Pulmonary haemodynamic response to exercise in highlanders versus lowlanders.

The aim of the study was to investigate the pulmonary haemodynamic response to exercise in Central Asian high- and lowlanders. This was a cross-sectional study in Central Asian highlanders (living >2500 m) compared with lowlanders (living <800 m), assessing cardiac function, including tricuspid regurgitation pressure gradient (TRPG), cardiac index and tricuspid annular plane systolic excursion (TAPSE) by echocardiography combined with heart rate and oxygen saturation measured by pulse oximetry (S pO2 ) during submaximal stepwise cycle exercise (10 W increase per 3 min) at their altitude of residence (at 760 m or 3250 m, respectively). 52 highlanders (26 females; aged 47.9±10.7 years; body mass index (BMI) 26.7±4.6 kg·m-2; heart rate 75±11 beats·min-1; S pO2 91±5%;) and 22 lowlanders (eight females; age 42.3±8.0 years; BMI 26.9±4.1 kg·m-2; heart rate 68±7 beats·min-1; S pO2 96±1%) were studied. Highlanders had a lower resting S pO2 compared to lowlanders but change during exercise was similar between groups (highlanders versus lowlanders -1.4±2.9% versus -0.4±1.1%, respectively, p=0.133). Highlanders had a significantly elevated TRPG and exercise-induced increase was significantly higher (13.6±10.5 mmHg versus 6.1±4.8 mmHg, difference 7.5 (2.8 to 12.2) mmHg; p=0.002), whereas cardiac index increase was slightly lower in highlanders (2.02±0.89 L·min-1 versus 1.78±0.61 L·min-1, difference 0.24 (-0.13 to 0.61) L·min-1; p=0.206) resulting in a significantly steeper pressure-flow ratio (ΔTRPG/Δcardiac index) in highlanders 9.4±11.4 WU and lowlanders 3.0±2.4 WU (difference 6.4 (1.4 to 11.3) WU; p=0.012). Right ventricular-arterial coupling (TAPSE/TRPG) was significantly lower in highlanders but no significant difference in change with exercise in between groups was detected (-0.01 (-0.20 to 0.18); p=0.901). In highlanders, chronic exposure to hypoxia leads to higher pulmonary artery pressure and a steeper pressure-flow relation during exercise.

Bosentan reduces pulmonary artery pressure in high altitude residents.

UNLABELLED: Endothelin-1 (ET-1) plays a critical role in the regulation of pulmonary vascular tone. The aim of this study was to investigate the role of ET-1 in the pathogenesis of high altitude pulmonary arterial hypertension (HAPH). METHODS: Pulmonary artery pressure (PAP) was measured by echocardiography in permanent residents of the Kyrgyz Republic (3200-4000 m above sea level) both before and 3 h after a single oral dose of ET receptor antagonist, bosentan (125 mg). Plasma ET-1 levels were measured by ELISA assay. Genomic DNA was extracted from peripheral blood samples and the frequency of -3a and -4a alleles of the ET-1 gene determined by PCR. RESULTS: Plasma ET-1 in HAPH highlanders was significantly higher than in healthy subjects (7.05±2.35 vs. 4.65±1.65 pg/ml, p<0.002). After the treatment with 125 mg bosentan, systolic PAP decreased from 46±1.9 to 37±2.2 mm Hg (p<0.01), and pulmonary artery acceleration time (PAAT) increased from 0.086±0.001 to 0.098±0.001 sec (p<0.001). The frequency of the -4a allele was significantly higher in HAPH patients compared to healthy highlanders (0.43 vs. 0.3, χ(2)=4.3, p=0.03). CONCLUSION: Increased ET-1 levels play an important role in development of HAPH.