Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart

Am J Physiol Heart Circ Physiol. 2024 Mar 29. doi: 10.1152/ajpheart.00749.2023. Online ahead of print.ABSTRACTNicotine is the primary addictive component in tobacco products. Through its actions on the heart and autonomic nervous system, nicotine exposure is associated with electrophysiological changes and increased arrhythmia susceptibility. To assess underlying mechanisms, we treated rabbits with transdermal nicotine (NIC, 21 mg/day) or control (CT) patches for 28 days prior to performing dual optical mapping of transmembrane potential (RH237) and intracellular Ca2+ (Rhod-2 AM) in isolated hearts with intact sympathetic innervation. Sympathetic nerve stimulation (SNS) was performed at the 1st - 3rd thoracic vertebrae, and β-adrenergic responsiveness was additionally evaluated following norepinephrine (NE) perfusion. Baseline ex vivo HR and SNS stimulation threshold were higher in NIC vs. CT (P = 0.004 and P = 0.003, respectively). Action potential duration alternans emerged at longer pacing cycle lengths (PCL) in NIC vs. CT at baseline (P = 0.002) and during SNS (P = 0.0003), with similar results obtained for Ca2+ transient alternans. SNS shortened the PCL at which alternans emerged in CT but not NIC hearts. NIC exposed hearts tended to have slower and reduced HR responses to NE perfusion, but ventricular responses to NE were comparable between groups. While fibrosis was unaltered, NIC hearts had lower sympathetic nerve density (P = 0.03) but no difference in NE content vs...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research