Department of Exercise Sciences, Brigham Young University, Provo, UT, USA.
J Physiol. 2021 Oct;599(20):4581-4596. doi: 10.1113/JP281900. Epub 2021 Sep 28.
Limb disuse has profound negative consequences on both vascular and skeletal muscle health. The purpose of this investigation was to determine whether repeated application of passive heat, applied to the knee extensor muscles, could mitigate the detrimental effects of limb disuse on vascular function. This was a randomized, single-blinded placebo controlled trial. Twenty-one healthy volunteers (10 women, 11 men) underwent 10 days of unilateral lower limb immobilization and were randomized to receive either a daily 2 h sham (Imm) or heat treatment (Imm+H) using pulsed shortwave diathermy. Vascular function was assessed with Doppler ultrasound of the femoral artery and the passive leg movement technique. Biopsies of the vastus lateralis were also collected before and after the intervention. In Imm, femoral artery diameter (FAD) and PLM-induced hyperaemia (HYP) were reduced by 7.3% and 34.3%, respectively. Changes in both FAD (4% decrease; P = 0.0006) and HYP (7.8% increase; P = 0.003) were significantly attenuated in Imm+H. Vastus lateralis capillary density was not altered in either group. Immobilization significantly decreased expression of vascular endothelial growth factor (P = 0.006) and Akt (P = 0.001), and increased expression of angiopoietin 2 (P = 0.0004) over time, with no differences found between groups. Immobilization also upregulated elements associated with remodelling of the extracellular matrix, including matrix metalloproteinase 2 (P = 0.0046) and fibronectin (P = 0.0163), with no differences found between groups. In conclusion, limb immobilization impairs vascular endothelial function, but daily muscle heating via diathermy is sufficient to counteract this adverse effect. These are the first data to indicate that passive muscle heating mitigates disuse-induced vascular dysfunction. KEY POINTS: Limb disuse can be unavoidable for many of reasons (i.e. injury, bed rest, post-surgery), and can have significant adverse consequences for muscular and vascular health. We tested the hypothesis that declines in vascular function that result from lower limb immobilization could be mitigated by application of passive heat therapy. This report shows that 10 days of limb immobilization significantly decreases resistance artery diameter and vascular function, and that application of passive heat to the knee extensor muscle group each day for 2 h per day is sufficient to attenuate these declines. Additionally, muscle biopsy analyses showed that 10 days of heat therapy does not alter capillary density of the muscle, but upregulates multiple factors indicative of a vascular remodelling response. Our data demonstrate the utility of passive heat as a therapeutic tool to mitigate losses in lower limb vascular function that occur from disuse.
肢体废用对血管和骨骼肌肉健康都有深远的负面影响。本研究旨在确定反复应用被动热是否可以减轻肢体废用对血管功能的不利影响。这是一项随机、单盲、安慰剂对照试验。21 名健康志愿者(10 名女性,11 名男性)接受了 10 天的单侧下肢固定,并随机接受每日 2 小时的假(Imm)或热治疗(Imm+H)使用脉冲短波透热疗法。使用多普勒超声评估股动脉和被动腿部运动技术的血管功能。干预前后还采集了股外侧肌的活检。在 Imm 中,股动脉直径(FAD)和 PLM 诱导的充血(HYP)分别减少了 7.3%和 34.3%。Imm+H 中 FAD(减少 4%;P=0.0006)和 HYP(增加 7.8%;P=0.003)的变化明显减弱。两组的股外侧肌毛细血管密度均无变化。随着时间的推移,Imm 显著降低了血管内皮生长因子(VEGF)(P=0.006)和 Akt(P=0.001)的表达,并增加了血管生成素 2(Angiopoietin 2)的表达(P=0.0004),但两组之间没有差异。Imm 还上调了与细胞外基质重塑相关的元素,包括基质金属蛋白酶 2(MMP2)(P=0.0046)和纤维连接蛋白(FN)(P=0.0163),但两组之间没有差异。总之,肢体固定会损害血管内皮功能,但通过透热疗法进行每日肌肉加热足以抵消这种不良影响。这些是第一个表明被动肌肉加热减轻废用引起的血管功能障碍的数据。关键点:肢体废用可能由于多种原因(例如受伤、卧床休息、手术后)而不可避免,并且会对肌肉和血管健康产生重大不利影响。我们测试了这样一个假设,即下肢固定导致的血管功能下降可以通过应用被动热疗来缓解。本报告显示,10 天的肢体固定显著降低了阻力动脉直径和血管功能,而每天 2 小时的被动热应用足以减轻这些下降。此外,肌肉活检分析表明,10 天的热疗不会改变肌肉的毛细血管密度,但会上调多个表明血管重塑反应的因素。我们的数据表明,被动热作为一种治疗工具,可用于减轻因废用而导致的下肢血管功能丧失。