This project will test the hypothesis that pedicled grafts of skeletal muscle can be used to replace segments of ventricular myocardium. Such muscle grafts have a potential for increasing ventricular volume (in hypolastic ventricles), or replacing diseased portions of the ventricle (in ischemic heart disease). Canine skeletal muscle will be transformed from low oxidative, fast-twitch, fatigue-resistant muscle fibers to high oxidative, slow-twitch, fatigue-resistant muscle fibers by direct and motor nerve stimulation using high and low frequency electrical impulses. Slow-twitch muscle fibers are similar to myocardial muscle. The mechanism by which transformation occurs will be investigated by morphologic, histochemical and electromyographic studies including electrophoresis of different myosins. Initial studies will determine the best means to induce muscle fiber transformation (high or low frequency stimulation, direct or motor nerve) and which of 4 muscles--diaphragm, latissimus dorsi, pectoralis major or rectus abdominis--is most suitable. Skeletal muscles grafts placed in right and left ventricles will be extensively studied to determine electrical threshold pattern of activation of the ventricles, contractility of the graft, changes in size, thickness, volume, histology and histochemical characteristics of the graft and changes in blood flow. Extensive hemodynamic studies using cardiac pressure and flow measurements, angiography, echocardiography and gated blood pool scans will be made to determine the contribution of conditioned pedicled muscle grafts to ventricular contractility. Ventricular function curves and changes in myocardial contractility independent of preload and afterload will be made in animals with ventricular muscle grafts and inert teflon paches at rest, during simulated exercise and with volume loading. This comprehensive research plan should indicate whether or not pedicled skeletal muscle grafts can provide contractile substitutes for segments of myocardium.
