Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Division, Katholieke Universiteit Leuven, Leuven, Belgium;
J Appl Physiol (1985). 2013 Sep;115(6):775-84. doi: 10.1152/japplphysiol.00302.2012. Epub 2013 Jul 11.
Controlled mechanical ventilation (CMV) is known to result in rapid and severe diaphragmatic dysfunction, but the recovery response of the diaphragm to normal function after CMV is unknown. Therefore, we examined the time course of diaphragm function recovery in an animal model of CMV. Healthy rats were submitted to CMV for 24-27 h (n = 16), or to 24-h CMV followed by either 1 h (CMV + 1 h SB, n = 9), 2 h (CMV + 2 h SB, n = 9), 3 h (CMV + 3 h SB, n = 9), or 4-7 h (CMV + 4-7 h SB, n = 9) of spontaneous breathing (SB). At the end of the experiment, the diaphragm muscle was excised for functional and biochemical analysis. The in vitro diaphragm force was significantly improved in the CMV + 3 h SB and CMV + 4-7 h SB groups compared with CMV (maximal tetanic force: +27%, P < 0.05, and +59%, P < 0.001, respectively). This was associated with an increase in the type IIx/b fiber dimensions (P < 0.05). Neutrophil influx was increased in the CMV + 4-7 h SB group (P < 0.05), while macrophage numbers remained unchanged. Markers of protein synthesis (phosphorylated Akt and eukaryotic initiation factor 4E binding protein 1) were significantly increased (±40%, P < 0.001, and ±52%, P < 0.01, respectively) in the CMV + 3 h SB and CMV + 4-7 h SB groups and were positively correlated with diaphragm force (P < 0.05). Finally, also the maximal specific force generation of skinned single diaphragm fibers was increased in the CMV + 4-7 h SB group compared with CMV (+45%, P < 0.05). In rats, reloading the diaphragm for 3 h after CMV is sufficient to improve diaphragm function, while complete recovery occurs after longer periods of reloading. Enhanced muscle fiber dimensions, increased protein synthesis, and improved intrinsic contractile properties of diaphragm muscle fibers may have contributed to diaphragm function recovery.
控制机械通气（CMV）会导致膈肌迅速而严重的功能障碍，但 CMV 后膈肌恢复正常功能的恢复反应尚不清楚。因此，我们在 CMV 的动物模型中检查了膈肌功能恢复的时间过程。健康大鼠接受 CMV 24-27 小时（n=16），或接受 24 小时 CMV 后接受 1 小时（CMV+1 h SB，n=9）、2 小时（CMV+2 h SB，n=9）、3 小时（CMV+3 h SB，n=9）或 4-7 小时（CMV+4-7 h SB，n=9）自主呼吸（SB）。实验结束时，取出膈肌进行功能和生化分析。与 CMV 相比，CMV+3 h SB 和 CMV+4-7 h SB 组的体外膈肌力明显提高（最大强直力：+27%，P<0.05 和+59%，P<0.001）。这与 IIx/b 型纤维尺寸的增加有关（P<0.05）。CMV+4-7 h SB 组中性粒细胞浸润增加（P<0.05），而巨噬细胞数量保持不变。蛋白质合成标志物（磷酸化 Akt 和真核起始因子 4E 结合蛋白 1）在 CMV+3 h SB 和 CMV+4-7 h SB 组中均显著增加（分别增加+40%，P<0.001 和+52%，P<0.01），并与膈肌力呈正相关（P<0.05）。最后，与 CMV 相比，CMV+4-7 h SB 组的去神经化单膈肌纤维的最大比力生成也增加（+45%，P<0.05）。在大鼠中，CMV 后再负荷 3 小时足以改善膈肌功能，而较长时间的再负荷会导致完全恢复。增强的肌纤维尺寸、增加的蛋白质合成和改善的膈肌肌纤维内在收缩特性可能有助于膈肌功能的恢复。
