Department of Radiology and Medical Imaging University of Virginia Charlottesville VA.
Department of Experimental Physiology and Pathophysiology Medical University of Białystok Bialystok Poland.
J Am Heart Assoc. 2023 May 16;12(10):e026950. doi: 10.1161/JAHA.122.026950. Epub 2023 May 15.
Background Cardiac metabolic abnormalities are present in heart failure. Few studies have followed metabolic changes accompanying diastolic and systolic heart failure in the same model. We examined metabolic changes during the development of diastolic and severe systolic dysfunction in spontaneously hypertensive rats (SHR). Methods and Results We serially measured myocardial glucose uptake rates with dynamic 2-[F] fluoro-2-deoxy-d-glucose positron emission tomography in vivo in 9-, 12-, and 18-month-old SHR and Wistar Kyoto rats. Cardiac magnetic resonance imaging determined systolic function (ejection fraction) and diastolic function (isovolumetric relaxation time) and left ventricular mass in the same rats. Cardiac metabolomics was performed at 12 and 18 months in separate rats. At 12 months, SHR hearts, compared with Wistar Kyoto hearts, demonstrated increased isovolumetric relaxation time and slightly reduced ejection fraction indicating diastolic and mild systolic dysfunction, respectively, and higher (versus 9-month-old SHR decreasing) 2-[F] fluoro-2-deoxy-d-glucose uptake rates (Ki). At 18 months, only few SHR hearts maintained similar abnormalities as 12-month-old SHR, while most exhibited severe systolic dysfunction, worsening diastolic function, and markedly reduced 2-[F] fluoro-2-deoxy-d-glucose uptake rates. Left ventricular mass normalized to body weight was elevated in SHR, more pronounced with severe systolic dysfunction. Cardiac metabolite changes differed between SHR hearts at 12 and 18 months, indicating progressive defects in fatty acid, glucose, branched chain amino acid, and ketone body metabolism. Conclusions Diastolic and severe systolic dysfunction in SHR are associated with decreasing cardiac glucose uptake, and progressive abnormalities in metabolite profiles. Whether and which metabolic changes trigger progressive heart failure needs to be established.
背景 心肌代谢异常存在于心力衰竭中。很少有研究在同一模型中观察舒张和收缩性心力衰竭伴随的代谢变化。我们检查了自发性高血压大鼠（SHR）中舒张和严重收缩功能障碍发展过程中的代谢变化。
方法和结果 我们通过体内动态 2-[F]氟-2-脱氧-d-葡萄糖正电子发射断层扫描连续测量 9、12 和 18 个月大的 SHR 和 Wistar Kyoto 大鼠的心肌葡萄糖摄取率。心脏磁共振成像在同一大鼠中确定收缩功能（射血分数）和舒张功能（等容舒张时间）和左心室质量。在不同的大鼠中于 12 和 18 个月进行心脏代谢组学分析。在 12 个月时，与 Wistar Kyoto 心脏相比，SHR 心脏表现出等容舒张时间增加和射血分数略有降低，分别表示舒张和轻度收缩功能障碍，以及更高（与 9 个月大的 SHR 降低相比）的 2-[F]氟-2-脱氧-d-葡萄糖摄取率（Ki）。在 18 个月时，只有少数 SHR 心脏保持与 12 个月 SHR 相似的异常，而大多数则表现出严重的收缩功能障碍、舒张功能恶化和明显降低的 2-[F]氟-2-脱氧-d-葡萄糖摄取率。SHR 的左心室质量与体重比升高，严重收缩功能障碍更为明显。在 12 和 18 个月的 SHR 心脏中，心脏代谢物的变化不同，表明脂肪酸、葡萄糖、支链氨基酸和酮体代谢存在进行性缺陷。
结论 SHR 的舒张和严重收缩功能障碍与心脏葡萄糖摄取减少以及代谢物谱的进行性异常相关。代谢变化是否以及哪些变化引发进行性心力衰竭尚需确定。
