Abstract 12881: Noninvasive In Vivo Assessment of Cardiac Metabolism in Dobutamine-stressed Ischemic Rat Hearts Using Hyperpolarized 13 C MRI

Abstract

Introduction and Hypothesis: Conventional metabolic imaging methods such as PET, dobutamine stress echo or late gadolinium enhancement do not directly detect the functional state of the critical organelle in oxidative metabolism, the mitochondrion. Hyperpolarized (HP) 13 C-metabolic imaging has been used to assess mitochondrial function in preclinical models and is an exciting new imaging method for evaluating the ischemic myocardium noninvasively. This study aims to evaluate myocardial response to dobutamine stress in ischemic rat hearts using HP-[1- 13 C]pyruvate. Methods: Metabolism of HP[1- 13 C]pyruvate was investigated in male SD rats in four groups: 1. normal myocardium (NM), 2. ischemic myocardium (IM), 3. NM+dobutamine, 4. IM+dobutamine. The myocardial ischemic model was developed by partial occlusion of the coronary artery as described in earlier studies by others. For dobutamine stress HP-MRS, intra-peritoneal injection of 1.5 mg/kg of dobutamine was administered before positioning the animal in the MRI scanner. 13 C data were acquired 7 days after the surgery in a 4.7 T MRI scanner using a Varian 60 mm dual-tuned 1 H/ 13 C linear volume coil. Anatomical 1 H images were acquired for slice planning and positioning. 13 C intensity maps were generated and displayed as overlays on grayscale 1 H images. In separate experiments, in vivo HP- 13 C-MRS data acquisition was initiated immediately after the pyruvate injection. Results: The HP signals from [1- 13 C]lactate, [1- 13 C]alanine, and 13 C-bicarbonate were detected in real-time 13 C spectra from hearts following injection of HP[1- 13 C]pyruvate. In hearts with partial coronary ligation, the MRS data were acquired from a mixture of ischemic and nonischemic myocardium. A 27% decrease in bicarbonate production was observed in hearts with ischemic myocardium compared to control hearts. After stimulation of NM hearts with dobutamine, less bicarbonate was produced from HP-pyruvate likely due to an increased contribution of other endogenous substrates to acetyl-CoA. Production of bicarbonate was unchanged in IM hearts following adrenergic stimulation. Conclusions: Our results demonstrated that decreased oxidative metabolism of pyruvate as a result of myocardial ischemia and dobutamine stress.