31P-NMR analysis of congestive heart failure in the SHHF/Mcc-facp rat heart.
31P-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 micro 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 micro 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 Pi 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 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.
Michael O'Donnell
J
J
Biophysics Program, The Ohio State University, Columbus 43210, USA.
Narayan
P
P
Bailey
M Q
MQ
Abduljalil
A M
AM
Altschuld
R A
RA
McCune
S A
SA
Robitaille
P M
PM
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003401:Creatine / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes; D051381:Rats; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
D000227:Adenine Nucleotides; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003401:Creatine