BMPS: Belzer Machine Perfusion Solution (KPS1 from Organ Recovery Systems). UW: University of Wisconsin solution (ViaSpan from Barr Laboratories). HTS/M: HypoThermo-sol/Maintenance (BioLife Solutions). HTS/P: HypoThermosol-Purge (BioLife Solutions). Unisol-I: Unisol-Intracellular Base (Organ Recovery Systems). Unisol-E: Unisol-Extracel-lular base (Organ Recovery Systems). * = mg/l. ** = U/l. @ = at 25°C. $ = at 0°C
Based upon the principles that have emerged from isolated organ preservation studies, an attempt was made to incorporate the important characteristics in the formulation of the hypothermic blood substitute solutions, and components that might fulfill multiple roles were selected wherever possible. Conceptually, this strategy would maximize the intrinsic qualities of the solutions that, by design as universal tissue-preservation solutions, would inevitably be a hybrid of other hypothermic perfusates and storage-media.
The composition of the new hypothermic blood substitutes is listed in Table 2.3 and the rationale for their formulation is described in Chapter 8 and elsewhere.28,67,190,221 These solutions have been shown to protect the brain, heart, and visceral organs during 3.5 hours of cardiac arrest and global ischemia in an asanguineous canine model during controlled profound hypothermia at less than 10°C.28,66,67 More recently, this approach has been applied experimentally to animal models (porcine and canine) of hemorrhagic shock.139,140,222-224,225 This novel approach to clinical suspended animation (or corporoplegia, meaning literally "body paralysis"226) has been explored for resuscitation after traumatic hemorrhagic shock in preclinical models relevant to both civilian and military applications.225,139,222,223 In exsanguinating cardiac arrest (CA) conventional resuscitation attempts are futile and result in 100% mortality.
In prior research studies our collaborators at the University of Pittsburgh introduced the use of cold aortic saline flush at the start of CA to rapidly induce protective hypothermia during prolonged CA (120 min) for hemostasis followed by resuscitation.222,223 Using a canine model, they showed that a saline flush to a brain temperature of 10°C resulted in normal survival after 90 minutes, but not consistently after CA = 120 minutes. However, an additional study in which Unisol plus the antioxidant Tempol was evaluated as a comparative "optimized flush" showed a markedly improved outcome in regards to physiology, neurology, and brain histology after 120 minutes CA compared with the saline flush.
In separate studies, our collaborators at the Uniformed Services University of the Health Sciences have developed a porcine model of uncontrolled lethal hemorrhage in which a combination of the Maintenance and Purge solutions were used in a cardiopulmonary bypass (CPB) technique to effect profound hypothermia and prolonged cardiac arrest (60 minutes) with resuscitation after surgical repair of the vascular deficit induced to effect exsanguinations.139,140 In the most recent study, after rewarming and discontinuation of CPB, pigs were recovered and monitored for 6 weeks for neurological deficits, cognitive function (learning new skills), and organ dysfunction. Detailed examination of brains was performed at 6 weeks. All the normothermic control animals died, whereas 90% of the HBS animals survived and were neurologically intact, displayed normal learning and memory capability, and had no long-term organ dysfunction. Profound hypothermia markedly diminished total body metabolic activity as evidenced by significantly lower buildup of lactic acid during the periods of hypothermia and rewarming. Histologic examination of brains from the HBS survivors after 6 weeks revealed no ischemic damage in any of the animals, in marked contrast to the brains from control animals, which all showed diffuse ischemic damage.225
Successful application of this technique to man would provide a greater than threefold extension of the current limits of less than one hour for "safe" arrest without a high risk of neurological complications. This novel approach to bloodless surgery would significantly broaden the window of opportunity for surgical intervention in a variety of currently inoperable cases, principally in the areas of cardiovascular surgery, neurosurgery, and emergency trauma surgery. This provides further evidence for the protective properties of solutions such as Unisol used for global tissue preservation during whole-body perfusion in which the microvasculature of the heart and brain are especially vulnerable to ischemic injury.28 Moreover, the application of solution design for clinical suspended animation under conditions of ultraprofound hypothermia places the HBS solutions HypoThermosol and Unisol in a unique category as universal preservation media for all tissues in the body. In contrast, all other preservation media, including the most widely used commercial solutions such as UW-ViaSpan are established for specific organs, or groups of organs (e.g., UW for abdominal organs and Celsior, Cardiosol, or Custodiol for thoracic organs).128,204 Moreover, the demonstrated efficacy of these synthetic, acellular, hypothermic blood-substitute solutions justifies their consideration for multiple organ harvesting from cadaveric and heart-beating donors.227
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