Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Avenue, 43-229 CHS, Los Angeles, CA, 90095, USA.
Division of Pulmonary and Critical Care Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Eur J Appl Physiol. 2019 Oct;119(10):2375-2389. doi: 10.1007/s00421-019-04222-6. Epub 2019 Sep 6.
The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE).
We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO)/[Hb] ≤ 0.8 and VO < 80% predicted in the absence of a cardiac or pulmonary mechanical limit. Those with peak (Ca-vO)/[Hb] > 0.8, VO ≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO < [1.5 × HCO + 6].
Prevalence of impaired SOE as the sole cause of exertional intolerance was 12.5% (32/257). At peak exercise, poor SOE and HV had less acidemic arterial blood compared to NL (pHa = 7.39 ± 0.05 vs. 7.38 ± 0.05 vs. 7.32 ± 0.02, p < 0.001), which was explained by relative hypocapnia (PaCO = 29.9 ± 5.4 mmHg vs. 31.6 ± 5.4 vs. 37.5 ± 3.4, p < 0.001). For a subset of poor SOE, this relative alkalemia, also seen in mixed venous blood, was associated with a normal PvO nadir (28 ± 2 mmHg vs. 26 ± 4, p = 0.627) but increased SvO at peak exercise (44.1 ± 5.2% vs. 31.4 ± 7.0, p < 0.001).
We identified a cohort of patients whose exercise limitation is due only to systemic oxygen extraction, due to either an intrinsic abnormality of skeletal muscle mitochondrion, limb muscle microcirculatory dysregulation, or hyperventilation and left shift the oxyhemoglobin dissociation curve.
运动不耐受的临床研究通常集中在心肺疾病上，而外周因素往往被忽视。我们假设存在一部分患者，他们的主要运动受限是由于全身氧提取异常（SOE）所致。
我们回顾了 313 例因不明原因运动不耐受而进行有创心肺运动试验（iCPET）的连续患者的结果。由于 SOE 不良导致的运动极限定义为峰值运动时（Ca-vO）/[Hb] ≤ 0.8 和 VO < 80%预测值，且不存在心脏或肺机械限制。那些具有峰值（Ca-vO）/[Hb] > 0.8、VO ≥ 80%且无心脏或肺部限制的患者被认为是正常的。正常组再分为过度通气者（HV）和正常者（NL）。过度通气定义为峰值 PaCO < [1.5 × HCO + 6]。
作为运动不耐受唯一原因的 SOE 受损的患病率为 12.5%（32/257）。在峰值运动时，与 NL 相比，SOE 不良和 HV 的动脉血更偏碱性（pHa = 7.39 ± 0.05 比 7.38 ± 0.05 比 7.32 ± 0.02，p < 0.001），这是由于相对低碳酸血症（PaCO = 29.9 ± 5.4 mmHg 比 31.6 ± 5.4 比 37.5 ± 3.4，p < 0.001）所致。对于 SOE 不良的亚组，这种静脉混合血中也存在的相对碱血症与正常的 PvO 最低值（28 ± 2 mmHg 比 26 ± 4，p = 0.627）有关，但在峰值运动时 SvO 增加（44.1 ± 5.2% 比 31.4 ± 7.0，p < 0.001）。
我们确定了一组患者，他们的运动受限仅由于全身氧提取异常所致，这可能是由于骨骼肌线粒体的内在异常、肢体肌肉微循环失调，或过度通气和氧合血红蛋白解离曲线左移所致。
