DeGrado T R, Holden J E, Ng C K, Raffel D M, Gatley S J
Department of Medical Physics, University of Wisconsin, Madison 53706.
Eur J Nucl Med. 1989;15(2):78-80. doi: 10.1007/BF00702623.
The use of 15-p-iodophenyl-beta-methyl-pentadecanoic acid (beta Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both beta Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, beta Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond beta Me-IPPA-CoA in the oxidative pathway.
在离体灌注的工作大鼠心脏中,评估了15-对碘苯基-β-甲基-十五烷酸(β-Me-IPPA)作为核医学研究中长链脂肪酸(LCFA)利用指标的应用。在推注β-Me-IPPA及其直链对应物15-对碘苯基-十五烷酸(IPPA)后,获得了放射性的时间进程(残留曲线)。IPPA动力学清楚地表明,肉碱棕榈酰转移酶I抑制剂2-[5(4-氯苯基)戊基]环氧乙烷-2-羧酸盐(POCA)导致脂肪酸氧化出现与血流无关的损害。相比之下,β-Me-IPPA动力学对脂肪酸氧化速率和长链脂肪酸净利用的变化不敏感。对冠状动脉流出物和心脏匀浆中放射性标记物质的分析表明,甲基化脂肪酸很容易掺入复合脂质中,但作为氧化底物较差。POCA并没有显著改变示踪剂的代谢,这表明示踪剂在氧化途径中除了β-Me-IPPA-CoA之外代谢很差。