Department of Kinesiology, Kansas State University, Manhattan, Kansas.
Department of Applied Physiology and Kinesiology, Center for Exercise Science, University of Florida, Gainesville, Florida.
J Appl Physiol (1985). 2019 Aug 1;127(2):423-431. doi: 10.1152/japplphysiol.00189.2019. Epub 2019 May 30.
Mechanical ventilation (MV) is a life-saving intervention, yet with prolonged MV (i.e., ≥6 h) there are time-dependent reductions in diaphragm blood flow and an impaired hyperemic response of unknown origin. Female Sprague-Dawley rats (4-8 mo, = 118) were randomized into two groups; spontaneous breathing (SB) and 6-h (prolonged) MV. After MV or SB, vasodilation (flow-induced, endothelium-dependent and -independent agonists) and constriction (myogenic and α-adrenergic) responses were measured in first-order (1A) diaphragm resistance arterioles in vitro, and endothelial nitric oxide synthase (eNOS) mRNA expression was quantified. Following prolonged MV, there was a significant reduction in diaphragm arteriolar flow-induced (SB, 34.7 ± 3.8% vs. MV, 22.6 ± 2.0%; ≤ 0.05), endothelium-dependent (via acetylcholine; SB, 64.3 ± 2.1% vs. MV, 36.4 ± 2.3%; ≤ 0.05) and -independent (via sodium nitroprusside; SB, 65.0 ± 3.1% vs. MV, 46.0 ± 4.6%; ≤ 0.05) vasodilation. Compared with SB, there was reduced eNOS mRNA expression ( ≤ 0.05). Prolonged MV diminished phenylephrine-induced vasoconstriction (SB, 37.3 ± 6.7% vs. MV, 19.0 ± 1.9%; ≤ 0.05) but did not alter myogenic or passive pressure responses. The severe reductions in diaphragmatic blood flow at rest and during contractions, with prolonged MV, are associated with diaphragm vascular dysfunction which occurs through both endothelium-dependent and endothelium-independent mechanisms. Following prolonged mechanical ventilation, vascular alterations occur through both endothelium-dependent and -independent pathways. This is the first study, to our knowledge, demonstrating that diaphragm arteriolar dysfunction occurs consequent to prolonged mechanical ventilation and likely contributes to the severe reductions in diaphragmatic blood flow and weaning difficulties.
机械通气（MV）是一种救生干预措施，但长时间 MV（即≥6 小时）会导致膈肌血流减少和充血反应受损，其原因尚不清楚。将 4-8 月龄雌性 Sprague-Dawley 大鼠（n=118）随机分为两组：自主呼吸（SB）和 6 小时（延长）MV。MV 或 SB 后，在体外测量一级（1A）膈肌阻力小动脉的血管舒张（血流诱导、内皮依赖性和非内皮依赖性激动剂）和收缩（肌源性和α-肾上腺素能）反应，并定量测量内皮型一氧化氮合酶（eNOS）mRNA 表达。与 SB 相比，长时间 MV 后，膈肌小动脉血流诱导性舒张（SB，34.7±3.8% vs. MV，22.6±2.0%；≤0.05）、内皮依赖性舒张（通过乙酰胆碱；SB，64.3±2.1% vs. MV，36.4±2.3%；≤0.05）和非内皮依赖性舒张（通过硝普钠；SB，65.0±3.1% vs. MV，46.0±4.6%；≤0.05）显著降低。与 SB 相比，eNOS mRNA 表达减少（≤0.05）。与 SB 相比，长时间 MV 降低了去氧肾上腺素诱导的血管收缩（SB，37.3±6.7% vs. MV，19.0±1.9%；≤0.05），但不改变肌源性或被动压力反应。MV 时间延长导致静息和收缩时膈肌血流严重减少，与膈肌血管功能障碍有关，这种功能障碍通过内皮依赖性和非内皮依赖性机制发生。在长时间机械通气后，血管改变通过内皮依赖性和非内皮依赖性途径发生。据我们所知，这是第一项研究表明，膈肌小动脉功能障碍发生于长时间机械通气后，可能导致膈肌血流严重减少，并导致撤机困难。
