Decreased arterial PO2, not O2 content, increases blood flow through intrapulmonary arteriovenous anastomoses at rest

Alveolar hypoxia causes increased blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) in healthy humans at rest. However, it is unknown whether the stimulus regulating hypoxia-induced QIPAVA is decreased arterial P-O2 (P-aO2) or O-2 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 QIPAVA. 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14% and 12.5% O-2, for 30 min each, in a randomized order, before (CON) and after isovolaemic haemodilution (10% of BV withdrawn and replaced with an equal volume of 5% human serum albumin-saline mixture) to reduce [Hb] (Low [Hb]). P-aO2 was measured at the end of each condition and QIPAVA 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. P-aO2 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% O-2, respectively. QIPAVA significantly increased as P-aO2 decreased and, despite reduced C-aO2, was similar at iso-P-aO2. These data suggest that, with alveolar hypoxia, low P-aO2 causes the hypoxia-induced increase in QIPAVA. Whether the low P-O2 is detected at the carotid body, airway and/or the vasculature remains unknown.