The Physiological Basis of Rotator Cuff Muscle Rehabilitation

描述（由申请人提供）：肌腱病是骨骼肌与其骨性附着点之间连接的进行性变性。肩部是肌腱病最常见的部位，60岁以上的人中有30%经历过肩袖相关损伤。临床上，这些损伤表现为肩部疼痛、虚弱和僵硬，以及日常生活活动的障碍。肌腱病是一种进行性疾病，因此随着肌腱撕裂尺寸和损伤持续时间的增加，观察到肌肉中更严重的萎缩性变化。这些变更：肌肉收缩、萎缩、纤维化和神经损伤与不良的治疗结果相关，因为肌肉变得对常规康复有抵抗力。我们的中心假设是，肩袖撕裂引起连续的肌肉萎缩和纤维化，导致一个临界阈值，超过该阈值，康复运动复合肌肉纤维化和变性，进一步损害功能恢复。然而，与肩袖肌腱撕裂严重程度相关的肌肉的生化、细胞和机械特征在人类中的定义很差。在这项提案中，我们的目标是了解这些肌肉的结构，机械和生理特性。为了实现这一目标，Special Aim 1将使用MRI和直接组织测量来量化与肩袖撕裂和修复相关的肌肉结构变化。使用术中采集的组织，Specific Aim 2将测量整个肌肉、肌束和单个肌细胞的被动力学特性和蛋白质浓度，以确定肌肉僵硬度增加的机制。在一次明确的术前运动后，特定目标3将确定哪些患者对运动有反应，肌肉肥大、纤维化和脂肪生成表达谱。这些患者将在术后随访6个月，以测量力量和肌肉恢复情况。这些实验将阐明肌腱撕裂后肩袖肌肉的结构、力学、生理健康和适应潜力。这一贡献是重要的，因为它是连续研究的第一步，预计将导致新的运动，药理学和外科手术干预，旨在逆转阻碍患者康复的萎缩性肌肉变化。在我们看来，这项提议是创新的，因为它利用了新的组织测试和MRI方法来测量活体人类的肌肉结构、功能和适应性。由于缺乏这种机制，我们对肌腱病患者肌肉萎缩性改变的认识受到限制。它们的成功完成将对肩袖撕裂的临床治疗产生直接影响，因为它们将提供直接证据和非侵入性方法，用于识别对标准临床护理有反应和无反应的患者。从长远来看，这些数据将有助于物理治疗师 为肌腱病相关肌肉萎缩患者设计独特的个性化康复策略。

DESCRIPTION (provided by applicant): Tendinopathy is a progressive degeneration of the link between a skeletal muscle and its bony insertion. The shoulder is the most common site of tendinopathy, with 30% of individuals over 60 years of age experiencing rotator cuff-related injuries. Clinically, these injuries manifest as shoulder pain, weakness and stiffness, and impairments in activities of daily living. Tendinopathy is a progressive condition, so as tendon tear size and duration of injury increase, more severe atrophic changes in the muscle are observed. These changes: muscle retraction, atrophy, fibrosis, and nerve injury are associated with poor treatment outcomes, as muscles become resistant to conventional rehabilitation. Our central hypothesis is that rotator cuff tears induce a continuum of muscle atrophy and fibrosis, leading to a critical threshold, beyond which rehabilitation exercise compounds muscle fibrosis and degeneration, further impairing functional recovery. However, the biochemical, cellular, and mechanical characteristics of muscles associated with the spectrum of rotator cuff tendon tear severities are poorly defined in humans. In this proposal, our goal is to understand the structural, mechanical and physiological properties of these muscles. To achieve this goal, Specific Aim 1 will use MRI and direct tissue measurements to quantify muscle architectural changes associated with rotator cuff tears and repairs. Using tissue harvested intraoperatively, Specific Aim 2 will measure the whole muscle, muscle fascicle, and single muscle cell passive mechanical properties and protein-concentrations to identify the mechanism of increased muscle stiffness. Following a defined bout of pre-operative exercise, Specific Aim 3 will identify which patients respond to exercise with muscle hypertrophic, fibrotic, and adiopgenic expression profiles. These patients will be followed for six months post-operatively to measure strength and muscle recovery. These experiments will elucidate the structural, mechanical, physiological health and the adaptive potential of rotator cuff muscles after tendon tear. This contribution is significant because it is the first step in a continuum of research that is expecte to lead to novel exercise, pharmacological, and surgical interventions aimed at reversing atrophic muscle changes that obstruct patient recovery. The proposal is innovative, in our opinion, because it utilizes novel tissue testing and MRI methods to measure muscle structure, function, and adaptation in living humans. The absence of which has limited our understanding of atrophic muscle changes in all patients with tendinopathy. Their successful completion will have an immediate impact on the clinical treatment of rotator cuff tears because they will provide direct evidence and a non-invasive method for identifying patients who will respond and not respond to standard clinical care. In the long-term, these data will aid physical therapists in the design of unique, individualized rehabilitation strategies for patients with tendinopathy-related muscle atrophy.