Abstract：
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, postexertional malaise, and orthostatic intolerance, but its pathophysiology is poorly understood. Pharmacologic cholinergic stimulation was used to test the hypothesis that neurovascular dysregulation underlies exercise intolerance in ME/CFS.
Does neurovascular dysregulation contribute to exercise intolerance in ME/CFS, and can its treatment improve exercise capacity?
Forty-five subjects with ME/CFS were enrolled in a single-center, randomized, double-blind, placebo-controlled trial. Subjects were assigned in a 1:1 ratio to receive a 60-mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). A second iCPET was performed 50 min later. The primary end point was the difference in peak exercise oxygen uptake (Vo2). Secondary end points included exercise pulmonary and systemic hemodynamics and gas exchange.
Twenty-three subjects were assigned to receive pyridostigmine and 22 to receive placebo. The peak Vo2 increased after pyridostigmine but decreased after placebo (13.3 ± 13.4 mL/min vs -40.2 ± 21.3 mL/min; P < .05). The treatment effect of pyridostigmine was 53.6 mL/min (95% CI, -105.2 to -2.0). Peak vs rest Vo2 (25.9 ± 15.3 mL/min vs -60.8 ± 25.6 mL/min; P < .01), cardiac output (-0.2 ± 0.6 L/min vs -1.9 ± 0.6 L/min; P < .05), and right atrial pressure (1.0 ± 0.5 mm Hg vs -0.6 ± 0.5 mm Hg; P < .05) were greater in the pyridostigmine group compared with placebo.
Pyridostigmine improves peak Vo2 in ME/CFS by increasing cardiac output and right ventricular filling pressures. Worsening peak exercise Vo2, cardiac output, and right atrial pressure following placebo may signal the onset of postexertional malaise. We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS.
ClinicalTrials.gov; No.: NCT03674541; URL: www.
gov.
Does neurovascular dysregulation contribute to exercise intolerance in ME/CFS, and can its treatment improve exercise capacity?
Forty-five subjects with ME/CFS were enrolled in a single-center, randomized, double-blind, placebo-controlled trial. Subjects were assigned in a 1:1 ratio to receive a 60-mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). A second iCPET was performed 50 min later. The primary end point was the difference in peak exercise oxygen uptake (Vo2). Secondary end points included exercise pulmonary and systemic hemodynamics and gas exchange.
Twenty-three subjects were assigned to receive pyridostigmine and 22 to receive placebo. The peak Vo2 increased after pyridostigmine but decreased after placebo (13.3 ± 13.4 mL/min vs -40.2 ± 21.3 mL/min; P < .05). The treatment effect of pyridostigmine was 53.6 mL/min (95% CI, -105.2 to -2.0). Peak vs rest Vo2 (25.9 ± 15.3 mL/min vs -60.8 ± 25.6 mL/min; P < .01), cardiac output (-0.2 ± 0.6 L/min vs -1.9 ± 0.6 L/min; P < .05), and right atrial pressure (1.0 ± 0.5 mm Hg vs -0.6 ± 0.5 mm Hg; P < .05) were greater in the pyridostigmine group compared with placebo.
Pyridostigmine improves peak Vo2 in ME/CFS by increasing cardiac output and right ventricular filling pressures. Worsening peak exercise Vo2, cardiac output, and right atrial pressure following placebo may signal the onset of postexertional malaise. We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS.
ClinicalTrials.gov; No.: NCT03674541; URL: www.
gov.
摘要：
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）的特点是顽固性疲劳，运动后不适，和直立不耐受，但对其病理生理学了解甚少。药物胆碱能刺激用于检验以下假设：神经血管失调是ME/CFS中运动不耐受的基础。
神经血管失调是否会导致ME/CFS的运动不耐受，它的治疗可以提高运动能力吗？
单中心纳入了45名患有ME/CFS的受试者，随机化，双盲,安慰剂对照试验。在进行有创心肺运动试验（iCPET）后，以1：1的比例分配受试者，以接受60mg剂量的口服吡啶斯的明或安慰剂。50分钟后进行第二次iCPET。主要终点是峰值运动摄氧量（Vo2）的差异。次要终点包括运动肺和全身血流动力学和气体交换。
23名受试者被分配接受吡啶斯的明，22名受试者被分配接受安慰剂。峰值Vo2在吡啶斯的明后增加，但在安慰剂后下降（13.3±13.4mL/minvs-40.2±21.3mL/min；P<0.05）。吡啶斯的明的治疗效果为53.6mL/min（95％CI，-105.2至-2.0）。峰值与静息Vo2（25.9±15.3mL/minvs-60.8±25.6mL/min；P<.01），心输出量（-0.2±0.6L/minvs-1.9±0.6L/min；P<0.05），与安慰剂组相比，吡啶斯的明组的右心房压（1.0±0.5mmHgvs-0.6±0.5mmHg；P<.05）更高。
吡啶斯的明通过增加心输出量和右心室充盈压来改善ME/CFS的峰值Vo2。恶化的峰值运动Vo2，心输出量，安慰剂后的右心房压力可能表明运动后不适的发作。我们建议，可治疗的神经血管失调是ME/CFS急性运动不耐受的基础。
ClinicalTrials.gov；编号：NCT03674541；URL：www。
政府。
神经血管失调是否会导致ME/CFS的运动不耐受，它的治疗可以提高运动能力吗？
单中心纳入了45名患有ME/CFS的受试者，随机化，双盲,安慰剂对照试验。在进行有创心肺运动试验（iCPET）后，以1：1的比例分配受试者，以接受60mg剂量的口服吡啶斯的明或安慰剂。50分钟后进行第二次iCPET。主要终点是峰值运动摄氧量（Vo2）的差异。次要终点包括运动肺和全身血流动力学和气体交换。
23名受试者被分配接受吡啶斯的明，22名受试者被分配接受安慰剂。峰值Vo2在吡啶斯的明后增加，但在安慰剂后下降（13.3±13.4mL/minvs-40.2±21.3mL/min；P<0.05）。吡啶斯的明的治疗效果为53.6mL/min（95％CI，-105.2至-2.0）。峰值与静息Vo2（25.9±15.3mL/minvs-60.8±25.6mL/min；P<.01），心输出量（-0.2±0.6L/minvs-1.9±0.6L/min；P<0.05），与安慰剂组相比，吡啶斯的明组的右心房压（1.0±0.5mmHgvs-0.6±0.5mmHg；P<.05）更高。
吡啶斯的明通过增加心输出量和右心室充盈压来改善ME/CFS的峰值Vo2。恶化的峰值运动Vo2，心输出量，安慰剂后的右心房压力可能表明运动后不适的发作。我们建议，可治疗的神经血管失调是ME/CFS急性运动不耐受的基础。
ClinicalTrials.gov；编号：NCT03674541；URL：www。
政府。
