| Background:Pinacidil is a type of ATP-sensitive K+channel opener. The preconditioning ofpinacidil has a good protective effect in myocardial ischemia reperfusion injury.However, myocardial ischemia is difficult to be predicted in clinical practise, so theapplication of pinacidil is subject to certain restrictions. Some studies suggested thatdrug preconditioning and postconditioning may have the same protective target.Pinacidil postconditioning simulated the protection mechanism of ischemiareconditioning to reduce myocardial ischemia and reperfusion injury.Objective:The purpose of the study was to investigate the beneficial effect of different dosesof Pinacidil postconditioning on myocardial reperfusion damage in rabbit and observedose-related cardioprotective effect.Methods:1. Grouping40male rabbits were randomly divided into5groups:(1) Sham operation group,(2)ischemia-reperfusion in the control group,(3) pinacidil high dose group (200μg/kg),(4)pinacidil on middle dose group (100μg/kg),(5) pinacidil on low dose group (50μg/kg)(n=8).2. Model PreparationSham group: the silk was fed through the back of left descending artery (LAD),without ligation of the LAD. I/R group: ligation of the LAD for30min, thenreperfusion for120min. Pinacidil high dose group: pinacidil200μg/kg infusionthrough the left ventricular catheter right after reperfusion (in10s), repeat the followingsteps as I/R group. Pinacidil middle dose group: gave pinacidil100μg/kg. Pinacidil low dose group: gave pinacidil50μg/kg.3. Indicators for monitoringAfter modeling success, using Medlab bio-signal acquisition systems to recordthe changes of LVSP and LVEDP continuously, and detect plasma CK activity andMDA content before ischemia,ischemia for30min, reperfusion for60min and120minseparately. After the end of the experiment, acquired the myocardial samples, usingEvans blue/chlorinated triphenyl tetrazolium double staining to detect myocardialischemia and infarct area, using RT-PCR to detect Bcl-2and Bax gene expression ofischemic myocardium.Results:Reperfusion for120min, compared with ischemia-reperfusion group, middledose and low-dose group, the LVSP level increased significantly (p <0.05); the LVEDPlevel decreased significantly (p <0.05); MDA level decreased significantly (p <0.05);Bcl-2mRNA expression increased significantly (p <0.05); Bax mRNA expressiondecreased significantly (p <0.05). Compared with I/R group, the heart functionparameters, the MDA level, the expression of Bcl-2and Bax mRNA had no significantdifference (P>0.05) in high dose group. Plasma CK activity of different concentrationsof the pinacidil decreased significantly (P <0.05).Conclusion:1. middle dose and low dose of pinacidil had protective effect in ischemicreperfusion injury.2. The high dose pinacidil didn’t have obvious effect on ischemia and reperfusionmyocardium. |
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