Energy Deregulation Precedes Alteration in Heart Energy Balance in Young Spontaneously Hypertensive Rats: A Non Invasive In Vivo31P-MR Spectroscopy Follow-Up Study.
BACKGROUND
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
Veronique
V
Deschodt-Arsac
L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
Laurent
L
Arsac
L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
Julie
J
Magat
L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
Jerome
J
Naulin
L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
Bruno
B
Quesson
L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France; Hôpital cardiologique Haut-Lévêque, CHU de Bordeaux, Pessac, France.
Pierre
P
Dos Santos
D000255:Adenosine Triphosphate / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D007545:Isoproterenol / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000318:Adrenergic beta-Agonists; D010725:Phosphocreatine; D010758:Phosphorus; D000255:Adenosine Triphosphate; D007545:Isoproterenol