Hino T, Hayase N, Chiba K, Ichihara K, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Methods Find Exp Clin Pharmacol. 1989 Jun;11(6):373-8.
In dogs anesthetized with pentobarbital, the anterior descending coronary artery (LAD) was partially occluded to reduce LAD flow to about half of the original flow (partial occlusion). Myocardial pH (MpH) was measured by the use of a micro glass pH electrode. MpH decreased from 7.5-7.63 to 6.82-6.86 30 min after partial occlusion of the LAD. Nipradilol (0.3 mg/kg) was injected intravenously 30 min after partial occlusion, which continued for a further 60 min after nipradilol injection. Nipradilol decreased blood pressure and heart rate, and significantly increased myocardial pH which had been decreased by partial occlusion, within 60 min after injection. Nipradilol-induced restoration of the myocardial [H+] (calculated from the pH data), that had been increased by partial occlusion, was 48.5%. Bradycardia induced by nipradilol was not a determinant factor in the pH effect of nipradilol, because even in the paced heart, nipradilol restored the myocardial [H+] that had been increased by partial occlusion. These results indicate that nipradilol attenuates ischemia-induced myocardial acidosis, suggesting the favorable effect of nipradilol on ischemic myocardium. The favorable effect of nipradilol may be due to the beta-adrenoceptor antagonistic effect rather than the vasodilating effect.
在戊巴比妥麻醉的犬中,对冠状动脉前降支(LAD)进行部分闭塞,使LAD血流减少至原血流的约一半(部分闭塞)。使用微型玻璃pH电极测量心肌pH值(MpH)。LAD部分闭塞30分钟后,MpH从7.5 - 7.63降至6.82 - 6.86。部分闭塞30分钟后静脉注射尼普地洛(0.3mg/kg),注射尼普地洛后再持续60分钟。尼普地洛降低血压和心率,并在注射后60分钟内显著提高因部分闭塞而降低的心肌pH值。尼普地洛使因部分闭塞而升高的心肌[H⁺](根据pH数据计算)恢复了48.5%。尼普地洛诱发的心动过缓不是其pH效应中的决定因素,因为即使在起搏心脏中,尼普地洛也能使因部分闭塞而升高的心肌[H⁺]恢复。这些结果表明,尼普地洛可减轻缺血诱导的心肌酸中毒,提示尼普地洛对缺血心肌有有益作用。尼普地洛的有益作用可能归因于β - 肾上腺素能受体拮抗作用而非血管舒张作用。