An alternative to mechanical ventricular assist devices, heart transplantation, and conventional pharmacotherapy is needed as a treatment for the 400,000 patients each year that develop irreversible congestive heart failure (CHF). This revised application addresses all of the Study Section's suggestions and describes research which is designed to determine the effect of cardiomyoplasty (CMP) upon morbidity and mortality in dogs with spontaneously occurring congestive cardiomyopathy; a condition that closely mimics its human counterpart but progresses over an 18 month period to the point of 100% mortality. The research is the out-. growth of extensive preliminary work that includes: the discovery of an electrical stimulation method for conditioning skeletal muscle to be fatigue resistant without loss of contractile force; the determination of optimal electrical stimulation methods for skeletal muscle when used for cardiac assistance; the design and construction of a prototype implantable and functionally responsive pacemaker to stimulate translocated skeletal muscle that is used in CMP procedures; and the effect of CMP in chronically implanted healthy dogs and dogs with heart failure. In addition, a series of acute and chronic studies performed in our laboratory and elsewhere have shown the feasibility of skeletal muscle powered circulatory assistance in healthy dogs. We now propose a random, prospective study to examine the effect of CMP, using the latissimus dorsi muscle, upon survival in dogs with progressive, degenerative cardiomyopathy. The study is designed to investigate the mechanism by which CMP may provide benefit since the subjective improvement observed in the more than 130 human patients that have undergone CMP procedures has not consistently been associated with objective data that shows circulatory assistance. Specifically, we will determine whether the enveloping muscle simply serves as an external stent to the failing, dilated heart or whether the contractile force of the muscle is necessary to produce hemodynamic changes. We will monitor cardiac output, central venous pressure, left and right ventricular end diastolic pressures, pulmonary capillary wedge pressure, and left ventricular ejection fraction at frequent intervals after CMP surgery in dogs that have no stimulated tetanic contractions of the translocated muscle, and in operated dogs that do have stimulated tetanic contracts of the translocated muscle. The proposed research will be conducted by an experienced and qualified interdisciplinary team, supported by extramural consultation with: one of the most experienced surgeons approved to perform CMP in the United States; a cardiologist to support our clinical followup; and an anesthesiologist to support the operative procedure. The results of this research will provide essential data for existing and future human clinical trials of this promising treatment modality for intractable chronic heart failure.
| Geddes, L A; Janas, W; Cook, J et al. (1994) Stroke volume with dynamic cardiomyoplasty during ventricular fibrillation in the acute dog. Jpn Heart J 35:73-80 |
| Voytik, S L; Przyborski, M; Badylak, S F et al. (1993) Differential expression of muscle regulatory factor genes in normal and denervated adult rat hindlimb muscles. Dev Dyn 198:214-24 |
