Decreased arterial PO2, not O2 content, increases blood flow through intrapulmonary arteriovenous anastomoses at rest. (9th June 2016)

• Record Type: Journal Article
• Authors: Duke, Joseph W.; Davis, James T.; Ryan, Benjamin J.; Elliott, Jonathan E.; Beasley, Kara M.; Hawn, Jerold A.; Byrnes, William C.; Lovering, Andrew T.
• Is Part Of: Journal of physiology. Volume 594:Number 17(2016:Sep.)
• Page Start: 4981
• Page End: 4996
• Publication Date: 2016-06-09
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP272211
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Key points: 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 P O 2 ( P a O 2 ) or O2 content ( C a O 2 ) 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 a O 2 was reduced by 10% by lowering the haemoglobin concentration (isovolaemic haemodilution; Low [Hb]). Q IPAVA, assessed by transthoracic saline contrast echocardiography, significantly increased as P a O 2 decreased and, despite reduced C a O 2 (via isovolaemic haemodilution), was similar at iso‐ P a O 2 . These data suggest that, with alveolar hypoxia, low P a O 2 causes the hypoxia‐induced increase in Q IPAVA, although where and how this is detected remains unknown. Abstract: 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 P O 2 ( P a O 2 ) or O2 content ( C a O 2 ). C a O 2 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 a O 2 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]). P a O 2 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. P a O 2 was no different between CON and Low [Hb], although C a O 2 was 10.4%, 9.2% and 9.8% lower at 18%, 14% and 12.5% O2, respectively. Q IPAVA significantly increased as P a O 2 decreased and, despite reduced C a O 2, was similar at iso‐ P a O 2 . These data suggest that, with alveolar hypoxia, low P a O 2 causes the hypoxia‐induced increase in Q IPAVA . Whether the low P O 2 is detected at the carotid body, airway and/or the vasculature remains unknown. Key points: 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 P O 2 ( P a O 2 ) or O2 content ( C a O 2 ) 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 a O 2 was reduced by 10% by lowering the haemoglobin concentration (isovolaemic haemodilution; Low [Hb]). Q IPAVA, assessed by transthoracic saline contrast echocardiography, significantly increased as P a O 2 decreased and, despite reduced C a O 2 (via isovolaemic haemodilution), was similar at iso‐ P a O 2 . These data suggest that, with alveolar hypoxia, low P a O 2 causes the hypoxia‐induced increase in Q IPAVA, although where and how this is detected remains unknown.