Transport of hypoxanthine from plasma to cerebrospinal fluid and vitreous humor in newborn pigs

Abstract

To determine whether an elevated level of hypoxanthine in cerebrospinal fluid or vitreous humor might reflect a high plasma hypoxanthine concentration, or whether it necessarily represents local tissue hypoxia, we infused hypoxanthine intravenously to normoxemic and normotensive piglets (n = 6). Hypoxanthine was measured in different body fluids using HPLC. During the 8 hours of infusion hypoxanthine increased in plasma (from 30 +/- 6 mumol/l (mean +/- SD) before the infusion to 68 +/- 20 mumol/l at the end of the infusion, p < 0.01), cerebrospinal fluid (CSF) (19 +/- 8 to 43 +/- 9 mumol/l, p < 0.05) and vitreous humor (15 +/- 5 to 30 +/- 6 mumol/l, p < 0.05). After infusion, hypoxanthine values in all three fluids were similar to those seen in pigs after severe hypoxia. Hypoxanthine in vitreous humor and plasma were significantly correlated (r = 0.80, 95% confidence interval 0.47-0.93, p < 0.001). Urinary excretion of hypoxanthine increased almost 40 times from 0.12 +/- 0.14 to 4.6 +/- 2.9 mumol/kg/h indicating that renal excretion of hypoxanthine is not achieved just by passive filtration. We conclude that in newborn piglets hypoxanthine can pass from plasma to CSF and vitreous humor. Thus an increased CSF hypoxanthine concentration is not definite proof that significant cerebral hypoxia has occurred.

Plasma hypoxanthine reacts more abruptly to changes in oxygenation than base deficit and uric acid in newborn piglets

“…Previously, vitreous humor Hyp has been used as an indicator of past hypoxia [18], and a high correlation between plasma and vitreous humor Hyp has been found [15]. We have made two new findings indicating that Hyp in vitreous humor is not simply a filtration product from plasma.…”

“…ROOTWELT et al [14] did not find major differences in time to normalization for BD and plasma Hyp after hypoxia. Previously, elimination half time of BD and Hyp in plasma for pigs have been estimated to be 40 min [17] and 40-55 min [15,17] respectively. Lactate is eliminated more slowly with a half life of 85 min [17].…”

“…This finding indicates that the SIDS victims had experienced sustained respiratory failure prior to death. Hyp in vitreous humor has been fund to correlate well with plasma Hyp [15]. Later, STOLTENBERG et al [21] tested two different models of hypoxia in newborn piglets in an effort to reproduce the high levels of Hyp found in vitreous humor of the SIDS victims.…”