Hypoxia, not pulmonary vascular pressure, induces blood flow through intrapulmonary arteriovenous anastomoses

• Published in: The Journal of physiology 2015-02, Vol.593 (3), p.723-737
• Main Authors: Tremblay, Joshua C., Lovering, Andrew T., Ainslie, Philip N., Stembridge, Mike, Burgess, Keith R., Bakker, Akke, Donnelly, Joseph, Lucas, Samuel J.E., Lewis, Nia C.S., Dominelli, Paolo B., Henderson, William R., Dominelli, Giulio S., Sheel, A. William, Foster, Glen E.
• Format: Article
• Language: English
• Subjects: Acetazolamide - pharmacology; Adult; Arteriovenous Anastomosis - drug effects; Arteriovenous Anastomosis - physiology; Blood Pressure; Carbonic Anhydrase Inhibitors - pharmacology; Female; Humans; Hypoxia - physiopathology; Integrative; Lung - blood supply; Lung - drug effects; Male; Vasoconstriction; Vasodilator Agents - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2014.282962

Key points Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased by acute hypoxia during rest by unknown mechanisms. Oral administration of acetazolamide blunts the pulmonary vascular pressure response to acute hypoxia, thus permitting the observation of IPAVA blood flow with minimal pulmonary pressure change. Hypoxic pulmonary vasoconstriction was attenuated in humans following acetazolamide administration and partially restored with bicarbonate infusion, indicating that the effects of acetazolamide on hypoxic pulmonary vasoconstriction may involve an interaction between arterial pH and PCO2. We observed that IPAVA blood flow during hypoxia was similar before and after acetazolamide administration, even after acid–base status correction, indicating that pulmonary pressure, pH and PCO2 are unlikely regulators of IPAVA blood flow. Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased with exposure to acute hypoxia and has been associated with pulmonary artery systolic pressure (PASP). We aimed to determine the direct relationship between blood flow through IPAVA and PASP in 10 participants with no detectable intracardiac shunt by comparing: (1) isocapnic hypoxia (control); (2) isocapnic hypoxia with oral administration of acetazolamide (AZ; 250 mg, three times a day for 48 h) to prevent increases in PASP; and (3) isocapnic hypoxia with AZ and 8.4% NaHCO3 infusion (AZ + HCO3–) to control for AZ‐induced acidosis. Isocapnic hypoxia (20 min) was maintained by end‐tidal forcing, blood flow through IPAVA was determined by agitated saline contrast echocardiography and PASP was estimated by Doppler ultrasound. Arterial blood samples were collected at rest before each isocapnic–hypoxia condition to determine pH, [HCO3–] and Pa,CO2. AZ decreased pH (–0.08 ± 0.01), [HCO3–] (−7.1 ± 0.7 mmol l−1) and Pa,CO2 (−4.5 ± 1.4 mmHg; P