Intrapulmonary arteriovenous anastomoses in humans – response to exercise and the environment

Abstract

Intrapulmonary arteriovenous anastomoses (IPAVA) have been known to exist in human lungs for over 60 years. The majority of the work in this area has largely focused on characterizing the conditions in which IPAVA blood flow (Q IPAVA ) is either increased, e.g. during exercise, acute normobaric hypoxia, and the intravenous infusion of catecholamines, or absent/decreased, e.g. at rest and in all conditions with alveolar hyperoxia (F IO 2 = 1.0). Additionally,Q IPAVA is present in utero and shortly after birth, but is reduced in older (>50 years) adults during exercise and with alveolar hypoxia, suggesting potential developmental origins and an effect of age. The physiological and pathophysiological roles ofQ IPAVA are only beginning to be understood and therefore these data remain controversial. Although evidence is accumulating in support of important roles in both health and disease, including associations with pulmonary arterial pressure, and adverse neurological sequelae, there is much work that remains to be done to fully understand the physiological and pathophysiological roles of IPAVA. The development of novel approaches to studying these pathways that can overcome the limitations of the currently employed techniques will greatly help to better quantifyQ IPAVA and identify the consequences ofQ IPAVA on physiological and pathophysiological processes. Nevertheless, based on currently published data, our proposed working model is thatQ IPAVA occurs due to passive recruitment under conditions of exercise and supine body posture, but can be further modified by active redistribution of pulmonary blood flow under hypoxic and hyperoxic conditions. AbbreviationsA − aD O2 , alveolar-to-arterial partial pressure of O 2 difference; C aO2 , arterial O 2 content; F IO2 , fraction of inspired oxygen; HHT, hereditary haemorrhagic telangiectasia; HPV, hypoxic pulmonary vasoconstriction; IPAVA, intrapulmonary arteriovenous anastomoses; MAA, macroaggregates of albumin; MIGET, multiple inert gas elimination technique; Pv O2 , mixed venous partial pressure of O 2 ; P aO2 , arterial partial pressure of O 2 ; PASP, pulmonary artery systolic pressure; PAVM, pulmonary arteriovenous malformation; PFO, patent foramen ovale; S aO2 , arterial O 2 saturation; S pO2 , peripheral estimate of arterial O 2 saturation; 99m Tc-MAA, technetium-99m-labelled MAA; TIA, transient ischaemic attack; TTSCE, transthoracic saline contrast echocardiography;Q T , cardiac output;Q IPAVA , blood flow through IPAVA;Q S /Q T , shunt fraction;V O2 , O 2 consumption, ventilation to perfusion ratio (V/Q ).Andrew Lovering, PhD, is an integrative physiologist who has investigated a wide range of respiratory system questions from understanding how medullary respiratory neurons reconfigure their activity during hypoxia-induced periodic breathing in sleeping cats to understanding the roles of intracardiac and intrapulmonary shunt on the regulation of pulmonary gas exchange efficiency in humans exercising above 5000 m; he thinks that the patent foramen ov...

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

“…Despite such findings, as well as many others, the precise mechanism(s) regulating Q IPAVA under each respective condition remain incompletely known (Lovering et al . ).…”

Non‐invasive screening using ventilatory gas analysis to distinguish between chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension

“…Intrapulmonary shunt could result in lower P ET CO 2 and higher VE/VCO 2 values . Moreover, the effects of intrapulmonary shunts on pulmonary circulation and gas exchange are made apparent by posture change . In this study, postural change from sitting to supine significantly decreased P ET CO 2 and increased VE/VCO 2 in the CTEPH group.…”

“…35 Moreover, the effects of intrapulmonary shunts on pulmonary circulation and gas exchange are made apparent by posture change. 36 In this study, postural change from sitting to supine significantly decreased P ET CO 2 and increased VE/VCO 2 in the CTEPH group. However, P ET CO 2 remained unchanged and VE/VCO 2 significantly decreased in the PAH group.…”

Characterization of blood flow through intrapulmonary arteriovenous anastomoses and patent foramen ovale at rest and during exercise in stroke and transient ischemic attack patients

“…This filtering role can be compromised, however, by the presence of both intrapulmonary (eg, intrapulmonary arteriovenous anastomoses, IPAVA) and intracardiac (eg, patent foramen ovale, PFO) right‐to‐left shunts . The presence of these pathways does not guarantee that a patient will have a stroke or transient ischemic attack because there are large numbers of otherwise healthy humans, which have either blood flow through IPAVA (~30%) and/or PFO (25%–40%) under resting conditions . Nevertheless, with these pathways present and the propensity for emboli formation in individuals who may be prothrombotic, the opportunity exists for emboli of venous origin to bypass the pulmonary microcirculation.…”

“…1,2 The presence of these pathways does not guarantee that a patient will have a stroke or transient ischemic attack because there are large numbers of otherwise healthy humans, which have either blood flow through IPAVA (~30%) and/or PFO (25%-40%) under resting conditions. [3][4][5][6][7] Nevertheless, with these pathways present and the propensity for emboli formation in individuals who may be prothrombotic, the opportunity exists for emboli of venous origin to bypass the pulmonary microcirculation. Therefore, IPAVA and PFO may contribute to the etiology of stroke and TIA in some patients.…”