31P NMR analysis of congestive heart failure in the SHHF/Mce-facp rat heart

P-31-NMR was used to monitor myocardial bioenergetics in compensated and failing SHHF/MCC-fa(cp) (SHF) rat hearts. The SHHF/Mcc-fa(cp) (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 mu mol/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 mu mol/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 P-i and a drop in PCr. Compensated SHF hearts, however, were able to increase rate pressure products (RRP, mmHg x beats/min) from 44.5 +/- 1.4 to 66.6 +/- 3.4 K with dobutamine infusion, whereas hearts in endstage 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. (C) 1998 Academic Press Limited.