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  • Title: Caspase inhibitor zVAD.fmk reduces infarct size after myocardial ischaemia and reperfusion in rats but not in mice.
    Author: Mersmann J, Zacharowski PA, Schmitz I, Zacharowski K.
    Journal: Resuscitation; 2008 Dec; 79(3):468-74. PubMed ID: 18805622.
    Abstract:
    OBJECTIVE: Apoptosis of cardiomyocytes has been suggested to contribute to outcome following myocardial ischaemia and reperfusion (MI/R). Caspase inhibitors were developed as potential therapeutics for MI/R. However, various reports using the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) in the latter setting present conflicting results. Therefore, it is still unclear whether inhibition of apoptosis by caspase inhibitors promotes cardioprotection. MATERIALS AND METHODS: This study evaluated whether zVAD.fmk or novel caspase inhibitor quinoline-Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh) reduce myocardial infarct size in mice. Secondly, we tested zVAD.fmk's potential infarct-sparing effects in rats and whether these are accompanied by improved left ventricular function. RESULTS: In mice neither zVAD.fmk nor Q-VD-OPh reduced infarct size. In rats, however, zVAD.fmk reduced infarct size following ischaemia (25min) and reperfusion (7 days) by approximately 53%. This was, however, accompanied by an increase in left ventricular end-diastolic pressure. CONCLUSION: This study provides further evidence that abrogation of apoptosis via caspase inhibition might not be sufficient to effectively limit infarct size following MI/R.
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