Gregory R. duManoir

Cerebral and muscle tissue oxygenation in acute hypoxic ventilatory response test

Eight men were exposed to progressive isocapnic hypoxia for 10 min to test the hypothesis that (i) cerebral and muscle tissue would follow similar deoxygenation profiles during an acute hypoxic ventilatory response (AHVR) test; and (ii) strong cerebrovascular responsiveness to hypoxia would be related to attenuated cerebral deoxygenation. End-tidal O(2) concentration was reduced from normoxia (approximately 102 mmHg) to approximately 45 mmHg while arterial oxygen saturation (SpO2 %) declined from 98+/-1% to 77+/-7% (P<0.001). Near-infrared spectroscopy (NIRS)-derived local cerebral tissue (frontal lobe) deoxyhemoglobin increased 5.55+/-2.22 microM, while oxyhemoglobin and tissue oxygenation index decreased 2.57+/-1.99 microM and 6.2+/-3.4%, respectively (all P<0.001). In muscle (m. vastus lateralis) the NIRS changes from the initial normoxic level were non-significant. Cerebral blood velocity (V(mean), transcranial Doppler) in the middle cerebral artery increased from 53.4+/-10.4 to 60.6+/-11.6 cms(-1) (P<0.001). In relation to the decline in SpO2 % the mean rate of increase of V(mean) and AHVR were 0.33+/-0.19 cms(-1)%(-1) and 0.52+/-0.20l min(-1)%(-1), respectively. We conclude that cerebral, but not muscle, tissue shows changes reflecting a greater deoxygenation during acute hypoxia. However, the changes in NIRS parameters were not related to cerebrovascular responsiveness or ventilatory chemosensitivity during graded hypoxia.

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Information describing alterations in vascular function during either acute or prolonged normobaric or hypobaric hypoxia is sparse and often confounded by pathology and methodological limitations. We show that high altitude exposure in lowlanders is associated with impairments in both endothelial and smooth muscle function, and with increased central arterial stiffness; furthermore, in all of these respects, lowlanders’ vasculature becomes comparable to that of natives born and raised at altitude. Changes in endothelial function occur very rapidly in normobaric hypoxia, and partly under the influence of sympathetic nerve activity. Thus, a lifetime of high‐altitude exposure neither attenuates nor intensifies the impairments in vascular function observed with short‐term exposure in lowlanders; such impairment and altered structure likely translate into an elevated cardiovascular risk.

Cerebral and muscle deoxygenation, hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness during incremental exercise.

To examine if cerebral (frontal cortex) and skeletal muscle (m. vastus lateralis) deoxygenation and cerebral blood flow velocity (V(mean)) in the middle cerebral artery differentiated between normoxic and hypoxic (end-tidal P(O)(2) 71 mmHg) conditions, and if they were associated with hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness, 8 men performed incremental cycling trials (30W/min ramp) under normoxic (T1-N) and hypoxic (T1-H) conditions until volitional fatigue, or until arterial O2 saturation decreased below 80%. The tests were repeated (T2-N; T2-H) on another day with supplemental O2 (Sup-O2) at the end of exercise. The V(mean) response was similar in normoxia and hypoxia. In hypoxia compared to normoxia, cerebral deoxygenation ( upward arrow deoxyhemoglobin concentration (Delta[HHb]) and downward arrow tissue oxygenation index (TOI)) was greater at a given work rate. A strong hypoxic ventilatory chemosensitivity was associated with a rapid reduction of cerebral TOI (r=0.94, P<0.001). Muscle deoxygenation was similar in normoxia and hypoxia suggesting greater muscle blood flow in hypoxia compared to normoxia and thus the existence of control features that match muscle perfusion and O2 delivery tightly with O2 demand during exercise. Sup-O2 reduced both cerebral and muscle deoxygenation, at least transiently.

Changes in cerebral vascular reactivity and structure following prolonged exposure to high altitude in humans.

Although high‐altitude exposure can lead to neurocognitive impairment, even upon return to sea level, it remains unclear the extent to which brain volume and regional cerebral vascular reactivity (CVR) are altered following high‐altitude exposure. The purpose of this study was to simultaneously determine the effect of 3 weeks at 5050 m on: (1) structural brain alterations; and (2) regional CVR after returning to sea level for 1 week. Healthy human volunteers (n = 6) underwent baseline and follow‐up structural and functional magnetic resonance imaging (MRI) at rest and during a CVR protocol (end‐tidal PCO2 reduced by −10, −5 and increased by +5, +10, and +15 mmHg from baseline). CVR maps (% mmHg−1) were generated using BOLD MRI and brain volumes were estimated. Following return to sea level, whole‐brain volume and gray matter volume was reduced by 0.4 ± 0.3% (P < 0.01) and 2.6 ± 1.0% (P < 0.001), respectively; white matter was unchanged. Global gray matter CVR and white matter CVR were unchanged following return to sea level, but CVR was selectively increased (P < 0.05) in the brainstem (+30 ± 12%), hippocampus (+12 ± 3%), and thalamus (+10 ± 3%). These changes were the result of improvement and/or reversal of negative CVR to positive CVR in these regions. Three weeks of high‐altitude exposure is reflected in loss of gray matter volume and improvements in negative CVR.

Impact of type 2 diabetes on cardiorespiratory function and exercise performance

The aim of this study was to examine the impact of well‐controlled uncomplicated type 2 diabetes (T2D) on exercise performance. Ten obese sedentary men with T2D and nine control participants without diabetes matched for age, sex, and body mass index were recruited. Anthropometric characteristics, blood samples, resting cardiac, and pulmonary functions and maximal oxygen uptake (VO2max) and ventilatory threshold were measured on a first visit. On the four subsequent visits, participants (diabetics: n = 6; controls: n = 7) performed step transitions (6 min) of moderate‐intensity exercise on an upright cycle ergometer from unloaded pedaling to 80% of ventilatory threshold. VO2 (τVO2) and HR (τHR) kinetics were characterized with a mono‐exponential model. VO2max (27.0 ± 3.4 vs. 26.7 ± 5.0 mL kg−1 min−1; P = 0.85), τVO2 (43 ± 6 vs. 43 ± 10 sec; P = 0.73), and τHR (42 ± 17 vs. 43 ± 13 sec; P = 0.94) were similar between diabetics and controls respectively. The remaining variables were also similar between groups, with the exception of lower maximal systolic blood pressure in diabetics (P = 0.047). These results suggest that well‐controlled T2D is not associated with a reduction in VO2max or slower τVO2 and τHR.