Magnitude and time course of acute hypoxic pulmonary vasoconstriction in man

Morrell, Nicholas W.; Nijran, K. S.; Biggs, T.; Seed, W. A.

doi:10.1016/0034-5687(95)00002-u

Cited by 53 publications

(41 citation statements)

References 19 publications

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“…gradient that had a very similar pattern over time to the more pronounced rise induced by hypoxia in study A. The findings suggest that HIF-1 may be involved in the pulmonary vascular responses to hypoxia over times of 0.5-4 h. We are unable to comment on responses over a shorter period than 0.5 h, because measurements were not made within this period, although others have seen very rapid responses (14). Because both the response to hypoxia and the response to DFO are likely to be dependent on the dose used, interpretation of the relative magnitudes of the pulmonary vascular responses seen in study A and study B is difficult to undertake without further studies.…”

Section: Discussionmentioning

confidence: 65%

Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1

Balanos

Dorrington

Robbins

2002

Journal of Applied Physiology

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Balanos, George M., Keith L. Dorrington, and Peter A. Robbins. Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1. J Appl Physiol 92: 2501-2507, 2002. First published February 15, 2002 10.1152/japplphysiol.00965.2001.-Hypoxia-inducible factor (HIF)-1 is stabilized by hypoxia and iron chelation. We hypothesized that HIF-1 might be involved in pulmonary vascular regulation and that infusion of desferrioxamine over 8 h would consequently mimic hypoxia and elevate pulmonary vascular resistance. In study A, we characterized the pulmonary vascular response to 4 h of isocapnic hypoxia; in study B, we measured the pulmonary vascular response to 8 h of desferrioxamine infusion. For study A, 11 volunteers undertook two protocols: 1) 4 h of isocapnic hypoxia (endtidal PO 2 ϭ 50 Torr), followed by 2 h of recovery with isocapnic euoxia (end-tidal PO 2 ϭ 100 Torr), and 2) 6 h of air breathing (control). For study B, nine volunteers undertook two protocols while breathing air: 1) continuous infusion of desferrioxamine (4 g/70 kg) over 8 h and 2) continuous infusion of saline over 8 h (control). In both studies, pulmonary vascular resistance was assessed at 0.5-to 1-h intervals by Doppler echocardiography via the maximum pressure gradient during systole across the tricuspid valve. Results show a progressive rise in pressure gradient over the first 3-4 h with both isocapnic hypoxia (P Ͻ 0.001) and desferrioxamine infusion (P Ͻ 0.005) to increases of ϳ16 and 4 Torr, respectively. These results support a role for HIF-regulated gene activation in human hypoxic pulmonary vasoconstriction. hypoxia inducible factor-1; hypoxic pulmonary vasoconstriction; pulmonary circulation THERE IS EVIDENCE TO SUGGEST that the human pulmonary circulation responds to sustained hypoxia by developing a progressively more intense constriction over a period of a few hours. In anesthetized patients, Fiser et al. (4) observed a gradual decline in pulmonary venous admixture during unilateral atelectasis over 90 min, suggesting that blood flow diversion by hypoxic pulmonary vasoconstriction was intensifying during this time. Exposure of healthy humans to an 8-h isocapnic reduction in end-tidal oxygen partial pressure (PET O 2 ) to 50 Torr, approximately half its normal value, results in a progressive rise in pulmonary vascular resistance (PVR) over 2 h to ϳ2.5 times its euoxic value as determined by right heart catheterization (3).The mechanisms responsible for this slower component of the pulmonary vascular response to hypoxia remain unclear (13,22), but one possibility is that the transcriptional regulator hypoxia-inducible factor (HIF)-1 is involved, as it is in some other homeostatic responses to hypoxia (18). Yu et al. (23) examined the kinetics of induction of increased levels of the subunit HIF-1␣ in isolated ferret lungs exposed to 8 h of hypoxia. They found that HIF-1␣ was not detectable at 0 h, increased at 1-2 h, peaked at 4 h, and remained elevated thereafter (23). Furthermore, the work of Yu et ...

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Section: Discussionmentioning

confidence: 65%

Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1

Balanos

Dorrington

Robbins

2002

Journal of Applied Physiology

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“…However, Morrell et al [48] have described the dynamics of HPV over its first few minutes in eight healthy volunteers in whom regional hypoxia was induced by the sudden inflation of a catheter-tip balloon in the bronchus supplying the upper lobe of the left lung. In these experiments the bronchus was occluded shortly after the onset of a steady intravenous infusion of a short-lived (half-life t 1/2 =13 s), water-soluble, radioactive gas (krypton 81m, 81m Kr), and the index of a change in blood flow to the occluded left upper lobe during hypoxia was the change in 81m Kr signal in this area, measured using a gamma scintillation camera.…”

Section: Non-invasive Observation Of Hpv and Hcpvmentioning

confidence: 98%

Human pulmonary vascular responses to hypoxia and hypercapnia

Dorrington¹,

Talbot²

2004

Pflugers Arch - Eur J Physiol

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The ability of alveolar gas composition to influence pulmonary vascular tone has been appreciated for over 50 years. In particular, it has been proposed that both O2 and CO2 could play a role in the matching of perfusion to ventilation within the lung, improving the overall efficiency of gas exchange. A wide variety of experimental approaches has been used to investigate pulmonary vascular effects of the respiratory gases in a range of mammalian species. In this article, we review experiments performed in healthy humans, identify particular difficulties in the interpretation of such experiments, and discuss possible approaches to future study.

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“…Nonetheless, for this reason, perfusion was measured during the air-breathing segments only. The onset of hypoxic pulmonary vasoconstriction in humans occurs within minutes of exposure to hypoxia (34), but the duration of hyperoxia (20 breaths) is too short to have a large effect. In addition, limited experimental evidence suggests that hypoxic pulmonary vasoconstriction is not active under normal conditions.…”

Section: Limitationsmentioning

confidence: 99%

The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung

Henderson

Sá

Theilmann

et al. 2013

Journal of Applied Physiology

111

130

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Henderson AC, Sá RC, Theilmann RJ, Buxton RB, Prisk GK, Hopkins SR. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung. J Appl Physiol 115: 313-324, 2013. First published April 25, 2013 doi:10.1152/japplphysiol.01531.2012.-The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (V A/Q ) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional V A/Q ratio, the gravitational gradients in proton density, ventilation, perfusion, and V A/Q ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min Ϫ1 ·ml Ϫ1 ) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min Ϫ1 ·ml Ϫ1 ) images to obtain regional V A/Q ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (Ϫ0.17 Ϯ 0.10 ml·min, P ϭ 0.02) as was the slope of the perfusion-height relationship (Ϫ0.14 Ϯ 0.05 ml·min, P ϭ 0.02). There was a significant gravitational gradient in V A/Q ratio in both postures (P Ͻ 0.05) that was less in prone (0.09 Ϯ 0.08 cm Ϫ1 supine, 0.04 Ϯ 0.03 cm Ϫ1 prone, P ϭ 0.04). The gravitational gradients in ventilation, perfusion, and regional V A/Q ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of gravity on V A/Q matching. magnetic resonance imaging; arterial spin labeling; specific ventilation imaging; ventilation-perfusion ratio; gravity WHILE THE LUNG HAS A NUMBER of functions, it is primarily a gas exchange organ. 1 Ventilation-perfusion (V A/Q ) matching, such that regions of the lung that receive fresh gas also receive deoxygenated capillary blood, is the most important mechanism determining gas exchange efficiency (53). Although several mechanisms are thought to accomplish V A/Q matching in the healthy lung (see Ref. 18 for review), it is thought that passive mechanisms dominate under normal conditions. Such passive mechanisms include vascular branching structure and the effect of gravity on ventilation and perfusion (53).Modeling studies suggest that, because of the shape of the lungs within the thorax, the gradient of intrapleural pressures is more uniform in prone posture compared with supine (48). This predicts that the g...

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Magnitude and time course of acute hypoxic pulmonary vasoconstriction in man

Cited by 53 publications

References 19 publications

Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1

Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1

Human pulmonary vascular responses to hypoxia and hypercapnia

The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung

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