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.
['Malenfant|Simon|S|', 'Brassard|Patrice|P|', 'Paquette|Myriam|M|', 'Le Blanc|Olivier|O|', 'Chouinard|Audrey|A|', 'Nadeau|Valérie|V|', 'Allan|Philip D|PD|', 'Tzeng|Yu-Chieh|YC|', 'Simard|Sébastien|S|', 'Bonnet|Sébastien|S|', 'Provencher|Steeve|S|']
D000328:Adult D015415:Biomarkers D001783:Blood Flow Velocity D016022:Case-Control Studies D002560:Cerebrovascular Circulation D002628:Chemoreceptor Cells D017079:Exercise Tolerance D005260:Female D006439:Hemodynamics D006706:Homeostasis D006801:Humans D006976:Hypertension, Pulmonary D008297:Male D008875:Middle Aged D020768:Middle Cerebral Artery D008955:Models, Cardiovascular D010100:Oxygen D010101:Oxygen Consumption D017156:Photoplethysmography D012018:Reflex D017585:Ultrasonography, Doppler, Transcranial
cerebral oxygenation cerebrovascular reactivity to CO2 central chemoreceptor sensitivity cerebral ischemia exercise physiology