The Interventional Strategies And Electrophysiological Mechanism Of Ventricular Fibrillation In Different Heart Models Of Canine

Objective:1.To investigate the effects of Class III antiarrhthmic agents amiodarone versus ibutilide on ventricular fibrillation(VF)/defibrillation and hemodynamic status.2.To determine the anti-fibrillative effect of ibutilide and the related mechanism in healthy canine heart3.To evaluate the differences of ventricular fibrillation between healthy and heart failure canines.To further investigate the effect of ibutilide on defibrillation threshold(DFT)and VF activation property in heart failure canine heart.Methods:1.Hemodynamic evaluation,ventricular effective refractory period(ERP)were evaluated in twelve beagles.Canines were divided into 2 groups(6vs 6)and were given amiodarone and ibutilide respectively.By nducing short duration of VF,DFTs were acquired.Hemodynamic parameters,ERP and DFT were compared between pre and post-medication conditions.2.Ibutilide was given intravenously in six open-chest beagles.Before and after drug administration,episodes of VF(20s)were electrically induced and recorded with a 10×10 unipolar electrode plaque sutured on the lateral part of left ventricular epicardium.DFT and VF activation patterns including type of epicardial activation maps,VF cycle length(VF-CL),conduction velocity,wavelength(WL)and reentry incidence were measured.Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals(ARI)during pacing.3.Six canines were given rapide right ventricular pacing to create chronic heart failure model.Epicardial mapping plaque of 144 eletrodes and 6plunge needles were used to map the epicardial and transmural activation before and during induced VF.ARI,ERP,restitution property,VF pattern,temporal/spatial dispersion and DFT were compared between pre and post-medication conditions.Results:1.Compared to baseline,amiodarone significantly compromised hemodynamic status.Mean Arterial Pressure(MAP)was significantly decreased by 39%(96±17 mm Hg vs.59±27 mm Hg,P=0.014);systolic pressure d P/d T was significantly reduced from 1.4±0.4 to 0.8±0.3(P=0.008);heart rate was significantly slowed(126±32bpm vs 107±34bpm,P<0.05).Both amiodarone and ibutilde significantly prolonged ventricular ERP,but only ibutilide significantly decreased DFT(17±2J vs 9±1J,P<0.01).Ibutilide had no effect on canine's hemodynamics.2.Compared to baseline,ibutilide markedly decreased DFT by 31%(491±14vs 337±59 V,P<0.01),and significantly reduced the maximal slope of the restitution curve(1.34±0.08 vs 0.76±0.06,P<0.01)and its epicardial dispersion(0.36±0.09 vs 0.21±0.06,coefficient of variation,P=0.03).The dispersion of refractoriness was enhanced at the pacing cycle length of 300 ms to 160 ms by ibutilide.The drug significantly increased VF-CL(96±19 vs 112±20 ms,P<0.01)and WL(41±9 vs 52±14 mm,P=0.02)during VF,and reduced the reentry incidence by 25 %(0.08±0.02 vs 0.06±0.02,P<0.01).In the epicardial activation maps,ibutilide significantly reduced the percentage of more complex activation during VF.3.After 3 weeks of continuous rapide ventricular pacing,ERP and DFT were significantly different from that of healthy canine heart.Compared to HF baseline,ibutilide significantly reversed the elevated DFT(18±2J vs 13±2.7J,P<0.01).Corresponding to healthy heart,ARI restitution maximum slope and dispersion,VF activation frequency,incidence of reentry,VF complexity and temporal spatial dispersion were significantly ameliorated by ibutilide.Further more,spontaneous termination of venricular arrhythmias were observed after ibutilide medication.Conclusions:1.Intravenous amiodarone significantly affected hemodynamic status before and after defibrillation.Ibutilide significantly decreased DFT,but with no evident impact on hemodynamics.2.Intravenous ibutilide significantly decreased the DFT.It might due to reduction of activation pattern complexity during VF.3.Since ibutilide obviously reduced temporal spatial dispersion,this agent significantly improved the complexity of VF activation in canine failing heart.Organization of VF activation may lead to spontaneous termination of VF/VT.