CONTRACTION OF SKINNED FIBERS OF CARDIOMYOPATHIC HAMSTER

心肌病仓鼠皮纤维的收缩

• 批准号: 3156645
• 负责人: JAGDISH GULATI
• 金额: $ 13.38万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3156645
• 关键词: cellular pathology; congestive heart failure; genetic strain; human tissue; ionic strengths; isoproterenol; muscle contraction; muscle pharmacology; muscular dystrophy; myocardium disorder; pathology; prazosin; sarcoplasmic reticulum; striated muscles; verapamil

The overall objective of this project is to evaluate the intracellular mechanisms which alter the skeletal muscle function during the known progression of muscle dystrophies in genetically inbred cardiomyopathic Syrian hamsters and in humans with Duchhene muscular dystrophy. This strain of hamsters provides a reliably reproducible model of muscular dystrophy and congestive heart failure, and allows systematic studies of the myopathic processes. Human biopsy studies would allow direct application of this knowledge to the disease. These studies will be made with simplified skinned fiber preparations of muscles to rule out the complicating effects of heterogeneity and extracellular connective tissue. Such preparations will be obtained from psoas (fast muscle) and soleus (slow muscle) fibers in hamsters and from biopsies of quadriceps and gastrocnemius muscles and Duchhene patients. One specific objective is to measure the contraction properties of preparations of randomly selected fibers from each of the muscles, to determine a range of contraction properties within a given muscle and effect of the disease on this distribution. The physiological studies will be correlated with a morphological and histochemical changes in the sampled muscle as well as in the fiber studied. Therefore, the study will help with better characterizing the muscle disease and provide critical tests of the various hypotheses for pathogenesis of myopathy. The Ca and Sr sensitivity of force development and of intrinsic shortening speed will be measured to evaluate the changes in the regulation mechanism in the disease at several selected stages of development. Similarly, the sensitivity of these parameters to ionic strength will be determined to evaluate changes in properties of the specific rate constants of the cross-bridge turnover mechanism. Such studies will be made of the contraction transients as well and will be carried out for 30 days, 75 days, 150 days and 300 days hamsters. Another long term objective of the project is to evaluate the effects of therapeutic drugs (verapamil, isoproteronal and prazosin) on the various contraction derived from these studies of this project will help in the understanding as well as the cure of muscular dystrophy and also possibly of the myocardial failure in congestive disease.

本项目的总体目标是评估细胞内 改变骨骼肌功能的机制， 遗传性近交系心肌病性肌营养不良的进展 叙利亚仓鼠和Duchhene肌营养不良症患者。 这 仓鼠品系提供了一种可靠的可重复模型， 营养不良和充血性心力衰竭，并允许系统研究 肌病的过程 人体活检研究将允许直接 将这些知识应用于疾病。 将进行这些研究 用简化的皮肤纤维制备肌肉， 异质性和细胞外结缔组织的复杂影响。 这些制剂将从腰肌（快肌）和比目鱼肌中获得 (slow肌肉）纤维和来自四头肌的活组织检查， 腓肠肌和Duchhene患者。 一个具体目标是 测量随机选择的制备物的收缩性质， 每一块肌肉的纤维，以确定收缩范围 特定肌肉内的特性以及疾病对其的影响 分布 生理学研究将与 在取样的肌肉中的形态学和组织化学变化以及 纤维研究。 因此，研究将有助于更好地 描述肌肉疾病的特征，并提供各种 肌病发病机制假说。 Ca和Sr的敏感性 力的发展和内在的缩短速度将被测量， 评估疾病调节机制的变化， 选择发展阶段。 同样，这些敏感性 将确定离子强度的参数，以评估 跨桥翻转比速率常数的性质 机制 这样的研究也将由收缩瞬态 将分别执行30天、75天、150天和300天 仓鼠 该项目的另一个长期目标是评估 治疗药物（维拉帕米、异丙孕酮和哌唑嗪）对 从本项目的这些研究中得出的各种收缩将有助于 了解和治疗肌肉萎缩症， 可能是充血性疾病中的心肌衰竭。