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Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury
Author(s) -
Mocanu M M,
Baxter G F,
Yellon D M
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703336
Subject(s) - apoptosis , reperfusion injury , caspase , caspase 3 , myocardial infarction , ischemia , pharmacology , medicine , necrosis , programmed cell death , cardiology , chemistry , biochemistry
Ischaemia‐reperfusion injury causes cell death by both necrosis and apoptosis. Caspase activation is a major event in apoptosis. We therefore examined the effect 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 μ M ), a caspase‐8 inhibitor (Z‐IETD·fmk, 0.07 μ M ), a caspase‐9 inhibitor (Z‐LEHD·fmk, 0.07 μ M ) and a caspase‐3 inhibitor (Ac‐DEVD·cmk, 0.07 μ M ). 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; Ac‐DEVD·cmk 27.8±3.3; P <0.05 when compared with control value, 1‐way ANOVA). We conclude that caspase inhibition during early reperfusion protects myocardium against lethal reperfusion injury. British Journal of Pharmacology (2000) 130 , 197–200; doi: 10.1038/sj.bjp.0703336