Time course of hypoxic pulmonary vasoconstriction: a rabbit model of regional hypoxia.

Abstract

There is disagreement in the literature about the time required for hypoxic constriction of pulmonary vessels to reach its full intensity. Some studies suggest that only minutes are required, others that several hours are needed. We examined the time course over 6 h of changes in pulmonary shunt (as a fraction of cardiac output) following induction of unilateral hypoxia by collapse or liquid filling of the left lung in 47 anesthetized rabbits. The time course was examined at four degrees of lung inflation: during collapse and at airway pressures of 0.3 kPa, 0.6 kPa, and 0.9 kPa. The respective volumes (mean +/- SD) of the liquid-filled lung were estimated to be 6.4 +/- 1.0, 12.8 +/- 2.5, and 15.8 +/- 1.6 ml/kg body weight (BW). During sustained hypoxia (the period from 150 to 360 min after inducing hypoxia), shunt declined at a slow linear rate of 2.37 x 10(-4)/min, which was independent of lung inflation (p = 0.65 analysis of variance [ANOVA]) and significantly different from zero (p < 0.001). The stability of cardiac output in this animal model, as measured sequentially by thermodilution, was confirmed in a further 20 animals. The experiments provide evidence for a slow intensification of blood-flow diversion at a rate that does not depend upon the degree of lung inflation. Whether this change is a feature of hypoxic constriction itself, or some modulation of it, remains unclear.

One session of remote ischemic preconditioning does not improve vascular function in acute normobaric and chronic hypobaric hypoxia

“…Different, overlapping mechanisms might be responsible for the initial rapid increase and subsequent slow intensification of pulmonary artery pressures (Vejlstrup et al . ) in response to hypoxia, and delaying our measurements to 90–120 min might have yielded different results. However, at altitude, where subjects were hypoxic for 8–12 days, RIPC failed to elicit any changes in PASP, indicating that the time of measurement probably does not explain our lack of effect at SL.…”

NO and reactive oxygen species are involved in biphasic hypoxic vasoconstriction of isolated rabbit lungs

“…It has previously been found (4,21,22,32) in isolated lungs and in intact and open-chest animals that sustained alveolar hypoxia provokes a prolonged PAP elevation, but the underlying mechanisms have rarely been addressed. Our group (27) previously showed that a biphasic pressor response is regularly elicited by prolonged hypoxia in perfused rabbit lungs, and this was also noted in intact rabbits (21,22), in vivo perfused lungs of the dog, and intact dogs (4, 31) as well as in isolated ferret lungs (32). A new observation of the present study is the fact that 120-180 min of sustained (uninterrupted) alveolar hypoxia sufficed to cause a persistent elevation in posthypoxic "baseline" PAP.…”

Impact of Mitochondria and NADPH Oxidases on Acute and Sustained Hypoxic Pulmonary Vasoconstriction

“…For both the acute and sustained phase of HPV there is ongoing discussion whether mitochondria, NADPH oxidases, or alternative systems are the underlying oxygen sensors and whether they are regulated by identical or by different mechanisms (2,(6)(7)(8)(9). Biphasic hypoxic vasoconstrictor responses have repeatedly been shown to occur in isolated vessels, but few studies have focused on the regulation in the intact organ (9)(10)(11)(12)(13).…”