Abstract 4368119: Sex Differences in Myocardial Oxygen Supply-Demand Balance After Chronic Nicotine-Free E-Cigarette Exposure

Abstract

Introduction: Myocardial ischemia results from an imbalance between oxygen supply and demand, typically affecting the subendocardium. The diastolic pressure time index (DPTI) and systolic pressure time index (SPTI) are well-established surrogates for myocardial oxygen supply and demand, respectively. Their ratio (DPTI: SPTI), the subendocardial viability ratio (SEVR), serves as an indicator of subendocardial perfusion adequacy. Methods: A total of 41 young, healthy adult male and female Sprague Dawley rats (n=20 female; weight 187–273 g) were randomized and exposed to: 1) purified air (n=20) and 2) electronic cigarette vapor without nicotine (EC NIC(-), n=21). Rats were exposed by nose-only inhalation for 4-5 hours/day, 4 days/week, for a total of 8 weeks (puff frequency=1 puff/min, puff duration=2 seconds, at a flow rate of 1.67 L/min). For EC(-), a third-generation mod-type vaporizer (VaporFi VEX 150 TC mod, with Volt Tank) was used with a tobacco-flavored e-liquid containing a 50/50 volume ratio of propylene glycol and vegetable glycerin (PG/VG). After 8 weeks of exposure, the rats were anesthetized and catheterized to measure invasive aortic and left ventricular pressure waveforms. These waveforms were used to quantify SPTI, DPTI, and SEVR (Fig. 1). Results: Exposure to EC NIC(-) resulted in a significant change in myocardial oxygen supply in male rats (p<0.05) but not in females (Fig. 2). As there was no significant change in oxygen demand in either sex, male rats showed a significant reduction in the supply: demand ratio (SEVR) compared to air-exposed controls (Fig. 3). Conclusion: Our results suggest that chronic exposure to nicotine-free EC vapor alters myocardial oxygen dynamics in a sex-specific manner. Male rats exhibited impaired subendocardial perfusion following EC NIC(-) exposure, suggesting heightened vulnerability to ischemic imbalance. We propose these effects may be driven by sex-specific cardiac responses to components in the PG/VG base and flavoring agents, which can induce mild oxidative stress and vascular dysfunction, disrupting myocardial oxygen balance differently in males and females.