假设化学能的供应可能不足以为心力衰竭(HF)的正常机械泵功能提供燃料。肌酸激酶(CK)反应作为心脏的主要能量储备,并且它提供的三磷酸腺苷(ATP通量)的供应在人类HF中减少。然而,在人类心脏中,CK能量供应与所消耗的机械能之间的关系从未被量化。这项研究测试了减少的CK能量供应是否与HF患者的机械工作减少有关。
心脏机械功和CK通量,单位为W/kg,使用心脏压力-容量回路在休息时非侵入性地测量机械效率,14名健康受试者和27名轻度至中度HF患者的磁共振成像和磷谱。
在HF中,静息CK通量(126±46vs.179±50W/kg,p<0.002),平均值(6.8±3.1与10.1±1.5W/kg,p<0.001)和峰值(32±14vs.48±8W/kg,p<0.001)心脏机械工作率,以及心脏机械效率(53%±16vs.79%±3,p<0.001),与健康受试者相比,都减少了三分之一。此外,心脏CK通量与静息峰值和平均机械功率相关(p<0.01),和机械效率(p=0.002)。
这些首次非侵入性发现表明,轻度至中度人类HF的心脏机械工作和效率与CKATP能量供应成比例地降低,与HF的能量剥夺假设一致。CK能量供应超过静止时的机械功,但在一定范围内,可能会限制适度的活动,因此为HF治疗提供了一个有希望的目标。
ClinicalTrials.gov标识符:NCT00181259。
It has been hypothesized that the supply of chemical energy may be insufficient to fuel normal mechanical pump function in heart failure (HF). The creatine kinase (CK) reaction serves as the heart\'s primary energy reserve, and the supply of adenosine triphosphate (ATP flux) it provides is reduced in human HF. However, the relationship between the CK energy supply and the mechanical energy expended has never been quantified in the human heart. This study tests whether reduced CK energy supply is associated with reduced mechanical work in HF patients.
Cardiac mechanical work and CK flux in W/kg, and mechanical efficiency were measured noninvasively at rest using cardiac pressure-volume loops, magnetic resonance imaging and phosphorus spectroscopy in 14 healthy subjects and 27 patients with mild-to-moderate HF.
In HF, the resting CK flux (126 ± 46 vs. 179 ± 50 W/kg, p < 0.002), the average (6.8 ± 3.1 vs. 10.1 ± 1.5 W/kg, p <0.001) and the peak (32 ± 14 vs. 48 ± 8 W/kg, p < 0.001) cardiac mechanical work-rates, as well as the cardiac mechanical efficiency (53% ± 16 vs. 79% ± 3, p < 0.001), were all reduced by a third compared to healthy subjects. In addition, cardiac CK flux correlated with the resting peak and average mechanical power (p < 0.01), and with mechanical efficiency (p = 0.002).
These first noninvasive findings showing that cardiac mechanical work and efficiency in mild-to-moderate human HF decrease proportionately with CK ATP energy supply, are consistent with the energy deprivation hypothesis of HF. CK energy supply exceeds mechanical work at rest but lies within a range that may be limiting with moderate activity, and thus presents a promising target for HF treatment.
ClinicalTrials.gov Identifier: NCT00181259 .