There are two broad, long term objectives of this proposed research: the first is to evaluate the potential for an indirect method of myocardial revascularization using chronically electrically stimulated skeletal muscle as a rich source of collateral blood supply; the second is to develop a skeletal muscle pump which can be used as a right ventricle. Although these studies appear directed to different ends, they share many common techniques.
Five specific aims are proposed to develop these ideas. First, the response of goat muscle to chronic electrical stimulation will be investigated and compared to that from other species. Second, the pattern of stimulation that produces the highest, chronic, skeletal muscle blood flow will be established. Third, the protective effect of collateral blood supply from a skeletal muscle wrap on prevention of myocardial ischemia induced by acute coronary occlusion will be assessed, as well as any potential for development of a significant collateral supply from skeletal muscle to myocardium in conditions of chronic myocardial ischemia. Fourth, skeletal muscle ventricles (SMV) will be developed and sodded with endothelial cells. Fifth, SMVs will be connected to the circulation to replace the right ventricle. A successful result from either aspect would have clinical relevance. Some patients with ischemic heart disease are not candidates for present methods of direct myocardial revascularization, such as CABG or PTCA, because of significant distal vessel disease. Conditioned skeletal muscle has an abundant blood supply, and by apposing it to ischemic myocardium sufficient collateral blood flow may be provided to ameliorate ischemic symptoms, and maintain myocardial function. At present not all patients with a single ventricular chamber are candidates for a fontan procedure. Creation of a skeletal muscle ventricle that could perform as a right ventricle might help these patients. Techniques employed include histochemical, biochemical and immunohistochemical analyses of conditioned muscle, measurement of skeletal muscle and myocardial blood flow with radioactive microspheres, assessment of areas at risk for myocardial infarction and areas of infarction, production of chronic myocardial ischemia with ameroid constrictors, endothelial sodding using procedures developed at Thomas Jefferson, surgical experience in connecting the skeletal muscle ventricles to the circulation, and evaluation of SMV performance.
