Participation of Caspase-3-Like Protease in Necrotic Cell Death of Myocardium During Ischemia-Reperfusion Injury in Rat Hearts.

Abstract

This experimental study was designed to determine if caspase-3-like protease is activated during a short period of ischemia - reperfusion (I-R) that did not induce apoptosis, and whether protease-3-protease inhibitor could prevent myocardial I-R injury, especially necrotic cell death. The subjects were 20 isolated rat hearts; 10 were pretreated for 20 min with 100 micromol/L of the protease-3-protease inhibitor, peptide antagonist Asp-Glu-Val-Asp-CHO (DEVD) (Group D), and compared with the 10 no-pretreated hearts (Group C). The hearts were then subjected to 20, 30, 45, and 60 min of normothermic global ischemia followed by 30 min of reperfusion. Caspase-3-like protease was significantly elevated after 45 min and 60 min in ischemic hearts. Group D had reduced levels of caspase-3-like protease activity after 45 min and 60 min (302+/-58%, 378+/-69% of pre-ischemic control, respectively), as compared with Group C (542+/-74%, 689+/-85%, respectively) (p<0.05, p<0.05, respectively). Histological analysis also demonstrated a decrease in cellular damage in Group D, as the count ratio of necrotic cells with total cardiomyocytes was 38%, as compared with 78% in the control group (p<0.05). Caspase-3-like protease participated in I-R injury in rat hearts and inhibition of this protease resulted in a reduction of necrotic cell death.

CaMKII inhibition protects against necrosis and apoptosis in irreversible ischemia–reperfusion injury

“…Fig. 1B shows that contractile recovery during the reperfusion period was extremely depressed, in agreement with what has been already reported after long ischemic periods of global ischemia [26]. This modest recovery was almost doubled however, in the presence of CaMKII inhibition.…”

Heart Preservation Using Continuous Ex Vivo Perfusion Improves Viability and Functional Recovery

“…Suehiro et al previously reported a significant relationship between ATP levels during preservation and the recovery of systolic function. 10 In addition, prior studies show that inhibition of lipid peroxidation, 19 caspase-3, 20,21 and ET-1 22,23 all decrease ischemia -reperfusion injury.…”

Minimally-Diluted Blood Cardioplegia Supplemented With Potassium and Magnesium for Combination of 'Initial, Continuous and Intermittent Bolus' Administration

“…[23][24][25][26][27] As for cardioplegic myocardial protection, the composition and delivery method of the cardioplegic solution have been considered of most concern. Though only a combination of ordinary modifications, minimally-diluted BCP supplemented with potassium and magnesium seems to provide superior myocardial protection in comparison with the standard 4:1-diluted BCP for 'initial, continuous and intermittent bolus' BCP administration.…”