Trimetazidine attenuates high-altitude fatigue and cardiorespiratory fitness impairment: A randomized double-blinded placebo-controlled clinical trial
Trimetazidine attenuates high-altitude fatigue and cardiorespiratory fitness impairment: A randomized double-blinded placebo-controlled clinical trial
复制标题
曲美他嗪减轻高原疲劳和心肺健康损伤：一项随机双盲安慰剂对照临床试验
DOI：
10.1016/j.biopha.2019.109003
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发表时间：
2019-08-01
影响因子：
7.5
通讯作者：
Huang, Lan
中科院分区：
文献类型：
--
作者：
Yang, Jie;Zhang, Laiping;Huang, Lan
曲美他嗪（TMZ）具有优化心肌能量代谢的作用，是一种常用的抗缺血药物。我们的试验（ChiCTR-TRC-13003298）旨在探讨TMZ是否对急性高海拔暴露的高原疲劳（HAF）、心功能和心肺健康有任何预防作用，以及它是如何对HAF起作用的。39名健康的年轻受试者参加了一项随机双盲安慰剂对照试验，并在出发前14天随机服用口服TMZ （n = 20）或安慰剂（n = 19），每次20 mg，直到研究结束。在出发前和到达高地前分别进行2018年路易斯湖评分问卷、超声心动图、身体工作能力评估、心肌能量代谢循环指标和疲劳评估。随访时，TMZ显著降低高原患者HAF发生率（p = 0.038）、逆转心肺功能障碍发生率、左室收缩末期容积（LVESV, p = 0.032）和左室射血分数（LVEF, p = 0.015）。与安慰剂组相比，TMZ组在急性高暗示暴露后运动前（p < 0.001）和运动后（p = 0.012） LDH和乳酸水平显著降低（p = 0.025）。此外，左心室收缩功能的改善可能有助于TMZ治疗期间HAF的改善（LVEF, OR = 0.859, 95% CI = 0.741-0.996, p = 0.044）。综上所述，TMZ可以预防急性高原暴露期HAF、心肺功能损害、改善左心室收缩功能。该试验为TMZ的作用提供了新的见解，并为高原HAF和心肺功能障碍提供了新的证据。
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-allude 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 lid, 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-allude 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.