Selective ablation of the ligament of Marshall reduces ischemia and reperfusion-induced ventricular arrhythmias

Abstract

Cardiac sympathetic tone overdrive is a key mechanism of arrhythmia. Cardiac sympathetic nerves denervation, such as LSG ablation or renal sympathetic denervation, suppressed both the prevalence of VAs and the incidence of SCD. Accumulating evidence demonstrates the ligament of Marshall (LOM) is a key component of the sympathetic conduit between the left stellate ganglion (LSG) and the ventricles. The present study aimed to investigate the roles of the distal segment of LOM (LOMLSPV) denervation in ischemia and reperfusion (IR)-induced VAs, and compared that LSG denervation. Thirty-three canines were randomly divided into group 1 (IR group, n = 11), group 2 (LOMLSPV Denervation + IR, n = 9), and group 3 (LSG Denervation + IR, n = 13). Hematoxylin-Eosin (HE) and Immunohistochemistry staining revealed that LOMLSPV contained bundles of sympathetic but not parasympathetic nerves. IR increased the cardiac sympathetic tone [serum concentrations of noradrenaline (NE) and epinephrine (E)] and induced the prevalence of VAs [ventricular premature beat (VPB), salvo of VPB, ventricular tachycardia (VT), VT duration (VTD) and ventricular fibrillation (VF)]. Both LOMLSPV denervation and LSG denervation could reduce the cardiac sympathetic tone in Baseline (BS) [heart rate variability (HRV)]. Compared with group 1, LOMLSPV denervation and LSG denervation similarly reduced sympathetic tone [NE (1.39±0.068 ng/ml in group 2, 1.29±0.081 ng/ml in group 3 vs 2.32±0.17 ng/ml in group 1, P<0.05) and E (114.64±9.22 pg/ml in group 2, 112.60±9.69 pg/ml in group 3 vs 166.18±15.78 pg/ml in group 1, P<0.05),] and VAs [VT (0±3.00 in group 2, 0±1.75 in group 3 vs 8.00±11.00 in group 1, P<0.05) and VTD (0 ± 4 s in group 2, 0±0.88s in group 3 vs 10.0 ± 22.00s in group 1, P<0.05)] after 2h reperfusion. These findings indicated LOMLSPV denervation reduced the prevalence of VT by suppressing SNS activity. These effects are comparable to those of LSG denervation. In myocardial IR, the anti-arrhythmic effects of LOMLSPV Denervation may be related to the inhibition of the expression of NE and E.

Autonomic Neuromodulation for Preventing and Treating Ventricular Arrhythmias

“…(2008) found that neural activation of the LOM LSPV by norepinephrine injection caused accelerated junctional rhythms, idioventricular rhythms, and VT. LOM LSPV ablation reduced VAs occurrence induced by cesium combined with LSG stimulation in canines ( Wang et al., 2016a ). Additionally, in dogs with acute MI or ischemia-reperfusion models, LOM LSPV ablation ameliorated the prevalence of VAs by reducing sympathetic tone ( Liu et al., 2018 ; Ma et al., 2018 ). Therefore, the LOM may serve as a sympathetic conduit between the LSG and ventricles.…”

The protective role of vagus nerve stimulation in ischemia-reperfusion injury

“…The autonomic nervous system consists of the sympathetic and parasympathetic nervous systems, which counteract each other to maintain a dynamic balance in a normal physiological state. Studies have indicated a substantial increase in sympathetic activity during IR in the heart, kidney, and other organs, leading to an imbalance of the autonomic nervous system [ [76] , [77] , [78] , [79] ]. During myocardial IR in mice, rats, and dogs, norepinephrine (NE) and epinephrine concentrations in plasma and paraventricular nucleus increased significantly, accompanied by cardiac sympathetic nerve activation [ [76] , [77] , [78] ].…”

“…Studies have indicated a substantial increase in sympathetic activity during IR in the heart, kidney, and other organs, leading to an imbalance of the autonomic nervous system [ [76] , [77] , [78] , [79] ]. During myocardial IR in mice, rats, and dogs, norepinephrine (NE) and epinephrine concentrations in plasma and paraventricular nucleus increased significantly, accompanied by cardiac sympathetic nerve activation [ [76] , [77] , [78] ]. There was also a significant rise in the incidence of malignant arrhythmias, such as ventricular extrasystole and ventricular tachycardia [ 76 , 77 , [80] , [81] , [82] ].…”

“…During myocardial IR in mice, rats, and dogs, norepinephrine (NE) and epinephrine concentrations in plasma and paraventricular nucleus increased significantly, accompanied by cardiac sympathetic nerve activation [ [76] , [77] , [78] ]. There was also a significant rise in the incidence of malignant arrhythmias, such as ventricular extrasystole and ventricular tachycardia [ 76 , 77 , [80] , [81] , [82] ]. Wang et al [ 78 ] demonstrated a change in heart rate variability (HRV) after acute myocardial infarction (AMI).…”

“…Additionally, in the renal IRI model, excessive sympathetic activity can lead to the release of angiotensin Ⅱ and inflammatory factors, aggravating renal damage [ 7 ]. Studies have demonstrated that the regulation of the autonomic nervous system through ablation or blockade of the sympathetic nerve can significantly improve the IRI in various organs [ 76 , 88 ]. It is evident that ablating or blocking of the sympathetic nerve can lead to serious complications since it disrupts the normal physiological regulatory system.…”