Sullivan M J, Green H J, Cobb F R
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Circulation. 1991 Oct;84(4):1597-607. doi: 10.1161/01.cir.84.4.1597.
Exertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients.
We evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p less than 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p greater than 0.25), indicating comparable exercise end points. At rest in patients versus normals, there was a reduction in the activity of hexokinase (p = 0.08), citrate synthetase (p less than 0.02), succinate dehydrogenase (p = 0.0007), and 3-hydroxyacyl CoA dehydrogenase (p = 0.04). In patients, leg blood flow was decreased at rest, submaximal, and maximal exercise when compared to normal subjects (all p less than 0.05), and blood lactate accumulation was accelerated. In patients, during submaximal exercise blood lactate levels were not closely related to leg blood flow but were inversely related to rest citrate synthetase activity in skeletal muscle (r = -0.74, p less than 0.05). At peak exercise there were no intergroup differences in skeletal muscle glycolytic intermediates, adenosine nucleotides, or glycogen, whereas in patients compared to normal subjects less lactate accumulation and phosphocreatine depletion were noted (both p less than 0.05), suggesting that factors other than the magnitude of phosphocreatine depletion or lactate accumulation may influence skeletal muscle fatigue in this disorder.
The results of the present study suggest that in patients with chronic heart failure reduced aerobic activity in skeletal muscle plays an important role in mediating the early onset of anaerobic metabolism during exercise. Our findings are consistent with the concept that reduced aerobic enzyme activity in skeletal muscle is, in part, responsible for determining exercise tolerance and possibly the response to chronic intervention in patients with chronic heart failure.
劳力性疲劳在慢性心力衰竭患者中经常限制运动，与骨骼肌早期无氧代谢相关。本研究旨在检查这种疾病中骨骼肌对运动的代谢反应，并确定肌肉血流减少、骨骼肌生物化学和组织学与患者无氧代谢早期发作之间的关系。
我们评估了11例慢性心力衰竭患者（射血分数21±8%）和9名正常受试者在直立自行车运动期间的腿部血流、血乳酸和骨骼肌代谢反应（通过外侧股四头肌活检）。与正常受试者相比，患者的运动峰值耗氧量降低（13.0±3.3 ml/kg/min对30.2±8.6 ml/kg/min，p<0.01），而峰值呼吸交换率和股静脉氧含量无差异（p均>0.25），表明运动终点相当。与正常受试者相比，患者休息时己糖激酶活性降低（p = 0.08）、柠檬酸合酶活性降低（p<0.02）、琥珀酸脱氢酶活性降低（p = 0.0007）和3-羟酰基辅酶A脱氢酶活性降低（p = 0.04）。与正常受试者相比，患者在休息、次最大运动和最大运动时腿部血流均降低（p均<0.05），且血乳酸积累加速。在患者中，次最大运动期间血乳酸水平与腿部血流无密切关系，但与骨骼肌休息时柠檬酸合酶活性呈负相关（r = -0.74，p<0.05）。在运动峰值时，骨骼肌糖酵解中间产物、腺苷核苷酸或糖原在组间无差异，而与正常受试者相比，患者的乳酸积累和磷酸肌酸消耗较少（p均<0.05），这表明除磷酸肌酸消耗或乳酸积累程度外的其他因素可能影响这种疾病中的骨骼肌疲劳。
本研究结果表明，在慢性心力衰竭患者中，骨骼肌有氧活动降低在运动期间介导无氧代谢早期发作中起重要作用。我们的研究结果与以下概念一致，即骨骼肌有氧酶活性降低部分负责决定运动耐力，并可能决定慢性心力衰竭患者对慢性干预的反应。
