Rabkin S W
Cardiovascular Research Laboratories, University Hospital (Shaughnessy), University of British Columbia, Vancouver, Canada.
Pharmacol Toxicol. 1992 Nov;71(5):353-60. doi: 10.1111/j.1600-0773.1992.tb00561.x.
The effects of the opioid receptor agonists morphine and dynorphin on digoxin-induced arrhythmias were examined in guinea pigs that had received intravenous digoxin (50 mu/kg bolus plus 500 mu/kg/hr intravenously). Animals received either morphine (50 or 100 micrograms/kg) or dynorphin A(1-13) (50 or 100 micrograms/kg) or saline (the diluent) into the lateral cerebral ventricle (intracerebroventricularly) prior to digoxin. Morphine and dynorphin produced significant (P < 0.05) dose-dependent increases in the threshold of digoxin-induced arrhythmias. The mean digoxin dose at the development of fatal arrhythmias was 775 +/- 42 micrograms/kg in the control group but was significantly higher namely 958 +/- 45 micrograms/kg after 100 micrograms/kg of morphine ICV, and 984 +/- 47 micrograms/kg after 100 micrograms/kg of dynorphin A (1-13) intracerebroventricularly. In the absence of digoxin, the highest doses of each of these opioids did not produce arrhythmias. Changes in blood pressure and heart rate were unlikely explanations for the observed actions of these opioids as morphine accentuated the increase in blood pressure that accompanied digoxin while dynorphin was associated with a lower blood pressure with digoxin, despite similar effects on arrhythmias. In the control group, fatal digoxin-induced arrhythmias were ventricular tachyarrhythmias in two-thirds of cases and complete heart block in the rest. Morphine and dynorphin reduced the development of ventricular tachyarrhythmias. The role of the cholinergic system was explored, with morphine, utilizing atropine sulfate which crosses the blood brain barrier and atropine methylnitrate which does not enter the CNS. Atropine sulfate but not atropine methylnitrate reversed the effects of morphine on digoxin-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
在接受静脉注射地高辛（50微克/千克推注加500微克/千克/小时静脉滴注）的豚鼠中，研究了阿片受体激动剂吗啡和强啡肽对洋地黄毒苷诱导的心律失常的影响。在注射地高辛之前，动物经侧脑室（脑室内）分别注射吗啡（50或100微克/千克）或强啡肽A（1 - 13）（50或100微克/千克）或生理盐水（稀释剂）。吗啡和强啡肽使地高辛诱导的心律失常阈值出现显著（P < 0.05）的剂量依赖性升高。对照组中出现致命性心律失常时的平均地高辛剂量为775±42微克/千克，但在脑室内注射100微克/千克吗啡后显著升高，即958±45微克/千克，在脑室内注射100微克/千克强啡肽A（1 - 13）后为984±47微克/千克。在没有地高辛的情况下，这些阿片类药物的最高剂量均未引发心律失常。血压和心率的变化不太可能解释这些阿片类药物的观察作用，因为吗啡加剧了地高辛引起的血压升高，而强啡肽与地高辛合用时血压较低，尽管它们对心律失常的影响相似。在对照组中，三分之二的致命性地高辛诱导的心律失常为室性快速心律失常，其余为完全性心脏传导阻滞。吗啡和强啡肽减少了室性快速心律失常的发生。利用可穿过血脑屏障的硫酸阿托品和不能进入中枢神经系统的硝酸甲基阿托品，探讨了胆碱能系统在吗啡作用中的作用。硫酸阿托品而非硝酸甲基阿托品可逆转吗啡对地高辛诱导的心律失常的影响。（摘要截选至250词）
