Transpulmonary plasma ET-1 and nitrite differences in high altitude pulmonary hypertension.

Berger, Marc M. Christoph Dehnert, Damian M. Bailey, Andrew M. Luks, Elmar Menold, Christian Castell, Guido Schendler, Vitalie Faoro, Heimo Mairbäurl, Peter Bärtsch, and Eric R. Swenson. Transpulmonary plasma ET-1 and nitrite differences in high altitude pulmonary hypertension. High Alt. Med. Biol. 10:17-24, 2009.- Thirty-four mountaineers were studied at low (110 m) and high altitude (4559 m) to evaluate if increased pulmonary artery systolic pressure (PASP) at high altitude is associated with increased pulmonary endothelin-1 (ET-1) availability and alterations in nitrite metabolism across the lung. Blood samples were obtained using central venous and radial artery catheters for plasma ET-1 and nitrite. Pulmonary blood flow was measured by inert gas rebreathing to calculate transpulmonary exchange of plasma ET-1 and nitrite, and PASP was assessed by transthoracic Doppler echocardiography. After ascent to high altitude, PASP increased from 23 +/- 4 to 39 +/- 10 mmHg. Arterial and central venous plasma ET-1 increased, while plasma nitrite did not change significantly. At low altitude there was a transpulmonary loss of plasma ET-1, but a transpulmonary gain at high altitude. In contrast was a transpulmonary gain of plasma nitrite at low altitude and a transpulmonary loss at high altitude. PASP positively correlated with a transpulmonary gain of plasma ET-1 and negatively correlated with a transpulmonary loss of plasma nitrite. These results suggest that a transpulmonary gain of plasma ET- 1 is associated with higher PASP at high altitude. Transpulmonary loss of plasma nitrite indicates either less pulmonary nitric oxide (NO) production, which contributes to higher PASP, or increased NO bioavailability arising from nitrite reduction, which may oppose ET-1-mediated vasoconstriction.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

No change of lung volumes and compliance measured by body pletzysmography in AMS at 4559 m

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Endothelin receptors upregulated in circulating endothelial cells in HAPE?

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Indirect markers of pulmonary endothelial function correlate with pulmonary artery pressure at high altitude

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Increased metabolic activity of leukocytes in AMS-susceptibles

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Direct evidence for increased pulmonary free radical generation in AMS and HAPE.

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No evidence for interstitial lung oedema by extensive pulmonary function testing at 4,559 m.

The aim of the present study was to better understand previously reported changes in lung function at high altitude. Comprehensive pulmonary function testing utilising body plethysmography and assessment of changes in closing volume were carried out at sea level and repeatedly over 2 days at high altitude (4,559 m) in 34 mountaineers. In subjects without high-altitude pulmonary oedema (HAPE), there was no significant difference in total lung capacity, forced vital capacity, closing volume and lung compliance between low and high altitude, whereas lung diffusing capacity for carbon monoxide increased at high altitude. Bronchoconstriction at high altitude could be excluded as the cause of changes in closing volume because there was no difference in airway resistance and bronchodilator responsiveness to salbutamol. There were no significant differences in these parameters between mountaineers with and without acute mountain sickness. Mild alveolar oedema on radiographs in HAPE was associated only with minor decreases in forced vital capacity, diffusing capacity and lung compliance and minor increases in closing volume. Comprehensive lung function testing provided no evidence of interstitial pulmonary oedema in mountaineers without HAPE during the first 2 days at 4,559 m. Data obtained in mountaineers with early mild HAPE suggest that these methods may not be sensitive enough for the detection of interstitial pulmonary fluid accumulation.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability

High altitude (HA)-induced pulmonary hypertension may be due to a free radical-mediated reduction in pulmonary nitric oxide (NO) bioavailability. We hypothesised that the increase in pulmonary artery systolic pressure (PASP) at HA would be associated with a net transpulmonary output of free radicals and corresponding loss of bioactive NO metabolites. Twenty-six mountaineers provided central venous and radial arterial samples at low altitude (LA) and following active ascent to 4559 m (HA). PASP was determined by Doppler echocardiography, pulmonary blood flow by inert gas re-breathing, and vasoactive exchange via the Fick principle. Acute mountain sickness (AMS) and high-altitude pulmonary oedema (HAPE) were diagnosed using clinical questionnaires and chest radiography. Electron paramagnetic resonance spectroscopy, ozone-based chemiluminescence and ELISA were employed for plasma detection of the ascorbate free radical (A·−), NO metabolites and 3-nitrotyrosine (3-NT). Fourteen subjects were diagnosed with AMS and three of four HAPE-susceptible subjects developed HAPE. Ascent decreased the arterio-central venous concentration difference (a-cvD) resulting in a net transpulmonary loss of ascorbate, α-tocopherol and bioactive NO metabolites (P < 0.05 vs. LA). This was accompanied by an increased a-cvD and net output of A·− and lipid hydroperoxides (P < 0.05 vs. sea level, SL) that correlated against the rise in PASP (r= 0.56–0.62, P < 0.05) and arterial 3-NT (r= 0.48–0.63, P < 0.05) that was more pronounced in HAPE. These findings suggest that increased PASP and vascular resistance observed at HA are associated with a free radical-mediated reduction in pulmonary NO bioavailability