Imaging Regional Metabolic Changes in the Ischemic Rat Heart In Vivo Using Hyperpolarized [1-13C]Pyruvate.

We evaluated the use of hyperpolarized 13C magnetic resonance imaging (MRI) in an open-chest rat model of myocardial infarction to image regional changes in myocardial metabolism. In total, 10 rats were examined before and after 30 minutes of occlusion of the left anterior descending coronary artery using hyperpolarized [1-13C]pyruvate. Cardiac metabolic images of [1-13C]pyruvate and its metabolites [1-13C]lactate, [1-13C]alanine, and [13C]bicarbonate were obtained before and after ischemia. Significant reduction in the [1-13C]alanine and [1-13C]lactate signals were observed in the ischemic region post ischemia. The severity of the ischemic insult was verified by increased blood levels of troponin I and by using late contrast-enhanced MRI that showed enhanced signal in the ischemic region. This study shows that hyperpolarized MRI can be used to image regional metabolic changes in the in vivo rat heart in an open-chest model of ischemia reperfusion. Hyperpolarized MRI enables new possibilities for evaluating changes in cardiac metabolism noninvasively and in real time, which potentially could be used for research to evaluate new treatments and metabolic interventions for myocardial ischemia and to apply knowledge to future application of the technique in humans.

Enhancing the [13C]bicarbonate signal in cardiac hyperpolarized [1-13C]pyruvate MRS studies by infusion of glucose, insulin and potassium.

A change in myocardial metabolism is a known effect of several diseases. MRS with hyperpolarized (13)C-labelled pyruvate is a technique capable of detecting changes in myocardial pyruvate metabolism, and has proven to be useful for the evaluation of myocardial ischaemia in vivo. However, during fasting, the myocardial glucose oxidation is low and the fatty acid oxidation (ß-oxidation) is high, which complicates the interpretation of pyruvate metabolism with the technique. The aim of this study was to investigate whether the infusion of glucose, insulin and potassium (GIK) could increase the myocardial glucose oxidation in the citric acid cycle, reflected as an increase in the [(13)C]bicarbonate signal in cardiac hyperpolarized [1-(13)C]pyruvate MRS measurements in fasted rats. Two groups of rats were infused with two different doses of GIK and investigated by MRS after injection of hyperpolarized [1-(13)C]pyruvate. No [(13)C]bicarbonate signal could be detected in the fasted state. However, a significant increase in the [(13)C]bicarbonate signal was observed by the infusion of a high dose of GIK. This study demonstrates that a high [(13)C]bicarbonate signal can be achieved by GIK infusion in fasted rats. The increased [(13)C]bicarbonate signal indicates an increased flux of pyruvate through the pyruvate dehydrogenase enzyme complex and an increase in myocardial glucose oxidation through the citric acid cycle.