Effects Of Ablation Of The Distal Of The Ligament Of Marshall On Vulnerability To Atrial Fibrillation During Acute Heart Failure

Background:heart failure（HF）as a serious end stage of multiple cardiovascular diseases,often coincides with atrial fibrillation（AF）.The pathophysiology and risk factors for HF and AF are closely aligned,and affected patients are usually elderly with a significant burden of comorbidity.Autonomic imbalance,characterized by enhanced sympathetic activity,is an important role in the development and progression of HF and AF.Previous studies have shown that renal sympathetic denervation can bring the tone of the sympathetic nervous system down,thereby preventing and reversing the atrial remodeling of a heart failure model,result in effectively reducing the vulnerability to AF.The ligament of Marshall（LOM）is an epicardial structure deriving from the embryonic left superior vena cava.The distal of LOM(LOM_LSPV)which close to the left superior pulmonary vein and continue with pericardium,contains a large number of sympathetic nerve fibers.Our previous researches found that the LOM_LSPVmight be an important sympathetic conduit for the sympathetic innervation of the heart.Objective:To investigate the effect of ablation of LOM_LSPVon autonomic activity,cardiac function and vulnerability to atrial fibrillation in acute heart failure canine model induced by rapid ventricular pacing.Methods:Twenty-four healthy adult male mongrel dogs were randomly subdivided into control group（sham ablation,n=8）,LOM group(ablation LOM_LSPV,n=8)and LSG group（ablation the neuronal soma of left stellate ganglion,n=8）.Heart rate variability（HRV）,function of left stellate ganglion（LSG）,atrial electrophysiology parameters and the concentration of plasma norepinephrine（NE）was measured and analyzed.Burst pacing（20Hz,1ms,2×threshold,lasting for 5s each time）was performed three times per locus to induce AF,the inducibilities of episodes and the duration of AF were compared at baseline.Ablation was carried out after measurement above,and before all dogs underwent 3-hour high-rate（200-240 bpm）left ventricular pacing to induce acute heart failure.Repeat all the measurement just after ablation（ABL）and at the terminus of pacing（PT）,respectively.To verify the completion of the acute heart failure canine model and reflect changes in their heart function,transthoracic 2-dimensional echocardiography was implemented at baseline,PT and 3 hours after the terminus of pacing（PT-3h）,respectively.Animals were euthanized then chested to detect the anatomical relationship between LSG and LOM.The LOM_LSPVwithout ablation in the control group was stained by hematoxylin and eosin,tyrosine hydroxylase and choline acetyl transferase.Results:1.Compared with baseline,LOM_LSPVablation significantly,reduced the LF components and LF/HF,suppressed LSG function,prolonged effective refractory period（ERP）of left atrium and left atrial appendage at ABL（all p<0.05）.At the same time,the impact on reducing systolic blood pressure,concentration of serum NE,LF components and LF/HF,and inhibiting LSG function of the LOM group was less effective than the LSG group（all p<0.05）.No significant difference was observed between the LOM group and the LSG group in effects of extending atrial ERP（p>0.05）.2.When compared to the ABL,rapid left ventricular pacing significantly,reduced the left ventricular ejection fraction,raised the concentration of serum NE,increased the LF components and LF/HF,shortened the atrial ERP,elevated the sum of window of vulnerability（ΣWOV）,facilitated the inducibility of AF induced by burst pacing at PT（all p<0.05）.Meanwhile,the impact on suppressing increases in plasma NE concentrations,LF components and LF/HF induced by rapid ventricular pacing of the LOM group was less effective than the LSG group（all p<0.05）.Effects of improving LVEF,inhibiting ERP shortening,slowing the increase ofΣWOV and the inducibility of AF of the LOM group was not significantly different from that of the LSG group（all p>0.05）.3.Compared with PT,the LVEF,LVPW and IVSS of the LOM group showed a decreasing trend,while the LVEDV,LVESV and LAD increased at PT-3h,but the difference was not significant（all p>0.05）.Importantly,the LOM group restricted the increase of LAD more than the control group,as well as its effect of improving LVEF is better than that of control group,even better than the LSG group（all p<0.05）.4.During gross anatomical examination,it was clearly demonstrated that there was a visual neural connection between LSG and LOM.Histological studies showed abundant sympathetic nerve fibers in LOM_LSPV.Conclusions:LOM_LSPVablation could reduce the cardiac sympathetic nerve activity by destroying the conduit of upstream sympathetic nerve to the heart,thereby improving left ventricular function and left atrial diameter,suppressing atrial electrical remodeling,reducing the vulnerability to AF in canines with acute heart failure induced by rapid left ventricular pacing.LOM_LSPVmay be a useful target in AF ablation,especially in people who with highly cardiac sympathetic activation or suffering from organic heart disease,such as heart failure.