接受核苷治疗的高乳酸血症HIV感染患者运动能力的限制

Limitation of exercise capacity in nucleoside-treated HIV-infected patients with hyperlactataemia.

作者信息

Duong M, Dumas J P, Buisson M, Martha B, Piroth L, Grappin M, Waldner A, Chavanet P, Portier H

机构信息

Service des Maladies Infectieuses, Hôpital Universitaire du Bocage, Dijon, France.

出版信息

HIV Med. 2007 Mar;8(2):105-11. doi: 10.1111/j.1468-1293.2007.00439.x.

DOI:10.1111/j.1468-1293.2007.00439.x

PMID:17352767

Abstract

BACKGROUND

Inhibition of DNA polymerase gamma by nucleoside reverse transcriptase inhibitors (NRTIs) can cause mitochondrial dysfunction and cellular toxicity. Hyperlactataemia, which is a consequence of a shift in the metabolism of pyruvate, is an indicator of nucleoside-related mitochondrial toxicity.

METHODS

We evaluated exercise and oxidative capacities as well as circulatory and ventilatory responses to exercise in 24 HIV-infected patients on NRTIs presenting hyperlactataemia [mean (+/-standard deviation) fasted lactate=3.5+/-1.1 mmol/L]; 27 NRTI-treated patients with normal baseline lactate concentrations were used as controls (mean fasted lactate=1.6+/-0.3 mmol/L).

RESULTS

In the patients with hyperlactataemia, the average peak work capacity (1.7+/-0.6 W/kg) and peak oxygen consumption (VO(2)) (21+/-4 mL/kg/min) were significantly lower (P<0.01) than in control subjects (work, 2.1+/-0.4 W/kg; VO(2), 25+/-4 mL/kg/min). The capacity to increase oxygen extraction during exercise was significantly diminished in the hyperlactataemia group, as shown by a low peak systemic arteriovenous oxygen difference (a-vO(2)) difference compared with controls (11+/-3 vs 14+/-3 mL/dL; P=0.008), and as indicated by a linear correlation between VO(2) and systemic a-vO(2) difference (r(2)=0.76). During exercise, the increases in cardiac output relative to VO(2) (mean Delta cardiac output (Q)/DeltaVO(2)=8+/-3.6) and ventilation (mean Delta ventilation (VE)/DeltaVO(2)=48.6+/-13.2) were significantly higher in hyperlactataemia patients compared with controls (mean cardiac output Delta(Q)/DeltaVO(2)=6+/-2; mean DeltaVE/DeltaVO(2)=42+/-12.7; P=0.03).

CONCLUSIONS

The degree of exercise limitation in patients with nucleoside-related mitochondrial toxicity correlates directly with the severity of impaired muscle oxidative phosphorylation, as indicated by the capacity for muscle oxygen extraction. Exaggerated circulatory and ventilatory responses to exercise are direct consequences of the level of impaired muscle oxidative phosphorylation.

摘要

背景

核苷类逆转录酶抑制剂（NRTIs）抑制DNA聚合酶γ可导致线粒体功能障碍和细胞毒性。高乳酸血症是丙酮酸代谢改变的结果，是核苷相关线粒体毒性的一个指标。

方法

我们评估了24例接受NRTIs治疗且出现高乳酸血症的HIV感染患者（平均空腹乳酸水平=3.5±1.1 mmol/L）的运动和氧化能力，以及运动时的循环和通气反应；27例基线乳酸浓度正常的接受NRTIs治疗的患者作为对照（平均空腹乳酸水平=1.6±0.3 mmol/L）。

结果

高乳酸血症患者的平均峰值工作能力（1.7±0.6 W/kg）和峰值耗氧量（VO₂）（21±4 mL/kg/min）显著低于对照组（工作能力，2.1±0.4 W/kg；VO₂，25±4 mL/kg/min）（P<0.01）。与对照组相比，高乳酸血症组运动时增加氧摄取的能力显著降低，表现为峰值全身动静脉氧差（a-vO₂）较低（11±3 vs 14±3 mL/dL；P=0.008），且VO₂与全身a-vO₂差之间呈线性相关（r²=0.76）。运动期间，高乳酸血症患者的心输出量相对于VO₂的增加（平均Δ心输出量（Q）/ΔVO₂=8±3.6）和通气量的增加（平均Δ通气量（VE）/ΔVO₂=48.6±13.2）显著高于对照组（平均心输出量Δ（Q）/ΔVO₂=6±2；平均ΔVE/ΔVO₂=42±12.7；P=0.03）。