Effect of carvedilol on atrioventricular conduction in the ischemic heart.
We compared the effects of carvedilol on atrial-His and His-ventricular conduction with those of propranolol in isolated rat hearts. Hearts were perfused retrograde, and atrial-His and His-ventricular intervals were measured. The effective doses that increased conduction times by 25% were 10(-6) M for atrial-His and 3x10(-6) M for His-ventricular for propranolol, and 8x10(-8) M for atrial-His and 10(-8) M for His-ventricular for carvedilol. Prazosin did not affect the atrial-His and His-ventricular intervals. After ischemia-reperfusion, atrial-His and His-ventricular intervals increased to a greater extent with 10(-6) M carvedilol. To determine the direct membrane effect, we examined the transmembrane action potential in guinea pig papillary muscle. Both drugs decreased the maximum upstroke velocity equally. Our data indicate that carvedilol had a greater effect on atrioventricular conduction in the setting of ischemia-reperfusion than did propranolol. This effect of carvedilol was not due to its alpha-adrenoceptor blocking property or to a direct membrane effect.
Horio
T
T
The First Department of Internal Medicine, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Aichi-ken, Nagoya, Japan. horioto@rcs.tokai.west.ntt.co.jp
Ito
S
S
Aoyama
M
M
Takeda
Y
Y
Suzumura
H
H
Nakata
K
K
Yamada
Y
Y
Suzuki
S
S
Fukutomi
T
T
Itoh
M
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002036:Bundle of His / Q000187:drug effects* / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D006168:Guinea Pigs; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology / Q000627:therapeutic use; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol; D011224:Prazosin