Bontemps L, Demaison L, Dubois F, Pernin C, Mathieu J P, Vidal M, Comet M, Cuchet P
Laboratoire de Physiologie Animale, CNRS UA 632, Saint-Martin-d'Hères, France.
Int J Rad Appl Instrum B. 1987;14(5):459-65. doi: 10.1016/0883-2897(87)90110-3.
In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.
为了通过外部检测研究心肌代谢，从不同区室放射性的时间-活度曲线获得了关于γ发射碘化脂肪酸（IHA）代谢的定量信息。然后建立了一个四室数学模型；室0、1、2和3分别对应血管内IHA、细胞内IHA、酯化形式以及IHA线粒体氧化产生的碘化物。我们将该模型应用于脂肪酸氧化抑制剂POCA（2-[5-(4-氯苯基)戊基]-环氧乙烷-2-羧酸盐）影响的研究。用含有浓度不断增加的POCA的 Krebs 液灌注离体大鼠心脏20分钟。然后在冠状动脉网络入口处推注IHA。记录心脏放射性水平30分钟，并模拟不同浓度POCA下IHA在四个室中的分布情况。该药物似乎增加了IHA在心肌中的滞留，并减缓了降解和储存速度；这些变化呈剂量依赖性。这些结果与细胞内分析所得结果一致。所提出的方法可靠且灵敏，是心脏代谢药理学研究的一个有趣实验。
