Cardiac energy metabolism during development of hypertensive heart failure

在肥厚性心脏中，主要的心肌能量底物从脂肪酸转换为葡萄糖。然而，心肌中ATP和高能磷酸盐含量在心肌肥厚时降低。因此，肥厚心肌中有限的能量产生可能有助于心力衰竭的发展。本研究旨在探讨达尔盐敏感（DS）大鼠和耐盐（DR）大鼠心肌脂肪酸和葡萄糖代谢的一系列变化。为了评估心脏脂肪酸和葡萄糖代谢，使用^<131> i -9-甲基五酸（9MPA）和^<14> c -脱氧葡萄糖（DG）进行定量双示踪放射自显影。用薄层色谱法测定9MPA的代谢产物，用正糖-高胰岛素-葡萄糖钳法测定胰岛素刺激下的葡萄糖摄取。DS大鼠在12周龄发育为代偿性左室肥厚，18周龄发展为心力衰竭。与DR大鼠相反，DS大鼠的主要能量底物随着年龄的增长从脂肪酸转变为葡萄糖。DS大鼠β-氧化处理的9MPA代谢物与心肌总摄取的比例随着年龄的增长而下降，但DR大鼠不变。在12和18周龄的DS大鼠中，胰岛素刺激的DG摄取增加明显减弱。因此，脂肪酸氧化和胰岛素刺激的葡萄糖转运能力在非衰竭肥厚性心脏中已经受损。目前的结果表明，肥厚心脏的有限代谢能力可能在代偿性肥厚到心力衰竭的过渡中起作用。

In hypertrophic hearts, major myocardial energy substrate switches from fatty acid to glucose. However, myocardial contents of ATP and high-energy phosphates are reduced in cardiac hypertrophy. Therefore, a limited energy production in hypertrophied myocardium may contribute to the development of heart failure. The purpose of the present study was to investigate serial changes in myocardial fatty acid and glucose metabolism in Dahl salt-sensitive (DS) rats and salt-resistant (DR) rats.To evaluate cardiac fatty acid and glucose metabolism, quantitative dual-tracer autoradiography, using ^<131>I-9-methylpentadecanoic acid (9MPA), and ^<14>C-deoxyglucose (DG), was performed. Metabolic products of 9MPA were determined by a thin-layer chromatography and euglycemic hyperinsulinemic glucose clamp method was applied to determine insulin-stimulated glucose uptake. DS rats were developed to compensated LV hypertrophy at 12 weeks old, and advanced to heart failure at 18 weeks old. In contrast of DR rats, the major energy substrate switches from fatty acid to glucose with ages in DS rats. The ratio of 9MPA metabolites processed by β-oxidation to total myocardial uptake decreased with ages in DS rats, but was unchanged in DR rats. In 12 and 18 weeks old DS rats, the insulin-stimulated increases in DG uptake were markedly attenuated. Thus the capacity of fatty acid oxidation and insulin-stimulated glucose transport was already impaired in nonfailing hypertrophic heart.The present results suggest that a limited metabolic capacity of hypertrophied heart may play a role in a transition from compensated hypertrophy to heart failure.