Nicotine Exacerbates Arrhythmogenesis in Rabbit Right Ventricular Outflow Tract Triggered by Chronic Obstructive Pulmonary Disease

PMCID: PMC12176695

PMID: 40533933

DOI: 10.1111/jcmm.70664

Journal: Journal of cellular and molecular medicine

Publication Date: 2025-6-18

Authors: Chan C, Lin F, Chen Y, Higa S, Chen S, et al.

Key Points

• COPD and nicotine independently increase ventricular tachycardia risk, with nicotine exacerbating arrhythmogenic potential
• 89% of nicotine-treated COPD RVOTs exhibited nonsustained VTs, compared to 8.3% in control groups (p = 0.001)
• Sympathetic overactivity and calcium signaling dysregulation are primary mechanisms underlying COPD-related ventricular arrhythmias

Summary

This experimental study investigated the arrhythmogenic mechanisms of ventricular tachycardia (VT) in chronic obstructive pulmonary disease (COPD), with a specific focus on the role of nicotine in right ventricular outflow tract (RVOT) electrical and structural remodeling. Using a rabbit model with human leukocyte elastase-induced COPD, researchers examined how COPD and nicotine exposure independently and synergistically contribute to ventricular arrhythmia risk through complex electrophysiological changes.

The study revealed that both COPD and nicotine treatment significantly increased VT incidence, with nicotine-treated COPD RVOTs demonstrating the highest arrhythmogenesis. Key mechanistic findings included altered ionic currents, prolonged action potential duration, increased fibrosis, and dysregulated calcium signaling. Critically, the arrhythmias were suppressed by inhibitors targeting protein kinase A (PKA), calcium/calmodulin-dependent protein kinase II (CaMKII), and sodium-calcium exchanger (NCX) pathways, suggesting these molecular mechanisms play crucial roles in VT development.