Cardioprotection Effect Of Morphine Preconditioning On Cardiomyocytes Hypoxia-reoxygenation Injury Of Adriamycin-induced Adult Chronic Congestive Heart Failure

Objective: Heart failure is a serious threat to the health of the patient as a commonclinical critically ill patient, which is the final performance of a variety ofcardiovascular diseases.We tested whether morphine preconditioning retains itscardioprotection in chronic congestive heart failure rat induced by Adriamycin in vitro,and to find the possible mechanism. And Andramycin heart damage has been paid moreand more attention for the reason that the drugs’ obvious effect on human tumor inclinical. On the other hand, it’s common that heart ischemia-reperfusion injury ownsnormal high incident, which has been protected by the classic ischemia preconditioning.Methods: Chronic congestive heart failure was induced by tail vein injection ofAdriamycin (2mg/kg weekly for6weeks) in male220-250gmail Sprauge-Dawley rats.Isolation of cardiomyocytes using0.05%type II collagenase was performed in thesecond week after thelast injection of adriamycin, and treated with hypoxiapreconditioning (HPC) or morphine preconditioning (MPC,0.03,0.1,0.3,1,3μmol/L)after48h normoxic culture. MPC was induced by three cycles of5-min perfusion ofmorphine interspersed with5-min of drug-free.Naloxone and Naltrindole were added at10min before hypoxia-reoxygenation forobserving the mechanism(s) in this process. And cardiomyocytes were divided into ninegroups: control group (CON), hypoxia preconditioning group (HPC), morphinepreconditioning group (MPC,1μmol/L), HPC and Naloxone (HPC+Nal), HPC andNaloxone (HPC+Nat), MPC and Naloxone (MPC+Nal), MPC and Naloxone (MPC+Nat) and Naloxone and Naloxone group as self-control.Cell survival was measured by MTT and Trypan blue exclusion, and impairment ofmitochondrial membrane was determined by the levels of LDH and CK. Hoechststaining could evaluate the account of apoptotic myocytes after treatments.Results: Cardioprotection effect of morphine preconditioning was showndose-dependent and1μmol/L may be the optimal dose for CHF cardiomyocytesexposing to H/R with myocytes survival47.4%increase and LDH release38.1%reduction comparing with H/R excellently. However, there were not any amelioration ofprotecting myocytes from injury of H/R occurred in HPC group. But the antyapoptosiseffect of MPC was abolished by pretreatment with Naloxone (10μM), and blocked byNaltrindole(1μM) partly.Conclusion: HPC exerted no amelioration on hypoxia-reoxygenation in adriamycininduced chronic congestive heart failure rats in vitro, MPC can confer cardioprotection,this effect was mediated through cardiac opioid receptor, may be-opioid receptoractually.