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% (
= 0.03, 0.05 Hz) and 47% (
< 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.
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.
In pulmonary arterial hypertension (PAH), the six-minute walk test (6MWT) is believed to be representative of patient's daily life physical activities (DL(PA)). Whether DL(PA) are decreased in PAH ...and whether the 6MWT is representative of patient's DL(PA) remain unknown.
15 patients with idiopathic PAH (IPAH) and 10 patients with PAH associated with limited systemic sclerosis (PAH-SSc) were matched with 15 healthy control subjects and 10 patients with limited systemic sclerosis without PAH. Each subject completed a 6MWT. The mean number of daily steps and the mean energy expenditure and duration of physical activities >3 METs were assessed with a physical activity monitor for seven consecutive days and used as markers of DL(PA).
The mean number of daily steps and the mean daily energy expenditure and duration of physical activities >3 METs were all reduced in PAH patients compared to their controls (all p<0.05). The mean number of daily steps correlated with the 6MWT distance for both IPAH and PAH-SSc patients (r = 0.76, p<0.01 and r = 0.85, p<0.01), respectively.
DL(PA) are decreased in PAH and correlate with the 6MWT distance. Functional exercise capacity may thus be a useful surrogate of DL(PA) in PAH.
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.
The novel findings of this study are that 6 weeks of submaximal and supramaximal high‐intensity interval training to exhaustion reduce dynamic cerebral autoregulation irrespective of training intensity in endurance‐trained men. However, these training protocols do not influence resting cerebral blood flow in these individuals. The results indicate the cerebrovasculature of endurance‐trained men has an attenuated ability to react to large and rapid changes in blood pressure following high‐intensity interval training.
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.
The physiological response during the endurance shuttle walk test (ESWT), the cycle endurance test (CET) and the incremental shuttle walk test (ISWT) remains unknown in PAH. We tested the hypothesis ...that endurance tests induce a near-maximal physiological demand comparable to incremental tests. We also hypothesized that differences in respiratory response during exercise would be related to the characteristics of the exercise tests.
Within two weeks, twenty-one PAH patients (mean age: 54(15) years; mean pulmonary arterial pressure: 42(12) mmHg) completed two cycling exercise tests (incremental cardiopulmonary cycling exercise test (CPET) and CET) and three field tests (ISWT, ESWT and six-minute walk test (6MWT)). Physiological parameters were continuously monitored using the same portable telemetric device.
Peak oxygen consumption (VO(2peak)) was similar amongst the five exercise tests (p = 0.90 by ANOVA). Walking distance correlated markedly with the VO(2peak) reached during field tests, especially when weight was taken into account. At 100% exercise, most physiological parameters were similar between incremental and endurance tests. However, the trends overtime differed. In the incremental tests, slopes for these parameters rose steadily over the entire duration of the tests, whereas in the endurance tests, slopes rose sharply from baseline to 25% of maximum exercise at which point they appeared far less steep until test end. Moreover, cycling exercise tests induced higher respiratory exchange ratio, ventilatory demand and enhanced leg fatigue measured subjectively and objectively.
Endurance tests induce a maximal physiological demand in PAH. Differences in peak respiratory response during exercise are related to the modality (cycling vs. walking) rather than the progression (endurance vs. incremental) of the exercise tests.
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 (PETCO2) 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 PETCO2 and SpO2, as wells as a higher minute‐ventilation/CO2 production ratio (V˙E/V˙CO2 ratio). An uncoupling between changes in MCAv and PETCO2 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.
The novel findings of this study are that abnormal cerebrovascular responses to exercise are present during an endurance exercise protocol in patients with pulmonary arterial hypertension. It includes a reduction in cerebral oxygenation associated with higher minute‐ventilation/carbon dioxide production rather than endurance time, and an uncoupling between changes in mean blood velocity in the middle cerebral artery and end‐tidal carbon dioxide partial pressure during exercise in patients only. These findings add to the existing literature reporting abnormalities in cerebral blood flow determinants in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a unique disease. Properly speaking, it is not a disease of the lung. It can be seen more as a microvascular disease occurring mainly in the lungs and ...affecting the heart. At the cellular level, the PAH paradigm is characterized by inflammation, vascular tone imbalance, pulmonary arterial smooth muscle cell proliferation and resistance to apoptosis and the presence of in situ thrombosis. At a clinical level, the aforementioned abnormal vascular properties alter physically the pulmonary circulation and ventilation, which greatly influence the right ventricle function as it highly correlates with disease severity. Consequently, right heart failure remains the principal cause of death within this cohort of patients. While current treatment modestly improve patients' conditions, none of them are curative and, as of today, new therapies are lacking. However, the future holds potential new therapies that might have positive influence on the quality of life of the patient. This article will first review the clinical presentation of the disease and the different molecular pathways implicated in the pathobiology of PAH. The second part will review tomorrow's future putative therapies for PAH.
In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early imaging studies documented that ...pulmonary vascular thickening was specifically associated with COVID-19 pneumonia, implying a potential tropism of the virus for the pulmonary vasculature. Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage, and lung coagulopathy promoting endothelial dysfunction and microthrombosis. These features are strikingly similar to what is seen in pulmonary vascular diseases. Although the consequences of COVID-19 on the pulmonary circulation remain to be explored, several viruses have been previously thought to be involved in the development of pulmonary vascular diseases. Patients with preexisting pulmonary vascular diseases also appear at increased risk of morbidity and mortality. The present article reviews the molecular factors shared by coronavirus infection and pulmonary vasculature defects, and the clinical relevance of pulmonary vascular alterations in the context of COVID-19.
Abstract only
Cerebral blood flow (CBF) is generally higher in women compared to men at rest. Although accumulating evidence supports sex differences in CBF regulation, findings remain contradictory ...for dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity to carbon dioxide (CVR
CO2
). Cardiorespiratory fitness represents an indicator of cardiovascular health. However, we have recently reported that dCA is reduced in young fit men compared to controls, and that dCA is attenuated in young fit women compared to fit men. However, the influence of sex on CVR
CO2
in these young fit individuals remains misunderstood. The aim of this study was to examine the influence of sex on CVR
CO2
in young fit individuals. Changes in middle cerebral artery mean blood velocity (MCA
vmean
; transcranial doppler), mean arterial pressure (MAP; photoplethysmography), heart rate (HR; ECG) and pulmonary ventilation (spirometer) were measured in 29 young fit individuals (women n=10, men n=19), in response to changes in end‐tidal partial pressure of carbon dioxide (P
ET
CO
2
; gas analyzer) during the modified Duffin hyperoxic rebreathing test. Women were tested in the early follicular phase. CVR
CO2
, as well as hemodynamic and ventilatory chemosensitivity, were characterized using linear regressions on the rebreathing portion of the test after the determined ventilatory recruitment threshold. While age was not different between groups (26 ± 6 vs. 27 ± 5 years,
P
= 0.92), height: (1.64 ± 0.06 vs. 1.77 ± 0.08 m;
P
< 0.0001), body weight (60 ± 6 vs. 72 ± 10 kg;
P
= 0.0009) and maximal oxygen uptake (48.4 ± 3.8 vs. 57.9 ± 6.8 mL
−1
kg
−1
min
−1
;
P
< 0.0001) were lower in women. At rest, MCA
vmean
(72 ± 8 cm/s vs. 62 ± 11 cm/s;
P
= 0.02) and HR (73 ± 8 vs. 64 ± 11 bpm;
P
= 0.02) were higher in women, whereas MAP was not different between groups (100 ± 19 vs. 97 ± 10 mm Hg;
P
= 0.73). CVR
CO2
was higher in women compared to men, both in absolute
(
1.59 ± 0.78 vs. 0.35 ± 1.51 cm/s/mm Hg,
P
= 0.01) and normalized terms
(
2.19 ± 0.97 vs. 0.54 ± 2.41 %/mm Hg,
P
= 0.02). Hemodynamic and respiratory chemosensitivity responses during CO
2
rebreathing were not different between groups (all
P
> 0.05). These results indicate that the cerebrovasculature of young fit women is more sensitive to CO
2
than men despite comparable hemodynamic and ventilatory chemosensitivity responses.
Support or Funding Information
S.I., L.L. and S.M. have been supported by a doctoral training scholarship from the Fonds de recherche du Québec ‐ Santé (FRQS)
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