Mechanical ventilation reduces rat diaphragm blood flow and impairs oxygen delivery and uptake.
Mechanical ventilation reduces rat diaphragm blood flow and impairs oxygen delivery and uptake.
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DOI：
10.1097/ccm.0b013e31825b933a
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发表时间：
2012-10
影响因子：
8.8
通讯作者：
Behnke BJ
中科院分区：
文献类型：
--
作者：
Davis RT 3rd;Bruells CS;Stabley JN;McCullough DJ;Powers SK;Behnke BJ
尽管机械通气（MV）是呼吸衰竭患者的救命干预措施，但延长MV通常与许多并发症（包括脱机问题）相关。在收缩骨骼肌时，氧气供应不足会限制氧化磷酸化，导致肌肉疲劳。然而，是否延长MV的结果减少动脉血，并诱导在隔膜中的O2供需不平衡仍然未知。我们测试了这一假设，即长期控制MV的结果在大鼠动脉血流量和微血管PO2的时间依赖性减少，延长MV将减少隔膜的能力，增加血流量，肌肉收缩的反应。与30分钟的MV相比，6小时的MV导致隔膜血流量减少75%（通过放射性标记的微球），这在肋间肌或高氧化性后肢肌中没有发生（例如，比目鱼肌）。隔膜微血管PO2（通过磷光淬灭）也有时间依赖性下降。此外，与30分钟的MV相比，6小时的MV显著损害了隔膜在电诱导收缩期间增加血流量的能力，导致隔膜O2摄取减少约80%。相比之下，麻醉动物6小时的自主呼吸并没有改变膈肌血流或在电诱导收缩期间增加血流的能力。这些新的重要发现表明，MV延长会导致膈肌增加血流以满足收缩活动对O2需求的能力呈时间依赖性下降，可能是难以脱机的关键因素。虽然需要额外的实验来证实，这是诱人的推测，这种呼吸机引起的肺氧合下降可能会促进缺氧诱导的膈肌纤维中活性氧的产生，并有助于呼吸机引起的膈肌萎缩和收缩功能障碍。
Although mechanical ventilation (MV) is a life-saving intervention in patients suffering from respiratory failure, prolonged MV is often associated with numerous complications including problematic weaning. In contracting skeletal muscle, inadequate O2 supply can limit oxidative phosphorylation resulting in muscular fatigue. However, whether prolonged MV results in decreased diaphragmatic blood and induces an O2 supply-demand imbalance in the diaphragm remains unknown. We tested the hypothesis that prolonged controlled MV results in a time-dependent reduction in rat diaphragmatic blood flow and microvascular PO2 and that prolonged MV would diminish the diaphragm’s ability to increase blood flow in response to muscular contractions. Compared to 30 min of MV, 6 hrs of MV resulted in a 75% reduction in diaphragm blood flow (via radiolabeled microspheres), which did not occur in the intercostal muscle or high-oxidative hindlimb muscle (e.g., soleus). There was also a time-dependent decline in diaphragm microvascular PO2 (via phosphorescence quenching). Further, when contrasted to 30 min of MV, 6 hrs of MV significantly compromised the diaphragm’s ability to increase blood flow during electrically-induced contractions which resulted in a ~80% reduction in diaphragm O2 uptake. In contrast, 6 hrs of spontaneous breathing in anesthetized animals did not alter diaphragm blood flow or the ability to augment flow during electrically-induced contractions. These new and important findings reveal that prolonged MV results in a time-dependent decrease in the ability of the diaphragm to augment blood flow to match O2 demand in response to contractile activity and could be a key contributing factor to difficult weaning. Although additional experiments are required to confirm, it is tempting to speculate that this ventilator-induced decline in diaphragmatic oxygenation could promote a hypoxia-induced generation of reactive oxygen species in diaphragm muscle fibers and contribute to ventilator-induced diaphragmatic atrophy and contractile dysfunction.