Submitted on February 23, 2009
Revised on April 22, 2009
Accepted on May 7, 2009
Abnormal energetics and ATP depletion in pressure-overload mouse hearts: in vivo high-energy phosphate concentration measures by non-invasive magnetic resonance
Ashish Gupta1, Vadappuram P Chacko2, and Robert G. Weiss3*
1 Johns Hopkins
2 The Johns Hopkins University
3 Johns Hopkins University
* To whom correspondence should be addressed. E-mail: rweiss{at}jhmi.edu.
31P magnetic resonance spectroscopy (MRS) offers a unique means to non-invasively quantify the major cardiac high-energy phosphates, creatine phosphate (PCr) and adenosine triphosphate (ATP) that are critical for normal myocardial contractile function and viability. Spatially localized 31P MRS has been used to quantify the in vivo PCr/ATP of murine hearts, including those with pressure-overload hypertrophy induced by thoracic aortic constriction (TAC). To date there has been no approach for measuring the absolute tissue concentrations of PCr and ATP in the in vivo mouse heart which promise a better understanding of high-energy metabolism. A method to quantify in vivo murine myocardial concentrations of PCr and ATP utilizing an external reference is described, validated, and applied to normal and TAC hearts. This new method does not prolong the scan times in mice beyond those previously required to measure PCr/ATP. The new method renders [ATP] of 5.0±0.9 (mean±S.D.) and [PCr] of 10.4±1.4 µmol/gram-wet-wt in normal mouse hearts (n=7) and significantly lower values in TAC hearts (n=10) of 4.0±0.8 and 6.7±2.0 µmol/gram-wet-wt for [ATP] (p<0.04) and [PCr] (p<0.001), respectively. The in vivo MR [ATP] results are in good agreement with those obtained using an in vitro enzyme luminescent assay of perchloric acid extracts of the same hearts. In conclusion, a validated 31P MRS method for quantifying [ATP] and [PCr] in the in vivo mouse heart using spatial localization and an external reference is described and used to demonstrate significant reductions in not only PCr/ATP but in [ATP] in hypertrophied TAC hearts.
