Effects Of Mid-myocardial Pacing On Transmural Dispersion Of Repolarization And Conduction In Vitro And Vivo Ventricular Of Dogs

Objective:To investigate the effects of different pacing sites on the transmural dispersion ofrepolarization (TDR) through the left ventricular wedge preparation model. To furtherverify the vitro results, some other experiments were implemented in vivo canine.We build a sinoatrial node damage model in canines induced by formaldehydeinjected. All the canines were given endocardial, M layer and the epicardial pacingwith smultaneous recording of monophasic action potentials duration (MAPD) of thethree cardial layers, TDR, conduction time of different myocardial layers and otherparameters. This study would further confirm that amplification of TDR was one ofthe electrophysiological mechanisms of proarrhythmic effects of biventricular pacingand explore the use of M layer pacing technology to improve cardiacresynchronization therapy (CRT) pacing mode, which reducing or avoiding thepotential risk of biventricular pacing.Research Methods：In vitro exprements:24healthy canines weighed15~20Kg were were randomisedinto two groups: normal group (normal Tyrode’s solution perfusion, n=12) andibutilide group (Ibutilide solution perfusion, n=12). All animals were producedarterially perfused LV wedge preparations. ECG and APD were simultaneouslyrecorded form epicardial, midmyocardial, and endocardial cells.In vivo exprements:12mongrel canines were chosed which produced sinoatrialnode damage model induced by formaldehyde injected. The intimal surface ECG andmonophasic action potentials (MAP) were simultaneously recorded. Statisticalanalysis was done using SPSS17.0software. Data of electrophysiological parameterswere presented as Mean and standard deviations (SD). One-way analysis of variance(ANOVA) was performed on evaluating difference of electrophysiological parametersamong Endo pacing, M pacing and Epi pacing. The Student–Newman–Keuls (SNKtest) was used as a post hoc test in the subsequent multiple comparative analysis. TheT test was applied in comparison of electrophysiological parameters between control and ibulitide group. To evaluate difference of electrophysiological parameters ofperfusion before and after ibulitide, paired t test was performed. Criterion forstatistical significance was P<0.05.Results:In vitro experiment:(1) In control group, APD of the three layers have no difference under differentpacing sites. M cells displayed a longest APD when epicardial cell was the shortest,endocardial cell between them. In ibulitide group, the three layers’ APD wereprolonger some degrees than control group in the same pacing site (P <0.05). Butcompared between the different parts of the pacing, APD was no significantdifference (P>0.05). M cells displayed a longest APD when epicardial cell were theshortest, endocardial cell between them.(2) In control group,TDR and Tp-Te interval have significant difference amongepicardial layer, M layer and epicardial layer. However, there was differencebetween epicardial pacing and endocardial pacing, or epicardial pacing and M pacing,but not in endocardial and M. In ibulitide group, TDR and Tp-Te interval increased inthe same pacing site comparaed with control group. The same with the control group,there was difference between epicardial pacing and endocardial pacing, or epicardialpacing and M pacing, but not in endocardial and M.(3) The different pacing site have influence on the myocardial layers activationsequence.The conduction time between midmyocardium and epicardium(TM-Epi)increased after the pacing mode shifted from Endo pacing to Epi pacing(P＜0.05), butnot in the Endo to M pacing shift (P＞0.05). As also showed in ibulitide group.(4) In a total of8preparations, ventricular tachycardia occurred in2preparationsduring Epi pacing, but not M or Endo pacing. One was induced by programmedelectrical stimulation at an S1-S2interval of250ms. The other was spontaneous, asshown in Fig.2,3. In this example, ischemia prolonged TDR from34ms to63msduring Endo and M pacing. Epi pacing caused a further prolongation of TDR to111ms. During M and Endo pacing, a number of extrasystoles occurred, but ventricular tachycardia could not be induced at any coupling interval tested. Whenbasic stimulation was shifted to epicardium, ventricular arrhythmia occurredfrequently.2, in vivo experiment(1) Pacing rate was fixed at60beats/min. There were no difference ofmonophasic action potentials duration (MAPD) of the three layers with pacing sites.M cells displayed a longest MAPD when epicardial cell was the shortest, endocardialcell between them. After injection of ibulitide, MAPD of the three layers increasedthan before. But compared between the different parts of the pacing, APD was nosignificant difference (P>0.05). M cells displayed a longest APD when epicardial cellwere the shortest, endocardial cell between them.(2) Pacing rate was fixed at60beats/min.①Epicardial pacing increased theTDR and TM-Epi comparaed with endocardial pacing or M layer pacing, when therewere no diffenence between endocardial pacing and M pacing.②After use ofibulitide, TDR were more longer than before at the same pacing frequency. But theTM-Epi have no significant difference. As in vitro experiment, a shift from Endo orM to Epi pacing caused a further prolongation of TDR.(3) ventricular tachycardia have not induced by programmed electricalstimulation whether use ibulitide or not.Conclution:M pacing have not increased the existing TDR whether in vitro or in vivocompared with endocardial pacing. M pacing can effectively avoid the amplication ofTDR which caused by the change of activation sequence of cardial layers, andeffectively prevent TDR-related arrhythmia.