Cholinergic stimulation improves electrophysiological rate adaptation during pressure overload-induced heart failure in rats

Document Type

Journal Article

Publication Date

12-1-2020

Journal

American Journal of Physiology - Heart and Circulatory Physiology

Volume

319

Issue

6

DOI

10.1152/AJPHEART.00293.2020

Keywords

Electrophysiology; Heart failure; Neurocardiology; Optical mapping; Parasympathetic stimulation

Abstract

Left ventricular (LV) electrical maladaptation to increased heart rate in failing myocardium contributes to morbidity and mortality. Recently, cardiac cholinergic neuron activation reduced loss of contractile function resulting from chronic transverse-ascending aortic constriction (TAC) in rats. We hypothesized that chronic activation of cardiac cholinergic neurons would also reduce TAC-induced derangement of cardiac electrical activity. We investigated electrophysiological rate adaptation in TAC rat hearts with and without daily chemogenetic activation of hypothalamic oxytocin neurons for downstream cardiac cholinergic neuron stimulation. Sprague-Dawley rat hearts were excised, perfused, and optically mapped under dynamic pacing after 16 wk of TAC with or without 12 wk of daily chemogenetic treatment. Action potential duration at 60% repolarization (APD ) and conduction velocity (CV) maps were analyzed for regional rate adaptation to dynamic pacing. At lower pacing rates, untreated TAC induced elevated LV epicardial APD . Fitted APD steady state (APD ) was reduced in treated TAC hearts. At higher pacing rates, treatment heterogeneously reduced APD , compared with untreated TAC hearts. Variance of conduction loss was reduced in treated hearts compared with untreated hearts during fast pacing. However, CV was markedly reduced in both treated and untreated TAC hearts throughout dynamic pacing. At 150 ms pacing cycle length, APD versus diastolic interval dispersion was reduced in treated hearts compared with untreated hearts. Chronic activation of cardiac cholinergic neurons improved electrophysiological adaptation to increases in pacing rate during the development of TAC-induced heart failure. This provides insight into the electrophysiological benefits of cholinergic stimulation as a treatment for patients with heart failure. 60 60 60 ss 60 60

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