Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury

Abstract

Ischaemia-reperfusion injury causes cell death by both necrosis and apoptosis. Caspase activation is a major event in apoptosis. We therefore examined the e ect of caspase inhibitors during reperfusion upon myocardial infarction. Rat isolated hearts were subjected to 35 min coronary occlusion and 120 min reperfusion. Treatment groups were perfused with caspase inhibitors during early reperfusion. We assessed a non-selective caspase inhibitor (Z-VAD×fmk, 0.1 mM), a caspase-8 inhibitor (Z-IETD×fmk, 0.07 mM), a caspase-9 inhibitor (Z-LEHD×fmk, 0.07 mM) and a caspase-3 inhibitor (Ac-DEVD×cmk, 0.07 mM). All caspase inhibitors limited infarct size (infarct-risk ratio per cent: control 38.5+2.6; Z-VAD×fmk 24.6+3.4; Z-LEHD×fmk 19.3+2.4; Z-IETD×fmk 23.0+5.4; AcDEVD×cmk 27.8+3.3; P50.05 when compared with control value, 1-way ANOVA). We conclude that caspase inhibition during early reperfusion protects myocardium against lethal reperfusion injury.

Taurine Attenuates Hepatic and Cardiac Damage and Apoptosis in Rabbits Fed a High-Fat Diet

“…The present results confirmed this report and demonstrated that a moderate hypercholesterolemia (2% cholesterol diet for 8 weeks) also increased myocardial apoptosis. Several studies stated that inhibition of apoptosis by a variety of pharmacological and genetic approaches results in smaller infarction (Brocheriou et al, 2000;Mocanu et al, 2001) and improved cardiac function (Abbate et al, 2002;Chatterjee et al, 2003). Taurine, is known as to protect various disorders and has been demonstrated to have beneficial effects in nephropathy, cardiomyopathy and neuropathy, (Szymanski and Winiarska, 2008).…”

Pioglitazone attenuates myocardial ischemia-reperfusion injury via up-regulation of ERK and COX-2

“…Evidence indicates that apoptosis is a significant contributor to myocardial cell death after I/R. Studies have demonstrated that the pharmacologic inhibition of the apoptotic signaling cascade can attenuate the apoptotic and necrotic components of cell death (16,17). In addition to the apoptotic component of cell death contributing to the extension of infarct size during reperfusion, Zhao et al (18) demonstrated that pharmacologic inhibition of the reperfusion-induced apoptotic component of cell death also resulted in improved contractile function of ischemic canine hearts.…”

Combination of necroptosis and apoptosis inhibition enhances cardioprotection against myocardial ischemia–reperfusion injury

“…in isolated rat hearts [21]. Of note, if the apoptotic pathway is not completely blocked by this concentration of Z-VAD, we cannot absolutely rule out that the enhanced reduction in infarct size by the combination of Z-VAD and necrostatin-1 could be in part due to suppression of apoptosis by necrostatin-1.…”