Continuous reduction in cerebral oxygenation during endurance exercise in patients with pulmonary arterial hypertension.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) have lower cerebral blood flow (CBF) and oxygenation compared to healthy sedentary subjects, the latter negatively correlating with exercise capacity during incremental cycling exercise. We hypothesized that patients would also exhibit altered CBF and oxygenation during endurance exercise, which would correlate with endurance time. METHODS: Resting and exercise cardiorespiratory parameters, blood velocity in the middle cerebral artery (MCAv; transcranial doppler) and cerebral oxygenation (relative changes in cerebral tissue oxygenation index (ΔcTOI) and cerebral deoxyhemoglobin (ΔcHHb); near-infrared spectroscopy) were continuously monitored in nine PAH patients and 10 healthy-matched controls throughout endurance exercise. Cardiac output (CO), systemic blood pressure (BP) and oxygen saturation (SpO2 ), ventilatory metrics and end-tidal CO2 pressure (PET CO2 ) were also assessed noninvasively. RESULTS: Despite a lower workload and endurance oxygen consumption, similar CO and systemic BP, ΔcTOI was lower in PAH patients compared to controls (p < .01 for interaction). As expected during exercise, patients were characterized by an altered MCAv response to exercise, a lower PET CO2 and SpO2 , as wells as a higher minute-ventilation/CO2 production ratio ( V˙E/V˙CO2 ratio). An uncoupling between changes in MCAv and PET CO2 during the cycling endurance exercise was also progressively apparent in PAH patients, but absent in healthy controls. Both cHHb and ΔcTOI correlated with V˙E/V˙CO2 ratio (r = 0.50 and r = -0.52; both p < .05 respectively), but not with endurance time. CONCLUSION: PAH patients present an abnormal cerebrovascular profile during endurance exercise with a lower cerebral oxygenation that correlate with hyperventilation but not endurance exercise time. These findings complement the physiological characterization of the cerebral vascular responses to exercise in PAH patients.

Implications of habitual endurance and resistance exercise for dynamic cerebral autoregulation.

NEW FINDINGS: What is the central question of this study? Does habitual resistance and endurance exercise modify dynamic cerebral autoregulation? What is the main finding and its importance? To the authors' knowledge, this is the first study to directly assess dynamic cerebral autoregulation in resistance-trained individuals, and potential differences between exercise training modalities. Forced oscillations in blood pressure were induced by repeated squat-stands, from which dynamic cerebral autoregulation was assessed using transfer function analysis. These data indicate that dynamic cerebral autoregulatory function is largely unaffected by habitual exercise type, and further document the systemic circulatory effects of regular exercise. ABSTRACT: Regular endurance and resistance exercise produce differential but desirable physiological adaptations in both healthy and clinical populations. The chronic effect of these different exercise modalities on cerebral vessels' ability to respond to rapid changes in blood pressure (BP) had not been examined. We examined dynamic cerebral autoregulation (dCA) in 12 resistance-trained (mean ± SD, 25 ± 6 years), 12 endurance-trained (28 ± 9 years) and 12 sedentary (26 ± 6 years) volunteers. The dCA was assessed using transfer function analysis of forced oscillations in BP vs. middle cerebral artery blood velocity (MCAv), induced via repeated squat-stands at 0.05 and 0.10 Hz. Resting BP and MCAv were similar between groups (interaction: both P ≥ 0.544). The partial pressure of end-tidal carbon dioxide ( PETCO2 ) was unchanged (P = 0.561) across squat-stand manoeuvres (grouped mean for absolute change +0.6 ± 2.3 mmHg). Gain and normalized gain were similar between groups across all frequencies (both P ≥ 0.261). Phase showed a frequency-specific effect between groups (P = 0.043), tending to be lower in resistance-trained (0.63 ± 0.21 radians) than in endurance-trained (0.90 ± 0.41, P = 0.052) and -untrained (0.85 ± 0.38, P = 0.081) groups at slower frequency (0.05 Hz) oscillations. Squat-stands induced mean arterial pressure perturbations differed between groups (interaction: P = 0.031), with greater changes in the resistance (P < 0.001) and endurance (P = 0.001) groups compared with the sedentary group at 0.05 Hz (56 ± 13 and 49 ± 11 vs. 35 ± 11 mmHg, respectively). The differences persisted at 0.1 Hz between resistance and sedentary groups (49 ± 12 vs. 33 ± 7 mmHg, P < 0.001). These results indicate that dCA remains largely unaltered by habitual endurance and resistance exercise with a trend for phase to be lower in the resistance exercise group at lower fequencies.

Six weeks of high-intensity interval training to exhaustion attenuates dynamic cerebral autoregulation without influencing resting cerebral blood velocity in young fit men.

Elevated cardiorespiratory fitness (CRF) is associated with reduced dynamic cerebral autoregulation (dCA), but the impact of exercise training per se on dCA remains equivocal. In addition, resting cerebral blood flow (CBF) and dCA after high-intensity interval training (HIIT) in individuals with already high CRF remains unknown. We examined to what extent 6 weeks of HIIT affect resting CBF and dCA in cardiorespiratory fit men and explored if potential changes are intensity-dependent. Endurance-trained men were assigned to group HIIT85 (85% of maximal aerobic power, 1-7 min effort bouts, n = 8) and HIIT115 (115% of maximal aerobic power, 30 sec to 1 min effort bouts, n = 9). Training sessions were completed until exhaustion 3 times/week over 6 weeks. Mean arterial pressure (MAP) and middle cerebral artery mean blood velocity (MCAvmean ) were measured continuously at rest and during repeated squat-stands (0.05 and 0.10 Hz). Transfer function analysis (TFA) was used to characterize dCA on driven blood pressure oscillations during repeated squat-stands. Neither training nor intensity had an effect on resting MAP and MCAvmean (both P > 0.05). TFA phase during 0.10 Hz squat-stands decreased after HIIT irrespective of intensity (HIIT85 : 0.77 ± 0.22 vs. 0.67 ± 0.18 radians; HIIT115 : pre: 0.62 ± 0.19 vs. post: 0.59 ± 0.13 radians, time effect P = 0.048). These results suggest that HIIT over 6 weeks have no apparent benefits on resting CBF, but a subtle attenuation in dCA is seen posttraining irrespective of intensity training in endurance-trained men.

Cardiac remodeling after six weeks of high-intensity interval training to exhaustion in endurance-trained men.

High-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate, and cardiac cavities' size and function in endurance-trained adults. Seventeen endurance-trained men underwent 24-h ambulatory blood pressure monitoring and Doppler echocardiography at baseline and after 6 wk of HIIT. Participants were divided into 2 groups [85% maximal aerobic power (HIIT85), n = 8 and 115% maximal aerobic power (HIIT115), n = 9] to compare the impact of different HIIT intensities. Ambulatory blood pressure monitoring and cardiac chambers' size and function were similar between groups at baseline. HIIT reduced heart rate (55 ± 8 vs. 51 ± 7 beats/min; P = 0.003), systolic blood pressure (121 ± 11 vs. 118 ± 9 mmHg; P = 0.01), mean arterial pressure (90 ± 8 vs. 89 ± 6 mmHg; P = 0.03), and pulse pressure (52 ± 6 vs. 49 ± 5 mmHg; P = 0.01) irrespective of training intensity. Left atrium volumes increased after HIIT (maximal: 50 ± 14 vs. 54 ± 14 mL; P = 0.02; minimal: 15 ± 5 vs. 20 ± 8 mL; P = 0.01) in both groups. Right ventricle global longitudinal strain lowered after training in the HIIT85 group only (20 ± 4 vs. 17 ± 3%, P = 0.04). In endurance-trained men, 6 wk of HIIT reduced systolic blood pressure and mean arterial pressure and increased left atrium volumes irrespective of training intensity, whereas submaximal HIIT deteriorated right ventricle systolic function.NEW & NOTEWORTHY The novel findings of this study are that 6 wk of high-intensity interval training increases left atrial volumes irrespective of training intensity (85 or 115% maximal aerobic power), whereas the submaximal training decreases right ventricular systolic function in endurance-trained men. These results may help identify the exercise threshold for potential toxicity of intense exercise training for at-risk individuals and ideal exercise training regimens conferring optimal cardiovascular protection and adapted endurance training for athletes.

Dynamic cerebral autoregulation is attenuated in young fit women.

Young women exhibit higher prevalence of orthostatic hypotension with presyncopal symptoms compared to men. These symptoms could be influenced by an attenuated ability of the cerebrovasculature to respond to rapid blood pressure (BP) changes [dynamic cerebral autoregulation (dCA)]. The influence of sex on dCA remains unclear. dCA in 11 fit women (25 ± 2 years) and 11 age-matched men (24 ± 1 years) was compared using a multimodal approach including a sit-to-stand (STS) and forced BP oscillations (repeated squat-stand performed at 0.05 and 0.10 Hz). Prevalence of initial orthostatic hypotension (IOH; decrease in systolic ≥ 40 mmHg and/or diastolic BP ≥ 20 mmHg) during the first 15 sec of STS was determined as a functional outcome. In women, the decrease in mean middle cerebral artery blood velocity (MCAvmean ) following the STS was greater (-20 ± 8 vs. -11 ± 7 cm sec-1 ; P = 0.018) and the onset of the regulatory change (time lapse between the beginning of the STS and the increase in the conductance index (MCAvmean /mean arterial pressure) was delayed (P = 0.007). Transfer function analysis gain during 0.05 Hz squat-stand was ~48% higher in women (6.4 ± 1.3 vs. 3.8 ± 2.3 cm sec-1 mmHg-1 ; P = 0.017). Prevalence of IOH was comparable between groups (women: 4/9 vs. men: 5/9, P = 0.637). These results indicate the cerebrovasculature of fit women has an attenuated ability to react to rapid changes in BP in the face of preserved orthostasis, which could be related to higher resting cerebral blood flow allowing women to better face transient hypotension.

Diminished dynamic cerebral autoregulatory capacity with forced oscillations in mean arterial pressure with elevated cardiorespiratory fitness.

The effect that cardiorespiratory fitness has on the dynamic cerebral autoregulatory capacity during changes in mean arterial pressure (MAP) remains equivocal. Using a multiple-metrics approach, challenging MAP across the spectrum of physiological extremes (i.e., spontaneous through forced MAP oscillations), we characterized dynamic cerebral autoregulatory capacity in 19 male endurance athletes and eight controls via three methods: (1) onset of regulation (i.e., time delay before an increase in middle cerebral artery (MCA) conductance [MCA blood velocity (MCAv)/MAP] and rate of regulation, after transient hypotension induced by sit-to-stand, and transfer function analysis (TFA) of MAP and MCAv responses during (2) spontaneous and (3) forced oscillations (5-min of squat-stand maneuvers performed at 0.05 and 0.10 Hz). Reductions in MAP and mean MCAv (MCAVmean) during initial orthostatic stress (0-30 sec after sit-to-stand) and the prevalence of orthostatic hypotension were also determined. Onset of regulation was delayed after sit-to-stand in athletes (3.1 ± 1.7 vs. 1.5 ± 1.0 sec; P = 0.03), but rate of regulation was not different between groups (0.24 ± 0.05 vs. 0.21 ± 0.09 sec-1; P = 0.82). While both groups had comparable TFA metrics during spontaneous oscillations, athletes had higher TFA gain during 0.10 Hz squat-stand versus recreational controls (P = 0.01). Reductions in MAP (P = 0.15) and MCAVmean (P = 0.11) during orthostatic stress and the prevalence of initial orthostatic hypotension (P = 0.65) were comparable between groups. These results indicate an intact ability of the cerebral vasculature to react to spontaneous oscillations but an attenuated capability to counter rapid and large changes in MAP in individuals with elevated cardiorespiratory fitness.

Compromised Cerebrovascular Regulation and Cerebral Oxygenation in Pulmonary Arterial Hypertension.

BACKGROUND: Functional cerebrovascular regulatory mechanisms are important for maintaining constant cerebral blood flow and oxygen supply in heathy individuals and are altered in heart failure. We aim to examine whether pulmonary arterial hypertension (PAH) is associated with abnormal cerebrovascular regulation and lower cerebral oxygenation and their physiological and clinical consequences. METHODS AND RESULTS: Resting mean flow velocity in the middle cerebral artery mean flow velocity in the middle cerebral artery (MCAvmean); transcranial Doppler), cerebral pressure-flow relationship (assessed at rest and during squat-stand maneuvers; analyzed using transfer function analysis), cerebrovascular reactivity to CO2, and central chemoreflex were assessed in 11 patients with PAH and 11 matched healthy controls. Both groups also completed an incremental ramp exercise protocol until exhaustion, during which MCAvmean, mean arterial pressure, cardiac output (photoplethysmography), end-tidal partial pressure of CO2, and cerebral oxygenation (near-infrared spectroscopy) were measured. Patients were characterized by a significant decrease in resting MCAvmean (P<0.01) and higher transfer function gain at rest and during squat-stand maneuvers (both P<0.05). Cerebrovascular reactivity to CO2 was reduced (P=0.03), whereas central chemoreceptor sensitivity was increased in PAH (P<0.01), the latter correlating with increased resting ventilation (R2=0.47; P<0.05) and the exercise ventilation/CO2 production slope (V˙E/V˙CO2 slope; R2=0.62; P<0.05) during exercise for patients. Exercise-induced increases in MCAvmean were limited in PAH (P<0.05). Reduced MCAvmean contributed to impaired cerebral oxygen delivery and oxygenation (both P<0.05), the latter correlating with exercise capacity in patients with PAH (R2=0.52; P=0.01). CONCLUSIONS: These findings provide comprehensive evidence for physiologically and clinically relevant impairments in cerebral hemodynamic regulation and oxygenation in PAH.

Evidence for hysteresis in the cerebral pressure-flow relationship in healthy men.

The cerebrovasculature is more efficient at compensating for pharmacologically induced transient hypertension versus transient hypotension. Whether this phenomenon exists during nonpharmacologically induced hypertension and hypotension is currently unknown. We compared the percent change in mean velocity in the middle cerebral artery (MCAvmean) per percent change in mean arterial pressure (MAP) (%ΔMCAVmean/%ΔMAP) during transient hypertension and hypotension induced during squat-stand maneuvers performed at 0.05 Hz (20-s cycles) and 0.10 Hz (10-s cycles) in 58 male volunteers. %ΔMCAvmean/%ΔMAP was attenuated by 25% (P = 0.03, 0.05 Hz) and 47% (P < 0.0001, 0.10 Hz) during transient hypertension versus hypotension. Thus, these findings indicate that the brain in healthy men is better adapted to compensate for physiologically relevant transient hypertension than hypotension.NEW & NOTEWORTHY The novel finding of this study is that the change in middle cerebral artery mean flow velocity is attenuated during hypertension compared with hypotension physiologically induced by oscillations in blood pressure in men. These results support that the human brain is more effective at compensating for transient hypertension than hypotension.