title: Vagal control of cardiac electrical activity and wall motion during ventricular fibrillation in large animals.
abstract: Vagal inputs control pacemaking and conduction systems in the heart. Anatomical evidence suggests a direct ventricular action, but functional evidence that separates direct and indirect (via the conduction system) vagal actions is less well established. We studied vagus nerve stimulation (VNS) during sinus rhythm and ventricular fibrillation (VF) in pigs and sheep to determine: 1) the range of unilateral and bilateral actions (inotropic and chronotropic) and 2) whether VNS alters left ventricular motion and/or electrical activity during VF, a model of abnormal electrical conduction of the left ventricle that excludes sinus and atrioventricular nodal function. Adult pigs (N=8) and sheep (N=10) were anesthetized with urethane and mechanically ventilated. VNS was performed in animals at 1, 2, 5, 10, 20, 50, and 100Hz for 20s. VF was induced with direct current to the ventricles or occlusion of the left anterior descending coronary artery. In 4 pigs and 3 sheep, left ventricular wall motion was assessed from endocardial excursion in epicardial echocardiography. In sheep and pigs, the best frequency among those tested for VNS during sinus rhythm to produce sustained electrical and mechanical ventricular standstill was 50Hz for unilateral or bilateral stimulation. When applied during VF, bilateral VNS increased the variability of the dominant VF frequency, indicating a direct impact on the excitability of ventricular myocytes, and decreased endocardial excursion by more than 50% during VF. We conclude that the vagus nerve directly modulates left ventricular function independently from its effects on the conduction system.
authors: Department of Physiology & Pharmacology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, United States; Program in Neural and Behavioral Sciences, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, United States.
authors: Isaac
authors: I
authors: Naggar
authors: Department of Physiology & Pharmacology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, United States.
authors: Ko
authors: K
authors: Nakase
authors: Division of Cardiovascular Medicine, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, United States.
authors: Jason
authors: J
authors: Lazar
authors: Division of Cardiovascular Medicine, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, United States.
authors: Louis
authors: L
authors: Salciccioli
authors: Department of Electrical and Computer Engineering, Polytechnic Institute of New York University, 2 Metrotech Center, Brooklyn, New York 11201, United States.
authors: Ivan
authors: I
authors: Selesnick
authors: Department of Physiology & Pharmacology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, United States; Department of Neurology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, United States. Electronic address: mark.stewart@downstate.edu.
authors: Mark
authors: M
authors: Stewart
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000503:physiopathology*; D008297:Male; D012121:Respiration, Artificial; D012756:Sheep; D013045:Species Specificity; D013552:Swine; D014520:Urethane / Q000494:pharmacology; D014630:Vagus Nerve / Q000503:physiopathology*; D055536:Vagus Nerve Stimulation / Q000379:methods; D014693:Ventricular Fibrillation / Q000503:physiopathology*
chemical_list: D018686:Anesthetics, Intravenous; D014520:Urethane
keywords: Arrhythmia; Asystole; Cardiac conduction; Echocardiography; Vagus nerve stimulation