The inhibitory effects of carvedilol against arrhythmias induced by coronary reperfusion in anesthetized rats.
BACKGROUND
Previous study has shown the antiarrhythmic effects of carvedilol on isolated rat hearts, but little is known about the mechanism of this protective action. This article examines the inhibitory effect of carvedilol against arrhythmias induced by reperfusion in anesthetized rats. In addition, the results are compared with those with propranolol, superoxide dismutase (SOD) plus catalase, and a combination of both in order to elucidate the mechanism of the protective actions.


METHODS
Ninety percent of the rats in the control group showed lethal ventricular fibrillation (VF). Carvedilol at the doses of 0.03, 0.1, and 0.3 mg/kg significantly reduced the incidence of lethal VF to 0%, 0%, and 10%, respectively (P <.05). In contrast, propranolol at the doses of 0.3, 1.0, and 3.0 mg/kg and SOD (35,000 units/kg) plus catalase (400,000 units/kg) did not reduce the incidence of lethal VF (80%, 60%, 70%, and 70%, respectively). However, administration of a combination of propranolol (1.0 mg/kg) and SOD plus catalase completely inhibited the occurrence of lethal VF to 0% (P<.05).


CONCLUSIONS
These results indicate that carvedilol has the inhibitory effect against reperfusion arrhythmias in rats and suggest that the mechanism of action of this compound is related to the combined effects of beta-blocking and antioxidant.
Takusagawa
M
M
Second Department of Internal Medicine and the Department of Human Science Yamanashi Medical University, Tamaho, Yamanashi, Japan.
Komori
S
S
Matsumura
K
K
Osada
M
M
Kohno
I
I
Umetani
K
K
Ishihara
T
T
Sawanobori
T
T
Ijiri
H
H
Tamura
K
K
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000768:Anesthesia, General; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077261:Carvedilol; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol; D002374:Catalase; D013482:Superoxide Dismutase