Sex differences in global and regional cardiac function in response to acute hypoxia
Authors: Vildberg Lauren , Barton Gregory , McMillan Alan , Aggarwal Niti , Goss Kara , Eldridge Marlowe 
Published: November 2023

IntroductionIt is widely known that physiological differences between males and females result in differences in cardiac mass and volumes. There are conflicting results on whether differences in cardiac mass and volumes result in functional differences between males and females, with some reports suggesting increased or no difference in contractile function in females as compared to males. Moreover, very little information exists on whether cardiac sex differences exist under conditions of stress, such as hypoxia. Therefore, we hypothesized that females would demonstrate greater systolic and diastolic function during acute hypoxia. Using cardiac magnetic resonance imaging (MRI) we assessed global and regional cardiac functional response of males and females exposed to acute hypoxia.MethodsTen healthy pigs (5‐female) (45–50kg) were anesthetized, intubated and placed on mechanical ventilation (21% oxygen). After 25 minutes of normoxic breathing the inspired gas was switched to 12% oxygen to induce a hypoxic stress for 25 minutes. Cardiac MR imaging was performed to assess global and regional differences in cardiac function during normoxia and hypoxia. MR images were analyzed to determine left ventricular (LV) and right ventricular (RV) volumes and regional LV radial velocities in the same basal, midmyocardial and apical slice from each pig.ResultsThere were no differences in body weight, blood pressure or LV mass between sexes (p > 0.05). Other cardiac measures such as heart rate (HR), LV and RV volumes, cardiac output (CO) and fractional wall thickening were similar during normoxia (p > 0.05). In hypoxia, both sexes showed increases in HR, CO, apical fractional wall thickening (Fr WT) and LV ejection fraction (EF) (p < 0.05). A significant difference between the sexes was revealed, as females showed increased LVEF during hypoxia as compared to males (70.2 ± 2.4 vs 61.7 ± 2.6 p = 0.039, respectively). Additionally, radial expansion velocity at peak‐filling rate (PFR) was greater in females as compared to males during normoxia (−13.1 ± 1.2 cm/s vs −10.6 ± 0.3 cm/s p = 0.04, respectively) and hypoxia (−13.2 ± 0.4 cm/s vs −10.3 ± 1.8 cm/s p = 0.04, respectively).DiscussionNo differences were seen between male and female cardiac measures in normoxic conditions. LVEF increased despite no change in LV end diastolic volume and mean arterial pressure (MAP). This increased LVEF could have been due to our finding that LV apical Fr WT increased during hypoxia. Interestingly, under hypoxia, LVEF increased to a greater extent in females as compared to males, which may be explained by the finding that basal Fr WT decreased in males during hypoxia while females showed no changes. Additionally, we found that females demonstrated greater LV radial expansion velocity at PFR as compared to males under both conditions, suggesting increased diastolic function in females. These findings suggest that females exhibit increased cardiac function under hypoxic stress. Future work using 4D flow MRI during rest and stress scenarios is likely to further elucidate sex differences in cardiac function.Support or Funding InformationIntramural R&D