Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy
Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy
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DOI：
10.1152/ajpheart.00887.2007
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发表时间：
2007-12-01
影响因子：
4.8
通讯作者：
Recchia, Fabio A.
中科院分区：
文献类型：
--
作者：
Neglia, Danilo;De Caterina, Alberto;Recchia, Fabio A.
在静息状态下，衰竭的心脏将燃料使用转向更高的葡萄糖和更低的游离脂肪酸（FFA）氧化。我们假设扩张型心肌病（DCM）患者的慢性代谢异常与心肌葡萄糖摄取的正常增加和起搏应激时心脏机械效率的维持有关。在10名DCM患者和6名对照者中，我们通过血管内超声测量冠状动脉血流，并采集动脉和冠状静脉窦血液。通过输注[H-3]油酸盐和[C-13]乳酸盐并测量氧和代谢物的跨心肌动静脉差异，在基线、以130次/min心房起搏期间和恢复15 min时测定心肌代谢。在基线时，DCM患者表现为冠状动脉血流降低，FFA摄取和氧化减少，碳水化合物优先利用。在起搏期间，对照受试者的葡萄糖摄取增加了106%，但DCM患者的葡萄糖摄取与基线相比没有变化。DCM患者的乳酸释放增加了122%，但对照组没有增加。DCM患者的心脏机械效率在基线时与对照组相比没有差异，但在应激期间低34%。两组起搏均未改变脂肪酸摄取和氧化。我们的研究结果表明，在DCM中有优先利用碳水化合物，这是与减少流量和氧气消耗在休息和受损的能力，增加葡萄糖摄取在应力。这些代谢异常可能导致进行性心脏恶化，并代表了旨在调节心脏底物利用的治疗策略的目标。
Under resting conditions, the failing heart shifts fuel use toward greater glucose and lower free fatty acid (FFA) oxidation. We hypothesized that chronic metabolic abnormalities in patients with dilated cardiomyopathy (DCM) are associated with the absence of the normal increase in myocardial glucose uptake and maintenance of cardiac mechanical efficiency in response to pacing stress. In 10 DCM patients and 6 control subjects, we measured coronary flow by intravascular ultrasonometry and sampled arterial and coronary sinus blood. Myocardial metabolism was determined at baseline, during atrial pacing at 130 beats/min, and at 15 min of recovery by infusion of [H-3] oleate and [C-13]lactate and measurement of transmyocardial arteriovenous differences of oxygen and metabolites. At baseline, DCM patients showed depressed coronary flow, reduced uptake and oxidation of FFA, and preferential utilization of carbohydrates. During pacing, glucose uptake increased by 106% in control subjects but did not change from baseline in DCM patients. Lactate release increased by 122% in DCM patients but not in control subjects. Cardiac mechanical efficiency in DCM patients was not different compared with control subjects at baseline but was 34% lower during stress. Fatty acid uptake and oxidation did not change with pacing in either group. Our results show that in DCM there is preferential utilization of carbohydrates, which is associated with reduced flow and oxygen consumption at rest and an impaired ability to increase glucose uptake during stress. These metabolic abnormalities might contribute to progressive cardiac deterioration and represent a target for therapeutic strategies aimed at modulating cardiac substrate utilization.