Tuunanen Helena, Engblom Erik, Naum Alexandru, Scheinin Mika, Någren Kjell, Airaksinen Juhani, Nuutila Pirjo, Iozzo Patricia, Ukkonen Heikki, Knuuti Juhani
J Card Fail. 2006 Oct;12(8):644-52. doi: 10.1016/j.cardfail.2006.06.005.
Results on myocardial substrate metabolism in the failing heart have been contradictory. Insulin resistance, a common comorbidity in heart failure patients, and medical therapy may modify myocardial metabolism in complex fashions. Therefore, we characterized myocardial oxidative and free fatty acid (FFA) metabolism in patients with idiopathic dilated cardiomyopathy (IDCM) and investigated the contributions of insulin resistance and beta-blocker therapy.
Nineteen patients with IDCM (age 58 +/- 8 years, ejection fraction 33 +/- 8.8%) and 15 healthy controls underwent examination of myocardial blood perfusion, oxidative and FFA metabolism using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate and [(11)C]palmitate, respectively. Echocardiography was used to assess myocardial function, work, and efficiency of forward work. Insulin resistance was calculated using the homeostasis model assessment index (HOMA index) and the degree of beta-blockade was estimated with a beta-adrenoceptor occupancy test. IDCM patients were characterized by decreased cardiac efficiency (35 +/- 2 versus 57 +/- 12 mm Hg.L.g(-1), P < .0001) and reduced myocardial FFA uptake (5.5 +/- 2.0 versus 6.4 +/- 1.2 mumol.100 g(-1).min(-1), P < .05), but the FFA beta-oxidation rate constant was not changed. In the patients, myocardial FFA uptake was inversely associated with left ventricular (LV) ejection fraction (r = -0.63, P < .01), indicating that further depression of LV function induces an opposite switch to greater FFA uptake. The FFA beta-oxidation rate constant correlated positively with the HOMA index (r = 0.53, P < .05). In patients on beta-1 selective beta-blockers, beta-1 adrenoceptor occupancy correlated inversely with LV work, oxidative metabolism, and FFA uptake; similar relationships were not found in patients on nonselective beta-blocker.
Myocardial FFA metabolism is reduced in patients with IDCM. However, when LV function is further depressed and insulin resistance manifested, myocardial FFA uptake and oxidation are, in turn, upregulated. These findings may partly explain the discrepancies between previous studies about cardiac metabolism in heart failure.
关于衰竭心脏中心肌底物代谢的研究结果相互矛盾。胰岛素抵抗是心力衰竭患者常见的合并症，药物治疗可能以复杂的方式改变心肌代谢。因此，我们对特发性扩张型心肌病（IDCM）患者的心肌氧化和游离脂肪酸（FFA）代谢进行了特征分析，并研究了胰岛素抵抗和β受体阻滞剂治疗的作用。
19例IDCM患者（年龄58±8岁，射血分数33±8.8%）和15名健康对照者分别接受了正电子发射断层扫描以及使用[（15）O]H2O、[（11）C]醋酸盐和[（11）C]棕榈酸盐对心肌血流灌注、氧化和FFA代谢的检查。超声心动图用于评估心肌功能、做功和前向做功效率。使用稳态模型评估指数（HOMA指数）计算胰岛素抵抗，并通过β肾上腺素能受体占有率试验估计β受体阻滞剂的阻滞程度。IDCM患者的特征为心脏效率降低（35±2对57±12 mmHg·L·g-1，P<.0001）和心肌FFA摄取减少（5.5±2.0对6.4±1.2 μmol·100 g-1·min-1，P<.05），但FFAβ氧化速率常数未改变。在患者中，心肌FFA摄取与左心室（LV）射血分数呈负相关（r=-0.63，P<.01），表明LV功能的进一步降低会导致相反的转变，即FFA摄取增加。FFAβ氧化速率常数与HOMA指数呈正相关（r=0.53，P<.05）。在使用β1选择性β受体阻滞剂的患者中，β1肾上腺素能受体占有率与LV做功、氧化代谢和FFA摄取呈负相关；在使用非选择性β受体阻滞剂的患者中未发现类似关系。
IDCM患者的心肌FFA代谢降低。然而，当LV功能进一步降低且出现胰岛素抵抗时，心肌FFA摄取和氧化会相应上调。这些发现可能部分解释了先前关于心力衰竭心脏代谢研究之间的差异。
