Changes in purine metabolism and production of oxygen free radicals by intermittent partial umbilical cord occlusion in chronically instrumented fetal lambs

Abstract

Objective: Undetected umbilical-cord compression has been suggested to be implicated in unexplained fetal brain damage. We tested the hypothesis that the generation of oxygen-free radicals (OFRs) during intermittent partial umbilical cord occlusion might play a causal role in antenatal CNS injury.

Methods: Using 7 established chronically instrumented fetal lambs, intermittent partial occlusion of the umbilical circulation was produced according to the method of Clapp et al. for 1 of every 3 minutes for 2 hours. A microdialysis probe was implanted in the fetal brain white matter. Normal saline was infused, and the perfusate obtained at 2 micrograms/ min. Hypoxanthine (HX), xanthine (XA), and inosine-5-monophosphate (IMP) concentrations in the perfusate and blood samples obtained from fetal jugular veins were assayed by HPLC. Concurrently, the perfusate, which contained superoxide produced in the brain, when mixed with cypridina luciferin analogue extracorporally, caused chemiluminescence that in 4 cases was measured by a highly sensitive electronic fluorescence detector.

Results: (1) HX, XA, and IMP concentrations in the blood and perfusate were higher than in the control during the intermittent partial occlusion of the umbilical circulation period and returned to control levels during the recovery period. (2) The residual chemiluminescence of perfusate revealed that the intermittent partial occlusion of the umbilical circulation level was about 100% higher than the control level, and during the recovery period the level returned to the control level. (3) The chemiluminescence during the intermittent partial occlusion of the umbilical circulation period was inhibited by infusion through the fetal jugular vein of 1 micron polyethylene glycol conjugated superoxide dismutase.

Conclusion: During the intermittent partial occlusion of the umbilical circulation period the fetal brain tissue releases a large amount of OFRs, and a portion of these might be synthesized by the increased conversion of HX to XA. This phenomenon might play an important role in the etiology of fetal brain injury.