Decreased arterial P _O2 , not O₂ content, increases blood flow through intrapulmonary arteriovenous anastomoses at rest

The mechanism(s) that regulate hypoxia-induced blood flow through intrapulmonary arteriovenous anastomoses (Q_IPAVA) are currently unknown. Our previous work has demonstrated that the mechanism of hypoxia-induced Q_IPAVA is not simply increased cardiac output, pulmonary artery systolic pressure or sympathetic nervous system activity and, instead, it may be a result of hypoxaemia directly. To determine whether it is reduced arterial Po₂ (Pao₂) or O₂ content (Cao₂) that causes hypoxia-induced Q_IPAVA, individuals were instructed to breathe room air and three levels of hypoxic gas at rest before (control) and after C_aO2 was reduced by 10% by lowering the haemoglobin concentration (isovolaemic haemodilution; Low [Hb]). Q_IPAVA, assessed by transthoracic saline contrast echocardiography, significantly increased as Pao₂ decreased and, despite reduced C_aO2 (via isovolaemic haemodilution), was similar at iso- Pao₂. These data suggest that, with alveolar hypoxia, low Pao₂ causes the hypoxia-induced increase in Q_IPAVA, although where and how this is detected remains unknown. Alveolar hypoxia causes increased blood flow through intrapulmonary arteriovenous anastomoses (Q_IPAVA) in healthy humans at rest. However, it is unknown whether the stimulus regulating hypoxia-induced Q_IPAVA is decreased arterial Po₂ (Pao₂) or O₂ content (C_aO2 ). C_aO2 is known to regulate blood flow in the systemic circulation and it is suggested that IPAVA may be regulated similar to the systemic vasculature. Thus, we hypothesized that reduced C_aO2 would be the stimulus for hypoxia-induced Q_IPAVA. Blood volume (BV) was measured using the optimized carbon monoxide rebreathing method in 10 individuals. Less than 5 days later, subjects breathed room air, as well as 18%, 14% and 12.5% O₂, for 30 min each, in a randomized order, before (CON) and after isovolaemic haemodilution (10% of BV withdrawn and replaced with an equal volume of 5% human serum albumin–saline mixture) to reduce [Hb] (Low [Hb]). Pao₂ was measured at the end of each condition and Q_IPAVA was assessed using transthoracic saline contrast echocardiography. [Hb] was reduced from 14.2 ± 0.8 to 12.8 ± 0.7 g dl⁻¹ (10 ± 2% reduction) from CON to Low [Hb] conditions. Pao₂ was no different between CON and Low [Hb], although C_aO2 was 10.4%, 9.2% and 9.8% lower at 18%, 14% and 12.5% O₂, respectively. Q_IPAVA significantly increased as Pao₂ decreased and, despite reduced C_aO2 , was similar at iso-Pao₂. These data suggest that, with alveolar hypoxia, low Pao₂ causes the hypoxia-induced increase in Q_IPAVA. Whether the low Po₂ is detected at the carotid body, airway and/or the vasculature remains unknown.