Cardioprotective potential of carvedilol.
Carvedilol is a multiple-action cardiovascular agent that is a nonselective beta-adrenoceptor antagonist and a vasodilator. beta-Adrenoceptor antagonists reduce myocardial work, secondary to reductions in heart rate and contractility, both in animals and in humans. For these reasons, carvedilol may improve survival of acutely ischemic myocardium. The additional vasodilating activity of carvedilol, further reducing myocardial work by decreasing afterload and ventricular wall tension, may provide additional salvage over that afforded by beta-adrenoceptor blockade alone. The comparative ability of carvedilol and propranolol to reduce infarct size in experimental models of acute myocardial infarction in the rat, pig and dog has been investigated utilizing a variety of experimental techniques. In the pig, the calcium channel antagonist, diltiazem, was also included as a second comparator agent. Infarct size was examined on stained tissue sections using quantitative image analysis. In the rat, carvedilol (1 mg/kg) reduced infarct size by 47% (p < 0.01, n = 11), and in the pig, carvedilol, at doses of 0.3 and 1 mg/kg, reduced infarct size by 46% (p < 0.05, n = 6) and 89% (p < 0.001, n = 6), respectively. In dogs subjected to ischemia and reperfusion, carvedilol (1 mg/kg) reduced infarct size by 78% (p < 0.02, n = 6), and in dogs subjected to permanent left anterior descending coronary artery occlusion, carvedilol, at doses of 0.3 and 1 mg/kg, reduced infarct size by 46 and 63%, respectively (p < 0.02, n = 12-16). In all studies, the extent of myocardial survival on carvedilol exceeded that on propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Ruffolo
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Department of Pharmacology, SmithKline Beecham Pharmaceuticals p.l.c., King of Prussia, Pa. 19406.
Bril
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Feuerstein
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GZ
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D004110:Diltiazem / Q000627:therapeutic use; D004285:Dogs; D016166:Free Radical Scavengers; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D011412:Propanolamines / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013556:Swine, Miniature; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D016166:Free Radical Scavengers; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D011433:Propranolol; D004110:Diltiazem