1. Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss
- Author
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Crystal M. Ripplinger, Zhen Wang, Beth A. Habecker, Yanyan Jiang, Srinivas Tapa, Lianguo Wang, and Samantha D. Francis Stuart
- Subjects
0301 basic medicine ,Male ,Sympathetic Nervous System ,Myocardial Infarction ,Adrenergic ,Action Potentials ,lcsh:Medicine ,Stimulation ,030204 cardiovascular system & hematology ,Arrhythmias ,Inbred C57BL ,Cardiovascular ,Mice ,0302 clinical medicine ,Receptors ,2.1 Biological and endogenous factors ,Myocardial infarction ,Aetiology ,lcsh:Science ,Multidisciplinary ,Cardiac electrophysiology ,Heart ,Heart Disease ,cardiovascular system ,Cardiology ,Cardiac ,medicine.drug ,medicine.medical_specialty ,Ischemia ,Diastole ,Article ,03 medical and health sciences ,Dopamine ,Internal medicine ,Receptors, Adrenergic, beta ,medicine ,Animals ,Ventricular fibrillation ,Neurodegeneration ,Heart Disease - Coronary Heart Disease ,business.industry ,Myocardium ,lcsh:R ,Isoproterenol ,Neurosciences ,Ventricular tachycardia ,Arrhythmias, Cardiac ,medicine.disease ,Mice, Inbred C57BL ,Electrophysiology ,030104 developmental biology ,Calcium ,beta ,lcsh:Q ,Cardiac Electrophysiology ,business - Abstract
Myocardial infarction (MI) can result in sympathetic nerve loss in the infarct region. However, the contribution of hypo-innervation to electrophysiological remodeling, independent from MI-induced ischemia and fibrosis, has not been comprehensively investigated. We present a novel mouse model of regional cardiac sympathetic hypo-innervation utilizing a targeted-toxin (dopamine beta-hydroxylase antibody conjugated to saporin, DBH-Sap), and measure resulting electrophysiological and Ca2+ handling dynamics. Five days post-surgery, sympathetic nerve density was reduced in the anterior left ventricular epicardium of DBH-Sap hearts compared to control. In Langendorff-perfused hearts, there were no differences in mean action potential duration (APD80) between groups; however, isoproterenol (ISO) significantly shortened APD80 in DBH-Sap but not control hearts, resulting in a significant increase in APD80 dispersion in the DBH-Sap group. ISO also produced spontaneous diastolic Ca2+ elevation in DBH-Sap but not control hearts. In innervated hearts, sympathetic nerve stimulation (SNS) increased heart rate to a lesser degree in DBH-Sap hearts compared to control. Additionally, SNS produced APD80 prolongation in the apex of control but not DBH-Sap hearts. These results suggest that hypo-innervated hearts have regional super-sensitivity to circulating adrenergic stimulation (ISO), while having blunted responses to SNS, providing important insight into the mechanisms of arrhythmogenesis following sympathetic nerve loss.
- Published
- 2020
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