This randomized double-blinded placebo-controlled clinical trial recruited 39 volunteers. The volunteers were assigned to the trimetazidine (TMZ, oral intake TMZ 20 mg, tid) and the placebo groups. All of them were carried out to highland area (3400 m) from sea level area (400 m). Our results demonstrated that TMZ treatment 14 days before departure prevented high-altitude fatigue, cardiorespiratory fitness impairment and improved left ventricular systolic function during acute high-altitude exposure. This trial provides new insights into the effect of TMZ and novel evidence against high-altitude fatigue and cardiorespiratory fitness impairment at high altitudes.

Trimetazidine (TMZ) has been shown to optimize myocardial energy metabolism and is a common anti-ischemic agent. Our trial (ChiCTR-TRC-13003298) aimed to explore whether TMZ has any preventive effect on high-altitude fatigue (HAF), cardiac function and cardiorespiratory fitness upon acute high-altitude exposure and how it works on HAF. Thirty-nine healthy young subjects were enrolled in a randomized double-blinded placebo-controlled trial and were randomized to take oral TMZ (n = 20) or placebo (n = 19), 20 mg tid, 14 days prior to departure until the end of study. The 2018 Lake Louise Score questionnaire, echocardiography, assessments of physical working capacity, circulating markers of myocardial energy metabolism and fatigue were performed both before departure and arrival at highland. At follow-up, TMZ significantly reduced the incidence of HAF (p = 0.038), reversed cardiorespiratory fitness impairment, decreased left ventricular end-systolic volume (LVESV, p = 0.032) and enhanced left ventricular ejection fraction (LVEF, p = 0.015) at highland. Relative to the placebo group, the TMZ group had significantly lower LDH (p = 0.025) and lactate levels before (p < 0.001) and after (p = 0.012) physical exercise after acute high-altitude exposure. Additionally, improved left ventricular systolic function might have contributed to ameliorating HAF during TMZ treatment (LVEF, OR = 0.859, 95% CI = 0.741-0.996, p = 0.044). In conclusion, our results demonstrated that TMZ could prevent HAF, cardiorespiratory fitness impairment and improves left ventricular systolic function during acute high-altitude exposure. This trial provides new insights into the effect of TMZ and novel evidence against HAF and cardiorespiratory fitness impairment at highland.