Abstract
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 [1-13C] pyruvate magnetic resonance spectroscopy (MRS). Hyperpolarized 13C 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 [1-13C] metabolites with pH were analyzed by Spearman’s correlation test. The AMI/R and necrosis groups showed significantly higher ratios of [1-13C] lactate (Lac)/bicarbonate (Bicar) and [1-13C] Lac/total carbon (tC), and lower ratios of 13C Bicar/Lac + alanine (Ala), and 13C Bicar/tC than those of the sham-operated control group. Moreover, the necrosis group showed significantly higher ratios of [1-13C] Lac/Bicar and [1-13C] Lac/tC, and lower ratios of 13C Bicar/Lac + Ala and 13C 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 [1-13C] Lac/Bicar and [1-13C] Lac/tC were negatively correlated with pH levels, whereas 13C Bicar/Lac + Ala and 13C Bicar/tC levels were positively correlated with pH levels. The levels of [1-13C] Lac and 13C 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.
Highlights
Cardiovascular diseases remain the leading cause of mortality and morbidity worldwide[1]
There were no significant differences in body weights (g) between sham-operated control rats and rats with acute myocardial ischemia-reperfusion (AMI/R) injury, and sham-operated control rats and rats with AMI-induced necrosis (319.5 ± 13.6 vs. 317.0 ± 11.7 and 318.1 ± 10.4 vs. 316.2 ± 9.8, respectively)
Animal numbers were low, we found a reasonably high overall accuracy of hyperpolarized 13C magnetic resonance spectroscopy (MRS) to differentiate AMI/R and necrosis from sham-operated control, and necrosis from AMI/R at Bicar/Lac + Ala cutoff values and Lac/Bicar cutoff values indicated by the Youden index, whereas Bicar/total carbon (tC) and Lac/tC cutoff values had a low degree of accuracy
Summary
Cardiovascular diseases remain the leading cause of mortality and morbidity worldwide[1]. Reperfusion is the goal of therapy in patients with ST-elevation myocardial infarction because the reopening of an acutely occluded coronary artery reduces the size of the myocardial infarction. This approach is associated with transient contractile dysfunction, arrhythmias, metabolic acidosis, and increased release of myocardial enzymes, which paradoxically can compound the cellular metabolic changes that occur in ischemia[4]. Early detection of the acute metabolic alterations that occur during ischemia-reperfusion injury and necrosis may further our understanding of the underlying mechanisms of cardiac disease and would aid in the development of new clinical diagnostic strategies in patients with acute myocardial infarction undergoing acute revascularizations. A few hyperpolarized 13C MRS studies[7,17] have reported changes in metabolites in an animal model of myocardial ischemia-reperfusion, to the best of our knowledge, an in vivo MRS study has not yet been done of hyperpolarized [1-13C] Pyr focusing on differential metabolic changes in both acute myocardial ischemia-reperfusion (AMI/R) injury and necrosis with different pH values for further clinical translation
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