Jeffrey F M, Alvarez L, Diczku V, Sherry A D, Malloy C R
Department of Radiology, UT Southwestern Medical Center, Mary Nell and Ralph B. Rogers Magnetic Resonance Center, Dallas, TX 75235-9085, USA.
J Cardiovasc Pharmacol. 1995 Mar;25(3):469-72. doi: 10.1097/00005344-199503000-00018.
Perhexiline maleate, originally classified as a calcium antagonist, is in use as an antianginal agent. The mechanism of its protective effect is unknown, but there is speculation that it involves a modification of myocardial substrate utilization, in which glycolytic sources are used rather than fatty acids. This hypothesis was tested by employing [13C]NMR isotopomer analysis to measure substrate selection in the working rat heart. Substrate utilization was measured from a mixture of substrates present at their physiological concentration, as follows: acetoacetate, glucose, lactate and long-chain fatty acids. Control perfusions were compared with those perfused with perhexiline. It was found that perhexiline increased lactate utilization, which reduced the extent of fatty acid and endogenous substrate oxidation. There was also a significant increase in cardiac output for a small and insignificant increase in oxygen consumption, which suggested an improvement in myocardial efficiency. Thus, it was confirmed by direct measurement that this drug does modify substrate oxidation, which suggests that further investigations of the role that this agent can play in the management of ischemic heart disease would be beneficial.
马来酸哌克昔林最初被归类为钙拮抗剂，现用作抗心绞痛药物。其保护作用机制尚不清楚，但有人推测它涉及心肌底物利用的改变，即使用糖酵解来源而非脂肪酸。通过采用[13C]NMR 同位素异构体分析来测量工作大鼠心脏中的底物选择，对这一假设进行了验证。从以生理浓度存在的底物混合物中测量底物利用情况，具体如下：乙酰乙酸、葡萄糖、乳酸和长链脂肪酸。将对照灌注与用哌克昔林灌注的情况进行比较。发现哌克昔林增加了乳酸利用，这降低了脂肪酸和内源性底物氧化的程度。在氧耗量有少量且不显著增加的情况下，心输出量也有显著增加，这表明心肌效率有所提高。因此，通过直接测量证实该药物确实改变了底物氧化，这表明进一步研究该药物在缺血性心脏病管理中所能发挥的作用将是有益的。
