Comparative effects of cardioselective versus noncardioselective beta blockade on subendocardial blood flow and contractile function in ischemic myocardium

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The comparative effects of three beta adrenergic antagonists, bevantolol (CI-775, a new cardioselective agent), practolol and propranolol, on regional myocardial blood flow and contractile function distal to a severe flow-limiting stenosis of the left circumflex coronary artery were studied in the anesthetized dog. Equivalent beta 1 receptor blocking doses of each agent were administered 30 minutes after production of a stenosis sufficient to reduce resting coronary blood flow and contractile force approximately 40 percent. Regional myocardial blood flow and contractile force were measured with radioactive labeled microspheres and Brodie-Walton strain gauge arches, respectively. After treatment with propranolol (0.3 mg/kg), subepicardial flow in the ischemic area decreased significantly whereas subendocardial flow was maintained, resulting in an increased endocardial/epicardial blood flow ratio (0.59 ± 0.05 to 0.93 ± 0.09) (mean ± standard error of the mean). No significant change was observed in contractile performance of the ischemic area. Practolol (1.0 mg/kg) also produced a significant increase in endocardial/epicardial ratio (0.59 ± 0.05 to 0.69 ± 0.10) in the ischemic myocardium. Contractile performance remained unchanged. In contrast, after treatment with bevantolol (1.0 mg/kg), subendocardial flow (0.64 ± 0.13 to 0.77 ± 0.13 ml/min per g) and contractile function increased significantly (36.0 ± 11.0 percent) in ischemic myocardium. A marked increase in endocardial/ epicardial ratio (0.59 ± 0.05 to 0.93 ± 0.09) was also observed. These results suggest that a redistribution of blood flow within an ischemic region of the myocardium occurs with either beta 1 or a simultaneous beta 1 and beta 2 receptor blockade. Furthermore, these data indicate a possible advantage of a new cardioselective beta adrenergic antagonist, bevantolol, in improving ischemic subendocardial blood flow and contractile function.