Altered systemic ketone body metabolism in advanced heart failure.
Altered systemic ketone body metabolism in advanced heart failure.
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发表时间：
2011
影响因子：
0.9
通讯作者：
Ajit H. Janardhan;Jane Chen;P. Crawford
中科院分区：
文献类型：
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作者：
Ajit H. Janardhan;Jane Chen;P. Crawford
心力衰竭是一种全身性疾病，其中心肌和骨骼肌都表现出能量代谢的改变。衰竭的心肌表现为游离脂肪酸和葡萄糖的利用受损，这是心肌能量产生的主要底物。酮体通常对能量平衡有适度的贡献，但心力衰竭时酮体的血清浓度升高。为了解晚期心力衰竭患者的酮体代谢情况，我们直接测定了11例接受电生理检查的晚期心力衰竭患者和10例健康对照者的心脏和骨骼肌的酮体利用率，并测定了动脉、冠状窦和中心静脉床的代谢物浓度，以得出心肌和血管肌肉的酮体利用率。正如预期，心力衰竭患者的平均心肌动静脉氧差显著增加（8.3 ± 0.4 mL/dL，对照组为7 ± 0.5 mL/dL; P = 0.05）。虽然平均心肌酮体提取率相对不变，心力衰竭患者的骨骼肌酮体利用率显著低于对照组（0.49 ± 0.05 vs 0.54 ± 0.06，P = 0.53）（0.18 ± 0.06，对照组0.4 ± 0.04; P = 0.01）。在这项初步研究中，心力衰竭与酮体代谢的组织特异性改变有关。在晚期心力衰竭中，肾脏-肌肉酮体利用受损，而心肌酮体利用得以保留。未来的研究需要确定酮体代谢是否作为心力衰竭中骨骼肌病变和疲劳的动态定量生物标志物。
Heart failure is a systemic disease in which both myocardium and skeletal muscle exhibit alterations of energy metabolism. Failing myocardium exhibits impaired utilization of free fatty acids and glucose, which are major substrates for myocardial energy production. Ketone bodies normally provide a modest contribution to energy balance, but serum concentrations of ketone bodies are elevated in heart failure. To profile ketone body metabolism in advanced heart failure, we directly measured ketone body utilization by heart and skeletal muscle.Metabolite concentrations in arterial, coronary sinus, and central venous beds were measured to derive myocardial and skeletal-muscle ketone body utilization in 11 patients with advanced heart failure and 10 healthy control subjects who were undergoing electrophysiologic procedures. As expected, the mean myocardial arteriovenous oxygen difference was significantly increased in the heart-failure patients (8.3 ± 0.4 mL/dL, vs 7 ± 0.5 mL/dL in the control subjects; P = 0.05). Although the mean myocardial ketone body extraction ratio was relatively unchanged (0.49 ± 0.05 in heart-failure patients vs 0.54 ± 0.06 in control subjects, P = 0.53), skeletal-muscle ketone body utilization was markedly lower in the heart-failure patients (0.18 ± 0.06, vs 0.4 ± 0.04 in control subjects; P = 0.01).In this preliminary study, heart failure was associated with tissue-specific alteration of ketone body metabolism. In advanced heart failure, skeletal-muscle ketone body utilization was impaired, whereas myocardial ketone body utilization was preserved. Future studies are needed to determine whether ketone body metabolism serves as a dynamic quantitative biomarker of skeletal myopathy and fatigue in heart failure.