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 (Q̇IPAVA ) 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 (FIO2 = 1.0). Additionally, Q̇IPAVA 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 of Q̇IPAVA 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 quantify Q̇IPAVA and identify the consequences of Q̇IPAVA on physiological and pathophysiological processes. Nevertheless, based on currently published data, our proposed working model is that Q̇IPAVA 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.

Figure 1. IPAVA working model

Diagram summarizing the working model for how active and passive regulation of the pulmonary circulation could determine the recruitment and perfusion of intrapulmonary arteriovenous anastomoses (IPAVA) under various conditions. IPAVA are considered to be few in number and >25 μm in diameter (top vessel branch) while capillaries are considered to be many in number and <10 μm in diameter (all others); each panel is within an isogravitational plane so we are not suggesting top or bottom blood flow preference is dependent upon gravity. Small/thin vessels with pink background void of erythrocytes and microspheres represent no pulmonary perfusion but the potential for recruitment is possible, whereas areas with erythrocytes and/or microspheres represent areas that are being perfused. Yellow spheres represent intravenously injected microspheres. A, at rest breathing air. _T is ∼5 l min^-1 and there is only passive recruitment of a small portion of the available pulmonary vasculature with little, or no _IPAVA, and consequently there is no appearance of microspheres in the pulmonary venous effluent and/or left ventricle. Large black arrow represents direction of blood flow. B, increased _T during exercise or intravenous inotropic drug infusion breathing air. _T is at least double resting values (≥10 l min⁻¹), which causes passive recruitment of a larger proportion of the pulmonary vasculature that contains IPAVA, such that IPAVA are passively recruited/perfused. Subsequently microspheres appear in the pulmonary venous effluent and/or left ventricle and the volume of _IPAVA increases as the intensity of exercise increases. Large black arrow represents direction of blood flow. C, at rest breathing hypoxic gas. _T is slightly increased to ∼7 l min⁻¹, depending upon the severity of hypoxia. Hypoxia causes an active redistribution of pulmonary blood flow via varying degrees of hypoxic pulmonary vasoconstriction (or other unknown active redistribution mechanism) towards those areas of the lung with IPAVA, and consequently, IPAVA are passively recruited/perfused. Subsequently microspheres appear in the pulmonary venous effluent and/or left ventricle and the volume of _IPAVA increases as the severity of hypoxia increases (i.e. decreases). Large black arrow represents direction of blood flow. D, increased _T during exercise or intravenous catecholamine infusion breathing 100% O₂. _T is at least double resting values (≥10 l min^-1), but with alveolar hyperoxia ( = 1.0). Hyperoxia causes an active redistribution of pulmonary blood flow, either hyperoxic vasoconstriction of areas containing IPAVA or hyperoxic vasodilatation of areas without IPAVA (or other unknown active redistribution mechanism). Consequently, IPAVA are not recruited/perfused and no microspheres appear in the pulmonary venous effluent and/or left ventricle. Large black arrow represents direction of blood flow.