Background: Reduced levels of creatine and total adenine nucleotides (sum of ATP, ADP and AMP) are hallmarks of chronic
heart failure and restoring these pools is predicted to be beneficial by maintaining the diseased heart in a more favourable
energy state. Ribose supplementation is thought to support both salvage and re-synthesis of adenine nucleotides by
bypassing the rate-limiting step. We therefore tested whether ribose would be beneficial in chronic heart failure in control
mice and in mice with elevated myocardial creatine due to overexpression of the creatine transporter (CrT-OE).
Methods and Results: Four groups were studied: sham; myocardial infarction (MI); MI+ribose; MI+CrT-OE+ribose. In a pilot
study, ribose given in drinking water was bioavailable, resulting in a two-fold increase in myocardial ribose-5-phosphate
levels. However, 8 weeks post-surgery, total adenine nucleotide (TAN) pool was decreased to a similar amount (8–14%) in all
infarcted groups irrespective of the treatment received. All infarcted groups also presented with a similar and substantial
degree of left ventricular (LV) dysfunction (3-fold reduction in ejection fraction) and LV hypertrophy (32–47% increased
mass). Ejection fraction closely correlated with infarct size independently of treatment (r2 = 0.63, p<0.0001), but did not
correlate with myocardial creatine or TAN levels.
Conclusion: Elevating myocardial ribose and creatine levels failed to maintain TAN pool or improve post-infarction LV
remodeling and function. This suggests that ribose is not rate-limiting for purine nucleotide biosynthesis in the chronically
failing mouse heart and that alternative strategies to preserve TAN pool should be investigated
