The research project dealt with the factors which limit the recovery of cardiac function following a moderate normothermic ischemia. The major findings were that, ischemia caused drastic degradation of myocardial high energy phosphate compounds, and the accumulated adenine nucleosides were washed out by the reperfusion of coronary system, resulting in postischemic myocardial low ATP levels and mechanical dysfunction. The lack of precursors of adenine nucleotides and the presence of a futile cycle, which converted AMP synthesized from salvage pathway and IMP synthesized from De novo pathway to membrane-permeable adenine nucleosides, were considered the main limiting factors restricting the recovery of ATP levels and function in postischemic failing heart. The strategy to reverse the ischemic damage in such a heart was (1) to supplement ribosyl equivalent and adenine equivalent for the regeneration of adenine nucleotides and (2) to inhibit catabolism and the continuous loss of adenine nucleosides Ribose and adenine through salvage pathway, and ribose, glutamine, glycine, and aspartic acid through De novo pathway, as well as concanavalin A by decreasing the loss of adenine nucleosides, were found to be positively inotropic in postischemic heart. The administration of paired ribosyl equivalent and adenine equivalent was synergistically effective with concanavalin A in promoting postischemic myocardial ATP regeneration and mechanical function. The capability of postischemic myocardial ATP regeneration was similarly enhanced via either adenine salvage pathway or De novo pathway providing that the supply of paired ribosyl equivalent and adenine equivalents were adequate. The regeneration rate of ATP established in this research was 0.187-0.196 umoles/min/g dry heart wt which was the fastest found in all current literatures
