| Objectives: (1)Part one: To determine the regulative effects of adenosineA~1 receptor agonist R-phenylisopropyladenosine(R-PIA) on the heat rate(HR)and the cardiac function in rats. (2) Part two: To investigate whether R-PIAcould induce delayed myocardial protection of pharmacological preconditioningand to investigate the role of nitric oxide Synhase (NOS), ATP-sensitivepotassium channel (K~ATP) and myocardial nuclear facor-kappa B (NF-kB) indelayed cardioprotection of R-PIA, so as to obtain some evidences on clinicalvalue of R-PIA in cardioprotection.Methods: (1) Part one: Forty male Wistar rats were randomly divided intofive groups (8 rats for each ): Group normal saline, Group R-PIA 0.03mg/kg,Group R-PIA 0.04mg/kg, Group R-PIA 0.05mg/kg; Group R-PIA 0.03mg/kg plusDPCPX (an adenosine A~1 receptor antagonist ) 0.2mg/kg. After beinganesthetized, rats were inserted plastic cannula into left ventricular (LV) caviythrough carotid artery,and the hemodynamics indexes of LV were continuouslymonitored and processed by Cardio2 pressure sisnal processing software. Atdifferent point before and after Subcutaneous administration of the trugs, theparameters of HR, LV-PSP, LV-DP±dp/dt~max,(the maximum ofshortening velocity of myocardium under unloading ) and RPP were recorded.The data wer Processed by SPSS 8.0 statistics analysis software.(2) Part two: Eighty male Wistar rats were randomly divided into five groups(l6 rats for each ): Group normal saline, Group R-PIA; Group R-PIA plusDPCPX, Group R-PIA plus L-NNA (a nitrogen monoxide synthase inhibitor );Group R-PIA plus Gli (an inhibitor of ATP sensitive potassium channel ). Ratswer fed as usual for 24 hours after subcutaneous administration of drugs andinserted plastic cannula into LV cavity through carotid artery after anesthesia.LV pressure curve, HR and heart rhythm were continually monitored andanalyzed by Cardio2 software. Electrocardiography was recorded by multiplephysiological signals recorder. Rats underwent 30 min of regional myocardialischemia followed by l20 min of reperfusion, and then the hearts werefarvested for infarct size determination (TTC stain) in 8 rats each group. LVmyocardial samples in the other 8 rats each group were obtained. A half of eachsample was frozen immediately in liquid nitrogen and then stored at-70℃ forassessment of myocardial nuclear factor -kappa B(NF-kB) binding activitys(eleCtrophootic mobility shift assay), and the other half of each sample wasfixed in 4% parafOrmaldehyde solUtion for dotednation of myOcardial cellsaPoPtosis in sfor tissue seCtion (oc assay). The daa wer Processed bySPSS 8.0 stallStics analysis sobo.ReSultS: (1) Part one: @ A dose-dePenden negatbo chronotrPic effect onthe heart was PrOduced by RM in anasthatised rats, The decrease of HR wasStarted frOm 5 mn aller RPIA SUbCUtaneos injeCtion and got the loweSt vafueduring l5~30 ndn affer adndulstfallon of RPIA. The the of R4IA on HR~aily lishenat ana disavnearea atrins 90-l20 dri. @ m temnoopinhibition of LV funCtion induced by RPIA Wen to mbomum during l5-30 ninand tended to weaken at 60 ndn aller adchstration of the drug. @ The LVPSP was teInPorarily lowerd by R4IA subcutaneos injeCtion and this effecttended to vhash at 30 ndn aller adIninistration of it. @ The RPP, an indexrefleCting myocardial Oxygen requirement, was significanly reduced by RPIAttis effat of RPIA on the RPP cOuld laSt for a longer time than on the inhibitionof LV funotion.(2) Part tWo: O The myocardial infarction size (MIS) in grouP R4IAwas sighficanly less than thOse in grou nonnal Saine and grou RWIA plusDPCPX (P all <0.0l), Ther was no sigulfican differnce in MIS betWen grouPRPIA pIus L-NNA and grOU R4IAop.05), The MIS in grou RPIA plus Giwas signifiCanly 1ess than that in grou nOnnal saline (P<0.0l), bu ~ficantlymore than tha in grou RM ew.05). @ DUring myocardial ischenda, theincidences of bOth Ventricular taChycardia (VT) and ven...
|
PDF Full Text Request