Schulze Kiana M, Weber Ramona E, Horn Andrew G, Hageman K Sue, Kenney Nathan J, Behnke Bradley J, Poole David C, Musch Timothy I
Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA.
J Physiol. 2025 Jan;603(2):337-351. doi: 10.1113/JP287549. Epub 2024 Dec 3.
Pulmonary hypertension (PH) is a chronic, progressive disease characterized by pulmonary vascular remodelling, dyspnoea and exercise intolerance. Key facets of dyspnoea and exercise intolerance include skeletal and respiratory muscle contractile and metabolic disturbances; however, muscle perfusion during exercise has not been investigated. We hypothesized that diaphragm blood flow ( ) would be increased and locomotory muscle would be decreased during submaximal treadmill running in PH rats compared to healthy controls. Female Sprague-Dawley rats were injected (i.p.) with monocrotaline to induce PH (n = 16), or a vehicle control (n = 15). Disease progression was monitored via echocardiography. When moderate disease severity was confirmed, maximal oxygen uptake ( ) tests were performed. Rats were given >24 h to recover, and then fluorescent microspheres were infused during treadmill running (20 m/min, 10% grade; ∼40-50% maximal speed attained during the test) to determine tissue . In PH rats compared with healthy controls, was lower (84 (7) vs. 67 (11) ml/min/kg; P < 0.001), exercising diaphragm was 35% higher and soleus was 28% lower. Diaphragm was negatively correlated with soleus and in PH rats. Furthermore, there was regional redistribution in the diaphragm in PH compared to healthy rats, which may represent or underlie diaphragmatic weakness in PH. These findings suggest the presence of a pathological respiratory muscle blood flow steal phenomenon in PH and that this may contribute to the exercise intolerance reported in patients. KEY POINTS: Pulmonary hypertension (PH) impairs exercise tolerance, which is associated with skeletal and respiratory muscle dysfunction. Increased work of breathing in PH may augment diaphragm blood flow and lower locomotory muscle blood flow during exercise, hindering exercise tolerance. Our findings demonstrate that respiratory muscle blood flow is increased while the locomotory muscle is decreased in PH compared to healthy rats during exercise, suggesting that blood flow is preferentially redistributed to sustain ventilatory demand. Furthermore, blood flow is regionally redistributed within the diaphragm in PH, which may underlie diaphragm dysfunction. Greater respiratory muscle work at a given workload in PH commands higher respiratory muscle blood flow, impairing locomotory muscle oxygen delivery and compromising exercise tolerance, which may be improved by therapeutics which target the diaphragm vasculature.
肺动脉高压（PH）是一种慢性进行性疾病，其特征为肺血管重塑、呼吸困难和运动不耐受。呼吸困难和运动不耐受的关键方面包括骨骼和呼吸肌的收缩及代谢紊乱；然而，运动期间的肌肉灌注情况尚未得到研究。我们推测，与健康对照相比，在次极量跑步机跑步过程中，肺动脉高压大鼠的膈肌血流量（ ）会增加，而运动肌的血流量会减少。给雌性斯普拉格-道利大鼠腹腔注射（i.p.）野百合碱以诱导肺动脉高压（n = 16），或注射溶剂对照（n = 15）。通过超声心动图监测疾病进展。当确认疾病严重程度为中度时，进行最大摄氧量（ ）测试。让大鼠恢复超过24小时，然后在跑步机跑步（20米/分钟，坡度10%；约为 测试期间达到的最大速度的40 - 50%）过程中注入荧光微球，以确定组织血流量。与健康对照相比，肺动脉高压大鼠的 较低（84（7）对67（11）毫升/分钟/千克；P < 0.001），运动时膈肌血流量高35%，比目鱼肌血流量低28%。在肺动脉高压大鼠中，膈肌血流量与比目鱼肌血流量及 呈负相关。此外与健康大鼠相比，肺动脉高压大鼠膈肌存在区域血流量重新分布，这可能是肺动脉高压患者膈肌无力的表现或原因。这些发现表明肺动脉高压中存在病理性呼吸肌血流窃取现象，这可能是患者运动不耐受的原因。要点：肺动脉高压（PH）损害运动耐量，这与骨骼和呼吸肌功能障碍有关。肺动脉高压中呼吸功增加可能会在运动期间增加膈肌血流量并降低运动肌血流量，从而妨碍运动耐量。我们的研究结果表明，与健康大鼠相比，运动期间肺动脉高压大鼠的呼吸肌血流量增加而运动肌血流量减少，这表明血流量优先重新分布以维持通气需求。此外，肺动脉高压大鼠膈肌内血流量存在区域重新分布，这可能是膈肌功能障碍的原因。在给定工作量下，肺动脉高压中更大的呼吸肌功需要更高的呼吸肌血流量，损害运动肌的氧气输送并损害运动耐量，针对膈肌血管系统的治疗可能会改善这种情况。
