Abstract
Objective: Ischemia/reperfusion (I/R) injury due to cardioplegic arrest is a problem in patients with reduced LV function. We investigated the effect of chronic versus acute administration of the selective endothelin-A receptor antagonist TBC-3214Na during I/R in failing hearts. Methods: Male SD rats underwent coronary ligation. 3 days post infarction group 1 (n=11) was administered TBC-3214Na continuously with their drinking water, group 2 and 3 received placebo. 7 weeks post infarction hearts were evaluated on a blood perfused working heart during 60′ ischemia and 30′ reperfusion. In group 2 (n=10) TBC-3214Na and in group 3 placebo were added to cardioplegia during ischemia. Data: At similar infarct size postischemic recovery of cardiac output (group1: 91±10%, group2: 86±11% vs. placebo: 52±15%; p<0,05) and external heart work (group1: 90±10%, group2: 85±13% vs. placebo: 51±17%, p<0,05) was significantly enhanced in group 1+2 while recovery of coronary flow was only improved in group 2 (group2: 121±23% vs. group1: 75±13%, placebo: 64±15%, p<0,05). In group 2 myocardial oxygen delivery and high energy phosphates were enhanced accompanied by a lower lactate production, and transmission electron microscopy revealed less ultrastructural damage. Conclusion: Ultrastructural and biochemical evaluation indicates an improvement in capillary perfusion only under acute TBC-3214Na administration during ischemia/reperfusion resulting in a better cardiac function post ischemia.
Published Version
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