| AIM: The goal of this study was to investigate the effects of κ-opioid receptor (k-OR)on stretch-induced electrophysiological changes of isolated acute myocardial infractedrat hearts, including monophasic action potential duration (MAPD) changes andincidence of arrhythmias through the pretreatment of a selective k-OR agonistU50488H and a selective k-OR antagonist nor-BNI. Moreover, we observed k-ORgene expression and k-OR protein expression changes of isolated acute myocardialinfracted rat hearts after stretch to explore the role and mechanisms of k-OR onstretch-induced electrophysiological changes of isolated acute myocardial infractedrat hearts.METHODS: Male Sprague-Dawley rats (n=55) were randomly divided into fivegroups: sham operated group (SO, n=11), U50488H-treated group (U50488H, n=11),myocardial infarction group (MI, n=11), U50488H-treated myocardial infarctiongroup (MI+U50488H, n=11) and nor-BNI treated myocardial infarction group(MI+nor-BNI, n=11). After the stable Langendorff isolated heart perfusion for20minutes (SO group and U50488H group) after ligation of left anterior descendingartery of the hearts for30minutes, the hearts were stretched for1minute by alteringthe volume of latex balloon to△V=0.1ml,0.2ml,0.3ml of the left ventricular.Left ventricular pressure (LVP), monophasic action potential duration (MAPD),premature ventricular contraction (PVC), ventricular tachycardia (VT) and ventricularfibrillation (VF) were observed for1minute. The expression κ-opioid receptor mRNAand protein of left ventricular myocardial tissue (the marginal zone of infractedmyocardium) in the five groups were measured by RT-PCR and Western blottechniques. RESULTS:1.MAPD90significantly increased in all five groups after stretch. On thecontrary, MAPD20and MAPD50were not changed after stretch.In contrast to SOgroup, MAPD90in the MI and MI+nor-BNI groups increased significantly beforestretch (P <0.05) and after stretch (P <0.01). MAPD90in the MI group was increasedcompared with that of the MI+U50488H group（P﹤0.05或P﹤0.01）, but decreasedcompared with that of the MI+nor-BNI group after stretch (P <0.05).2. After stretch, the numbers of PVCs were increased in five groups（P﹤0.01). The numbers of PVCs in the MI group were increased significantly beforestretch and after stretch compared to the SO group（P﹤0.01),but it was notchanged significantly in U50488H group（P＞0.05). In contrast to SO group, thenumbers of PVCs in MI+nor-BNI group were higher (P﹤0.01)and lower inMI+U50group (P﹤0.01). There were no ventricular tachycardias or ventricularfibrillations in the SO group, U50488H group and MI+U50488H group. Afterstretch, the numbers of VTs were increased in MI group (P﹤0.01) and thenumbers of VFs were increased in MI+nor-BNI group (P﹤0.05). Furthermore, thenumbers of VFs were increased in MI+nor-BNI group compared with that in MIgroup.3. The arrhythmia score in the MI and MI+nor-BNI groups was higher than thatof the SO group (P<0.01), but there were no significant changes between U50488Hgroup and SO group（P＞0.05）. Furthermore, the arrhythmia score in the MI+nor-BNIgroup was higher than that in MI group after stretch (P<0.01). The arrhythmia scoreof the MI+U50488H group was lower than that of MI group after stretch (P <0.01).4. The expressions of k-OR mRNA and protein are increased in U50488H group,MI group and MI+U50488H group(P<0.05). In contrast to MI group, the expressionsof k-OR mRNA and protein in MI+U50488H groups increased significantly (P<0.01).On the contrary, the expressions of k-OR mRNA and protein in MI+nor-BNI groupdecreased significantly (P<0.01) CONCLUSION: Stretching the myocardium could elicit significant changes inMAPD and more complex and lethal ventricular arrhythmias. Moreover, theexogenous k-OR modulation could suppress stretch-induced electrophysiologicalchanges and play an anti-arrhythmogenic role in stretch-induced arrhythmias afterAMI. Furthermore, the expressions of k-OR mRNA and protein were upregulatedafter stretching the infarcted myocardium. The upregulation of k-OR expressioncontributed to the anti-arrhythmogenic role of k-OR. |
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