Fisher James P, Flück Daniela, Hilty Matthias P, Lundby Carsten
School of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia - Okanagan, Kelowna, British Columbia, Canada.
Exp Physiol. 2018 Jan 1;103(1):77-89. doi: 10.1113/EP086493. Epub 2017 Nov 12.
What is the central question of this study? High-altitude hypoxia increases muscle sympathetic nerve activity (MSNA), but whether intravenous infusion of dopamine, to blunt the responsiveness of the carotid chemoreceptors, reduces MSNA at high altitude is not known. What is the main finding and its importance? Muscle sympathetic nerve activity was elevated after 15-17 days of high-altitude hypoxia (3454 m) compared with values at 'sea level' (432 m). However, intravenous dopamine infusion to blunt the responsiveness of the carotid chemoreceptors did not significantly decrease MSNA either at sea level or at high altitude, suggesting that high-altitude sympathoexcitation arises via a different mechanism. High-altitude hypoxia causes pronounced sympathoexcitation, but the underlying mechanisms remain unclear. We tested the hypothesis that i.v. infusion of dopamine to attenuate carotid chemoreceptor responsiveness would reduce muscle sympathetic nerve activity (MSNA) at high altitude. Nine healthy individuals [mean (SD); 26 (4) years of age] were studied at 'sea level' (SL; Zurich) and at high altitude (ALT; 3454 m; 15-17 days after arrival), both while breathing the ambient air and during an acute incremental hypoxia test (eight 3 min stages; partial pressure of end-tidal O 90-45 mmHg). Intravenous infusions of dopamine (3 μg kg min ) and placebo (saline) were administered on both study days, according to a single-blind randomized cross-over design. Sojourn to high altitude decreased the partial pressure of end-tidal O (to ∼60 mmHg) and increased minute ventilation [V̇E; mean ± SEM, SL versus ALT: saline, 8.6 ± 0.5 versus 11.3 ± 0.6 l min ; dopamine, 8.2 ± 0.5 versus 10.6 ± 0.8 l min ; P < 0.05] and MSNA burst frequency by ∼80% [SL versus ALT: saline, 16 ± 3 versus 28 ± 4 bursts min ; dopamine, 16 ± 4 versus 31 ± 4 bursts min ; P < 0.05) when breathing the ambient air, but were not different with dopamine. Increases in MSNA burst frequency and V̇E during the acute incremental hypoxia test were greater at ALT than SL (P < 0.05). Dopamine did not affect the magnitude of the MSNA burst frequency response to acute incremental hypoxia at either SL or ALT. However, V̇E was lower with dopamine than saline administration throughout the acute incremental hypoxia test at ALT. These data indicate that i.v. infusion of low-dose dopamine to blunt the responsiveness of the carotid chemoreceptors does not significantly decrease MSNA at high altitude.
本研究的核心问题是什么?高海拔低氧会增加肌肉交感神经活动(MSNA),但静脉输注多巴胺以减弱颈动脉化学感受器的反应性是否会降低高海拔地区的MSNA尚不清楚。主要发现及其重要性是什么?与“海平面”(432米)时的值相比,高海拔低氧(3454米)15 - 17天后肌肉交感神经活动升高。然而,静脉输注多巴胺以减弱颈动脉化学感受器的反应性,在海平面或高海拔地区均未显著降低MSNA,这表明高海拔交感神经兴奋是通过不同机制产生的。高海拔低氧会引起明显的交感神经兴奋,但其潜在机制仍不清楚。我们检验了这样一个假设,即静脉输注多巴胺以减弱颈动脉化学感受器的反应性会降低高海拔地区的肌肉交感神经活动(MSNA)。对9名健康个体[平均(标准差);26(4)岁]在“海平面”(SL;苏黎世)和高海拔地区(ALT;3454米;到达后15 - 17天)进行了研究,研究期间他们既呼吸环境空气,也进行急性递增低氧试验(八个3分钟阶段;呼气末氧分压90 - 45mmHg)。根据单盲随机交叉设计,在两个研究日分别静脉输注多巴胺(3μg·kg⁻¹·min⁻¹)和安慰剂(生理盐水)。在高海拔地区停留会降低呼气末氧分压(至约60mmHg),并增加分钟通气量[V̇E;平均值±标准误,SL与ALT相比:生理盐水组,8.6±0.5与11.3±0.6升/分钟;多巴胺组,8.2±0.5与10.6±0.8升/分钟;P<0.05],并且在呼吸环境空气时MSNA爆发频率增加约80%[SL与ALT相比:生理盐水组,16±3与28±4次爆发/分钟;多巴胺组,16±4与31±4次爆发/分钟;P<0.05),但多巴胺组与安慰剂组无差异。在急性递增低氧试验期间,ALT组的MSNA爆发频率和V̇E的增加幅度大于SL组(P<0.05)。多巴胺对SL或ALT时急性递增低氧引起的MSNA爆发频率反应幅度均无影响。然而,在ALT的整个急性递增低氧试验中,多巴胺组的V̇E低于生理盐水组。这些数据表明,静脉输注低剂量多巴胺以减弱颈动脉化学感受器的反应性并不会显著降低高海拔地区的MSNA。