Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Oct 1999
Comparative StudyCombination of a calcium antagonist, a lipid-peroxidation inhibitor, and an angiotensin AT1-receptor antagonist provides additive myocardial infarct size-limiting effect in pigs.
The calcium antagonist felodipine, the lipid-peroxidation inhibitor H290/51, and the angiotensin II type 1 (AT1)-receptor antagonist candesartan all exert beneficial effects on myocardial ischemia/reperfusion injury. This study was undertaken to test the hypothesis that a combination of these drugs with different pharmacologic properties could exert additive cardioprotective effects. Anesthetized pigs were subjected to 45 min of left anterior descending coronary artery occlusion followed by 240 min of reperfusion. ⋯ The infarct size in the cocktail group was significantly smaller than that in the groups given felodipine, H290/51, or candesartan alone. These results demonstrate that a combination of a calcium antagonist, a lipid-peroxidation inhibitor, and an angiotensin AT1-receptor antagonist has an additive effect on infarct limitation, indicating that combined therapy with agents having different pharmacologic modes of action may provide better cardioprotection than any of the drugs alone. The findings also support the view that reperfusion injury is possibly mediated by a combination of mechanisms.