| The causes and symptoms of neuromuscular disorders vary significantly depending on the pathomechanism. Treatment of such disorders is in part hampered by lack of adequate tools for diagnosis, also by in many cases by a poor understanding of the underlying etiologies. Therefore, the purpose of this thesis was to develop improved methodologies to quantitatively evaluate neuromuscular disorders and, more specifically, the means to identify underlying contractile properties of the skeletal muscles which contribute to diagnosis and treatment of such disorder. This thesis consisted of in vivo human studies including those in a clinical setting and also in vitro investigation of isolated swine skeletal muscles in attempts to identify novel pharmacological therapies to treat weakness due to potential ischemia. Specifically, apparatuses and protocols were developed to quantitatively access human extremities, biceps and neck muscles, with the intention that these new approaches could be applied in clinical settings as a means to determine both progression and treatment efficacy in patients with progressive or nonprogressive neuromuscular disorders. It was determined that the reproducibility and reliability of the developed methods were within acceptable ranges, and it should be noted that the methods avoided problems associated with voluntary efforts. Both the biceps and neck muscle approaches are currently being used to evaluate diagnosis and newly developed treatment efficacy of patients in clinical settings. In regards to the potential pharmacological treatment methodology which was tested in vitro in swine skeletal muscles, it was shown that delta-opioid agonists successfully prevented ischemic insult. Additionally, hibernation induction trigger, when administered to the muscle of a non-hibernator (swine) also conferred this protective effect. More specifically, identification of effective doses and administration protocols in this project have provided guidelines for the potential application of such methodologies to patients at risk for episodic weakness such as those within an intensive care unit. |
