In vivo myocardial infarct size reduction by a caspase inhibitor administered after the onset of ischemia

The aim of this study was to determine the effect of different administrati on protocols on the cardioprotective efficacy of the non-selective, irrever sible caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) and bocaspartyl-(OMe)-fluoromethylketone (BocD.fmk) in a rat in vivo ischemia and reperfusion paradigm. Hearts were made ischemic for 45 m in and reperfused for 180 min. Under these conditions, it was determined th at zVAD.fmk was cardioprotective when administered before or after the onse t of ischemia, whereas BocD.fmk was efficacious only when administered befo re the onset of ischemia. This is the first report of in vivo cardioprotect ion by a caspase inhibitor when administered after the onset of ischemia. ( C) 2000 Elsevier Science B.V. All rights reserved.