Activity profile of calpains Ⅰ and Ⅱ in chronically infarcted rat myocardium - influence of the calpain inhibitor CAL 9961

摘要

1 The calpains have been proposed to be activated following cardiac ischaemia and to contribute to myocyte damage after myocardial infarction (MI). In this study, the activity of calpains Ⅰ and Ⅱ in the infarcted and non-infarcted rat myocardium and the action of the selective calpain inhibitor, CAL 9961, has been investigated. 2 MI was induced by permanent ligation of the left coronary artery. One, 3, 7 and 14 days post MI, the enzymes calpain Ⅰ and Ⅱ were separated from homogenates of the interventricular septum (IS) and left ventricular free wall (LVFW) by chromatography on DEAE-Sepharose. The activity of the calpains was measured in sham-operated and MI animals chronically treated with placebo or CAL 9961 (15 mg kg~(-1) d~(-1) s.c.) in a synthetic substrate assay. Treatment was started 3 days before MI induction. 3 Calpain Ⅰ activity reached highest values in IS 14 days post MI, whereas maximum activity of calpain Ⅱ was measured in LVFW 3 days post MI. In experiments in vitro, CAL 9961 completely inhibited both calpains. In vivo, chronic treatment of MI animals with CAL 9961 partially prevented the increase in calpain Ⅰ activity in IS and reduced calpain Ⅱ activity in LVFW to sham levels. 4 Our findings demonstrate that calpains Ⅰ and Ⅱ are activated after MI, however, both enzymes differ in their regional and temporal activation within the infarcted myocardium. Chronic inhibition of these enzymes with CAL 9961 might limit the calpain-induced myocardial damage and preserve cardiac structural integrity post MI.