Catecholamine-induced opening of intrapulmonary arteriovenous anastomoses in healthy humans at rest

Abstract

The mechanism or mechanisms that cause intrapulmonary arteriovenous anastomoses (IPAVA) to either open during exercise in subjects breathing room air and at rest when breathing hypoxic gas mixtures, or to close during exercise while breathing 100% oxygen, remain unknown. During conditions when IPAVA are open, plasma epinephrine (EPI) and dopamine (DA) concentrations both increase, potentially representing a common mechanism. The purpose of this study was to determine whether EPI or DA infusions open IPAVA in resting subjects breathing room air and, subsequently, 100% oxygen. We hypothesized that these catecholamine infusions would open IPAVA. We performed saline-contrast echocardiography in nine subjects without a patent foramen ovale before and during serial EPI and DA infusions while breathing room air and then while breathing 100% oxygen. Bubble scores (0-5) were assigned based on the number and spatial distribution of bubbles in the left ventricle. Pulmonary artery systolic pressure (PASP) was estimated using Doppler ultrasound, while cardiac output (Q(C)) was measured using echocardiography. Bubble scores were significantly greater during EPI infusions of 80-320 ng·kg(-1)·min(-1) compared with baseline when subjects breathed room air; however, bubble scores did not increase when they breathed 100% oxygen. At comparable Q(C) and PASP, intravenous DA (16 μg·kg(-1)·min(-1)) and EPI (40 ng·kg(-1)·min(-1)) resulted in identical bubble scores. Subsequent studies revealed that β-blockade did not prevent hypoxia-induced opening of IPAVA. We suggest that increases in Q(C) or PASP (or both) secondary to EPI or DA infusions open IPAVA in normoxia. The closing mechanism associated with breathing 100% oxygen is independent from the opening mechanisms.

Histologic Evidence of Intrapulmonary Anastomoses by Three-Dimensional Reconstruction in Severe Bronchopulmonary Dysplasia

“…The existence of IAAV that bridge pulmonary arteries and veins has been identified in the late-gestation fetus (13)(14)(15), but IAAV are believed to disappear during the late neonatal period (15), and their potential physiologic roles are controversial. Such vessels have been suggested as contributing to intrapulmonary shunt in adults during catecholamine infusion, with exercise, and in an older patient with BPD (11,12,(25)(26)(27)(28)(29). Our findings support the hypothesis that IAAV are prominent and persist in the preterm infants with severe BPD and our speculation that such vessels contribute to hypoxemia from intrapulmonary anastomoses with sustained respiratory insufficiency in severe BPD.…”

“…Previous physiologic data suggest that right-to-left intrapulmonary shunt pathways exist in adults, as demonstrated by echocardiographic studies during exercise, with exposure to hypoxia and during infusions of catecholamines (12,(26)(27)(28)(29). Furthermore, IAAV are present in pathologic conditions in adult lungs after cavopulmonary shunt operations (30) and with hepatopulmonary syndrome (31).…”

Resting arterial hypoxaemia in subjects with chronic heart failure, pulmonary hypertension and patent foramen ovale

“…The subjects with CHF in this study were taking several medications, including β-blockers. We have previously shown that hypoxia-induced shunting through IPAVA is not impacted by β-blockade when changes inQ T are relatively minimal (Laurie et al 2012). However, a doubling ofQ T caused by catecholamine infusion can increaseQ IPAVA when subjects without PFO are breathing room air and 40% O 2 (Elliott et al 2014).…”

“…Saline contrast echocardiography was performed at rest, as detailed previously, to detectQ IPAVA (Laurie et al 2010(Laurie et al , 2012Elliott et al 2011;. Briefly, a 20-or 22-gauge I.V.…”

Transient Intrapulmonary Shunting in a Patient Treated With β2-Adrenergic Agonists for Status Asthmaticus

“…4 The fact that only brief periods of hyperoxia are needed suggests that O 2 acts locally on the vasculature. Recently, Laurie et al 12 echocardiographically observed IPAVs in a group of healthy adults infused with epinephrine, evidenced by the observation of agitated bubble contrast in the left ventricle .5 cardiac cycles after right heart opacification. Right-to-left bubble passage was eliminated by 100% O 2 breathing.…”