Pierce Gary L, Magyari Peter M, Aranda Juan M, Edwards David G, Hamlin Scott A, Hill James A, Braith Randy W
Department of Applied Physiology and Kinesiology, Center for Exercise Science, College of Health and Human Performance, University of Florida, Gainesville, FL, USA.
Clin Transplant. 2007 Jan-Feb;21(1):94-100. doi: 10.1111/j.1399-0012.2006.00589.x.
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.
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.
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.
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.
骨骼肌肌病是慢性心力衰竭（HF）的一个标志。表型变化包括肌球蛋白重链（MHC）纤维类型从氧化型的MHC I型向更多糖酵解型的MHC IIx纤维转变，氧化酶活性降低，糖酵解酶活性增加。然而，心脏移植后肌肉肌病是否会逆转尚不清楚。本研究的目的是确定心脏移植对终末期HF患者骨骼肌代谢酶储备和MHC纤维类型的影响。
前瞻性研究了13例HF受试者，在心脏移植前和移植后2个月进行研究，并对其中一个亚组（n = 6）在移植后8个月进行研究。对股外侧肌进行骨骼肌活检，并使用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳确定相对MHC组成。分别进行乳酸脱氢酶（LDH）、柠檬酸合酶（CS）和3-羟基酰基辅酶A脱氢酶（HACoA）酶活性测定，以评估糖酵解、氧化和β-氧化代谢酶储备。
心脏移植后2个月，LDH活性（130.5±13.3对106.1±13.2微摩尔/克湿重/分钟，p < 0.05）、CS活性（14.0±1.2对9±0.9微摩尔/克湿重/分钟，p < 0.05）和HACoA活性（4.5±0.48对3.6±0.3微摩尔/克湿重/分钟，p < 0.05）降低。在8个月时，LDH活性恢复（139.0±11微摩尔/克湿重/分钟），但与移植前相比，CS或HACoA活性未恢复。心脏移植后2个月，肌肉MHC I型百分比（28.7±3.5%对25.3±3.0%，p = 无显著性差异）、MHC IIa型百分比（33.2±2.0%对34.6±1.9%，p = 无显著性差异）或MHC IIx型百分比（38.1±2.8%对40.1±3.7%，p = 无显著性差异）纤维类型无显著变化。然而，与移植前相比（p < 0.05），移植后8个月MHC I型百分比（19.3±6.
