Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution

Be, Marshall; Cw, Hanson; Frasch, F.; Marshall, Carol Lynn

doi:10.1007/bf01720916

Cited by 150 publications

(98 citation statements)

References 17 publications

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“…Indeed, a large fraction of the intraregional perfusion to TR ROIs (66%) was associated with units in which sV a was, on average, 20 times lower than normal (sV a ϭ 0.004 vs. 0.078 in Table 1). Assuming V a/Q at baseline was unity and that the regional reduction of 30% in Q of the TR ROIs was exclusive to the low-ventilation units of that ROI, V a/Q would be about 0.095, a level that would yield an alveolar Pa O 2 of less than 50 mm Hg, and thus would be sufficiently low to induce HPV (35,36). (The details of this calculation can be found in the online supplement.)…”

Section: Alterations In Regional Perfusionmentioning

confidence: 99%

Regional Pulmonary Perfusion, Inflation, and Ventilation Defects in Bronchoconstricted Patients with Asthma

Harris

Winkler

Tgavalekos

et al. 2006

Am J Respir Crit Care Med

104

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Rationale: Bronchoconstriction in asthma leads to heterogeneous ventilation and the formation of large and contiguous ventilation defects in the lungs. However, the regional adaptations of pulmonary perfusion (Q ) to such ventilation defects have not been well studied. Methods: We used positron emission tomography to assess the intrapulmonary kinetics of intravenously infused tracer nitrogen-13 ( 13 NN), and measured the regional distributions of ventilation and perfusion in 11 patients with mild asthma. For each subject, the regional washout kinetics of 13 NN before and during methacholineinduced bronchoconstriction were analyzed. Two regions of interest (ROIs) were defined: one over a spatially contiguous area of high tracer retention (TR) during bronchoconstriction and a second one covering an area of similar size, showing minimal tracer retention (NR). Results: Both ROIs demonstrated heterogeneous washout kinetics, which could be described by a two-compartment model with fast and slow washout rates. We found a systematic reduction in regional Q to the TR ROI during bronchoconstriction and a variable and nonsignificant change in relative Q for NR regions. The reduction in regional Q was associated with an increase in regional gas content of the TR ROI, but its magnitude was greater than that anticipated solely by the change in regional lung inflation. Conclusion: During methacholine-induced bronchoconstriction, perfusion to ventilation defects are systematically reduced by a relative increase in regional pulmonary vascular resistance.Keywords: emission computed tomography; pulmonary gas exchange; vascular resistance; vasoconstriction; ventilation-perfusion ratio It is well established that severe heterogeneity of regional ventilation contributes significantly to gas exchange impairment in asthma. However, the extent to which regional pulmonary perfusion adapts to match changes in ventilation during an asthma attack is unknown. Evidence for severe heterogeneity of regional ventilation in patients with asthma has come from measurements with external scintillation counters (1, 2), single-photon emission computed tomography (CT) of Technegas (3), nuclear magnetic resonance imaging after a single-breath inhalation of hyperpolarized helium (4), and high-resolution CT (5-10). Most of these studies, however, did not quantify regional ventilation during normal breathing and did not evaluate the effect of bronchoconstriction on regional pulmonary perfusion.Changes in regional perfusion during bronchoconstriction (BC) have been measured using technetium ( 99m Tc)-labeled macroaggregated albumin (11,12). In one study, perfusion defects of segmental or smaller size were reported mainly at the periphery of middle or lower lung zones in children with asthma, despite normal chest X-rays, blood gases, and peak expiratory flows (13). That study, however, did not assess whether these perfusion defects corresponded to defects in ventilation. Another study assessed ventilation with krypton ( 81m Kr) gas and perfusion with 99m Tc ...

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Section: Alterations In Regional Perfusionmentioning

confidence: 99%

Regional Pulmonary Perfusion, Inflation, and Ventilation Defects in Bronchoconstricted Patients with Asthma

Harris

Winkler

Tgavalekos

et al. 2006

Am J Respir Crit Care Med

104

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“…It is known that variations in Pv O 2 can induce changes in pulmonary vascular tone independently of alveolar gas PO2 (14). Whether variations in Pv CO 2 independent of alveolar PCO2 (PACO 2 ; i.e., PETCO 2 ) have an effect on pulmonary vascular tone appears not to have been addressed in the literature.…”

Section: Subjectsmentioning

confidence: 99%

Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography

Balanos

Talbot

Dorrington

et al. 2003

Journal of Applied Physiology

152

101

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“…Carotid body (CB) chemoreceptor cells and pulmonary artery smooth muscle cells (PASMC) detect hypoxia with a very low threshold (PO 2 70-75 mmHg) (Gonzalez et al, 1994;Marshall et al, 1994) generating adaptive responses (Richalet, 1997;Gonzalez, 1998). In both cell types the hypoxic transduction cascade involves inhibition of O 2 -sensitive K + channels, activation of voltage operated Ca 2+ channels, and generation of Ca 2+ -dependent responses (López-Barneo et al, 1988;Post et al, 1992;Gonzalez et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Effects of mitochondrial poisons on glutathione redox potential and carotid body chemoreceptor activity

Gomez-Niño

Agapito

Obeso

et al. 2009

Respiratory Physiology & Neurobiology

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a b s t r a c tLow oxygen sensing in chemoreceptor cells involves the inhibition of specific plasma membrane K + channels, suggesting that mitochondria-derived reactive oxygen species (ROS) link hypoxia to K + channel inhibition, subsequent cell depolarization and activation of neurotransmitter release. We have used several mitochondrial poisons, alone and in combination with the antioxidant N-acetylcysteine (NAC), and quantify their capacity to alter GSH/GSSG levels and glutathione redox potential (E GSH ) in rat diaphragm. Selected concentrations of mitochondrial poisons with or without NAC were tested for their capacity to activate neurotransmitter release in chemoreceptor cells and to alter ATP levels in intact rat carotid body (CB). We found that rotenone (1 M), antimycin A (0.2 g/ml) and sodium azide (5 mM) decreased E GSH ; NAC restored E GSH to control values. At those concentrations mitochondrial poisons activated neurotransmitter release from CB chemoreceptor cells and decreased CB ATP levels, NAC being ineffective to modify these responses. Additional experiments with 3-nitroprionate (5 mM), lower concentrations of rotenone and dinitrophenol revealed variable relationships between E GSH and chemoreceptor cell neurotransmitter release responses and ATP levels. These findings indicate a lack of correlation between mitochondrialgenerated modifications of E GSH and chemoreceptor cells activity. This lack of correlation renders unlikely that alteration of mitochondrial production of ROS is the physiological pathway chemoreceptor cells use to signal hypoxia.

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Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution

Cited by 150 publications

References 17 publications

Regional Pulmonary Perfusion, Inflation, and Ventilation Defects in Bronchoconstricted Patients with Asthma

Regional Pulmonary Perfusion, Inflation, and Ventilation Defects in Bronchoconstricted Patients with Asthma

Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography

Effects of mitochondrial poisons on glutathione redox potential and carotid body chemoreceptor activity

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