Molecular Medicine, National Heart and Lung Institute, Imperial College, London, UK.
Crit Care Med. 2013 Apr;41(4):982-9. doi: 10.1097/CCM.0b013e318274671b.
Acute muscle wasting in the critically ill is common and causes significant morbidity. In a novel human model of acute muscle wasting following cardiac surgery, known or potential circulating modulators of muscle mass--insulin-like growth factor-1, myostatin, and growth and differentiation factor-15--were measured over a week. It was hypothesized that patients who developed acute muscle wasting would show distinct patterns of change in these mediators.
A prospective longitudinal observational study of high-risk elective cardiac surgical patients identifying, by ultrasound, those developing muscle wasting.
Tertiary cardiothoracic referral center: Royal Brompton Hospital, London, UK.
Forty-two patients undergoing elective high-risk cardiothoracic surgery.
Circulating insulin-like growth factor-1, myostatin, and growth and differentiation factor-15 were assayed preoperatively and over the first week postoperatively. The ability of growth and differentiation factor-15 to cause muscle wasting in vitro was determined in C2C12 myotubes.
Of the 42 patients, 23 (55%) developed quadriceps atrophy. There was an acute decrease in insulin-like growth factor-1 and unexpectedly myostatin, known mediators of muscle hypertrophy and atrophy, respectively. By contrast, plasma growth and differentiation factor-15 concentrations increased in all patients. This increase in growth and differentiation factor-15 was sustained at day 7 in those who developed muscle wasting (day 7 compared with baseline, p<0.01), but recovered in the nonwasting group (p>0.05). Insulin-like growth factor-1 did not recover in those who developed muscle wasting (day 7 compared with baseline, p<0.01) but did in the nonwasting group (p>0.05). Finally, we demonstrated that growth and differentiation factor-15 caused atrophy of myotubes in vitro.
These data support the hypothesis that acute muscle loss occurs as a result of an imbalance between drivers of muscle atrophy and hypertrophy. Growth and differentiation factor-15 is a potential novel factor associated with muscle atrophy, which may become a therapeutic target in patients with ICU acquired paresis and other forms of acute muscle wasting.
危重病患者的急性肌肉消耗很常见，会导致严重的发病率。在心脏手术后发生急性肌肉消耗的新型人体模型中，测量了已知或潜在的循环肌肉质量调节剂-胰岛素样生长因子-1、肌肉生长抑制素和生长分化因子-15-在一周内的变化。假设发生急性肌肉消耗的患者在这些介质中会显示出明显的变化模式。
对接受高风险择期心脏手术的高危患者进行前瞻性纵向观察性研究，通过超声识别出发生肌肉消耗的患者。
英国伦敦皇家布朗普顿医院的三级心胸转诊中心。
42 名接受择期高危心胸手术的患者。
在术前和术后第一周测量循环胰岛素样生长因子-1、肌肉生长抑制素和生长分化因子-15。在 C2C12 肌管中测定生长分化因子-15 引起肌肉消耗的能力。
在 42 名患者中，有 23 名（55%）出现股四头肌萎缩。分别为肌肉肥大和萎缩的已知调节剂胰岛素样生长因子-1 和肌肉生长抑制素，急性下降。相比之下，所有患者的血浆生长分化因子-15 浓度均升高。在发生肌肉消耗的患者中，这种生长分化因子-15 的增加在第 7 天持续（与基线相比，第 7 天，p<0.01），但在非消耗组中恢复（p>0.05）。在发生肌肉消耗的患者中，胰岛素样生长因子-1 未恢复（与基线相比，第 7 天，p<0.01），但在非消耗组中恢复（p>0.05）。最后，我们证明生长分化因子-15 在体外引起肌管萎缩。
这些数据支持这样一种假设，即急性肌肉损失是由于肌肉萎缩和肥大的驱动因素之间的不平衡所致。生长分化因子-15 是一种与肌肉萎缩相关的潜在新型因子，它可能成为 ICU 获得性瘫痪和其他形式的急性肌肉消耗患者的治疗靶点。
