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 produ ced by a 50% reduction in coronary flow (to similar to 5.0 ml min(-1) g(-1) giving a 50-55% rise in O-2 extraction and a 35% drop in O-2 sup ply/demand). Demand ischemia was produced by stimulation of workload a nd O-2 demand with 30 mu M norepinephrine at constant coronary now (55 -60% rise in O-2 extraction, 35-40% fall in O-2 supply/demand). Basal energy state ([ATP]/[ADP] . [P-i]) was lower in immature compared to m ature hearts, primarily due to reduced [PCr]. Despite a lower energy s tate, basal purine efflux was lowest in immature hearts. During supply ischemia reductions in [ATP]/[ADP] . [P-i] and elevations in [H+] wer e greatest in mature compared to immature hearts (P<0.05). Despite thi s 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, urine efflux increased more than 30-fold in immature and onl y four-fold in mature hearts. resulting in two-fold greater purine was hout in immature hearts. The data indicate that: (i) maturation increa ses basal energy state and, paradoxically. purine efflux, (ii) in imma ture hearts demand ischemia has a greater impact on energy state than supply ischemia, whereas there are minimal differences in the metaboli c effects of supply and demand ischemia in mature hearts, (iii) conseq uently while maturation is associated with a reduction in metabolic/bi oenergetic resistance to supply ischemia it is associated with increas ed resistance to demand ischemia, (iv) markedly reduced purine wash-ou t from mature myocardium may contribute to this increased resistance d uring demand ischemia, and (v) control of adenosine formation and puri ne efflux changes with maturation, and appears to involve mechanisms u nrelated to cytosolic energy metabolism. (C) 1996 Academic Press Limit ed