Autonomic boundary conditions for ventricular fibrillation and their implications for a novel defibrillation technique.
The sympathetic and parasympathetic divisions of the autonomic nervous system modulate cardiac rhythm and the probability of arrhythmia occurrence. Both increased sympathetic drive and hypoxia increase the likelihood for ventricular fibrillation (VF). Vagus nerve stimulation (VNS) can protect from fatal arrhythmias via cholinergic and nitrergic action. We sought to determine boundary conditions for VF and defibrillation by autonomic manipulations accompanied or not by hypoxic changes in urethane-anesthetized rats. VF was induced with (1) vagotomy, (2) systemic high-dose (>15 mg/kg) isoproterenol, and (3) hypoxemia. When VNS (50 Hz) produced cardiac standstill, it converted every VF episode (59/59). A nitric oxide synthase inhibitor did not reduce VNS efficacy (13/14 episodes converted), but addition of atropine reduced VNS efficacy (11/27 episodes converted). VF can be induced by autonomic derangements only under constrained conditions, including sympathetic over-activation, reduced parasympathetic input, and hypoxemia. VNS can provide an alternative method to defibrillate via its cholinergic action.
Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Box 31, Brooklyn, NY 11203, USA.
Isaac
I
Naggar
Sae
S
Uchida
Haroon
H
Kamran
Jason
J
Lazar
Mark
M
Stewart
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D026602:Nitrergic Neurons / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014628:Vagotomy / Q000379:methods; D055536:Vagus Nerve Stimulation / Q000379:methods; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D018377:Neurotransmitter Agents; D001285:Atropine; D019001:Nitric Oxide Synthase; D007545:Isoproterenol