Date on Master's Thesis/Doctoral Dissertation

12-2025

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Physiology and Biophysics

Degree Program

Physiology and Biophysics, PhD

Committee Chair

Carll, Alex

Committee Member

Collins, Helen

Committee Member

Jones, Steven

Committee Member

Metz, Cynthia

Committee Member

Maldonado, Claudio

Author's Keywords

Maternal health; ventricular premature beat; heart rate variability; electrocardiogram; beta-blocker

Abstract

Introduction. E-cigarettes (e-cigs) have been shown to be pro-arrhythmic in both human and male rodent studies; however, little is known about how e-cig use impacts patients with a predisposed heightened risk for arrhythmias, including pregnant women. Both pregnancy and e-cig use have independently been shown to increase heart rate, diminish heart rate variability, and increase ventricular premature beats, which is suspected to be due to sympathetic dominance. Importantly, β-blockers have been shown to reduce sympathetic activity, reduce heart rate, increase HRV, and reduce arrhythmias. Thus, the use of β-blockers may help prevent adverse health effects driven by sympathetic dominance from e-cig use. It remains unknown how e-cig use during gestation impacts maternal cardiovascular health. Thus, we hypothesize that e-cig exposure accentuates pregnancy-induced heart rate changes and evokes ventricular arrhythmias during pregnancy and postpartum. Methods. Pregnant 11-week-old C57BL/6J female mice instrumented with radio transmitters were exposed daily to filtered air (FA) ± propranolol or e-cig aerosols ± propranolol from 5 days before breeding until pup birth. Conscious electrocardiogram (ECG)-derived heart rate (HR), heart rate variability (HRV; 5-day averages), and ventricular premature beats (VPBs) were compared to a concurrent FA group and an initial FA exposure (baseline). Home-cage ECGs were collected for 24–48 hours before breeding, during labor, and three weeks postpartum. At three weeks postpartum, echocardiography and catecholamine analysis were performed on the dams. Results. Gestational e-cig exposure accentuates pregnancy-induced heart rate changes and evokes ventricular arrhythmia during gestation, parturition, and at three weeks postpartum, which were ameliorated by propranolol treatment. Additionally, at three weeks postpartum, we found that e-cig-exposed dams had shortened ventricular repolarization time, increased ejection fraction, and increased 3-methoxytyramine 3MT levels. Conclusions. Gestational e-cig exposure leads to sympathetic dominance and increased de novo arrhythmias throughout gestation and the parturition period. Importantly, these arrhythmias persisted until three weeks postpartum and three weeks since e-cig exposures ceased, alongside shortened ventricular repolarization time and increased ejection fraction. Mice treated with propranolol had ameliorated effects throughout gestation, parturition, and three weeks postpartum, indicating the chronotropic and arrhythmogenic effects of gestational e-cig use are sympathetically driven. Thus, this work has demonstrated the chronotropic, arrhythmogenic, and autonomic effects of gestational e-cig use throughout gestation, labor, and three weeks postpartum, thereby providing a foundation for future investigations into the underlying mechanisms.

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