Functional assessment of skeletal muscle ventricles after pumping for up to four years in circulation

Abstract

Background. The successful treatment of cardiac failure by heart transplantation is severely limited by the shortage of donor organs, and alternative surgical approaches are needed. An experimental approach that holds considerable promise is the skeletal muscle ventricle (SMV), an auxiliary blood pump formed from a pedicled graft of latissimus dorsi muscle and connected to the circulation in a cardiac assist configuration. Adaptive transformation, or conditioning, by electrical stimulation enables the skeletal muscle to perform a significant proportion of cardiac work indefinitely without fatigue. Methods. In 10 dogs, SMVs were constructed from the latissimus dorsi muscle, lined internally with pericardium, and conditioned by electrical stimulation to induce fatigue resistant properties. The SMVs were connected to the descending thoracic aorta via two 12-mm Gore-Tex conduits and the aorta was ligated between the two grafts. The SMV was stimulated to contract during the diastolic phase of alternate cardiac cycles. The animals were monitored at regular intervals. Results. At initial hemodynamic assessment, SMV contraction augmented mean diastolic blood pressure by 24.6% (from 61 ± 7 to 76 ± 9 mm Hg). Presystolic pressure was reduced by 15% (from 60 ± 8 to 51 ± 7 mm Hg) after an assisted beat. Four animals died early, 1 from a presumed arrhythmia, and 3 during propranolol-induced hypotension. The other 6 animals survived for 273, 596, 672, 779, 969, 1,081, and 1,510 days. Diastolic augmentation was 27.4% at 1 year (93 ± 9 vs 73 ± 6 mm Hg; n = 5), 34.7% at 2 years (85 ± 6 vs 63 ± 7 mm Hg; n = 3), 21.2% (89 ± 10 vs 73 ± 8 mm Hg; n = 2) at 3 years, and 34.5% (78 vs 58 mm Hg; n = 1) after 4 years in circulation. After 4 years, the isolated SMV was able to maintain a pressure of over 80 mm Hg while ejecting fluid at 20 mL/s. No animal showed evidence of SMV rupture or thromboembolism. Conclusions. The SMVs in this study provided effective and stable hemodynamic assistance over an extended period of time. There was no evidence that the working pattern imposed on the muscular wall of the SMV compromized its viability. Areas of fibrofatty degeneration were suggestive of early damage that future protocols should seek to minimize.