Carvedilol (Kredex) reduces infarct size in a canine model of acute myocardial infarction.
Carvedilol (Kredex) is a multiple action, antihypertensive agent that may also prove to be useful in the treatment of angina and congestive heart failure. Carvedilol combines in one molecule both beta-adrenoceptor blocking and vasodilating activities. Inasmuch as beta-adrenoceptor blocking agents are known to be cardioprotective and thereby reduce infarct size, it is logical to assume that carvedilol, likewise, would possess this desirable activity. Furthermore, the additional vasodilating activity of carvedilol could contribute to further reductions in infarct size by reducing myocardial work (and therefore myocardial oxygen demand) through reductions in both afterload and myocardial wall tension. As such, we have investigated the ability of carvedilol to reduce infarct size in a canine model of acute myocardial infarction. Carvedilol (1 mg/kg i.v.) or its vehicle, dimethylformamide, were administered 15 min before left circumflex coronary artery (LCX) occlusion. Following 1 h of LCX occlusion, dogs were reperfused through a critical stenosis and then allowed to recover for 24 h. Carvedilol-treated animals exhibited a 78% reduction in infarct size compared to vehicle controls, such that the percentage of the left ventricle infarcted was reduced significantly from 16.2 +/- 4.1% in control animals to 3.6 +/- 1.3% in animals treated with carvedilol (p = 0.017, n = 6). Stained tissue sections of the left ventricle were photographed, digitized and color-enhanced using an Image Analysis Computer System, and three-dimensional reconstruction of the left ventricle, including the infarcted areas, was performed.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.
S A
SA
Hamburger
F C
FC
Barone
G Z
GZ
Feuerstein
R R
RR
Ruffolo
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D003331:Coronary Vessels / Q000473:pathology; D004126:Dimethylformamide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006352:Heart Ventricles / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D011412:Propanolamines / Q000627:therapeutic use*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D004126:Dimethylformamide