Adaptation of energy metabolism of canine latissimus dorsi muscle in response to chronic electrical stimulation

Transformation of the latissimus dorsi (LD) muscle from a fast-twitch, fatigue-prone to a fatigue-resistant ("heart-like") muscle, necessary to allow its application in cardiac assist devices, can be induced by chronic electrical stimulation. In adult dogs we studied the nature and time course of myofibrillar and metabolic adaptations in the LD muscle when exposed in situ to 24 weeks of continuous electrical stimulation. In addition, the metabolic properties of the stimulated muscle were compared with those of canine cardiac muscle. The proportion of immunohistochemically identified type I fibres increased on stimulation from 28% to 80%, while that of type II fibres decreased from 69% to 16%. Fibres of intermediate type (IIC and IC) appeared transiently; the highest levels were found between 4 and 8 weeks of stimulation. The activities of fructose-6-phosphate kinase and lactate dehydrogenase (LDH), which before stimulation were similar to those in heart, decreased to 18% and 34% of their initial values respectively. However, the LDH isozyme pattern changed towards that typical for cardiac muscle. These changes indicate a markedly decreased flux capacity through the glycolytic pathway which, however, is directed more towards the oxidative conversion of substrates. The mitochondrial capacity (maximal palmitate oxidation and pyruvate dehydrogenase complex activities) of the muscle did not change and remained at a level less than half of that of cardiac ventricular muscle. Contents of adenine nucleotides and endogenous substrates were maintained during stimulation. No further changes in the observed adaptations occurred after week 12 of stimulation.