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Ventilatory and Cerebrovascular Responses to Hypercapnia in Pulmonary Arterial Hypertension
Author(s) -
Malenfant Simon,
Brassard Patrice,
Paquette Myriam,
Le Blanc Olivier,
Chouinard Audrey,
Bonnet Sébastien,
Provencher Steeve
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.774.21
Subject(s) - hyperventilation , hypercapnia , ventilation (architecture) , anesthesia , cerebral blood flow , medicine , arterial blood , middle cerebral artery , mean arterial pressure , cardiology , respiratory minute volume , hypocapnia , blood pressure , heart rate , respiratory system , acidosis , ischemia , mechanical engineering , engineering
BACKGROUND Patients with pulmonary arterial hypertension (PAH) exhibit excessive ventilation at rest and during exercise. This is generally attributed to an increased physiological dead space related to extensive vascular remodeling and ventilation‐perfusion mismatch as well as hyperventilation resulting in low arterial carbon dioxide partial pressure (PCO 2 ). However, mechanisms accounting for this hyperventilation remain elusive. We hypothesized that PAH patients exhibit enhanced central chemoreflex sensitivity, resulting in increased ventilator drive, hyperventilation and reduced cerebral blood flow. METHODS Central chemoreflex sensitivity was evaluated in 11 PAH patients and 11 healthy controls matched for age, sex and body mass index, using the modified hyperoxic hypercapnic rebreathing method. Participants underwent a 5‐minute period breathing room air. Then, they were asked to hyperventilate for one minute to an end‐tidal PCO 2 (P ET CO 2 ) of 20–25 mmHg, before they started to breathe in a rebreathing bag (air mixture containing 7% CO 2 and 93% O 2 ) until P ET CO 2 reached 60 mmHg. During this protocol, left middle cerebral artery mean flow velocity (MCAv mean ; transcranial Doppler), mean arterial pressure (MAP; finger photoplethysmography), P ET CO 2 and minute ventilation (V E ,) were continuously monitored. The linear regression slope of V E ‐P ET CO 2 characterized central chemoreflex sensitivity during the rebreathing period. Associations between central chemoreflex sensitivity, resting V E and MCAv mean were explored (Pearson's correlations). RESULTS Central chemoreflex sensitivity was significantly higher in PAH patients compared to controls (2.1 (0.3) vs 0.9 (0.2) L/min/mmHg; p=0.003). PAH patients also displayed lower P ET CO 2 (37 (5) vs 43 (5) mmHg; p=0.01) and increased V E (14 (2) vs 10 (2) L/min; p=0.0003) at baseline compared to controls. Central chemoreflex sensitivity correlated with resting V E (r=0.68; p=0.0005) and also inversely correlated with MCAv mean (r=−0.48; p=0.02), which was lower in PAH patients (59.3 (10.6) vs 74.2 (15.8) cm/s; p=0.01). CONCLUSION These results suggest that PAH patients exhibit reduced cerebral blood flow as a result of higher chemoreflex sensitivity and secondary hyperventilation. Alternatively, the reduction in cerebral blood flow induced by hypocapnia might decrease brain tissue carbon dioxide wash‐out, acidifying the cerebrospinal fluid and leading to a higher chemoreceptor stimulus and increased ventilation. Support or Funding Information Doctoral scholarship from Fond de Recherche du Québec ‐ Santé (FRQ‐S) to Simon Malenfant