Biochemical transformation of canine skeletal muscle for use in cardiac-assist devices.
Skeletal muscle has an inherent biochemical phenotypic plasticity that provides the possibility for it to be remodeled into a "heart-like" muscle for use in cardiac-assist devices. The purpose of this study was to chronically stimulate skeletal muscle electrically to transform the biochemical capacities of the three major subcellular systems (i.e., metabolic, calcium regulating, and contractile) to resemble those of heart muscle. The latissimus dorsi muscle (LDM) of mongrel dogs weighing 22-27 kg was stimulated via the thoracodorsal nerve at 2 Hz for 6-8 wk. This stimulation protocol reduced the phosphorylase (glycogenolytic) and phosphofructokinase (glycolytic) activities by 70%. The aerobic (citrate synthase activity) and fatty acid oxidative (3-hydroxyacyl-CoA dehydrogenase activity) capacities were not significantly increased by chronic stimulation and remained at about one-fourth those in the canine heart. The calcium-dependent sarcoplasmic reticulum adenosinetriphosphatase (ATPase) activity in the microsomal fraction, which was sixfold greater in the nonstimulated LDM than in the heart, was reduced by electrical stimulation to a level similar to that of the dog heart. The contractile capacity was evaluated by determining the percentage of types I and II fibers, the myofibrillar ATPase activity, and the proportion of myosin isoforms. The transformed muscle was comprised of 93 +/- 2% type I fibers, a myofibrillar ATPase activity similar to that in heart with primarily a slow-twitch muscle myosin isoform. In conclusion, electrical stimulation of canine LDM at 2 Hz for 6-8 wk resulted in two of the three biochemical systems, which confer physiological expression and fatigue resistance to muscle being transformed to resemble those of the myocardium.
Ianuzzo
C D
CD
Department of Biology and Physical Education, York University, North York, Ontario, Canada.
Hamilton
N
N
O'Brien
P J
PJ
Desrosiers
C
C
Chiu
R
R
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004285:Dogs; D004558:Electric Stimulation; D006353:Heart-Assist Devices; D006706:Homeostasis; D009119:Muscle Contraction; D009132:Muscles / Q000502:physiology*; D009206:Myocardium; D009210:Myofibrils / Q000201:enzymology; D010641:Phenotype; D010732:Phosphofructokinase-1 / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology
D015094:3-Hydroxyacyl CoA Dehydrogenases; D002950:Citrate (si)-Synthase; D006005:Phosphorylases; D010732:Phosphofructokinase-1; D000252:Calcium-Transporting ATPases; D002118:Calcium