Chronic high-dose creatine feeding does not attenuate left ventricular remodeling in rat hearts post-myocardial infarction

Objective: In heart failure, cardiac energy metabolism is compromised. The failing myocardium is characterized by reduced contents of both phosphoryla ted (phosphocreatine) and non-phosphorylated (free) creatine content as wel l as decreased energy reserve via creatine kinase (creatine kinase reaction velocity). These changes may contribute to cardiac dysfunction. The purpos e of the present study was to determine whether chronic feeding with high-d ose dietary creatine prevents the derangement of energy metabolism and the development of left ventricular remodeling in a rat model of heart failure, i.e. post-myocardial infarction (MI). Methods and results: Rats were subje cted to sham operation or left coronary artery ligation. Surviving rats wer e fed with 0% (untreated) or 3% creatine (related to weight of diet) for 8 weeks. Creatine feeding increased serum creatine levels significantly simil ar to 2-fold. Thereafter, hearts were isolated, perfused and left ventricul ar pressure-volume curves obtained. Steady state and dynamic (CK reaction v elocity) high-energy phosphate metabolism was determined with P-31 NMR spec troscopy. In both MI groups (treated n=8, untreated n=7), pressure-volume c urves were shifted right- and downward compared to both sham groups (treate d n=5, untreated 11=7), i.e. creatine had no effect on left ventricular rem odeling. Likewise, similar reductions of phosphocreatine, free creatine and creatine kinase reaction velocity (untreated sham 12.0+/-0.7 mmol/1Xs; unt reated MI 7.8+/-0.7*; treated sham 13.6+/-1.0; treated MI 7.2+/-1.1*; *p<0. 025 sham vs. MI) were found in both MI groups. Conclusions: Chronic creatin e feeding of post-MI rats is ineffective in preventing the functional and e nergetic derangements occurring post-MI. Inspite of increased serum creatin e levels, neither the normal nor the failing heart accumulates additional c reatine. (C) 1999 Elsevier Science B.V. All rights reserved.