Pant K K, Gurtu S, Sinha J N, Tangri K K, Bhargava K P
J Auton Pharmacol. 1984 Mar;4(1):11-5. doi: 10.1111/j.1474-8673.1984.tb00428.x.
In coronary artery ligated conscious dogs, intravenous (i.v.) injection of both morphine (8.0 mg/kg) and pethidine (12.0 and 24.0 mg/kg) inhibited the cardiac arrhythmia while naloxone (1.0 mg/kg) facilitated it. Intravenous pretreatment with naloxone completely blocked the morphine induced inhibition of the arrhythmia. Pethidine, however, elicited significant inhibition of the arrhythmia in the naloxone pretreated animals but its duration of action was markedly reduced. The temporal effect of i.v. injection of xylocaine (24.0 mg/kg) was parallel to that of pethidine (24.0 mg/kg) injected i.v. in the naloxone pretreated animals. In cervical spinal cord transected and bilaterally vagotomized dogs, i.v. injection of only 50.0 micrograms/kg of morphine elicited significant inhibition of the arrhythmia which was completely blocked by intrathecal pretreatment with a small dose (1.0 micrograms/kg) of naloxone. The same dose of naloxone, when given intravenously, failed to block the effect of morphine. The antiarrhythmic activity of morphine against the cardiac arrhythmia induced by coronary artery ligation appears to be due to activation of spinal opioid receptors. The local anaesthetic activity of pethidine contributes towards its early phase of antiarrhythmic activity.
在冠状动脉结扎的清醒犬中，静脉注射吗啡（8.0毫克/千克）和哌替啶（12.0和24.0毫克/千克）均能抑制心律失常，而纳洛酮（1.0毫克/千克）则会促进心律失常。静脉注射纳洛酮预处理可完全阻断吗啡诱导的心律失常抑制作用。然而，哌替啶在纳洛酮预处理的动物中仍能显著抑制心律失常，但其作用持续时间明显缩短。在纳洛酮预处理的动物中，静脉注射利多卡因（24.0毫克/千克）的时效与静脉注射哌替啶（24.0毫克/千克）相似。在颈脊髓横断并双侧迷走神经切断的犬中，静脉注射仅50.0微克/千克的吗啡就能显著抑制心律失常，而鞘内注射小剂量（1.0微克/千克）纳洛酮预处理可完全阻断这种作用。相同剂量的纳洛酮静脉注射时，则无法阻断吗啡的作用。吗啡对冠状动脉结扎诱导的心律失常的抗心律失常活性似乎是由于脊髓阿片受体的激活。哌替啶的局部麻醉活性有助于其早期抗心律失常活性。
