Myocardial Ischemia-Reperfusion Injury in the Isolated Heart

Inhibition of Myocardial Ischemia-Reperfusion Injury in the Isolated Heart 

The protective effects of the Mn(ii)-based SOD mimics against myocardial ischemia/reperfusion injury in the isolated rabbit heart and monkey heart have been investigated. Kilgore et subjected Langendorff perfused, isolated rabbit hearts to a 30 minute period of global ischemia followed by a 45 minute period of reperfusion. Upon reperfusion, an increase in left ventricular end-diastolic pressure occurred, which was attenuated when the hearts were perfused with 20/.iM SC-52608. Perfusion of SC-52608 also inhibited the release of creatine kinase and intracellular potassium, and reduced the extent of antibody binding to the intracellular protein myosin which occurs upon reperfusion of the ischemic heart. These studies indicated that SC-52608 is cardioprotective to the reperfused, ischemic isolated rabbit heart. 

Friedrichs et have also demonstrated a protective effect of SC-52608 from ischemia-reperfusion injury in the isolated primate heart. The isolated hearts were subjected to 35 minutes of global ischemia followed by 45 minutes of reperfusion. Perfusion of 48 SC-52608 attenuated the increase in end-dias- 

The SOD enzyme has been reported to protect against myocardial reperfusion to ischemic tissue however, there are also many reports in the literature that indicate the enzyme does not offer protection. In those cases where protection has been observed and dose responses have been examined, the SOD enzyme shows a bell-shaped dose-response curve. The discrepancy among reports of the effectiveness of the SOD enzyme may be due to a narrow bell-shaped dose-response curve, different doses of the enzyme, variable periods of ischemia and reperfusion and short half-lives of the SOD enzymes.  

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