Maturational Differences in Bioenergetic State and Purine Formation During “Supply” and “Demand” Ischemia

We examined metabolic effects of “supply” and “demand” ischemia in immature and mature rabbit hearts. Moderate supply ischemia was produced by a 50% reduction in coronary flow (to C5.0 ml min−1g−1giving a 50–55% rise in O2extraction and a 35% drop in O2supply/demand). Demand ischemia was produced by stimulation of workload and O2demand with 30μ norepinephrine at constant coronary flow (55–60% rise in O2extraction, 35–40% fall in O2supply/demand). Basal energy state ([ATP]/[ADP] • [Pi]) was lower in immature compared to mature hearts, primarily due to reduced [PCr]. Despite a lower energy state, basal purine efflux was lowest in immature hearts. During supply ischemia reductions in [ATP]/[ADP] • [Pi] and elevations in [H+] were greatest in mature compared to immature hearts (P<0.05). Despite this depressed energy state purine efflux did not increase significantly during supply ischemia. In contrast, during demand ischemia reductions in energy state were greatest in immature compared to mature hearts. Moreover, purine efflux increased more than 30-fold in immature and only four-fold in mature hearts, resulting in two-fold greater purine washout in immature hearts. The data indicate that: (i) maturation increases basal energy state and, paradoxically, purine efflux, (ii) in immature hearts demand ischemia has a greater impact on energy state than supply ischemia, whereas there are minimal differences in the metabolic effects of supply and demand ischemia in mature hearts, (iii) consequently while maturation is associated with a reduction in metabolic/bioenergetic resistance to supply ischemia it is associated with increased resistance to demand ischemia, (iv) markedly reduced purine wash-out from mature myocardium may contribute to this increased resistance during demand ischemia, and (v) control of adenosine formation and purine efflux changes with maturation, and appears to involve mechanisms unrelated to cytosolic energy metabolism.