Effects of carvedilol on left ventricular function and arrhythmias during repeated short-time myocardial ischemia in experimental pigs.
The effects of carvedilol, a new vasodilating beta-blocking drug, were studied in experimental pigs during short-term acute myocardial ischemia. In 21 anesthetized pigs 0.01, 0.03, and 0.1 mg/kg b.w. carvedilol was studied during repeated 2-min distal LAD-occlusions and a 60-min-period of ischemia. Left ventricular volume was continuously measured by the impedance catheter method. Intravenous administration of 0.01 mg/kg carvedilol resulted in a significant decrease of heart rate (-13%), dp/dtmax (-32%), and ejection fraction (-9%), slight changes of systolic pressure (-3%), and an increase of vascular resistance (+24%), indicating a beta-blocker effect without vasodilation-while the first vasodilatory effect was found at a dose of 0.1 mg/kg. During ischemia carvedilol had no influence on the time-course or the extent of systolic bulging of the ischemic myocardium, but the ischemia-induced decrease of left ventricular ejection fraction was diminished. Both during short-term ischemia, as well as during the 60-min-ischemia-period carvedilol significantly reduced ventricular premature beats. During the 60-min-ischemia-period activation delay measured from local DC-electrograms of the ischemic myocardium, as well as the occurrence of activation block were not altered by carvedilol, as was the incidence of ventricular fibrillation (69%). We conclude that at low dosages the beta-blocking effect of carvedilol exceeds the vasodilating properties. This may also hold true in patients with cardiac failure; they are more sensitive to beta-blocking drugs. During ischemia carvedilol slightly reduces the ischemia-dependent decrease of global ventricular function and it has an antiarrhythmic effect. Therefore, it may be protective in patients with acute myocardial infarction.
Höher
M
M
Department of Physiology, University of Cologne, FRG.
Friedrich
M
M
Sommer
T
T
Marten
A
A
Ehmer
B
B
Hombach
V
V
Hirche
H
H
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents; D002227:Carbazoles / Q000494:pharmacology*; D002307:Cardiography, Impedance; D000077261:Carvedilol; D002395:Catecholamines / Q000097:blood; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D002395:Catecholamines; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol