Measuring the link between cardiac mechanical function and metabolism during hyperpolarized 13C-pyruvate magnetic resonance experiments |
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| Institution: | 1. Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel;2. Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian 361005, China;1. Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc, Pôle de Recherche Cardiovasculaire, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium;2. Philips Clinical Research Board, Suresnes, France;3. Philips Research, Medical Imaging (Medisys), Suresnes, France;4. University Hospital of Caen, Caen, France;5. EA 4650, Caen University, FHU REMOD-VHF, Caen, France;2. Experimental MRI 7T Unit, IDIBAPS, Barcelona, Spain;4. IDIBAPS, Barcelona, Spain;5. Biophysics and Bioengineering Laboratory, University of Barcelona, Barcelona, Spain;6. Nuclear Medicine Department, Hospital Clínic, Barcelona, Spain;1. Department of Biochemistry, Medical University of Gdansk, Gdańsk, Poland;2. Department of Physiology, Medical University of Gdansk, Gdańsk, Poland;3. Institute of Applied Radiation Chemistry, Technical University of Lodz, Łódź, Poland;4. Department of Therapy Monitoring and Pharmacogenetics, Medical University of Gdansk, Gdańsk, Poland;5. Department of Surgery, Division of Cardiothoracic Surgery, University of Arizona, College of Medicine, Tuscon, USA |
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| Abstract: | PurposeThe goal of this study was to develop a methodology to investigate the relationship between contractile function and hyperpolarized (HP) 1-13C]pyruvate metabolism in a small animal model. To achieve sufficient signal from HP 13C compounds, HP 13C MRS/MRSI has required relatively large infusion volumes relative to the total blood volume in small animal models, which may affect cardiac function.MethodsEight female Sprague Dawley rats were imaged on a 4.7T scanner with a dual tuned 1H/13C volume coil. ECG and respiratory gated k-t spiral MRSI and an IDEAL based reconstruction to determine 1-13C]pyruvate metabolism in the myocardium. This was coupled with 1H cine MRI to determine ventricular volumes and mechanical function pre- and post-infusion of 1-13C]pyruvate. For comparison to the 1-13C]pyruvate experiments, three female Sprague Dawley rats were imaged with 1H cine MRI to determine myocardial function pre- and post-saline infusion.ResultsWe demonstrated significant changes in cardiac contractile function between pre- and post-infusion of 1-13C]pyruvate. Specifically, there was an increase in end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF). Additionally, the ventricular vascular coupling ratio (VVCR) showed an improvement after 1-13C]pyruvate infusion, indicating increased systolic performance due to an increased arterial load. There was a moderate to strong relationship between the downstream metabolic conversion of pyruvate to bicarbonate and a strong relationship between the conversion of pyruvate to lactate and the cardiac mechanical function response.ConclusionThe infusion of 1-13C]pyruvate resulted in demonstrable increases in contractile function which was related to pyruvate conversion to bicarbonate and lactate. The combined effects of the infusion volume and inotropic effects of pyruvate metabolism likely explains the augmentation in myocardial mechanical function seen in these experiments. Given the relationship between pyruvate metabolism and contractile function observed in this study, this methodological approach may be utilized to better understand cardiac metabolic and functional remodeling in heart disease. |
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