Effects of morphine postconditioning on ischemia-reperfusion injury in isolated rat hearts / 中华麻醉学杂志

ABSTRACT

Objective To determine whether morphine postconditioning (MP) could protect the heart against ischemia reperfusion (I/R) injury and which specific type(s) of the opioid receptor is involved in the cardioprotective effect produced by hiP. Methods Male SD rots weighing 180-200 g were killed after intraperitoneal heparin 500 U/kg. The hearts were immediately removed and passively perfused in a Langendorff apparatus with K-H solution gassed with 95% O2-5% CO2. HR and left ventricular systolic pressure (LVSP) were measured from a fluid-filled latex balloon in the left ventricle. Global myocardial ischemia was induced by interrupting perfusion for 45 min followed by 60 min reperfusion. The experiment was performed in 3 parts. In Part Ⅰ 32 isolated rat hearts were randomly divided into 4 groups (n = 8 each) group Ⅰ control received no treatment; group Ⅱ ,Ⅲ,Ⅳ were first perfused with K-H solution containing morphine 0.3, 3.0 and 30 μmol/L respectively for 10 min immediately after the end of ischemia followed by 50 min normal K-H solution perfusion. In part Ⅱ,the concentration of morphine in K-H solution which provided the best cardio-protective effects was chosen according to the result of Part Ⅰ , 32 isolated rat hearts were randomly divided into 4 groups ( n = 8 each) group Ⅰ received no treatment; gvoup Ⅱ,ⅢⅣ were first perfused with K-H solution containing morphine for 5, 10, 20 min respectively immediately after ischemia followed by 50 min peffusion with normal K-H solution. In part Ⅲ,the MP method which provided the best cardio-protective effects was chosen according to the result of Part Ⅱ , 37 isolated rat hearts were randomly divided into 5 groups group Ⅰ control (n=8);group Ⅱ-Ⅴ were first perfused for 10 min with K-H solution containing morphine (Ⅱ,n = 8)/morphine + naloxone 10 μmol/L(Ⅲ, n = 7)/morphine + nor-binaltorphimine 5 μmol/L (specific κ receptor antagonist, n = 7)/morphine + nalu'indole 5 μmol/L (specific δ receptor antagonist, n = 7) followed by 50 min reperfusion with normal K-H solution. Myocardial CK-MB activity was measured and myocardial infarct size (IS/AAR) determined (by 2,3,5-triphenyl tetrazolium staining) at the end of 60 min reperfusion.Results The postconditioning with morphine 3.0 μmol/L perfusion for 10 min provided the best cardio-protective effects in terms of IS/AAR and myocardial release of CK-MB. Nuloxone completely abolished the cardio-protective effects of MP. Nor-binaltorphimine partly reversed the protective effect of MP, while naltrindole had no effects on MP. Conclusion MP protects the heart against I/R injury via activating κ receptor.