Pharmacologic Preconditioning

A more clinically relevant mode of ischemic tolerance induction, known as pharmacologic preconditioning, uses clinically available drugs. For example, promising results have been shown using acetylsalicylic acid (33), as well as the antibiotics kanamycin and erythromycin (34,35). Erythropoietin has also been shown to induce tolerance to ischemia (36). Finally, preischemic exposure to volatile anesthetics, such as halothane and isoflurane, has also been reported to induce ischemic tolerance in the brain (37). In heart, other pharmacologic agents, including nitric oxide (NO) donors, adenosine-receptor agonists, endotoxin derivatives, or opioid-recep-tor agonists have been shown to mimic the preconditioning effect. Further understanding of the mechanisms underlying the induction and acquisition of tolerance in brain could lead to the development of new clinically useful pharmacologic agents based on their ability to mimic preconditioning and elaborate endogenous mechanisms of ischemic protection. Below, we review mechanisms proposed to mediate ischemic tolerance induction in brain.

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