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Detection of myocardial medium-chain fatty acid oxidation and tricarboxylic acid cycle activity with hyperpolarized [1-13 C]octanoate.
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2020-01-06 , DOI: 10.1002/nbm.4243 Hikari A I Yoshihara 1, 2 , Jessica A M Bastiaansen 2, 3 , Magnus Karlsson 4, 5 , Mathilde H Lerche 4, 5 , Arnaud Comment 2, 6, 7 , Juerg Schwitter 1, 8
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2020-01-06 , DOI: 10.1002/nbm.4243 Hikari A I Yoshihara 1, 2 , Jessica A M Bastiaansen 2, 3 , Magnus Karlsson 4, 5 , Mathilde H Lerche 4, 5 , Arnaud Comment 2, 6, 7 , Juerg Schwitter 1, 8
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Under normal conditions, the heart mainly relies on fatty acid oxidation to meet its energy needs. Changes in myocardial fuel preference are noted in the diseased and failing heart. The magnetic resonance signal enhancement provided by spin hyperpolarization allows the metabolism of substrates labeled with carbon-13 to be followed in real time in vivo. Although the low water solubility of long-chain fatty acids abrogates their hyperpolarization by dissolution dynamic nuclear polarization, medium-chain fatty acids have sufficient solubility to be efficiently polarized and dissolved. In this study, we investigated the applicability of hyperpolarized [1-13 C]octanoate to measure myocardial medium-chain fatty acid metabolism in vivo. Scanning rats infused with a bolus of hyperpolarized [1-13 C]octanoate, the primary metabolite observed in the heart was identified as [1-13 C]acetylcarnitine. Additionally, [5-13 C]glutamate and [5-13 C]citrate could be respectively resolved in seven and five of 31 experiments, demonstrating the incorporation of oxidation products of octanoate into the tricarboxylic acid cycle. A variable drop in blood pressure was observed immediately following the bolus injection, and this drop correlated with a decrease in normalized acetylcarnitine signal (acetylcarnitine/octanoate). Increasing the delay before infusion moderated the decrease in blood pressure, which was attributed to the presence of residual gas bubbles in the octanoate solution. No significant difference in normalized acetylcarnitine signal was apparent between fed and 12-hour fasted rats. Compared with a solution in buffer, the longitudinal relaxation of [1-13 C]octanoate was accelerated ~3-fold in blood and by the addition of serum albumin. These results demonstrate the potential of hyperpolarized [1-13 C]octanoate to probe myocardial medium-chain fatty acid metabolism as well as some of the limitations that may accompany its use.
中文翻译：
用超极化的[1-13 C]辛酸酯检测心肌中链脂肪酸的氧化和三羧酸循环的活性。
在正常情况下，心脏主要依靠脂肪酸氧化来满足其能量需求。在患病和衰竭的心脏中注意到心肌燃料偏好的变化。通过自旋超极化提供的磁共振信号增强功能允许在体内实时跟踪被碳13标记的底物的代谢。尽管长链脂肪酸的低水溶性通过溶解动态核极化消除了它们的超极化，但中链脂肪酸具有足够的溶解度，可以有效地极化和溶解。在这项研究中，我们调查了超极化[1-13 C]辛酸酯在体内测量心肌中链脂肪酸代谢的适用性。扫描注入大剂量[1-13 C]辛酸酯的大鼠，在心脏中观察到的主要代谢产物被鉴定为[1-13 C]乙酰肉碱。此外，可以在31个实验中的7个和5个中分别解析[5-13 C]谷氨酸盐和[5-13 C]柠檬酸盐，这表明辛酸的氧化产物并入三羧酸循环。推注后立即观察到血压的可变下降，并且该下降与标准化的乙酰肉碱信号（乙酰肉碱/辛酸酯）的降低相关。输注前延迟的增加减轻了血压的下降，这归因于辛酸酯溶液中残留气泡的存在。在进食和禁食12小时的大鼠之间，标准化的乙酰肉碱信号没有明显差异。与缓冲液相比，通过添加血清白蛋白，血液中[1-13 C]辛酸酯的纵向松弛被加速了约3倍。这些结果证明了超极化[1-13 C]辛酸酯探测心肌中链脂肪酸代谢的潜力以及其使用可能带来的一些局限性。
更新日期：2020-02-04
中文翻译：
用超极化的[1-13 C]辛酸酯检测心肌中链脂肪酸的氧化和三羧酸循环的活性。
在正常情况下，心脏主要依靠脂肪酸氧化来满足其能量需求。在患病和衰竭的心脏中注意到心肌燃料偏好的变化。通过自旋超极化提供的磁共振信号增强功能允许在体内实时跟踪被碳13标记的底物的代谢。尽管长链脂肪酸的低水溶性通过溶解动态核极化消除了它们的超极化，但中链脂肪酸具有足够的溶解度，可以有效地极化和溶解。在这项研究中，我们调查了超极化[1-13 C]辛酸酯在体内测量心肌中链脂肪酸代谢的适用性。扫描注入大剂量[1-13 C]辛酸酯的大鼠，在心脏中观察到的主要代谢产物被鉴定为[1-13 C]乙酰肉碱。此外，可以在31个实验中的7个和5个中分别解析[5-13 C]谷氨酸盐和[5-13 C]柠檬酸盐，这表明辛酸的氧化产物并入三羧酸循环。推注后立即观察到血压的可变下降，并且该下降与标准化的乙酰肉碱信号（乙酰肉碱/辛酸酯）的降低相关。输注前延迟的增加减轻了血压的下降，这归因于辛酸酯溶液中残留气泡的存在。在进食和禁食12小时的大鼠之间，标准化的乙酰肉碱信号没有明显差异。与缓冲液相比，通过添加血清白蛋白，血液中[1-13 C]辛酸酯的纵向松弛被加速了约3倍。这些结果证明了超极化[1-13 C]辛酸酯探测心肌中链脂肪酸代谢的潜力以及其使用可能带来的一些局限性。
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