REDUCTION IN SURGICAL ISCHEMIC-REPERFUSION INJURY WITH ADENOSINE AND NITRIC-OXIDE THERAPY

Ischemia and reperfusion impair the inherent capacity of the heart to protect itself from related pathophysiologic events by reducing endogenous oxygen radical scavengers and inhibitors. However, other endogenously produced agents, notably adenosine and nitric oxide, are produced during ischemia, reperfusion, or both. These autacoids have several cardioprotection actions in common, particularly antineutrophil effects and inhibition of endothelial-neutrophil interactions, which are key initial steps in ischemic-reperfusion injury. Studies have shown that nitric oxide exerts cardioprotection primarily during reperfusion. Adenosine, on the other hand, protects the myocardium to some extent during both ischemia and reperfusion, thereby covering both periods during which myocardial injury may be sustained during a cardiac operation. Native adenosine or active analogues, or donors of nitric oxide, may be given before or in conjunction with cardioplegia solutions. However, these endogenous agents can also be pharmacologically recruited to provide a new potent therapeutic approach against surgical ischemic-reperfusion injury. This article reviews the cardioprotective effects of primarily endogenous nitric oxide and adenosine in both nonsurgical and surgical models of ischemia-reperfusion injury. Both adenosine and nitric oxide provide potent cardioprotection in surgical and nonsurgical models of ischemia-reperfusion. An important mechanism in this cardioprotection is attenuation of neutrophil-mediated damage.