DELINEATION OF MYOCARDIAL OXYGEN UTILIZATION WITH CARBON-11-LABELED ACETATE

DELINEATION OF MYOCARDIAL OXYGEN UTILIZATION WITH CARBON-11-LABELED ACETATE
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DOI:
10.1161/01.cir.76.3.687
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发表时间:
1987-09-01
期刊:
影响因子:
37.8
通讯作者:
BERGMANN, SR
BERGMANN, SR
中科院分区:
医学1区
文献类型:
--
作者:
BROWN, M;MARSHALL, DR;BERGMANN, SR

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虽然正电子发射断层扫描(PET)与标记的脂肪酸划定梗死面积,并允许定性评估脂肪酸的利用,量化的氧化代谢是有限的,在缺血和再灌注期间的脂肪酸利用模式的复杂变化。由于心肌对乙酸盐的代谢没有葡萄糖或棕榈酸盐复杂,我们在37个用改良的Krebs-Henseleit缓冲液灌注的离体兔心脏中表征了放射性标记的乙酸盐的利用动力学,并在人体中进行了初步的断层摄影研究。(14 C-乙酸盐)表明,对照心脏(n = 4)中乙酸盐的稳态提取分数平均为61.5 +/- 4.0%,缺血心脏(n = 4)中为93.6 +/- 0.9%,缺血60分钟后再灌注的心脏为54.8 ± 4.0%(n = 3)。根据静脉流出物中14 CO2的流出率评估的14 C-乙酸盐氧化与不同代谢条件下的耗氧率密切相关(r = .97,p小于.001)。此外,在所有化学物质中的总14 C外排率(反映了心肌示踪剂的总清除率)和14 CO2外排率之间未观察到显著差异。在正常和缺血心肌中使用伽马探针外部测量的11 C-乙酸盐清除率与直接在流出液中测量的14 C-乙酸盐清除率(r = 0.99,p小于0.001)和总体心肌耗氧量(r = 0.95,p小于0.001)密切相关。PET显示11 C-醋酸盐在人心肌中的蓄积和清除动力学与体外放射性标记醋酸盐的蓄积和清除动力学相当。因此,外部可检测的11 C-乙酸清除率提供了心肌氧化代谢的定量指标,尽管中间代谢模式的变化会混淆常规使用的示踪剂(如葡萄糖和脂肪酸)对结果的解释。
Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man. Results of initial experiments with carbon-14-labeled acetate (14C-acetate) indicated that the steady-state extraction fraction of acetate averaged 61.5 +/- 4.0% in control hearts (n = 4), 93.6 +/- 0.9% in hearts rendered ischemic (n = 4), and 54.8 +/- 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of 14C-acetate, assessed from the rate of efflux of 14CO2 in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p less than .001). In addition, no significant differences were observed between rates of efflux of total 14C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of 14CO2. Clearance of 11C-acetate, measured externally with gamma probes in normal and ischemic myocardium, correlated closely with clearance of 14C-acetate measured directly in the effluent (r = .99, p less than .001) and with overall myocardial oxygen consumption (r = .95, p less than .001). Accumulation and clearance of 11C-acetate from human myocardium with PET demonstrated kinetics comparable to those seen with radiolabeled acetate in vitro. Thus externally detectable clearance of 11C-acetate provides a quantitative index of myocardial oxidative metabolism despite variation in the patterns of intermediary metabolism that confounds interpretation of results with conventionally used tracers such as glucose and fatty acid.