Vargish T, Beamer K C, Daly T, Head R
Surgery. 1987 Aug;102(2):171-7.
Earlier work has shown that morphine sulfate can produce a dose-related decrease in heart rate (HR) and cardiac output (CO) in isolated working rat hearts. This response is preventable with the use of the opiate receptor antagonist, naloxone hydrochloride. In this study, the stereospecificity of the opiate response was tested with the use of levorphanol tartrate and its d-isomer, dextrorphan, in our Langendorff rat heart model. The interaction of muscarinic receptor activity with the opiate response was tested by first adding bethanechol chloride to the perfusate in the presence and absence of atropine (5 X 10(-9) mmol/L). Our earlier studies with morphine sulfate were then repeated in the presence of the same concentration of atropine. At a concentration of 5 X 10(-6) mmol/L, levorphanol tartrate produced a significant decrease in CO (p less than 0.05), while a similar concentration of dextrorphan produced little change in either HR or CO. Bethanechol chloride, in a concentration of 3 X 10(-6) mmol/L, produced a significant decrease in HR and CO (p less than 0.05), which was prevented by atropine. When morphine sulfate was added to the standard perfusate (3 X 10(-4) mmol/L), HR and CO were significantly decreased (p less than 0.05). This change was not prevented by the addition of atropine. The opiate effect on myocardial function is mediated by a stereospecific opiate receptor, which acts independently of muscarinic receptor antagonism.
早期研究表明，硫酸吗啡可使离体工作大鼠心脏的心率（HR）和心输出量（CO）呈剂量依赖性降低。使用阿片受体拮抗剂盐酸纳洛酮可预防这种反应。在本研究中，我们在Langendorff大鼠心脏模型中使用酒石酸左啡诺及其d-异构体右啡烷测试了阿片反应的立体特异性。通过在灌注液中加入氯化氨甲酰胆碱（有无阿托品（5×10⁻⁹ mmol/L））来测试毒蕈碱受体活性与阿片反应的相互作用。然后在相同浓度的阿托品存在下重复我们早期关于硫酸吗啡的研究。在浓度为5×10⁻⁶ mmol/L时，酒石酸左啡诺使CO显著降低（p＜0.05），而相似浓度的右啡烷对HR或CO几乎没有影响。浓度为3×10⁻⁶ mmol/L的氯化氨甲酰胆碱使HR和CO显著降低（p＜0.05），阿托品可预防这种降低。当向标准灌注液（3×10⁻⁴ mmol/L）中加入硫酸吗啡时，HR和CO显著降低（p＜0.05）。加入阿托品并不能预防这种变化。阿片对心肌功能的作用由立体特异性阿片受体介导，该受体的作用独立于毒蕈碱受体拮抗作用。
