Hypoxia, not pulmonary vascular pressure, induces blood flow through intrapulmonary arteriovenous anastomoses. (23rd December 2014)

• Record Type: Journal Article
• 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.
• Is Part Of: Journal of physiology. Volume 593:Number 3(2015:Feb.)
• Page Start: 723
• Page End: 737
• Publication Date: 2014-12-23
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2014.282962
• Languages: English
• ISSNs: 0022-3751

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="tjp6467-sec-0010" sec-type="section"> <title>Key points</title> <p> <list id="tjp6467-list-0001" list-type="bullet"> <list-item> <p>Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased by acute hypoxia during rest by unknown mechanisms.</p> </list-item> <list-item> <p>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.</p> </list-item> <list-item> <p>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 <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgh3tp3ss7x" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6467:equation:tjp6467-math-0001" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">C</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula>.</p> </list-item> <list-item> <p>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 <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgh3tp3ss8g" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6467:equation:tjp6467-math-0002" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">C</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula> are unlikely regulators of IPAVA blood flow.</p> </list-item> </list> </p> </sec> <sec id="tjp6467-sec-0020" sec-type="section"> <title>Abstract</title> <p>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% NaHCO<sub>3</sub> infusion (AZ + HCO<sub>3</sub><sup>–</sup>) 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, [HCO<sub>3</sub><sup>–</sup>] and <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgh3tp3ssbk" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6467:equation:tjp6467-math-0003" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mrow><mml:mi mathvariant="normal">a</mml:mi><mml:mo>, </mml:mo><mml:mi mathvariant="normal">C</mml:mi></mml:mrow><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula>. AZ decreased pH (–0.08 ± 0.01), [HCO<sub>3</sub><sup>–</sup>] (−7.1 ± 0.7 mmol l<sup>−1</sup>) and <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgh3tp3ssdp" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6467:equation:tjp6467-math-0004" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mrow><mml:mi mathvariant="normal">a</mml:mi><mml:mo>, </mml:mo><mml:mi mathvariant="normal">C</mml:mi></mml:mrow><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula> (−4.5 ± 1.4 mmHg; <italic>P</italic> < 0.01), while intravenous NaHCO<sub>3</sub> restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (<italic>P</italic> < 0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (<italic>P</italic> < 0.001) following AZ administration while intravenous NaHCO<sub>3</sub> partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (<italic>P</italic> < 0.01) and was unrelated to PASP, cardiac output and pulmonary vascular resistance for all conditions. In conclusion, isocapnic hypoxia induces blood flow through IPAVA independent of changes in PASP and the influence of AZ on the PASP response to isocapnic hypoxia is dependent upon the H<sup>+</sup> concentration or <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgh3tp3srz0" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6467:equation:tjp6467-math-0005" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mrow><mml:mi mathvariant="normal">a</mml:mi><mml:mo>, </mml:mo><mml:mi mathvariant="normal">C</mml:mi></mml:mrow><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula>.</p> </sec> </abstract>