Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Division, Katholieke Universiteit Leuven, Leuven, Belgium.
Crit Care Med. 2011 Apr;39(4):777-82. doi: 10.1097/CCM.0b013e318206cca9.
Controlled mechanical ventilation results in diaphragmatic dysfunction, and oxidative stress has been shown to be an important contributor to ventilator-induced diaphragm dysfunction. We hypothesized that the administration of an antioxidant, N-acetylcysteine, would restore the redox balance in the diaphragm and prevent against the deleterious effects of controlled mechanical ventilation.
Randomized, controlled experiment.
Basic science animal laboratory.
Male Wistar rats, 14 wks old.
Anesthetized rats were submitted for 24 hrs to either spontaneous breathing receiving 150 mg/kg N-acetylcysteine (SBNAC) or saline (SBSAL) or to controlled mechanical ventilation receiving 150 mg/kg N-acetylcysteine (MVNAC) or saline (MVSAL).
After 24 hrs of controlled mechanical ventilation, diaphragmatic force production was significantly lower in MVSAL compared with all groups. Importantly, administration of N-acetylcysteine completely abolished this controlled mechanical ventilation-induced diaphragmatic contractile dysfunction. Diaphragmatic protein oxidation was significantly increased after 24 hrs of controlled mechanical ventilation (+53%, p < .01) in MVSAL animals, whereas administration of N-acetylcysteine prevented this controlled mechanical ventilation-induced oxidative stress. Diaphragmatic 20S proteasome activity was increased in MVSAL (+62%, p < .05). Further, compared with SBSAL, diaphragm caspase-3 activity was significantly increased in MVSAL (+279%, p < .001), and N-acetylcysteine treatment provided partial protection against caspase-3 activation. Diaphragmatic calpain activity was significantly increased after controlled mechanical ventilation (+137%, p < .001) in MVSAL animals, but N-acetylcysteine treatment protected against this event. Finally, significant negative correlations existed between calpain activity and diaphragm force production (r from -0.56 to -0.49, p < .05).
These data show that the administration of N-acetylcysteine protects the diaphragm from the deleterious effects of controlled mechanical ventilation. Specifically, N-acetylcysteine prevents against controlled mechanical ventilation-induced diaphragmatic oxidative stress and proteolysis and abolishes controlled mechanical ventilation-induced diaphragmatic contractile dysfunction.
控制机械通气会导致膈肌功能障碍，氧化应激已被证明是呼吸机诱导膈肌功能障碍的一个重要因素。我们假设抗氧化剂 N-乙酰半胱氨酸的给药将恢复膈肌的氧化还原平衡，并防止控制机械通气的有害影响。
随机对照实验。
基础科学动物实验室。
14 周龄雄性 Wistar 大鼠。
麻醉大鼠接受 24 小时自主呼吸，给予 150mg/kg N-乙酰半胱氨酸（SBNAC）或生理盐水（SBSAL），或接受 24 小时控制机械通气，给予 150mg/kg N-乙酰半胱氨酸（MVNAC）或生理盐水（MVSAL）。
在接受 24 小时控制机械通气后，MVSAL 组的膈肌收缩力明显低于所有组。重要的是，给予 N-乙酰半胱氨酸完全消除了这种控制机械通气诱导的膈肌收缩功能障碍。与 SBSAL 相比，24 小时控制机械通气后，MVSAL 动物的膈肌蛋白氧化显著增加（+53%，p<.01），而给予 N-乙酰半胱氨酸可防止这种控制机械通气诱导的氧化应激。与 SBSAL 相比，MVSAL 中的膈肌 20S 蛋白酶体活性增加（+62%，p<.05）。此外，与 SBSAL 相比，MVSAL 中的膈肌半胱天冬酶-3 活性显著增加（+279%，p<.001），N-乙酰半胱氨酸治疗提供了对半胱天冬酶-3 激活的部分保护。控制机械通气后，MVSAL 动物的膈肌钙蛋白酶活性显著增加（+137%，p<.001），但 N-乙酰半胱氨酸治疗可防止这种情况。最后，钙蛋白酶活性与膈肌收缩力之间存在显著的负相关（r 从-0.56 到-0.49，p<.05）。
这些数据表明，给予 N-乙酰半胱氨酸可保护膈肌免受控制机械通气的有害影响。具体而言，N-乙酰半胱氨酸可防止控制机械通气诱导的膈肌氧化应激和蛋白水解，并消除控制机械通气诱导的膈肌收缩功能障碍。
