Steady-state cerebral blood flow regulation at altitude: interaction between oxygen and carbon dioxide.

High-altitude ascent imposes a unique cerebrovascular challenge due to two opposing blood gas chemostimuli. Specifically, hypoxia causes cerebral vasodilation, whereas respiratory-induced hypocapnia causes vasoconstriction. The conflicting nature of these two superimposed chemostimuli presents a challenge in quantifying cerebrovascular reactivity (CVR) in chronic hypoxia. During incremental ascent to 4240 m over 7 days in the Nepal Himalaya, we aimed to (a) characterize the relationship between arterial blood gas stimuli and anterior, posterior and global (g)CBF, (b) develop a novel index to quantify cerebral blood flow (CBF) in relation to conflicting steady-state chemostimuli, and (c) assess these relationships with cerebral oxygenation (rSO2). On rest days during ascent, participants underwent supine resting measures at 1045 m (baseline), 3440 m (day 3) and 4240 m (day 7). These measures included pressure of arterial (Pa)CO2, PaO2, arterial O2 saturation (SaO2; arterial blood draws), unilateral anterior, posterior and gCBF (duplex ultrasound; internal carotid artery [ICA] and vertebral artery [VA], gCBF [{ICA + VA} × 2], respectively) and rSO2 (near-infrared spectroscopy). We developed a novel stimulus index (SI), taking into account both chemostimuli (PaCO2/SaO2). Subsequently, CBF was indexed against the SI to assess steady-state cerebrovascular responsiveness (SS-CVR). When both competing chemostimuli are taken into account, (a) SS-CVR was significantly higher in ICA, VA and gCBF at 4240 m compared to lower altitudes, (b) delta SS-CVR with ascent (1045 m vs. 4240 m) was higher in ICA vs. VA, suggesting regional differences in CBF regulation, and (c) ICA SS-CVR was strongly and positively correlated (r = 0.79) with rSO2 at 4240 m.

Spleen reactivity during incremental ascent to altitude.

The spleen contains a reservoir of red blood cells that are mobilized into circulation when under physiological stress. Despite the spleen having an established role in compensation to acute hypoxia, no previous work has assessed the role of the spleen during ascent to high altitude. Twelve participants completed 2 min of handgrip exercise at 30% of maximal voluntary contraction at 1,045, 3,440, and 4,240 m. In a subset of eight participants, an infusion of phenylephrine hydrochloride was administered at a dosage of 30 µg/l of predicted blood volume at each altitude. The spleen was imaged by ultrasound via a 2- to 5.5-MHz curvilinear probe. Spleen volume was calculated by the prolate ellipsoid formula. Finger capillary blood samples were taken to measure hematocrit. Spleen images and hematocrit were taken both before and at the end of both handgrip and phenylephrine infusion. No changes in resting spleen volume were observed between altitudes. At low altitude, the spleen contracted in response to handgrip [272.8 ml (SD 102.3) vs. 249.6 ml (SD 105.7), P = 0.009], leading to an increase in hematocrit (42.6% (SD 3.3) vs. 44.3% (SD 3.3), P = 0.023] but did not contract or increase hematocrit at the high-altitude locations. Infusion of phenylephrine led to spleen contraction at all altitudes, but only lead to an increase in hematocrit at low altitude. These data reveal that the human spleen may not contribute to acclimatization to chronic hypoxia, contrary to its response to acute sympathoexcitation. These results are explained by alterations in spleen reactivity to increased sympathetic activation at altitude. NEW & NOTEWORTHY The present study demonstrated that, despite the known role of the human spleen in increasing oxygen delivery to tissues during acute hypoxia scenarios, the spleen does not mobilize red blood cells during ascent to high altitude. Furthermore, the spleen's response to acute stressors at altitude depends on the nature of the stressor; the spleen's sensitivity to neurotransmitter is maintained, while its reflex response to stress is dampened.

Maternal cardioautonomic responses during and following exercise throughout pregnancy.

Blood pressure regulation during pregnancy is poorly understood. Cardiovagal baroreflex gain (BRG) is an important contributor to blood pressure regulation through its influence on heart rate. Heart rate fluctuations occur in response to various physiological stimuli and can be measured using heart rate variability (HRV). It is unclear how these mechanisms operate during pregnancy, particularly with regard to exercise. We examined BRG and HRV prior to, during, and following prenatal exercise. Forty-three pregnant (n = 10 first trimester (TM1), n = 17 second trimester (TM2), n = 16 third trimester (TM3)) and 20 nonpregnant (NP) women underwent an incremental peak exercise test. Beat-by-beat blood pressure (photoplethysmography) and heart rate (lead II electrocardiogram) were measured throughout. BRG (the slope of the relationship between fluctuations in systolic blood pressure and the R-R interval) and HRV (root mean square of the successive differences; RMSSD) were assessed at rest, during steady-state exercise (EX), and during active recovery. BRG decreased with gestation and was lower in the TM3 group than in the NP group (17.9 ± 6.9 ms/mm Hg vs 24.8 ± 7.4 ms/mm Hg, p = 0.017). BRG was reduced during EX in all groups. Resting HRV (RMSSD) also decreased with gestation and was lower in the TM3 group than in the NP group (29 ± 17 ms vs 48 ± 20 ms, p < 0.001). RMSSD was blunted during EX in all groups compared with rest. During active recovery, RMSSD was further blunted compared with EX in the NP group but not during pregnancy (TM1, TM2, and TM3). Compared with the nonpregnant controls, the pregnant women had lower BRG and HRV at rest, but comparable cardioautonomic control during both exercise and active recovery following peak exercise.

Maternal Physical Activity Is Associated With Improved Blood Pressure Regulation During Late Pregnancy.

BACKGROUND: Cardiovagal baroreflex gain (cBRG) reflects an individual's ability to buffer swings in blood pressure. It is not well understood how this mechanism is influenced by physical activity in pregnancy. Because pregnant women tend to engage in low levels of moderate-to-vigorous physical activity (MVPA) and high levels of sedentary behaviour, we sought to determine the influence of MVPA and sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy. METHODS: Fifty-eight third trimester (31.9 ± 3.0 weeks) normotensive pregnant women (31.2 ± 2.8 years) were tested. Heart rate (electrocardiogram) and blood pressure (systolic blood pressure and MAP; finger photoplethysmography) were collected on a beat-by-beat basis, and averaged over 3 minutes of rest. Spontaneous cBRG was calculated as the slope of the relationship between fluctuations in systolic blood pressure and heart rate. Objective measures of MVPA and sedentary behaviour were collected over a 7-day period using an ActiGraph accelerometer (model wGTX3-BT; ActiGraph LLC, Pensacola, FL). RESULTS: Participants spent 67.5 ± 7.9% of waking hours engaged in sedentary behaviour, and performed 68.6 ± 91.9 minutes of MVPA per week. Sedentary behaviour was not related to cBRG (r = -0.035; P = 0.793) or MAP (r = -0.033; P = 0.803). However, MVPA was positively associated with cBRG (r = 0.315; P = 0.016), but not MAP (r = -0.115; P = 0.389). The association between MVPA and cBRG remained significant after controlling for age, pre-pregnancy body mass index, gestational age, and wear time (r = 0.338; P = 0.013), indicating that women who engaged in greater amounts of MVPA showed increased cBRG. CONCLUSIONS: Our data suggest that increased MVPA, but not necessarily reduced sedentary behaviour, might be beneficial for reflex control of blood pressure during pregnancy.