Metabolic and functional responses of immature and mature rabbit hearts to hypoperfusion, ischemia, and reperfusion

Abstract

Relationships between contractile function and cytosolic metabolism were examined in mature and immature rabbit hearts during graded hypoperfusion, global ischemia, and reperfusion. Differences in basal contractile function and metabolic demand in immature and mature hearts were paralleled by differences in energy substrate indexed by the phosphorylation potential and phosphocreatine (PCr) levels but not by differences in ATP, pH, or inorganic phosphate (Pi). During graded hypoperfusion, contractility declined comparably in both age groups. Relative changes in [ATP], [PCr], and [Pi] were similar in both groups, whereas pH declined to a greater extent in mature hearts, and [Mg2+] declined to a greater extent in immature hearts. Contractile function correlated most consistently with [Pi] and supports the notion that Pi (and H+) are primary determinants of function in underperfused immature and mature hearts. Aerobic efficiency declined in immature but not mature hearts during hypoperfusion, reflecting an improved ratio of ATP formation relative to ATP hydrolysis in the hypoperfused immature myocardium. Finally, the enhanced contractile recovery from global ischemia in immature compared with mature hearts (to 93 +/- 4 vs. 79 +/- 2% of basal function) was unrelated to recovery of ATP, Pi, pH, Mg2+, [ATP]/[ADP].[Pi], or free-energy change of ATP hydrolysis. Age-related differences in maintenance of ATP may be related to enhanced metabolic activation of glycolysis coupled with better buffering of pH and an improved match between ATP hydrolysis and ATP formation in immature heart.