Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.
Physiol Genomics. 2011 Dec 16;43(24):1334-50. doi: 10.1152/physiolgenomics.00116.2011. Epub 2011 Oct 18.
Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients that is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents, corticosteroids (CS), and sepsis for 5 days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after 5 days' exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to 5 days' exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle-specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements, and sarcomeric proteins underlying the relative sparing of cranial vs. spinal nerve innervated muscles during exposure to the ICU intervention.
急性四肢瘫痪性肌病（AQM）是一种常见的危重病重症监护病房（ICU）患者获得性衰弱疾病，其特征是四肢瘫痪/四肢和躯干肌肉的广泛性无力。另一方面，咀嚼肌通常不受影响或受影响较小，但导致这种明显的肌肉特异性差异的机制尚不清楚。本研究旨在通过使用一种独特的猪模型模拟 ICU 条件，评估咀嚼肌和四肢肌肉的生理参数和基因表达谱，这些肌肉暴露于可能引发 AQM 的因素，如机械通气、固定、神经肌肉阻滞剂、皮质类固醇（CS）和脓毒症 5 天。单肌纤维横截面积和产生力的能力，即最大力与纤维横截面积的比值（比力），表明咀嚼肌单肌纤维横截面积和比力在 5 天的所有触发因素暴露后保持不变。这与四肢和躯干肌肉的观察结果形成鲜明对比，后者在 5 天的触发因素暴露后，比力明显下降。颅面和四肢肌肉之间观察到基因表达的显著差异，表明在暴露于 ICU 干预时，涉及转录和生长因子、热休克蛋白、基质金属蛋白酶抑制剂、氧化应激反应元件和肌节蛋白的高度复杂和肌肉特异性反应，从而使颅神经支配的肌肉相对于脊髓神经支配的肌肉相对不受影响。
