Post-ischemic administration of DY-9760e, a novel calmodulin antagonist, ameliorated ischemia/reperfusion injury in the rat heart

We assessed effects of a novel calmodulin antagonist, DY9760e in the rat heart subjected to ischemia/reperfusion (L/R) injury. Rats were subjected to a 30-minute coronary occlusion followed by a 24-hour reperfusion. An inert vehicle or DY-9760e, at a dose of 3 and 10 mg/kg, was intravenously administered for 20 minutes by starting at 20 minutes after coronary occlusion. After 24-hour reperfusion, the left ventricle was excised and sliced. The infarct size in the risk area was assessed by Evans blue /TTC staining. DY-9760e reduced the infarct size in a dose dependent manner. Furthermore, the effect of DY-9760e on ischemia-induced fodrin breakdown was examined. Increased fodrin breakdown was observed in the ischemic area at 24 hours after coronary occlusion. DY-9760e significantly inhibited the fodrin breakdown in the ischemic area at a dose of 10 mg/kg, which had a protective action against infarction. These results suggest that DY-9760e ameliorates myocardial I/R injury, and is a potential therapeutic agent for myocardial infarction in the acute stage.