Effects Of Hydromorphone Postconditioning On Ischemia-reperfusion Injury In Isolated Rat Hearts And Mitochondial Permeability Transition Pore

Objective: To investigate the effects of Hydromorphone postconditioning on ischemia-reperfusion injury in isolated rat hearts and mitochondial permeability transition pore（mPTP）.Methods: Forty male SD rats,aged 2-3 months,weighing 250-350 g,were anesthetized with intraperitoneal 10% chloral hydrate 350mg/kg and heparin 1000U/kg.The hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95%O2⁺5%CO2 at 36.5-37.5.Forty isolated rat hearts were randomly divided into 4 groups（n=10）: Control group（groupC）,groupI/R,Hydromorphone postconditioning group（groupH）and Hydromorphone⁺ Lonidamine postconditioning group（groupHL）.GroupC was perfused continuously for 120 min,the rest groups were perfused for 30 min and worked by 30 min of ischemia followed by 60 min reperfusion for I/R injury,groupH was received 10 min postconditioning with 0.3μmol/L Hydromorphone after 30 min ischemia,groupHL was received 0.3μmol/L Hydromorphone and 30μmol/L Lonidamine for postconditioning at the same time.The LVDP,LVEDP,HR,±dp/dtmax,Coronary flow（CF）were measured at 30 min perfusion（T₀）,30 min reperfusion（T2）and 60 min reperfusion（T₃）;the LDH,CK-MB,Tn-T were determined at 30 min perfusion（T₀）and reperfusion（T₃）;the NAD⁺ were determined at 30 min perfusion（T₀）and 15 min reperfusion（T₁）;infarct size was measured after the experiment. Results: There was no significant difference between the observation index at T₀. Compared with group C, LVDP, CF, ⁺dp/dtmax were significantly decreased and LVEDP, LDH, CKMB, Tn T, NAD⁺, infarct size were significantly increased in the rest groups（P<0.05）. Compared with group H, LVDP, CF, ±dp/dtmax, HR were significantly decreased and LVEDP, LDH, CK-MB, Tn-T, NAD⁺, infarct size were significantly increased in the group HL and group I/R（P<0.05）. There was no significant difference between group HL and group I/R except LDH and HR（P<0.05）. Conclusion: 0.3μmol/L Hydromorphone postconditioning can reduce the I/R injury in isolated rat hearts, and 30μmol/L Lonidamine（mPTP opener） can significantly abolished the effect of Hydromorphone on myocardial protection.