Recovery of postischemic myocardial ATP levels and hexosemonophosphate shunt activity

Abstract

Recovery of myocardial ATP levels after a period of ischemia is slow, requiring several days to return to normal. The biochemical limitation for ATP recovery appears to be the availability of the adenine nucleotide (AN) precursor, phosphoribosylpyrophosphate (PRPP), which is produced by the phosphorylation of ribose in the hexosemonophosphate shunt (HMP). In fact, ATP precursors, in particular ribose, have been shown to enhance the rate of postischemic ATP recovery. Infusion of exogenous ribose bypasses the rate-limiting steps in the HMP and speeds up adenine nucleotide (AN) biosynthesis. I propose another method for augmenting the rate of postischemic ATP recovery; increase the flux of substrate through the HMP. This would have the effect of making more PRPP available for AN biosynthesis. Effective physiologically and biologically tolerable means for enhancing HMP activity are presently available. These may be of significant utility in facilitating postischemic myocardial energy recovery.