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The Relations Between The Heart Functional Recovery And The Reduction Of Apoptotic Cardiomyocytes Under The Protection Of The Diazoxide Cardioplegic Solution

Posted on:2004-10-30Degree:MasterType:Thesis
Country:ChinaCandidate:X B WangFull Text:PDF
GTID:2144360095950291Subject:Cardiothoracic Surgery
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Background and Objectives : At present, hypothermic hyperkalemic cardioprotective solutions with untoward consequences including contractile dysfunction, conduction disturbances, abnormal transmembrane ion fluxes and cell swelling preseve safely the heart in periods of 4 to 6 hours only. An important limitation in heart transplantation is the inadequancy of current heart preservation techniques. In recent years that hyperpolarized cardioplegic solutions of potassium channel openers produce myocardial protection is similar and often superiors the traditional hyperkalemic cardioplegic solutions. Some studay have demonstrated that opening selective mitochondrial KATP not sarcolemmal KATP protects the donor heart and attenuates ischemia / reperfusion induced apoptosis. The purpose of our study was to investagate the relations between the donor heart functional recovery and the reduction of myocytes apoptosis induced by the ischemia / reperfusion.Methods: In a Krebs-Henseleit (KH) solution perfused isolated rabbit heart langendorff model, thirty-two rabbit hearts were randomly divided into four groups (n=8 for each group): DIA group (50 mol/L diazoxide mixed in KH solution), STH group (ST "Thomas solution), DIA+5-HD group (50 u mol/L diazoxide and 100 mol/L 5-hydro xydecanoic acid mixed in KH solution), KH group (KH solution). The hearts of every group underwent 6 hours of hypothermic (4 ) storage in the corresponding cardiorplegic solution. DP (left ventricular peak developed pressure),+dp/dtmax (maximal values of positive rate of left ventricular pressure), coronary flow (CF), enzyme release (creative kinase) were measured prior and following storage. The post-reperfusion recovery of DP +dp/dtmax, CF was expressed as the percentage of pre-ischemic control values. Time to cardioplegie solution delivery, time to mechanical and electrical arrest, myocardiol tissue water,adenosine triphosphate concentrate,MDA content were also measured. The apoptotic cardiomyocytes were identified by flow cytometer.Results : significant difference occurred in reduction of cardiomyocytes apoptosis, percentage of hemodynamic recovery and CF recovery,ATP store,MDA content. DIA group had better preservation than STH group (P <0.05). The two groups were similar(P >0.05)in time to heart arrest,enzyme realease and myocardial tissue water content. Likewise, there were significant differences between STH group and KH group (P<0.05) except cardioplegic solution delivery time,percentage of CF recovery,myocardial tissiue water contert (P>0.05). The protection of diazoxide was abolished by 5-HD, but not the effect of blood vessel dilatation. The data of DIA group,TSH group,DIA+5-HD group,KH group respectively as following:Time to cardioplegic solution delivery (minutes): 1.49 0.34, 2.22 0.29, 1.75 0.29, 2.37 0.39(P <0.05), time to mechanical arrest (seconds): 21.3 3.2, 20.4 3.4, 38.4 5.1, 37.5 6.9(P<0.05), time to electrical arrest (seconds): 22.7 3.5, 22.0 2.7,'39.6 5.3, 41.5 5.5(P <0.05), percentage of DP recovery (%): 67.9 6.7, 58.6 6.6, 23.1 4.0, 22.9 4.1(P <0.05), percentage of +dp/dtmax recovery (%):68.2 4.4, 58 3.7, 35.2 2.6, 37 3.1(P <0.05), percentage of CF recovery (%): 68.2 4.4, 58 3.7, 35.2 2.6, 37 3.1(P<0.05), creative kinase before preserving (u/dl): 144.10 20.03, 144.52 13.18, 142.80 13.25, 152.40 17.53(P>0.05), creative kinase after preserving (u/dl): 203.26 15.9, 212.29 19.82, 491.83 17.53, 485.16 14.03 (P<0.05), adenosine triphosphate concentrate of myocardiam after preserving (umol/g): 4.4 0.28, 3.1 0.27, 2.28 0.41, 1.93 0.42(P<0.05), myocardial water content (%): 78.48 0.24, 78.50 0.21, 78.62 0.34, 78.56 0.28(P>0.05), MDA content of myocardial tissue (nmolog-1 ): 50.97 8.0, 71.1 11.8, 93.6 12.3, 97.1 12.4(P< 0.05), apoptotic rate of cardiomyoctes (%): 3.91 0.32, 6.28 0.72, 10.68 0.92, 10.91 0.73(P <0.05).Conclusions: 1. Diazoxide cardioplegic solution avoided considerably the shortcomings of depolarized arrest of hyperkalemic solution. 2. Diazoxide protected the myocardium...
Keywords/Search Tags:Potassium channel opener, Diazoxide, Organ preservation solution, Heart transplantation, Myocardial ischemia reperfusion injury
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