Joukar Siyavash, Najafipour Hamid, Dabiri Shahriar, Sheibani Vahid, Esmaeili-Mahani Saeid, Ghotbi Payam, Amanallahi Foad, Joukar Farzin
Neuroscience Research Center, Kerman University of Medical Sciences, P.O. Box 7616914115, Kerman, Iran.
Cardiovasc Hematol Agents Med Chem. 2011 Oct;9(4):218-24. doi: 10.2174/187152511798120930.
Long-term co-administration of morphine and calcium channel antagonists (CCAs) is likely in some clinical conditions. Reciprocal interactions during chronic concomitant use of these agents are confirmed in central nervous system studies. However, there is little information regarding their chronic combination effects on the cardiovascular system. Present study was designed to assess the effects of chronic co-administration of morphine plus verapamil on some cardiovascular indices of rats with / without myocardial damage.
Animals were divided to control, morphine, verapamil and morphine plus verapamil groups each consisted of two subgroups, with and without heart injury. Rats were treated with increasing doses of morphine (10-20mg/kg, i.p.) or morphine plus verapamil (10mg/kg, i.p.) daily for 7 days. Heart injury was induced by isoproterenol (50 mg/kg, i.p.), then cardiac Troponin I was measured and on day 8, blood pressure and heart rate was recorded and then the hearts were histopathologically examined.
The results indicated that co-administration of morphine with verapamil has stronger cardioprotective effect than morphine or verapamil alone as confirmed by the lower Troponin I level and myocardial lesion grades. However, no additional effects on mean arterial pressure and Rate-Pressure product were observed in combined use of these drugs.
These findings suggest chronic co-administration of morphine and verapamil induced additive protective effects on rat heart exposed to myocardial injury comparing with each of them alone.
在某些临床情况下，吗啡与钙通道拮抗剂（CCAs）可能需要长期联合使用。在中枢神经系统研究中已证实，这些药物在慢性联合使用过程中存在相互作用。然而，关于它们对心血管系统的慢性联合作用的信息却很少。本研究旨在评估吗啡联合维拉帕米长期给药对有/无心肌损伤大鼠某些心血管指标的影响。
将动物分为对照组、吗啡组、维拉帕米组和吗啡加维拉帕米组，每组又分为有心脏损伤和无心脏损伤两个亚组。大鼠每天接受递增剂量的吗啡（10 - 20mg/kg，腹腔注射）或吗啡加维拉帕米（10mg/kg，腹腔注射），持续7天。通过异丙肾上腺素（50mg/kg，腹腔注射）诱导心脏损伤，然后测量心肌肌钙蛋白I，在第8天记录血压和心率，随后对心脏进行组织病理学检查。
结果表明，与单独使用吗啡或维拉帕米相比，吗啡与维拉帕米联合使用具有更强的心脏保护作用，这通过较低的肌钙蛋白I水平和心肌损伤分级得到证实。然而，联合使用这些药物时，未观察到对平均动脉压和心率 - 血压乘积有额外影响。
这些发现表明，与单独使用吗啡或维拉帕米相比，吗啡和维拉帕米长期联合给药对遭受心肌损伤的大鼠心脏具有相加的保护作用。
