Sex Differences in the Cerebral Hemodynamic Response to Hypercapnia in Young Adults

Abstract

Despite sexual dimorphism present in stroke and risk for Alzheimer’s disease, sex differences in cerebral blood flow regulation remain controversial. Discrepancies in the literature may be due to menstrual cycle control as well as the inherent difficulty of quantifying cerebral blood flow in humans. The purpose of this study was to evaluate the cerebral hemodynamic response to hypercapnia in young men and premenopausal women using two approaches: 1) transcranial Doppler ultrasound (TCD); and 2) 4D flow MRI. Twenty habitually physically active participants including young men (YM; n = 10, age = 24±2 y) and young women (YW; n = 10, age = 26±4 y) were studied. Young women were studied during days 2–6 of the menstrual cycle. During separate, randomized study visits, left middle cerebral artery (LMCA) velocity was measured with TCD and LMCA flow was measured with 4D flow MRI during normocapnia and two levels of hypercapnia (4% and 6% CO2). 4D flow MRI quantifies cerebral hemodynamic and angiographic data simultaneously. End‐tidal carbon dioxide and mean arterial pressure were continuously monitored with an anesthesia monitor. At baseline, LMCA velocity (YM: 53±3 cm/s vs. YW: 60±4 cm/s, p=0.15) and LMCA flow (YM: 121±10 ml/min vs. YW: 131±6 ml/min, p=0.41) were not significantly different between groups. There was a trend for YM to demonstrate a larger LMCA cross‐sectional area compared with YW at baseline (YM: 0.071±0.002 cm2 vs. YW: 0.065±0.002 cm2, p=0.052). In response to hypercapnia, the LMCA velocity response was not different between groups (YM: 1.17±0.29 cm/s/mmHg vs. YW: 1.24±0.17 cm/s/mmHg, p=0.83). However, YM demonstrated a greater LMCA flow response compared with YW (YM: 2.98±0.40 ml/min/mmHg vs. YW: 1.38±0.26 ml/min/mmHg, p<0.01), even when accounting for changes in blood pressure. In addition, the LMCA significantly vasodilated in YM in response to hypercapnia (p<0.05); however, there was no significant change in LMCA cross‐sectional area in response to hypercapnia in YW (p=0.13). These results suggest that young men have augmented cerebral blood flow response to hypercapnia compared with young women. In addition, due to small changes in vessel cross‐sectional area during hypercapnia, sex differences may be underestimated if cerebral blood velocity is used as a surrogate of blood flow.Support or Funding InformationSupported by the Wisconsin Alumni Research Foundation and the National Institutes of Health T32 HL‐007936.