Energy Deregulation Precedes Alteration in Heart Energy Balance in Young Spontaneously Hypertensive Rats: A Non Invasive In Vivo 31P-MR Spectroscopy Follow-Up Study

• Published in: PloS one Vol. 11; no. 9; p. e0162677
• Main Authors: Deschodt-Arsac, Veronique, Arsac, Laurent, Magat, Julie, Naulin, Jerome, Quesson, Bruno, Dos Santos, Pierre
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01-09-2016
• Subjects: Abnormalities; Adenosine triphosphate; Adrenergic receptors; Age; Animal models; ATP; Biology and Life Sciences; Calcium; Calcium signalling; Cardiology and cardiovascular system; Cardiomyocytes; Cardiovascular disease; Coils; Contamination; Coronary artery disease; Deregulation; Drug delivery systems; Energy; Energy balance; Heart; Heart diseases; Human health and pathology; Hypertension; Hypertrophy; In vivo methods and tests; Injection; Isoproterenol; Kinases; Laboratory animals; Life Sciences; Magnetic resonance imaging; Magnetic resonance spectroscopy; Mammals; Medicine and Health Sciences; Metabolism; Metabolites; Musculoskeletal system; Organs; Rats; Research and Analysis Methods; Rodents; Signal transduction; Spectroscopy; Spectrum analysis; Tachycardia; Time constant; Tissues and Organs; Ventricle
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0162677

Introduction Gradual alterations in cardiac energy balance, as assessed by the myocardial PCr/ATP-ratio, are frequently associated with the development of cardiac disease. Despite great interest for the follow-up of myocardial PCr and ATP content, cardiac MR-spectroscopy in rat models in vivo is challenged by sensitivity issues and cross-contamination from other organs. Methods Here we combined MR-Imaging and MR-Spectroscopy (Bruker BioSpec 9.4T) to follow-up for the first time in vivo the cardiac energy balance in the SHR, a genetic rat model of cardiac hypertrophy known to develop early disturbances in cytosolic calcium dynamics. Results We obtained consistent 31P-spectra with high signal/noise ratio from the left ventricle in vivo by using a double-tuned (31P/1H) surface coil. Reasonable acquisition time (<3.2min) allowed assessing the PCr/ATP-ratio comparatively in SHR and age-matched control rats (WKY): i) weekly from 12 to 21 weeks of age; ii) in response to a bolus injection of the ß-adrenoreceptor agonist isoproterenol at age 21 weeks. Discussion Along weeks, the cardiac PCr/ATP-ratio was highly reproducible, steady and similar (2.35±0.06) in SHR and WKY, in spite of detectable ventricular hypertrophy in SHR. At the age 21 weeks, PCr/ATP dropped more markedly (-17.1%±0.8% vs. -3,5%±1.4%, P<0.001) after isoproterenol injection in SHR and recovered slowly thereafter (time constant 21.2min vs. 6.6min, P<0.05) despite similar profiles of tachycardia among rats. Conclusion The exacerbated PCr/ATP drop under ß-adrenergic stimulation indicates a defect in cardiac energy regulation possibly due to calcium-mediated abnormalities in the SHR heart. Of note, defects in energy regulation were present before detectable abnormalities in cardiac energy balance at rest.