Thirty-nine healthy mountaineers participated in the study. Twenty-nine subjects (4 women) had a history of at least one documented episode of HAPE. The other 10 subjects (2 women) without history of a HAPE served as control subjects. The study was approved by the institutional ethical boards of the University Hospitals Zurich and Heidelberg. Subjects gave written informed consent to participate in the study.
Baseline measurements were performed at 490 m 2 to 4 weeks prior to the investigation at 4,559 m. At 490 m, subjects underwent clinical examination and bicycle exercise testing until exhaustion to assess the individual peak exercise capacity (mean ± SD, 270 ± 55 W). The following day, Doppler echocardiography was performed.
HAPE-S subjects were then randomized in a double-blind fashion to placebo, tadalafil ordered via My Canadian Pharmacy on https://mycanadian-pharmacy.net/cialis-and-methods-to-combat-erectile-dysfunction.html, or dexamethasone. Details on design of the study have been previously published. At 4,559 m, Doppler echocardiography was performed in the morning of the day after arrival.
Severe acute mountain sickness (AMS) requiring symptomatic treatment developed a few hours after arrival at 4,559 m in two participants receiving tadalafil. As a consequence, these two subjects were withdrawn from the previously published HAPE prevention analysis after initiation of treatment for AMS. Data of these two subjects served for analysis of a best-case scenario (neither of the two participants with HAPE) and a worst-case scenario (both with HAPE), whereas they were not considered for the evaluation of the systolic pulmonary artery pressure response to high altitude. One of these two subjects had to descend prematurely, whereas the other remained at 4,559 m and underwent echocardiography after an overnight stay. Since the primary aim of the present study was to evaluate the effect of elevated pulmonary artery pressure on LV diastolic function rather than to compare the two prophylactic medications, we opted to include the data of this subject in the analysis.
Echocardiography at Rest and During Exercise
Doppler echocardiography was performed with an integrated color Doppler system using a 4.0-MHz transducer (Toshiba Aplio 80; Toshiba; Tokyo, Japan). In the apical four-chamber view, transmitral inflow velocity (ie, peak early transmitral inflow peak velocity [E] and atrial transmitral inflow peak velocity [A]), isovolemic relaxation time, and pulmonary venous flow parameters were obtained as previously described. Color-coded Doppler tissue imaging was used to assess peak tissue velocity within the septal mitral annulus during early diastole (E’). LV ejection fraction (LVEF) was calculated using the single-plane area length method. Systolic right ventricular to atrial pressure gradient (RVPG) was calculated from the gradient across the tricuspid valve using the modified Bernoulli equation. Tricuspid regurgitation velocity was obtained from the right ventricular inflow or the apical four-chamber view. The regurgitant jet was first located by color Doppler, and the peak velocity was then measured using continuous-wave Doppler. If neither of these views revealed a representative continuous-wave Doppler signal, we additionally used a foreshortened four-chamber view.
After obtaining all recordings at rest, subjects started cycling on an ergometer in semirecumbent left-lateral position at a workload corresponding to 40% (mean, 108 ± 22 W) of individual peak exercise capacity. Apart from pulmonary venous flow, all Doppler echocardiographic parameters were reassessed during exercise. Study participants cycled for 2 min before echocardiographic recording was started. After this time period, two-dimensional recordings were first obtained. Doppler measurements where then recorded after 3 min of cycling. This protocol at an exercise level below the anaerobic threshold was chosen in order to warrant steady-state condition at the time of Doppler assessment. At 4,559 m, 70% of the workload (ie, 28% [mean, 76 ± 15 W] of the maximal performance at low altitude) was chosen using the same time intervals. The exercise level was reduced to compensate for the effects of high altitude on physical capacity.
At rest, RVPG was obtainable in all subjects, at 490 m as well as at 4,559 m. During exercise at 490 m, RVPG was not measurable in 2 of the 39 investigated mountaineers. At high altitude, RVPG during exercise was obtained in 32 of 38 subjects (84%). Three subjects were physically unable to exercise (one due to AMS and two because of prestages of HAPE); and in three others, the signal of the continuous-wave Doppler across the tricuspid valve was of insufficient quality. At 490 m, E/A ratio was obtained in all subjects under resting conditions. During exercise, fusion of the E and A waves occurred in four subjects precluding assessment of E/A ratio. At 4,559 m, E/A ratio could be evaluated in 37 of 38 mountaineers at rest (fusion in 1 patient) and in 30 subjects (79%) during exercise (3 subjects were unable to exercise; in 5 participants, fusion of the E and A waves occurred). The acquired images were analyzed off-line by a cardiologist who was blinded to all other data.
A general linear model for repeated measures was used for comparison of data obtained at rest and during exercise and for comparison of differences between values obtained at 490 m and 4,559 m. For group comparison of variables obtained at rest, t test or Mann-Whitney U test were used as appropriate. A probability value < 0.05 was considered statistically significant. Calculations were performed with a commercially available statistical package (SPSS for Windows 13.0; SPSS; Chicago, IL).