Influence of ribose, adenosine, and "AICAR" on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog.

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Abstract
Recovery of ATP after myocardial ischemia is limited by the slow adenine nucleotide de novo synthesis and the availability of precursors of the nucleotide salvage pathways. The adenine nucleotide de novo synthesis was determined in the dog by infusion of [14C]glycine and the acceleration of adenine nucleotide built up by intracoronary infusion of ribose together with [14C]glycine or radiolabeled 5-amino-4-imidazolecarboxamide riboside [AICAR] or adenosine in the same animal model and with the same dosage of substrate (9 mmol) in postischemic and nonischemic myocardial tissue. After 45 min of occlusion of a side branch of the left coronary artery, the ischemic area was reperfused for 3 h and needle biopsies were taken for biochemical analysis. Adenine nucleotide de novo synthesis was found to be very slow (1.5 nmol/g wet wt/h). The rate was doubled after ischemia. Adenine nucleotide synthesis was accelerated 5-fold by ribose, the basic substrate of the adenine nucleotide de novo synthesis, 9-fold by AICAR, an intermediate of the adenine nucleotide de novo synthesis and 90-fold by adenosine, a substrate of the nucleotide salvage pathway. Therefore, only adenosine infusion resulted in a measurable increase of ATP levels after 3 h of reperfusion, but over a longer time period, ribose or AICAR also can be expected to replenish reduced myocardial ATP faster than adenine nucleotide de novo synthesis. Studies with radiolabeled AICAR showed significant incorporation of radioactivity into 5-amino-4-imidazolecarboxamide ribose triphosphate which had also risen measurably during 5-amino-4-imidazolecarboxamide ribose infusion and which is not normally found in heart muscle.

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