The purpose of this study was to evaluate the cardioprotective effects of carvedilol, a β-adrenergic blocker and vasodilator, in two models of ischemic myocardial damage in the rat. Following coronary artery occlusion for 0.5 h and reperfusion for 24 h (MI/R group), left ventricular (LV) injury was determined by planimetric analysis of triphenyltetrazolium chloride-stained tissue, and polymorphonuclear leukocyte infiltration was assessed by measuring myeloperoxidase (MPO) activity. In the vehicle-treated MI/R group, infarct size was 14.2 ± 1.3% of the LV (n = 16), and MPO activity was increased to 2.8 ± 0.7 from 0.14 ± 0.03 U/g tissue in the vehicle-treated sham-occluded group (p < 0.01). Carvedilol (1 mg/kg i.v., 15 min prior to coronary artery occlusion and at 3.5 h following reperfusion) reduced myocardial infarct size to 7.5 ± 1.2% of the LV (n = 14; p < 0.01) and attenuated the increase in MPO activity to 1.4 ± 0.4 U/g tissue (p < 0.05). A lower dose of carvedilol (i.e. 0.3 mg/kg i.v.) did not limit myocardial infarct size or the increase in MPO activity. In a model of permanent coronary artery occlusion, 24-hour survival was reduced from 85% in sham-occluded animals (n = 38) to 44% in the vehicle-treated MI group (n = 84; p < 0.01). In comparison to the vehicle-treated MI group, carvedilol (0.3 mg/kg i.v., 15 min prior to coronary artery occlusion and 1 mg/kg 4 h after occlusion) improved survival by 55% (n = 64; p < 0.05, compared to the vehicle-treated MI group), whereas the same dose of propranolol (n = 42) had no significant effect on survival. These results indicate that carvedilol reduces myocardial ischemia/reperfusion injury, and significantly improves survival in a permanent coronary artery occlusion model of myocardial infarction.

Keywords:
Coronary artery occlusion, Myocardial ischemia, Rat, Myeloperoxidase activity, β-Adrenergic blocker, α-Adrenergic blocker
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© 1992 S. Karger AG, Basel
1992
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