Harmsen E, De Tombe P P, De Jong J W
Eur J Pharmacol. 1983 Jun 17;90(4):401-9. doi: 10.1016/0014-2999(83)90562-9.
Both nifedipine a calcium antagonist, and propranolol a beta-adrenergic blocker, are used as protective agents of the ischemic myocardium. In the clinical setting, the combination of the two drugs is used successfully although several case reports indicate potential dangers of the combination. For this reason we decided to study the combined effect of nifedipine and DL-propranolol in the isolated rat heart made ischemic for a short period of time. Apex displacement was taken as a measure of contractility. Release of the AMP catabolites adenosine, inosine, (hypo)xanthine and uric acid was used as a marker of ATP breakdown. Contractility during ischemia was not affected by the drugs. DL-Propranolol (30 or 150 micrograms/l) had no effect on ischemic myocardial purine release, while nifedipine (15 micrograms/l) reduced purine release during ischemia by 33% (P less than 0.02). The combination of 15 micrograms/l nifedipine and 150 micrograms/l DL-propranolol decreased purine release by 53% (P less than 0.005 vs. nifedipine). We conclude from these results that propranolol has a synergistic effect, adding to the beneficial action of nifedipine on ischemic myocardium.
钙拮抗剂硝苯地平与β-肾上腺素能阻滞剂普萘洛尔均被用作缺血心肌的保护剂。在临床环境中，两种药物联合使用取得了成功，尽管有几例病例报告表明联合使用存在潜在风险。因此，我们决定研究硝苯地平和DL-普萘洛尔在短期缺血的离体大鼠心脏中的联合作用。以心尖位移作为收缩力的指标。AMP分解代谢产物腺苷、肌苷、（次）黄嘌呤和尿酸的释放用作ATP分解的标志物。缺血期间的收缩力不受药物影响。DL-普萘洛尔（30或150微克/升）对缺血心肌嘌呤释放无影响，而硝苯地平（15微克/升）使缺血期间嘌呤释放减少33%（P<0.02）。15微克/升硝苯地平和150微克/升DL-普萘洛尔联合使用使嘌呤释放减少53%（与硝苯地平相比，P<0.005）。从这些结果我们得出结论，普萘洛尔具有协同作用，增强了硝苯地平对缺血心肌的有益作用。
