The metabolic basis for the enhanced tolerance of immature hearts to
ischemia remains to be elucidated. Loss of high-energy
phosphate nucleotides occurs during
ischemia/reperfusion in mature (adult) hearts through the breakdown of
adenosine triphosphate,
diphosphate, and monophosphate (nondiffusible) to
adenosine (freely diffusible). However, previous work has shown that after
ischemia nondiffusible
nucleotides are better retained by immature (neonatal) hearts than by mature hearts. The
enzyme responsible for the conversion of
adenosine monophosphate to
adenosine is
5'-nucleotidase. We therefore hypothesized lower activity of this
enzyme in neonatal than in adult myocardium. The purposes of this study were (1) to document
5'-nucleotidase activities in neonatal and adult rabbit myocardium and (2) to correlate differences of
5'-nucleotidase activity with functional recovery from
ischemia. Neonatal (5- to 10-day-old) and adult (4- to 6-month-old) rabbit hearts were isolated and perfused (retrograde Langendorff). A left ventricular balloon measured functional parameters. Hearts were subjected to 20 minutes of global 37 degrees C
ischemia and 10 minutes of reperfusion followed by freeze clamping. Tissue homogenates were assayed for
5'-nucleotidase by the linked formation of
nicotinamide-adenine dinucleotide at 340 nm (Arkesteijn method). Postischemic recovery of developed pressure was 86% +/- 3% in neonates (n = 5) versus 38% +/- 3% in adults (n = 8) (mean +/- standard deviation) (p less than 0.01).
5'-Nucleotidase activity was 4400 +/- 1208 nmol/min/gm in neonates (n = 5) versus 13,938 +/- 830 nmol/min/gm in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). We conclude that (1)
5'-nucleotidase activity is 68% lower in neonatal than in adult myocardium and (2) functional recovery after
ischemia inversely relates to
5'-nucleotidase activity.