Tikunov B, Levine S, Mancini D
Department of Medicine, Columbia Presbyterian Medical Center, New York, NY 10032, USA.
Circulation. 1997 Feb 18;95(4):910-6. doi: 10.1161/01.cir.95.4.910.
During rest and exercise, patients with heart failure hyperventilate; therefore, the diaphragm can be viewed as undergoing constant moderate-intensity exercise. Accordingly, we hypothesized that heart failure elicits adaptations in the diaphragm similar to those elicited by endurance exercise in the limb muscles of normal subjects.
Costal diaphragmatic biopsy samples were obtained from 7 normal subjects (age, 36 +/- 20 years) and 10 patients (age, 50 +/- 6 years; left ventricular ejection fraction, 18 +/- 8%) at the time of transplant or left ventricular assist-device placement. We measured the distribution of myosin heavy chain isoforms I, IIa, and IIb by SDS gel electrophoresis. We also measured the activities of the following enzymes: citrate synthase, a marker of oxidative metabolism; beta-hydroxyacyl-CoA dehydrogenase, a marker of lipolytic metabolism; and lactate dehydrogenase, a marker of glycolytic metabolism. In normal subjects, the distribution of myosin heavy chain isoforms I, IIa, and IIb was 43 +/- 2%, 40 +/- 2%, and 17 +/- 1%, respectively. In contrast, in heart failure subjects, the fiber distribution was 55 +/- 2%, 38 +/- 2%, and 7 +/- 2% for types I, IIa, and IIb, respectively. Therefore, in heart failure, myosin heavy chain I is increased (P < .0001) and myosin heavy chain IIb decreased from normal levels (P < .001). Additionally, citrate synthase activity (normal, 0.33 +/- 0.14; heart failure, 0.54 +/- 0.21 mumol.min-1.mg protein-1; P < .05) and beta-hydroxyacyl-CoA dehydrogenase activity (normal, 0.27 +/- 0.04; heart failure, 0.38 +/- 0.02 mumol.min-1.mg protein-1; P < .05) were greater in heart failure patients than in normal subjects, whereas lactate dehydrogenase activity was significantly less in heart failure patients than in normal subjects (normal, 11.6 +/- 4.6; heart failure,: 4.3 +/- 2.2 mumol.min-1.mg protein-1; P < .01).
In the diaphragm in heart failure, there is a shift from fast to slow myosin heavy chain isoforms with an increase in oxidative capacity and a decrease in glycolytic capacity. These diaphragmatic muscle changes are consistent with those elicited by endurance training of the limb muscles in normal subjects.
在休息和运动期间，心力衰竭患者会过度通气；因此，可认为膈肌在进行持续的中等强度运动。据此，我们推测心力衰竭会引起膈肌的适应性变化，类似于正常受试者肢体肌肉耐力运动所引发的变化。
在心脏移植或植入左心室辅助装置时，从7名正常受试者（年龄36±20岁）和10名患者（年龄50±6岁；左心室射血分数18±8%）获取肋部膈肌活检样本。我们通过SDS凝胶电泳测量肌球蛋白重链同工型I、IIa和IIb的分布。我们还测量了以下酶的活性：柠檬酸合酶，氧化代谢的标志物；β-羟酰基辅酶A脱氢酶，脂解代谢的标志物；以及乳酸脱氢酶，糖酵解代谢的标志物。在正常受试者中，肌球蛋白重链同工型I、IIa和IIb的分布分别为43±2%、40±2%和17±1%。相比之下，在心力衰竭受试者中，I型、IIa型和IIb型纤维分布分别为55±2%、38±2%和7±2%。因此，在心力衰竭时，肌球蛋白重链I增加（P < 0.0001），肌球蛋白重链IIb从正常水平下降（P < 0.001）。此外，柠檬酸合酶活性（正常，0.33±0.14；心力衰竭，0.54±0.21 μmol·min⁻¹·mg蛋白⁻¹；P < 0.05）和β-羟酰基辅酶A脱氢酶活性（正常，0.27±0.04；心力衰竭，0.38±0.02 μmol·min⁻¹·mg蛋白⁻¹；P < 0.05）在心力衰竭患者中高于正常受试者，而乳酸脱氢酶活性在心力衰竭患者中显著低于正常受试者（正常，11.6±4.6；心力衰竭，4.3±2.2 μmol·min⁻¹·mg蛋白⁻¹；P < 0.01）。
在心力衰竭患者的膈肌中，存在从快肌球蛋白重链同工型向慢肌球蛋白重链同工型的转变，氧化能力增加，糖酵解能力降低。这些膈肌肌肉变化与正常受试者肢体肌肉耐力训练所引发的变化一致。
