本公眾號(hào)每天分享一篇最新一期Anesthesia & Analgesia等SCI雜志的摘要翻譯，敬請(qǐng)關(guān)注并提出寶貴意見
Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats
背景與目的：通氣患者使用的麻醉藥物在阻礙膈肌功能中具有重要作用，它可能對(duì)撤機(jī)過(guò)程產(chǎn)生負(fù)面作用，進(jìn)而增加患者的死亡率。右美托咪定具有抗氧化和抗蛋白水解的特性，但同時(shí)也會(huì)降低肌肉對(duì)葡萄糖，這一過(guò)程將會(huì)損害膈肌的肌力。本研究驗(yàn)證了右美托咪定可能抑制機(jī)械通氣所致膈肌功能障礙的假設(shè)。
方法：將24只大鼠分為三組（每組8只）。前兩組大鼠行機(jī)械通氣24?小時(shí)，同時(shí)使用右美托咪啶或戊巴比妥鈉維持鎮(zhèn)靜，簡(jiǎn)稱干預(yù)組。第三組直接處死大鼠作為對(duì)照。測(cè)量膈肌肌力、肌纖維形態(tài)以及蛋白水解標(biāo)記物，蛋白氧化和脂質(zhì)過(guò)氧化，鈣穩(wěn)態(tài)的標(biāo)記物，和葡萄糖轉(zhuǎn)運(yùn)蛋白4（GLUT-4）水平。
結(jié)果：與對(duì)照組相比，兩組大鼠經(jīng)橫截面積校正后計(jì)算的膈肌肌力均顯著降低，而右美托咪定組與戊巴比妥鈉組相比肌力顯著降低（例如：100赫茲：-18%，p＜0.0001）。與戊巴比妥鈉組相比，右美托咪啶組沒(méi)有發(fā)生膈肌萎縮，但蛋白氧化水平增高（200% vs.73%，p= 0.0015），且引起肌肉萎縮的F-box蛋白上調(diào)減少（149% vs. 374%，P＜0.001），GLUT-4轉(zhuǎn)位減少（-73%，P＜0.0005）。同時(shí)激活鈣依賴性蛋白酶的自噬，并和戊巴比妥鈉相似，可產(chǎn)生脂質(zhì)過(guò)氧化作用。
結(jié)論：機(jī)械通氣24小時(shí)期間使用右美托咪定鎮(zhèn)靜，將惡化機(jī)械通氣所致的膈肌功能障礙。機(jī)制可能與損傷GLUT-4轉(zhuǎn)位有關(guān)。右美托咪啶雖能防止膈肌纖維萎縮，但并不能抑制氧化應(yīng)激和蛋白水解途徑的激活。
Breuer T, Bleilevens C, Rossaint R, et al
Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats.[J]
Anesthesiology, 2018, 128(4):1.
BACKGROUND:Anesthetics in ventilated patients are critical as any cofactor hampering diaphragmatic function may have a negative impact on the weaning progress and therefore on patients’mortality. Dexmedetomidine may display antioxidant and antiproteolytic properties, but it also reduced glucose uptake by the muscle, which may impair diaphragm force production. This study tested the hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic dysfunction.
METHODS:Twenty-four rats were separated into three groups (n = 8/group). Two groups were mechanically ventilated during either dexmedetomidine or pentobarbital exposure for 24?h, referred to as interventional groups. A third group of directly euthanized rats served as control. Force generation, fiber dimensions, proteolysis markers, protein oxidation and lipid peroxidation, calcium homeostasis markers, and glucose transporter–4 (Glut-4) translocation were measured in the diaphragm.
RESULTS:Diaphragm force, corrected for cross-sectional area, was significantly decreased in both interventional groups compared to controls and was significantly lower with dexmedetomidine compared to pentobarbital (e.g., 100 Hz: –18%, P < 0.0001). In contrast to pentobarbital, dexmedetomidine did not lead to diaphragmatic atrophy, but it induced more protein oxidation (200% vs. 73% in pentobarbital, P = 0.0015), induced less upregulation of muscle atrophy F-box (149% vs. 374% in pentobarbital, P < 0.001) and impaired Glut-4 translocation (–73%, P < 0.0005). It activated autophagy, the calcium-dependent proteases, and caused lipid peroxidation similarly to pentobarbital.
CONCLUSIONS:Twenty-four hours of mechanical ventilation during dexmedetomidine sedation led to a worsening of ventilation-induced diaphragm dysfunction, possibly through impaired Glut-4 translocation. Although dexmedetomidine prevented diaphragmatic fiber atrophy, it did not inhibit oxidative stress and activation of the proteolytic pathways.
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