Protective effects of simultaneous alpha and beta adrenergic receptor blockade on myocardial cell necrosis after coronary arterial occlusion in rats

Abstract

Alpha and beta adrenergic receptor blocking agents have each been separately shown to reduce the extent of ischemic necrosis. This study was designed to assess whether the simultaneous blockade of both alpha and beta adrenergic receptors achieved by labetalol is also effective in reducing infarct size. Moreover, the effects of labetalol were compared with those of propranolol. Accordingly, 127 rats were randomly assigned to four groups: Three groups underwent coronary arterial occlusion (the first group [n = 40] did not receive any drug treatment; the second [n = 29] received labetalol, 25 mg/kg subcutaneously, 5 minutes and 24 hours after coronary occlusion; the third [n = 25] received propranolol 5 mg/kg subcutaneously at the same times). The fourth group of 33 rats was subjected to sham operation. After randomization, no difference in mortality was found among the four groups. All rats were killed 48 hours after coronary occlusion and the total creatine kinase activity of the left ventricle was measured. From this value, infarct size was calculated and found to average 66.5 ± 2.6 percent (mean ± standard error of the mean [SEM]) of the left ventricle in control rats and 44.6 ± 4.1 percent in labetalol-treated rats (p < 0.01). In contrast, in propranolol-treated rats infarct size was 56.6 ± 3.3 percent of the left ventricle, a value smaller than that in control rats (p < 0.05), but higher than that in labetalol-treated rats (p < 0.05). Another 16 rats underwent coronary arterial occlusion: 10 of these were treated with labetalol, whereas the remaining 6 served as a control group. These rats were killed 48 hours after occlusion; infarct size was measured by planimetry on histologic sections of serial slices of the left ventricle and was found to be 40.6 ± 2.7 percent of the left ventricle in control rats and 27.8 ± 3.7 percent in labetalol-treated rats (p < 0.005). Finally, in yet another 36 rats, divided into control and labetalol-treated groups of 15 and 21 rats, respectively, coronary occlusion was performed. These rats were killed 21 days after occlusion and infarct size was measured on histologic sections. Planimetry showed size of the infarct to be 30.5 ± 2.4 percent of the left ventricle in control animals and 15.2 ± 1.2 percent (p < 0.01) in labetalol-treated rats, showing that the extent of scarring after coronary arterial occlusion can be reduced by labetalol. Thus, myocardium acutely jeopardized by ischemia can be preserved permanently by combined alpha and beta receptor blockade.