Chronic nicotine inhalation accelerates cardiac decompensation due to pressure overload
Authors: Edavettal Joshua , Fried Nicholas , Gardner Jason 
Published: May 2023

Background: Cardiovascular disease is the leading cause of death in the United States and is strongly associated with smoking. While cigarette smoking has declined, the use of electronic nicotine delivery systems (ENDS) has dramatically increased. We have previously shown that chronic nicotine inhalation leads to pulmonary hypertension and right ventricular remodeling in C57BL/6J mice. Nicotine exposure alone did not, however, cause significant left ventricular (LV) remodeling or dysfunction. In this study, we aimed to examine the effects of chronic nicotine inhalation on pressure overload (PO), hypothesizing that nicotine inhalation would abrogate adaptive cardiac remodeling and accelerate cardiac dysfunction. Methods: 7-week-old, male C57BL/6J mice were exposed to nicotine vapor or room air for one week prior to transverse aortic constriction (TAC) surgery to induce PO. Nicotine vapor was produced by bubbling room air through a free-base nicotine solution, diluted with additional room air, and delivered to exposure chambers. Air mice were housed in the same room but outside of the exposure chambers (n=11-12 per group). Following 1 week of surgical recovery, sham and TAC mice were exposed to nicotine vapor or room air for 12 hours per day for 9 weeks. Nicotine exposure was measured using serum cotinine and airflow was adjusted to achieve levels comparable to human ENDS users. Cotinine was not significantly different between sham (572±93 ng/mL) and TAC (617±102 ng/mL) mice. Echocardiography was used to track structural and functional changes in the LV at baseline and every two weeks after surgery. Results: At 10 weeks post-surgery, LV posterior wall thickness at systole (LVPW;s: 1.37±0.04 mm) and LVPW at diastole (LVPW;d: 1.05±0.03 mm) in air-TAC mice were significantly thickened versus both air-sham mice (LVPW;s: 1.05±0.04 mm; LVPW;d: 0.65±0.02 mm) and nicotine-TAC mice (LVPW;s: 1.05±0.03 mm; LVPW;d: 0.82±0.04 mm). There was no significant difference in LVPW;s between nicotine-TAC mice and nicotine-sham mice (1.06±0.02). LVPW;d was significantly thickened in nicotine-TAC mice versus nicotine-sham mice (0.65±0.01).The ejection fraction (EF) of air-TAC mice was 61.3±4.1% versus nicotine-TAC mice at 50.9±3.6%. Air-sham and nicotine-sham mice had EF of 68.3±2.6% and 68.7±1.8%, respectively. We also found that nicotine exposure led to reduced event free survival, where an event was described as EF less than 55%. Event free survival rate was 33% in nicotine-TAC mice versus and 54% in air-TAC mice. Event free survival was 100% in air-sham and nicotine-sham mice. Conclusions: Chronic nicotine inhalation reduces adaptive cardiac remodeling in response to TAC-induced pressure overload, leading to accelerated decompensation.

Research was funded by the National Institute of Health, National Heart, Lung, and Blood Institute – R01HL135635 (JG), R01HL135635-S1 (JG), and 1F30AA030472-01 (JE).

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.