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Eur J Heart Fail. 2013 Feb;15(2):130-40. doi: 10.1093/eurjhf/hfs192. Epub 2012 Dec 19.
Impaired energy metabolism has been implicated in the pathogenesis of heart failure. Hyperpolarized (13)C magnetic resonance (MR), in which (13)C-labelled metabolites are followed using MR imaging (MRI) or spectroscopy (MRS), has enabled non-invasive assessment of pyruvate metabolism. We investigated the hypothesis that if we serially examined a model of heart failure using non-invasive hyperpolarized [(13)C]pyruvate with MR, the profile of in vivo pyruvate oxidation would change throughout the course of the disease.
Dilated cardiomyopathy (DCM) was induced in pigs (n = 5) by rapid pacing. Pigs were examined using MR at weekly time points: cine-MRI assessed cardiac structure and function; hyperpolarized [2-(13)C]pyruvate was administered intravenously, and (13)C MRS monitored [(13)C]glutamate production; (31)P MRS assessed cardiac energetics [phosphocreatine (PCr)/ATP]; and hyperpolarized [1-(13)C]pyruvate was administered for MRI of pyruvate dehydrogenase complex (PDC)-mediated pyruvate oxidation via [(13)C]bicarbonate production. Early in pacing, the cardiac index decreased by 25%, PCr/ATP decreased by 26%, and [(13)C]glutamate production decreased by 51%. After clinical features of DCM appeared, end-diastolic volume increased by 40% and [(13)C]bicarbonate production decreased by 67%. Pyruvate dehydrogenase kinase 4 protein increased by two-fold, and phosphorylated Akt decreased by half. Peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase-1 gene expression decreased by a half and a third, respectively.
Despite early changes associated with cardiac energetics and (13)C incorporation into the Krebs cycle, pyruvate oxidation was maintained until DCM developed, when the heart's capacity to oxidize both pyruvate and fats was reduced. Hyperpolarized (13)C MR may be important to characterize metabolic changes that occur during heart failure progression.
能量代谢受损与心力衰竭的发病机制有关。极化（13）C 磁共振（MR）可通过磁共振成像（MRI）或光谱（MRS）对（13）C 标记代谢物进行跟踪，从而实现对丙酮酸代谢的非侵入性评估。我们假设，如果使用非侵入性极化 [(13)C]丙酮酸进行 MR 对心力衰竭模型进行连续检查，那么体内丙酮酸氧化的情况将在疾病过程中发生变化。
通过快速起搏在猪（n = 5）中诱导扩张型心肌病（DCM）。每周一次使用 MR 对猪进行检查：电影 MRI 评估心脏结构和功能；静脉内给予极化 [2-（13）C]丙酮酸，（13）C MRS 监测 [(13)C]谷氨酸的产生；（31）P MRS 评估心脏能量代谢 [磷酸肌酸（PCr）/ATP]；并给予极化 [1-（13）C]丙酮酸，用于通过 [(13)C]碳酸氢盐产生评估丙酮酸脱氢酶复合物（PDC）介导的丙酮酸氧化的 MRI。在起搏的早期，心输出量降低了 25%，PCr/ATP 降低了 26%，而 [(13)C]谷氨酸的产生降低了 51%。出现 DCM 的临床特征后，舒张末期容积增加了 40%，而 [(13)C]碳酸氢盐的产生减少了 67%。丙酮酸脱氢酶激酶 4 蛋白增加了两倍，磷酸化 Akt 减少了一半。过氧化物酶体增殖物激活受体-α和肉碱棕榈酰转移酶-1 的基因表达分别减少了一半和三分之一。
尽管与心脏能量代谢和（13）C 掺入三羧酸循环有关的早期变化，但直到 DCM 发展时，丙酮酸氧化才得以维持，此时心脏氧化丙酮酸和脂肪的能力都降低了。极化 [(13)C]MR 可能对特征代谢变化很重要，这些变化发生在心力衰竭进展过程中。
