31P-NMR Analysis of Congestive Heart Failure in the SHHF/Mcc-facpRat Heart

31P-NMR was used to monitor myocardial bioenergetics in compensated and failing SHHF/MCC-facp(SHF) rat hearts. The SHHF/Mcc-facp(spontaneous hypertension and heart failure) rat is a relatively new genetic model in which all individuals spontaneously develop congestive heart failure, most during the second year of life. Failing SHF rat hearts displayed a pronounced decrease in resting PCr:ATP ratios (P<0.001), which was explained by a significant (P<0.0001) drop in total creatine (47.2±3.1 nmol/mg protein) v age matched controls (106±3 nmol/mg protein). In end stage failure, NMR determined PCr was 2.9±0.1 μmol/g wet weight under basal conditions. In contrast, 6- and 20-month-old controls and compensated SHFs had PCr values of 5.3±0.1, and 5.1±0.5 and 5.1±0.2 μmol/g wet weight. Both compensated and failing SHF hearts were metabolically compromised when the rate pressure product (RPP) was increased, as evidenced by an increase in Piand a drop in PCr. Compensated SHF hearts, however, were able to increase rate pressure products (RRP, mmHg×beats/min) from 44.5±1.4 to 66.6±3.4 K with dobutamine infusion, whereas hearts in end-stage failure were able to increase their RPP from baseline values of 27±4 K to only 37±7 K. The data indicate that a pronounced decline in PCr and total creatine signals the transition from compensatory hypertrophy to decompensation and failure in the SHF rat model of hypertensive cardiomyopathy.