, as their autoregulation might be impaired and some degree of vasospasm might already be present. Opiates are administered (e.g., fentanyl, 5-10 mcg kg or sufentanil, 0.5-1.0 mcg kg) to ameliorate the sympathetic response to laryngoscopy and endotracheal intubation. To further blunt potential systemic hypertension, IV lidocaine (1.5-2.0 mg kg) is favored by many clinicians. In addition, administration of P-antagonists, such as esmolol (0.5 mg kg) or labetalol 10-20 mg kg), a second dose of the induction agent (e.g., thiopental 1-2 mg kg), or inhalation of a volatile anesthetic (e.g., isoflurane) during bag-mask...

Potential Therapeutic Applications

Congestive Heart Failure - Increased plasma levels of NPY are found in patients with cardiovascular disease, including hypertension and heart failure (31). Although a causal role for circulating NPY in these diseases has not been established, a correlation has been established between plasma NPY concentration and severity of left ventricular hypertrophy. NPY can contribute to cardiac hypertrophy via its hemodynamic effects on blood vessels through the NPY Y1 receptor (32). However, NPY can also produce cardiac hypertrophy by acting as a growth factor by directly activating p38, ERK and JNK in primary cardiomyocytes (33), or by potentiating the alpha-adrenergic agonist-induced activation of mitogen-activated protein kinase via the NPY Ys receptor (33). It has also been demonstrated that NPY can increase protein synthesis and or inhibit protein degradation via NPY Y5 receptors in SHR cardiomyocytes (34). NPY Y5 receptors may therefore represent a novel therapeutic target for drugs...

Wide Pulse Pressure Stiffness vs Diameter

It has long been assumed that systolic hypertension simply represents 'burned out' diastolic hypertension and that the age-related widening of PP in older age is simply the result of 'normal' aging. There is no doubt that there is increased aortic stiffness, wall thickness, and elastic modulus with age and that wide PP can arise from the loss of aortic storage capacity (or compliance) and the concomitant loss of elastic recoil function. In a sense, the proximal aorta is the third pumping chamber of the heart. Although its function is large Yet increased aortic wall stiffness does not explain the observation that elevated systolic BP is also the most common presentation of hypertension in middle age, when arterial elasticity is not necessarily abnormal 6, 9, 12, 19 , In these cases, increased aortic impedance is related primarily to smaller aortic diameter, not a stiffer aortic wall 19 . Inspection for the formula for Zc reveals that aortic diameter is profoundly important in the...

Initial Stabilization

Generalized sympathetic activation with high catecholamine levels, as well as pain and anxiety, generally cause elevated blood pressure after SAH. Because hypertension is associated with aneurysmal rerupture, it requires prompt treatment however, headache should be addressed first. Nimodipine, used routinely for prevention of vasospasm, and analgesics may be sufficient for blood pressure control in some patients, whereas others may require the administration of additional antihypertensive medications. The most widely employed agents are combined a-1 and P-blocker labetalol or other general P-blockers, none of which raises ICP. In the presence of a mass lesion or elevated ICP, the use of vasodilators engenders concern, especially venous dilators, such as sodium nitroprusside, which can raise ICP to a significant degree (16). Debate is ongoing regarding the appropriateness of administering agents that are pure arterial dilators, e.g., hydralazine, nicardipine, and angiotensin-converting...

Electrophysiologic Characteristics of Cardiac Arrhythmias That Commonly Occur Following Cardiac Surgery in Humans

Develop as a result of abnormal shortening and dispersion of atrial refractory period and abnormal slowing of atrial conduction velocity 51-55 . Such atrial electrophysiologic abnormalities may result from underlying valvular or myocardial dysfunction or systemic hypertension causing atrial stretch and enlargement, ischemia, or simply aging alone, and may be aggravated in the post-operative period by hemodynamic instability, increased sympathetic and vagal nervous system activity, pericardial inflammation, hypoxia, or electrolyte disturbances. Due to the fact that the reentrant circuits are predominately functionally determined, AFIB cannot be entrained nor terminated by rapid overdrive atrial pacing. Atrial fibrillation may be converted and suppressed by antiarrhythmic drugs, the most effective being those which prolong atrial refractoriness in a use-dependent manner. However, since AFIB involves multiple reentrant circuits, its cure requires creation of extensive linear lesions,...

Pulse Transmission in Conduit Arteries

Diastolic or mean BP, systolic BP is thus not constant throughout the arterial tree. Within an individual, smaller distal arteries have higher input impedances than large central arteries because of the combined impact of decreasing lumen diameter and increasing effective wall stiffness. This increasing arterial stiffness gradient leads to the phenomenon of true pulse pressure amplification (PPA), where the amplitude of the forward wave increases within large and medium-sized arteries, so that systolic BP is normally higher in the peripheral arteries than in the aorta. PPA is variable between individuals but follows certain rules 47 . With normal aging, there is a reversal of the normal tendency for distal arterial stiffness (PWV) to exceed central arterial stiffness, a phenomenon that would be expected to lower the degree of PPA observed 9 . Muscular conduit arteries (e.g. brachial or femoral arteries) in hypertension do not usually differ from normal arteries in their stiffness,...

Clinical Feeding Study Results

The Lyon Diet Heart study and the Indo-Mediterranean diet trial relied on behavior modification strategies to promote adoption of the Mediterranean diet plans to participants. Compliance with dietary recommendations was hard to assess and effects of on-traditional CVD risk factors hard to ascertain. In fact, in the Lyon Diet Heart study, end-of study assessment of the traditional CVD risk factors including blood pressure and lipids, were not different between groups.8 This finding was unexpected as emphasis on unsaturated fatty acids rather than saturated or trans-fatty acids would be expected to beneficially affect serum lipid levels.23 Likewise, dietary patterns emphasizing fruits and vegetables have been shown to substantially lower blood pressure and are discussed next.2 Hence determining the effects of the Mediterranean diet on traditional CVD risk factors, including blood pressure and lipids, and on markers of oxidative stress, may be best determined in a different setting...

Amplification and Reflection Central vs Peripheral BP

In the arm, the amplitude of the forward wave is generally much greater than the amplitude of the reflected wave, so brachial cuff systolic BP conveys information primarily about the forward wave, including PPA, but is largely blind to changes in wave reflection (fig. 3). In contrast, peak central systolic BP is the result of a different admixture of the forward and reflected pressure waves, where the pulse pressure generated by the forward pressure wave may be augmented by as much as 100 by the reflected wave. In such cases, there may be very little difference between central and peripheral peak systolic pressure 40 and thus very little apparent PPA. This does not mean that true PPA of the forward wave is absent, just that the sum of the forward and reflected waves in the aorta is equal to the degree of true PPA of the forward wave in the arm. PPA tends to be greater in young individuals with isolated systolic hypertension despite lower SVR 47 . central PP caused by the principal...

Small Arteries and Arterioles

Aging and disease modify vascular structure and function. Hypertension is associated with vasoconstriction, VSM hypertrophy and rarefaction in the microcirculation. Pulse volume, pressure, and velocity are important physiological variables that may function as biologic signals to the endothelium and VSM of the microcirculation. The capillary pulse volume modifies and in turn is modified by microcirculatory structure and function. For example, both MAP and PP affect glomerular filtration rate independently, presumably through direct effects on glomerular filtration pressure 61 . Increased systolic BP or PP is associated with a variety of disorders related to aging, including atherosclerotic cardiovascular disease 62, 63 , heart failure 64 , stroke 65, 66 , cognitive disorders 67-69 , white matter lesions 70, 71 , macular degeneration 72 , renal dysfunction 73 , osteoporosis 74 , and glucose intolerance 75-77 . Abnormal microcirculatory pulsation may participate in the pathogenesis of...

Rationale For Drugs Treating Heart Failure

Renin-Angiotensin - The activity of the renin-angiotensin system is elevated in patients with heart failure. Reduced cardiac output leads to renal hypoperfusion and to increased synthesis and release of renin into the circulation. Renin cleaves angiotensinogen to angiotensin I, and angiotensin converting enzyme (ACE) cleaves angiotensin I to angiotensin II (11 - 13). Increased production of angiotensin II has multiple physiological and biochemical actions. Angiotensin II binding to ATi receptors on smooth muscle cells causes contraction, vasoconstriction and increases peripheral vascular resistance, which deleteriously augments cardiac afterload (14). As a vasoconstrictor, angiotensin II causes hypertension that induces left ventricular remodeling and hypertrophy. Angiotensin II binding to cardiomyocyte ATi receptors directly stimulates hypertrophy leading to left ventricular enlargement, reduced myocyte contractility and reduced cardiac output (15, 16). Angiotensin II increases Na+...

Other Pathological Events

When differentiating asthma from other obstructive airways disease, it is always relevant to ask if family members experience the same symptoms. It is well recognized that asthma is the result of both genetic and environmental influences. Asthma, as with many other medical conditions, such as hypertension and diabetes mellitus, is a complex genetic disorder. It cannot be classified as an autosomal-dominant, recessive, or sex-linked pattern of inheritance. At the present time, several chromosomal regions have been identified to be strongly associated with asthma, such as 5q31, 6, 11q13, 12q, 13q14, and so on. The 5q31, for example, is on chromosome 5. It influences total IgE production, eosinophil count, IL-4, IL-5, and IL-13 production, CD14 expression, and so on. The completion of human genome sequencing will certainly help facilitate the process of identifying genes involved in asthma.

Rationale For The Use Of Direct Renin Inhibitors

Blockade of the RAAS is a primary treatment in many cardiovascular-renal diseases including hypertension, congestive heart failure and renal disease 3 . The ultimate goal of such therapy is to block the formation or action of Ang II, the principal effector of this pathway. Until the approval of aliskiren, the RAAS could be inhibited either at the step of conversion of Ang I to Ang II with Ang I converting enzyme inhibitors (ACEi) or at

Preclinical Models To Study Direct Renin Inhibitors

The road towards developing human renin inhibitors has been challenging with respect to establishing appropriate in vivo models in which to test the efficacy of these compounds. This difficulty relates, at least in part, to the prominent species specificity displayed by renin and the high primate specificity of potent human renin inhibitors. Thus, most inhibitors of human renin are only weakly effective in rats. Consequently, although rats are the most commonly used species in hypertension efficacy studies, such models have been of limited use to study human renin inhibitors 4 . Potent inhibitors of rat renin have allowed in vivo studies in this species however, the design of dual human-rat renin inhibitors has been extremely challenging 5,6 . Normotensive nonhuman primates such as cynomolgus, squirrel, rhesus and marmosets 7-9 , and dogs 10,11 , in which the RAAS is stimulated by a low salt diet and or a diuretic, have been used to demonstrate the efficacy of renin inhibition on BP,...

Mediterranean Diet Effects on Oxidative Stress

The direct relationship between traditional CVD risk factors and risk of atherosclerosis is well established. Dietary modifications which lower blood pressure and lipids provide a likely explanation for much of the risk reduction. However, oxidative stress, including oxidation of LDL-c (oxLDL) appears to be an important,

Role of obesity and body fat distribution in cardiometabolic risk

Complications which seem to affect every major organ system (Table 3.2). Specifically, obesity increases an individual's risk for cancer, gastrointestinal diseases, arthritis, and adversely affects psychological well-being. However, the major concern, as described in detail in this Atlas, is the markedly increased risk to develop diabetes and cardiovascular disease in those individuals who are obese. Specifically, obesity is significantly associated with both the traditional risk factors, i.e. hypertension, dyslipidemia, diabetes, and the non-traditional risk factors, i.e. fibrinogen and inflammatory markers, of cardiovascular disease. In addition,

Clinical Grading Scales

Regardless of the scale used, admission clinical grade predicts mortality. However, aSAH is a complex disease, with many causes of secondary deterioration, including rebleeding, delayed ischemia from vasospasm, hydrocephalus, cerebral edema, and a host of medical complications. For this reason, a patient's worst clinical grade during the course of hospitalization has a closer correlation with outcome than the admission grade (8). In addition to clinical grade, other important predictors of mortality and poor outcome after aSAH include age, aneurysm size, rebleeding, intraventricular hemorrhage, global cerebral edema, and physiologic derangements, such as hypertension or hypotension, hypoxia, hyperglycemia, and fever (9 ).

Section Ii Cardiovascular And Pulmonary Agents

Antihypertensive Agents Introduction - Pharmacologic therapy of hypertension decreases overall cardiovascular morbidity and mortality, but fails to show a clear reduction in the risk of coronary heart disease (CHD) (1-4). Although many explanations have been offered for the lack of demonstrated benefit for CHD, one hypothesis in continued focus involves the unfavorable metabolic and biochemical changes caused by diuretics or (3-adrenoceptor antagonists devoid of intrinsic sympathomimetic activity (5). These drugs were used in the majority of the hypertensive clinical trials completed to date and adversely affect many of the known risk factors for CHD, including hyperlipemia, hyperglycemia and elevated plasma catecholamine levels. These potentially deleterious changes might have offset expected benefits of blood pressure reduction. Since CHD is still the primary cause of death in the United States, long-acting calcium entry blockers, angiotensin converting enzyme (ACE)...

Arsenic Exposure And Population At Risk

A large number of epidemiological investigations have confirmed that high concentrations of arsenic are associated with skin lesions, peripheral vascular diseases, polyneuropathy, hepatopathy, diabetes mellitus, hypertension and a high risk of various skin cancers and internal cancers (Maloney, 1996). Moreover, an appropriate standard for arsenic in drinking water is still under discussion. Whether 0.01 mg l should replace 0.05 mg l as the standard has drawn much attention and caused many controversies among the researchers as well as the governments. North et al. (1997) suggested that the endemic areas can be divided into three groups (1) high dose regions where people ingest from one to several milligrams of arsenic per day (above 0.5 mg l) and where various skin and internal cancers and other health problems have been found (2) medium or intermediate dose regions, where intake ranges from 100 m to 1 mg per day (0.05-0.5 mg l or so), where health

Why are epinephrine and phenylephrine often added to local anesthetics What cautions are advisable regarding the use of

These drugs cause local tissue vasoconstriction, limiting uptake of the local anesthetic into the vasculature and thus prolonging its effects and reducing its toxic potential (see Question 14). Epinephrine, usually in 1 200,000 concentration, is also a useful marker of inadvertent intravascular injection. Epinephrine is contraindicated for digital blocks or other areas with poor collateral circulation. Systemic absorption of epinephrine may also cause hypertension and cardiac dysrhythmias, and caution is advised in patients with ischemic heart disease, hypertension, preeclampsia, and other conditions in which such responses may be undesirable.

Describe the etiology of tachyphylaxis with nitrovasodilators

Therapy with nitroglycerin is often confounded by tachyphylaxis, especially with long-term use, because of changes in the enzymatic machinery responsible for its transformation into NO. Tachyphylaxis may also be caused by adaptive changes in the vascular system itself. Nitrates may also be of limited clinical effect in the presence of a preload insensitive system and fixed pulmonary hypertension.

Discuss the types and mechanisms of action of selective vasodilating agents available for clinical use

Nicardipine is a short-acting selective calcium channel blocker (CCB) that acts on the arteriolar beds, providing easier titration and controlled reduction in systemic blood pressure. Nicardipine is becoming the arterial vasodilator of choice for cardiac surgery patients with hypertension since it has more selective coronary vasodilation than systemic vasodilation. The end result is a reduction in afterload increased stroke volume and increased coronary blood flow, which results in a favorable effect on myocardial oxygen balance. Onset is 5 to 15 minutes, and duration of action is 4 to 6 hours.

Family Medical History

'In your family - that is, your parents, brothers and sisters - are there any health problems that seem to run through the family ' You may prompt with suggestion such as diabetes, hypertension, and skin problems. This gives you information about predisposition, especially with diabetes and skin problems, and helps with differential diagnosis and may be a contributing factor in the reason for the visit, as for example with impotence or recurrent vaginal candidiasis.

Clinical Studies With Aliskiren

Results from an extensive clinical development plan for aliskiren continue to become available 61,77 . This renin inhibitor has a very long half-life ( 40 h) and consequently provides 24 h BP control 78 , despite its low absolute oral bioavailability of 2.6 in human 62 . Aliskiren consistently shows strong anti-hypertensive activity, at least as effective as ACEi or ARB, in patients with mild-moderate hypertension. The side effect profile is comparable to placebo. It is noteworthy that this

Limitations Of Animal Models

Human ICH usually occurs in the setting of longstanding comorbidities (e.g., tobacco use, diabetes, hypertension) and commonly in the presence of active drugs (e.g., antiplatelet, anticoagulant, statin). These conditions cannot be easily reproduced in animal models. For example, even spontaneously hypertensive rats are not likely to reproduce the decades-long effects in humans of elevated arterial pressure. Human ICH also varies by race, in incidence overall, and in incidence by age epoch, suggesting important and yet-to-be-discovered variations in genetic susceptibility. Inferences regarding treatment must also be drawn with caution. Findings have demonstrated significant benefits from mechanical and pharmacologic interventions that have not been reproduced in human trials, whether small and focused (51,119) or large and inclusive (120). Among the several potential explanations for these discrepancies, delay in treating ICH patients is the likeliest. However, toward improving the...

Arterial Stiffness and Extracellular Matrix

The growing prevalence and associated risk of arterial stiffness provide a major challenge to better understand the underlying causes and the resultant physiological impact of this condition. Structural components within the arterial wall, mainly collagen and elastin, are considered to be major determinants of arterial stiffness. Thus, quantitative and qualitative alterations of collagen and elastin fibers are involved in arterial stiffening that is associated with the aging process and disease states such as hypertension, diabetes, atherosclerosis, and chronic renal failure. Elucidation of mechanisms leading to the above alterations will aid in more specifically targeted therapeutic interventions because currently available cardiovascular medications fall short at reducing the stiffness of the large arteries. Reduction of arterial stiffness will likely have a significant impact on morbidity and mortality of older adults, as well as subjects suffering from cardiovascular and renal...

Pathology Of Hematoma And Mechanical Compression

Hematoma formation is not a monophasic event, and it may certainly expand. The cause of hematoma expansion is not yet clear, but it is attributed to progressive bleeding from the primary source, resulting from disruption of surrounding vessels, hypertension, or a coagulation deficit

Kallikreins in Normal Physiology

Little is known about the physiological functions of kallikreins in normal tissues. However, accumulating evidence indicates that kallikreins might have diverse functions, depending on the tissue and circumstances of expression. hK1 exerts its biological activity mainly through the release of lysyl-bradykinin (kallidin). It cleaves low-molecular weight kininogen to produce vasoactive kinin peptides. Intact kinin binds to bradykinin B2 receptor in target tissues and exerts a broad spectrum of biological effects including blood pressure reduction via vasodilatation, smooth muscle relaxation or contraction, pain induction, and mediation of the inflammatory response 177 . Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans 178 . It has also been reported that tissue kallikrein cleaves kininogen substrate to produce vasoactive kinin peptides that have been implicated in the proliferation of vascular smooth muscle...

Alcohol And The Cardiovascular System

Social drinking is often associated with a small rise of systolic blood pressure, which may have negligible effects in healthy adults. Cardiovascular events such as hypertension, stroke, arrhythmia, heart failure, and sudden death have been associated with heavy alcohol drinkers. In fact, chronic alcohol ingestion is a major cause of nonischemic cardiomyopathy in the Western world with an incidence ranging from 21-32 9 , Most common in middle-aged individuals who have consumed large amounts of alcohol for more than 10 years resulting in heart failure 10 , there is also an increased incidence of sudden death that apparently peaks about 50 years of age in the alcoholic population without heart failure.

Etiologic Factors For Intracerebral Hemorrhage

An ICH, classified as either primary or secondary, can be caused by a variety of factors (Table 1). Primary ICH refers to spontaneous hemorrhage from systemic hypertension. Hypertensive ICH usually occurs in middle-aged to older patients, and the hemorrhage might be attributed to small aneurysmal dilatations on the small, perforating cerebral arteries. These aneurysms are usually multiple, tend to occur in arteries < 25 pm in diameter, and might attain a diameter of up to 2 mm. These microaneurysms are usually seen in hypertensive patients and are occasionally seen in normotensive patients and in those over 65 years of age. Secondary ICH can occur due to a variety of underlying structural abnormalities, including a ruptured cerebral aneu-rysm, arteriovenous malformation, other vascular malformation, cerebral amyloid angiopathy, tumors, trauma, and vasculitis. ICH can also occur secondary to coagulopathy that results from thrombocytopenia and anticoagulant therapy. Thrombolytic...

Vitamin E Primary Prevention Trials

The Primary Prevention Project (PPP) was an open-label 2 x 2 factorial trial of vitamin E (300 mg d) and low-dose aspirin in 4,495 Italian men and women with one or more of the following CVD risk factors hypertension, hypercholesterolemia, diabetes, obesity, family history of premature MI, or age > 65 years.32 Since there was convincing evidence that aspirin was beneficial, the trial was stopped early after a mean follow-up of 3.6 years. At that time, vitamin E had no effect on any prespecified endpoint including the main combined endpoint of CVD death, nonfatal MI, and nonfatal stroke (RR 1.07 95 CI, 0.74-1.56). The negative result may have been due to insufficient statistical power or inadequate dosing of vitamin E.

Vitamin E Secondary Prevention Trials

The Heart Outcomes Prevention Evaluation (HOPE) study randomized 9,541 participants with CVD or diabetes and at least one other CVD risk factor (hypertension, hypercholesterolemia, smoking, low HDL, or microalbuminuria) into a study of vitamin E (400 IU daily), the angiotensin-converting enzyme inhibitor ramipril, both agents, or neither.45 The study was stopped early after a mean follow-up of 4.5 years because of the beneficial effects of ramipril. Vitamin E had no effect on the primary combined endpoint of MI, stroke, and CVD death (RR 1.05 95 CI, 0.95-1.16), and secondary analysis of various CVD endpoints (e.g., unstable angina, revascularization) also failed to show any reduced risk with vitamin E supplementation. The HOPE study had high rates of compliance and used large doses of vitamin E, and an extension of the trial, HOPE-The Ongoing Outcomes (HOPE-TOO) continued to follow nearly 4,000 participants for a median duration of 7.0 years.46 In HOPE-TOO, vitamin E supplementation...

Blood Pressure Management

The accurate assessment of the hemodynamic state in ICH patients is of primary importance during their early management. The vast majority of acute stroke patients present with elevated blood pressure as clinical manifestation of a long-standing premorbid condition, as a physiologic response to the acute neurologic insult, or as a combination of both. In the unusual situation in which hypotension occurs, etiologic causes, such as hypovolemia, neuro cardio-genic cardiac dysfunction, or significant bleeding at a remote site, must be investigated and treated aggressively, once demonstrated. Vascular access must be adequate for all diagnostic and therapeutic interventions. Central venous access should be considered for patients who require administration of vasoactive drugs or who have inadequate peripheral vein caliber to accommodate the large-bore catheters that are necessary for resuscitation. Insertion of an arterial catheter should be considered in patients in whom measurement of...

Blood Pressure Large Arteries and Atherosclerosis

It is generally accepted that the increased cardiovascular morbidity and mortality in hypertension are related to target organ damage. Classically, the target organs are heart, brain, and kidneys. This brief report examines whether high arterial pressure may also affect other organs, such as aorta and large arteries. An attempt was also made to elucidate the relationship between disorders of the aorta and large arteries and other cardiovascular risk factors to the pathophysiology and treatment of patients with hypertension and its severe comorbid disease, atherosclerosis. High Blood Pressure and Disorders of the Aorta and Large Arteries The positive correlation between arterial pressure and adverse cardiovascular events is certainly well documented. It was Sir George Pickering who vigorously opposed the idea of dividing blood pressure into normotension and hypertension stating that ' the various complications, like myocardial infarction and stroke, are also quantitatively related to...

Treatment Of Precipitating Factors

Primary and secondary prevention of spontaneous ICH require optimal blood pressure control. The Systolic Hypertension in the Elderly Program study reported that treatment of isolated systolic hypertension in the elderly profoundly decreased the risk of ICH (63 ). In younger nonhypertensive patients, further investigations, such as cerebral angiography, are warranted due to the high prevalence of aneurysms and AVMs. Older patients are at higher risk for brain tumors, both primary and metastatic, and a brain MRI is recommended in such cases. Amyloid angiopathy is a common etiologic factor in older patients, with multiple lobar hemorrhages, who do not have significant history of hypertension (64). Based on preliminary animal testing (65), the efficacy of the antiamyloidotic agent Cerebril is currently being tested in the setting of lobar hemorrhage related to amyloid angiopathy (Phase II Pilot Study of the Safety, Tolerability, and Pharmacokinetics of Cerebril in Patients with Lobar...

Laboratory Evaluation

Laboratory measurements that should raise concern for portal hypertension include abnormal liver chemistries and other serum markers of chronic liver disease. Elevated aminotransferases signal hepatocellular injury, but there is no correlation between the degree of transaminase elevation and the severity of histologic injury. Cholestatic liver chemistries (increased alkaline phosphatase, GGT) may reflect chronic biliary obstruction from PBC or PSC. Hypoalbuminemia and elevated prothrombin time suggest possible decreased hepatic synthetic function. Thrombocytopenia is commonly found in patients with portal hypertension, splenomegaly, and platelet sequestration. An abdominal ultrasound examination that demonstrates a large-diameter portal vein in combination with a platelet count of 140,000 mm3 or less is a sensitive predictor of portal hypertension (5).

Metabolic Regulation and Autoregulation

Autoregulation refers to the ability of a vascular bed to constrict and dilate, in order to maintain flow constant during changes in perfusion pressure. In the coronary circulation, autoregulation is most effective between pressures of 40 and 160 mmHg. The range of pressures over which autoregulation can be observed is different for the subendo-cardium, as compared with the subepicardium. Thus, flow will begin to decrease at pressures < 70-75 mmHg in the subendocardium, as opposed to substantially lower pressures in the more superficial layers of the heart (41). Importantly, chronic hypertension shifts the range of pressures over which autoregulation occurs in the subendocardium such that flow will begin to decline at even higher pressures. This may be related to changes in subendocardial perfusion pressure (discussed earlier) and thus may also explain the propensity for the subendocardium to develop ischemia in the setting of myocardial hypertrophy. Of note, during both...

What is controlled hypoventilation with permissive hypercapnia

Protecting the lung than on maintaining eucapnia. The set VT is lowered to a range of approximately 4 to 6 ml kg IBW in an attempt to keep the Peak airway pressure (Paw) below 35 to 40 cm H2O and the static plateau pressure below 30 cm H2O. Several studies in ARDS and status asthmaticus have shown a decrease in barotrauma, intensive care days, and mortality. The PCO2 is allowed to rise slowly to a level of up to 80 to 100 mm Hg. If pH falls below 7.20, it may be treated with a buffer. Alternatively one may wait for the normal kidney to retain bicarbonate in response to the hypercapnia. Permissive hypercapnia is usually well tolerated. Potential adverse effects include cerebral vasodilation leading to increased ICP, and intracranial hypertension is the only absolute contraindication to permissive hypercapnia. Increased sympathetic activity, pulmonary vasoconstriction, and cardiac arrhythmias may occur but are rarely significant. Depression of cardiac contractility may be a problem in...

Success friendship and dominance

As a final example of a social motive, we all vary with respect to our liking for power. This is concerned with wanting to be dominant and or to be recognised as of high status or good repute. Those with a high need for power tend to have high blood pressure and high catecholamine levels, which means that they are relatively argumentative, tend to be angry, play much sport and have trouble sleeping. Of course, as well as there being large variation in the need for power, there is a similarly large variation in how people use whatever power they might have. At one extreme are social goals and at the other personal ambition and aggrandisement very different styles of leadership might result.

Susceptibility To Carotid Atherosclerosis

In a recent study in northeastern Taiwan, the prevalence of carotid atherosclerosis was significantly associated with the genetic polymorphism of glutathione S-transferase (GST) P1, but not with GST M1 and T1 (Wang, 1999). The odds ratio of developing carotid atherosclerosis was around two-fold for those who had variant genotypes of GST P1 (VV WV) compared with those having a wild genotype (WW) after adjustment for arsenic concentration in drinking water, age, sex, hypertension, and genotypes of p53 codon 72. The genetic polymorphism of p53 codon 72 was also associated with the risk of carotid atherosclerosis. The multivariate-adjusted odds ratio of developing carotid atherosclerosis was 1.6 for those who had variant genotypes of p53 codon 72 (VV WV) compared with those who had a wild genotype (WW).

Metabolism And Inactivation

A review of the current literature reveals that people with hypertension are also likely to suffer from insulin resistance, glucose intolerance and hyperinsulinaemia (Sowers, 1991). Likewise, hypertension is prevalent in obese and diabetic patients. Insulin deficiency at the cellular level may be a common mechanism in the development of hypertension in patients with Type-I or Type-II diabetes mellitus. Essential hypertension appears to be an insulin-resistant state (Sowers, 1991). Insulin resistance may engender hypertension by increasing peripheral vascular resistance and also by increasing salt retention at the level of the kidney. Therefore effective antihypertensive therapy should include agents that do not adversely affect carbohydrate metabolic abnormalities. Commonly used antihypertensive agents, such as thiazide, thiazide-like diur tica and 3-blockers, are associated with glucose intolerance and increased insulin resistance (Sowers, 1991). In contrast, angiotensin-converting...

Atrial Natriuretic Peptide

Angiotensin-aldosterone system, indicating that ANP may play an important role in regulating fluid balance (73,74). Elevated plasma concentrations of ANP have been reported In a variety of diseases including hypertension, congestive heart failure (CHF) and renal failure (75-77). In addition, a correlation has been reported between decreases in ejection fraction in patients with heart failure and increases in plasma ANP (75).

Prevention Of Portal Hypertensive Bleeding

Prevention of the first and subsequent variceal hemorrhages requires a blend of pharmacologic and endoscopic therapies. Several studies have evaluated the efficacy of pharmacotherapy to decrease the risk of bleeding in patients with known portal hypertension. Pharmacologic efforts at prevention have focused on reducing portal hypertension by reducing portal blood flow, whereas endoscopic techniques strive to obliterate varices prophylactically. Nonselective (-adrenergic antagonists such as nadolol or propanolol are widely regarded as the first step to prevent variceal hemorrhage. By blocking (1 and (2 receptors, drugs such as nadolol and propanolol reduce cardiac output ((1) and block mesenteric vasodilation ((2). The effect on ( 2 receptors in the splanchnic bed allows unopposed vasoconstriction mediated by a-adrenergic receptors. Thus, both decreased inotropy and chronotropy by the heart and unopposed splanchnic vasoconstriction combine to decrease portal blood flow. The optimal...

A patient has a left bundlebranch block that is new compared to the ECG from 2 years ago How should I proceed

Even in the absence of an acute MI, an LBBB may indicate underlying structural heart disease such as a dilated cardiomyopathy or left ventricular hypertrophy. History and physical examination looking for signs and symptoms of angina, heart failure, syncope, hypertension, and valvular heart disease, are important. For elective situations echocardiography is reasonable to lookfor structural heart disease. Some practitioners obtain stress imaging (such as with adenosine or persantine nuclear perfusion scintigraphy) to exclude chronic ischemic heart disease as a cause of LBBB.

Properties of the Coronary Microcirculation

A particularly important aspect of endothelial regulation of vasomo-tion is that endothelial-mediated vasodilation is abnormal in a variety of pathological conditions. These include atherosclerosis, hypercholester-olemia, diabetes, hypertension, cigarette smoking, and aging. The mechanisms underlying these abnormal endothelium-dependent responses have been the subject of substantial debate. Deficiencies of the substrate for eNOS, l-arginine, and the co-factor tetrahydrobiopterin have all been implicated, as well as the endogenous competitor of l- arginine for eNOS, asymmetric dimethylarginine. Abnormalities of G protein signaling, resulting in reduced activation of eNOS in response to endothelial cell receptor activation, have also been shown to occur. A substantial body of data suggests that in some of these conditions (hypercholesterolemia, hypertension, and diabetes), increased production of vascular superoxide (*02-) occurs. Superoxide reacts very rapidly with NO*, leading to the...

Reducing Blood Pressure Naturally

Reducing Blood Pressure Naturally

Do You Suffer From High Blood Pressure? Do You Feel Like This Silent Killer Might Be Stalking You? Have you been diagnosed or pre-hypertension and hypertension? Then JOIN THE CROWD Nearly 1 in 3 adults in the United States suffer from High Blood Pressure and only 1 in 3 adults are actually aware that they have it.

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