Abstract
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 < 0.01), while intravenous NaHCO3 restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (P < 0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (P < 0.001) following AZ administration while intravenous NaHCO3 partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (P < 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(+) concentration or Pa,CO2.
Highlights
The anatomical evidence of intrapulmonary arteriovenous anastomoses (IPAVA) is established in many mammals, including baboons, dogs, and humans (Tobin & Zariquiey, 1950; Tobin & Wilder, 1953; Tobin, 1966; Lovering et al, 2007; Stickland et al, 2007)
By directly manipulating the pulmonary pressure response to isocapnic hypoxia with AZ we extend the findings of previous reports and illustrate that the magnitude of blood flow through IPAVA in response to isocapnic hypoxia is unrelated to changes in pulmonary artery systolic pressure (PASP), cardiac output (Qc), or pulmonary vascular resistance (PVR)
In conclusion, we found that manipulating pulmonary artery pressure during isocapnic hypoxia has no effect on the magnitude of blood flow through IPAVA
Summary
The anatomical evidence of intrapulmonary arteriovenous anastomoses (IPAVA) is established in many mammals, including baboons, dogs, and humans (Tobin & Zariquiey, 1950; Tobin & Wilder, 1953; Tobin, 1966; Lovering et al, 2007; Stickland et al, 2007). IPAVA vessel diameter has been shown to be up to 200 μm in adults (Tobin, 1966), potentially indicating a transpulmonary pathway for erythrocytes that bypasses the alveoli This has been demonstrated in isolated human lungs; transpulmonary passage of microspheres exists, even if the microspheres are too large (50 μm) to pass through the alveolar capillaries (7-10 μm) (Lovering et al, 2007). Its physiological contribution as an anatomical shunt remains a matter of debate (Hopkins et al, 2009; Lovering et al, 2009a), recent work by Bryan et al (2012) and Elliott et al (2014) indicate that blood flow through IPAVA does contribute to pulmonary gas exchange efficiency Given these potential protective (i.e. reduced capillary stress) and detrimental (i.e. decreased gas exchange efficiency) effects of blood flow through IPAVA, it is important to understand the stimuli or mechanisms responsible for regulating blood flow through IPAVA
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