The Effects of TUC-73, TUC-74 and (+)-Cyanidanol-3 on Ischemic/Reperfusion Damage in Isolated Rabbit Hearts
DeWitt, Coleen C.
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Myocardial infarction, or heart attack, is the leading cause of death in America today. Myocardial ischemia, which is a reduction in coronary flow such that the oxygen supply to the myocardium is not adequate to supply the oxygen demands of the tissues, is often the cause of this fatal event. The damage associated with ischemia and reperfusion (the return of flow) has been attributed to many factors. In these experiments, the Langendorff isolated rabbit heart model was used to examine the effects of two novel chemical entities, TUC-73 and TUC-74, on the heart after it was subjected to 30 min. of global ischemia. (+)-Cyanidanol-3 (Catechin), which was previously found to be protective against ischemic/reperfusion injury, was used as a reference compound. TUC-73 and (+)Cyanidanol- 3 both exhibited dose response effects. TUC-73 was the most effective, while TUC-74 failed to have any significant effects. Based upon these results, these compounds and structurally similar compounds will be tested in vivo and will undergo biochemical testing to determine the mechanisms of action.