Beta Adrenergic Regulation of Intrapulmonary Arteriovenous Anastomoses in Intact Rat and Isolated Rat Lungs

Abstract

Intrapulmonary arteriovenous anastomoses (IPAVA) allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol. We also evaluated IPAVA recruitment in intact rats with hypoxia and the beta-adrenergic receptor blocker propranolol. We found that IPAVA are recruited in the intact rat by isoproterenol and their recruitment by hypoxia can be minimized by propranolol, suggesting a role for the adrenergic system in the recruitment of IPAVA by hypoxia. IPAVA recruitment is completely abolished by ventilation with 100% oxygen. Isoproterenol also recruits IPAVA in isolated rat lungs. The fact that isoproterenol can recruit IPAVA in isolated lungs, without increased pulmonary flow, suggests that elevated cardiac output is not required for IPAVA recruitment.

AltitudeOmics: effect of reduced barometric pressure on detection of intrapulmonary shunt, pulmonary gas exchange efficiency, and total pulmonary resistance

“…Field study. In the field study, bubble score (presumably indicative of Q IPAVA ) at the highest exercise workload achieved at sea level within a given subject was significantly higher compared with bubble scores at the same workload at 5,260 m. The decrease in bubble score, observed at 5,260 m, supports data from Foster et al (20) and Bates et al (2). However in both the field and chamber studies, the reduction in bubble score occurred acutely, whereas the bubble scores obtained by Foster et al (20) and Bates et al (2) were recorded after 3 wk of acclimatization to 5,050 m. This suggests an unknown effect of hypobaria on left heart bubble contrast, which seems to occur with or without acclimatization to extreme altitude.…”

“…2 indicates that bubble persistence also depends on the diffusivity, D, of a gas. The diffusivity of a gas in a liquid depends on the viscosity of the liquid (57); that is, increasing the viscosity of a liquid increases bubble stability (2,46). However, in our study, there were no significant differences in hematocrit in our subjects between conditions.…”

“…With respect to the issue of oxygenation, the degree of hyperoxia is an important consideration when measuring Q IPAVA . We have previously shown that breathing 100% O 2 reduces Q IPAVA , as detected by TTSCE (44), and this is supported by animal studies using conditions that enhance Q IPAVA -detected microspheres (2,53). In the current study, we used only mild hyperoxia to keep alveolar PO 2 values in hypobaric conditions (17,200 ft) similar to those at Denver altitude (5,280 ft).…”

“…The purpose of this study was to investigate the possible reason for the reduction in Q IPAVA in hypobaria that was observed previously (2,20). In the field study, we attempted to explore the effect of acclimatization on Q IPAVA , but to our surprise, bubble scores were lower on acute ascent to high altitude compared with sea level.…”

“…Blood viscosity has also been suggested to play a role in the stability of saline contrast microbubbles (2). The viscosity of blood depends on both the plasma viscosity and hematocrit (77).…”