Activity-Rest Regimen of Latissimus Dorsi Stimulation for Cardiomyoplasty: Anatomy, Isomyosins and Sustained Power of Sheep LD up to One Year

A prudent explanation of the clinical effect of dynamic cardiomyoplasty is that a minimal systolic assistance enhances the chronic elastic girdle effect of the transposed Latissimus Dorsi (LD). Slowness of the contraction-relaxation cycle and reduced power output of a fully conditioned LD limit its systolic support. Steady partial transformation of LD could increase power output by taking advantage of a faster contraction-relaxation cycle. To avoid full fast-to-slow transformation of LD, we chronically tested a daily activity-rest regimen of muscle stimulation in a simplified experimental model. To mimic loss of resting tension which occurs in cardiomyoplasty, sheep LD after tenotomy of distal aponeurosis were resutured in shortened position and ITREL neurostimulators (Medtronic) connected to intramuscular electrodes were implanted according to the Medtronic Protocol. From two weeks after surgery shortened LD were burst-stimulated either 10 or 24 hr per day, the stimulators being programmed to the settings that elicited just fatiguing contractions in the shortened LD. Full-day activated LD were stimulated six months and then left unstimulated for additional six months, while the half-day activated muscles were stimulated up to one year. Two weeks after surgery and two, four, six and twelve months after stimulation, fusion frequency of tetanic contraction, power output, and fatigue resistance of LD were assessed. To allow histological and molecular characterization of the two groups of stimulated muscles, LD were biopsied at six months of stimulation, and sheep sacrificed at twelve months to collect macrosopic anatomical records and perform molecular and histological analyses of proximal, intermediate and distal muscle specimens. After one year of 10 hr/day electrostimulation the gross anatomy of the LD were substantially conserved in comparison with contralateral, normal muscles (about 10% atrophy accompanied by minor fat infiltration and fibrosis). Isomyosin analysis shown that even after one year of stimulation the 10 hr/day stimulated LD contained large amounts of fast type myosin, in particular MHC2A, the isoform of fast-oxidative fibers, less prone to fatigue than the type 2B fibers of which normal LD of adult sheep is very rich. Though after six months of 24 hr/day stimulation LD were fully converted to type 1 myosin, after additional six months of resting these LD were white in appearance, atrophic (about 40%), fibrotic, and their isomyosin pattern as mixed as the LD stimulated 10 hr/day for twelve months. Accordingly, after four and six months of stimulation the frequency of tetanic fusion was higher (i.e., the contraction-relaxation cycle was faster) in 10 hr/day stimulated LD than in 24 hr/day stimulated LD; the difference disappeared at one year since the fusion frequency of the rested LD recovered to values of the one-year 10 hr/day stimulated LD. Of foremost importance is the fact that from two-month up to one-year of stimulation the sustained power output per muscle of the 10 hr /day stimulated LD (that is of the daily rested muscle) is three to four times higher than that of the 24 hr/day activated LD. From two and at least up to twelve months of stimulation the sustained power of the "daily-rested" LD become higher than that of the heart at rest. In conclusion, results of our activity-rest daily regimen are encouraging: sheep LD loses very low contractile mass, and its power is equal or bigger than that of the left ventricle, since it seems to achieve a stable intermediate state of fast-to-slow transformation when stimulated