Effect of heart transplantation on skeletal muscle metabolic enzyme reserve and fiber type in end-stage heart failure patients

Abstract

Background: Skeletal muscle myopathy is a hallmark of chronic heart failure (HF). Phenotypic changes involve shift in myosin heavy chain (MHC) fiber type from oxidative, MHC type I, towards more glycolytic MHC IIx fibers, reductions in oxidative enzyme activity, and increase in glycolytic enzyme activity. However, it is unknown if muscle myopathy is reversed following heart transplantation. The purpose of this study was to determine the effect of heart transplantation on skeletal muscle metabolic enzyme reserve and MHC fiber type in end-stage HF patients.

Methods: Thirteen HF subjects were prospectively studied before and two months after heart transplantation and a subgroup (n = 6) at eight months after transplantation. Skeletal muscle biopsy of the vastus lateralis was performed and relative MHC composition was determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Lactate dehydrogenase (LDH), citrate synthase (CS), and 3-hydroxyacyl-CoA-dehydrogenase (HACoA) enzyme activity assays were performed to assess glycolytic, oxidative, and beta-oxidative metabolic enzyme reserves, respectively.

Results: Lactate dehydrogenase activity (130.5 +/- 13.3 vs. 106.1 +/- 13.2 micromol/g wet wt/min, p < 0.05), CS activity (14.0 +/- 1.2 vs. 9 +/- 0.9 micromol/g wet wt/min, p < 0.05), and HACoA activity (4.5 +/- 0.48 vs. 3.6 +/- 0.3 micromol/g wet wt/min, p < 0.05) decreased two months after heart transplantation. At eight months, LDH activity was restored (139.0 +/- 11 micromol/g wet wt/min), but not CS or HACoA activity compared with before transplantation. There was no significant change in muscle %MHC type I (28.7 +/- 3.5% vs. 25.3 +/- 3.0%, p = NS), %MHC type IIa (33.2 +/- 2.0% vs. 34.6 +/- 1.9%, p = NS), or %MHC type IIx (38.1 +/- 2.8% vs. 40.1 +/- 3.7%, p = NS) fiber type two months after heart transplantation. However, %MHC type I (19.3 +/- 6.6%) was decreased and %MHC type IIx (51.0 +/- 6.5%) was increased at eight months after (p < 0.05) compared with before transplantation.

Conclusions: Skeletal muscle glycolytic, oxidative, and beta-oxidative enzymatic reserves are diminished early after heart transplantation, with reduced oxidative capacity persisting late in the first year. The myopathic MHC phenotype present in end-stage HF persists early in the post-operative state and declines further by eight months.