Quantitative Medical Imaging Section, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
Research Institute of Medical Sciences, Chonnam National University, Gwangju, Republic of Korea.
Sci Rep. 2019 Dec 5;9(1):18427. doi: 10.1038/s41598-019-54965-7.
This study aimed to investigate real-time early detection of metabolic alteration in a rat model with acute myocardial ischemia-reperfusion (AMI/R) injury and myocardial necrosis, as well as its correlation with intracellular pH level using in vivo hyperpolarized [1-C] pyruvate magnetic resonance spectroscopy (MRS). Hyperpolarized C MRS was performed on the myocardium of 8 sham-operated control rats and 8 rats with AMI/R injury, and 8 sham-operated control rats and 8 rats with AMI-induced necrosis. Also, the correlations of levels of [1-C] metabolites with pH were analyzed by Spearman's correlation test. The AMI/R and necrosis groups showed significantly higher ratios of [1-C] lactate (Lac)/bicarbonate (Bicar) and [1-C] Lac/total carbon (tC), and lower ratios of C Bicar/Lac + alanine (Ala), and C Bicar/tC than those of the sham-operated control group. Moreover, the necrosis group showed significantly higher ratios of [1-C] Lac/Bicar and [1-C] Lac/tC, and lower ratios of C Bicar/Lac + Ala and C Bicar/tC than those of the AMI/R group. These results were consistent with the pattern for in vivo the area under the curve (AUC) ratios. In addition, levels of [1-C] Lac/Bicar and [1-C] Lac/tC were negatively correlated with pH levels, whereas C Bicar/Lac + Ala and C Bicar/tC levels were positively correlated with pH levels. The levels of [1-C] Lac and C Bicar will be helpful for non-invasively evaluating the early stage of AMI/R and necrosis in conjunction with reperfusion injury of the heart. These findings have potential application to real-time evaluation of cardiac malfunction accompanied by changes in intracellular pH level and enzymatic activity.
本研究旨在通过体内 1-¹³C 丙酮酸磁共振波谱（MRS）研究急性心肌缺血再灌注（AMI/R）损伤和心肌坏死大鼠模型中代谢变化的实时早期检测及其与细胞内 pH 值的相关性。对 8 只假手术对照组大鼠和 8 只 AMI/R 损伤大鼠以及 8 只假手术对照组大鼠和 8 只 AMI 诱导坏死大鼠的心肌进行了 1-¹³C MRS 检测。采用 Spearman 相关检验分析[1-C]代谢物水平与 pH 值的相关性。AMI/R 组和坏死组的 [1-C]乳酸（Lac）/碳酸氢盐（Bicar）和 [1-C] Lac/总碳（tC）比值明显升高，C Bicar/Lac+Ala 和 C Bicar/tC 比值明显降低，与假手术对照组相比。此外，坏死组 [1-C] Lac/Bicar 和 [1-C] Lac/tC 比值明显升高，C Bicar/Lac+Ala 和 C Bicar/tC 比值明显降低，与 AMI/R 组相比。这些结果与体内曲线下面积（AUC）比值的模式一致。此外，[1-C] Lac/Bicar 和 [1-C] Lac/tC 水平与 pH 值呈负相关，而 C Bicar/Lac+Ala 和 C Bicar/tC 水平与 pH 值呈正相关。[1-C] Lac 和 C Bicar 的水平有助于结合心脏再灌注损伤，非侵入性评估 AMI/R 和坏死的早期阶段。这些发现对于实时评估伴随细胞内 pH 值和酶活性变化的心脏功能障碍具有潜在的应用价值。
