Establishment of a model to evaluate biochemical indices of skeletal muscle repai

Clinicians utilize therapeutic agents such as ultrasound in attempts to promote the repair of skeletal muscle damaged by injury or disease, yet the biochemical and physiological bases for such treatments have not been well established. Quantifiable biochemical markers of the various phases of skeletal muscle repair have not been used to assess the efficacy of such treatments or to maximize their beneficial potential. I attempted to identify objectively assayable parameters of integral events in both the degradative and early regenerative phases of skeletal muscle repair. These parameters were used to evaluate the effect of therapeutic agents on the repair process.;In this study rat anterior tibialis muscle was utilized as a model system for human muscle injury and repair. A controlled level of injury was inflicted by injection of lidocaine, a local anesthetic, or direct trauma. The initial, degradative stages of muscle repair were analyzed by periodic monitoring of serum levels of creatine kinase (EC 2.7.3.2, CK). As a measure of the progression and extent of muscle cell regeneration, tissue activity of the enzyme ornithine decarboxylase (EC 4.1.1.17, ODC) was assayed. This enzyme is rate-limiting in the biosynthesis of the polyamines essential for mammalian cell and tissue growth. Analysis of each of the biochemical markers was correlated with histological events of repair determined by light microscopy.;As part of this project I determined whether an increase in ornithine decarboxylase was an obligatory event in skeletal muscle tissue regeneration, and subsequently, used changes in the expression pattern of ODC as a marker of modifications in the repair rate of this tissue. Injured muscle tissue was treated with various therapeutic ultrasound protocols, and the biochemical indices described above were evaluated for differences from sham-treated controls in either timing or amplitude.;This study attempted to establish a model system where creatine kinase and ornithine decarboxylase can be utilized as useful indices of alterations in the progression of skeletal muscle degradation and regeneration. This system is of potential value in developing new therapeutic protocols, and it may also be used to provide greater insight into mechanisms of skeletal muscle repair and how they are regulated.