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Effect of carvedilol on atrioventricular conduction in the ischemic heart
1The 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
Insights
Carvedilol significantly impacts atrioventricular conduction during ischemia-reperfusion more than propranolol. This effect is independent of alpha-adrenoceptor blockade or direct membrane actions.
Area of Science:
- Cardiovascular Pharmacology
- Electrophysiology
Background:
- Beta-blockers are crucial in managing cardiovascular diseases.
- Understanding their effects on cardiac conduction, especially during ischemia, is vital.
Purpose of the Study:
- To compare the effects of carvedilol and propranolol on cardiac conduction.
- To investigate the influence of ischemia-reperfusion on these effects.
- To elucidate the mechanisms underlying carvedilol's actions.
Main Methods:
- Isolated rat heart perfusion to measure atrial-His and His-ventricular intervals.
- Assessment of transmembrane action potentials in guinea pig papillary muscle.
- Induction of ischemia-reperfusion to simulate cardiac stress.
Main Results:
- Carvedilol demonstrated a greater impact on atrial-His and His-ventricular conduction compared to propranolol at equivalent effective doses.
- Both carvedilol and propranolol reduced maximum upstroke velocity similarly, suggesting a direct membrane effect.
- During ischemia-reperfusion, carvedilol exacerbated increases in conduction intervals more than propranolol.
Conclusions:
- Carvedilol exerts a more pronounced effect on atrioventricular conduction during ischemia-reperfusion than propranolol.
- This enhanced effect is not attributable to alpha-adrenoceptor blockade or direct membrane depolarization.
- Carvedilol's unique properties may offer specific advantages in managing cardiac conditions involving conduction disturbances during ischemic events.
Abstract:
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.