Effects of deferoxamine, a chelator of free iron, on Na+, K+-ATPase activity of cortical brain cell membrane during early reperfusion after hypoxia-ischemia in newborn lambs

Free iron chelation after hypoxia-ischemia can reduce free radical-induced damage to brain cell membranes and preserve electrical brain activity. We investigated whether chelation of free iron with deferoxamine (DFO) preserved cortical cell membrane activity of Na+,K+-ATPase and electrocortical brain activity (ECBA) of newborn lambs during early reperfusion after severe hypoxia-ischemia. Hypoxia was induced in 16 lambs by decreasing the fraction of inspired oxygen to 0.07 for 30 min, followed by a 5-min period of hypotension (mean arterial blood pressure <35 mm Hg). ECBA (in microvolts) was measured using a cerebral function monitor. Immediately after hypoxia and additional ischemia, eight lambs received DFO (2.5 mg/kg, i.v.), and seven lambs received a placebo (PLAC). Two lambs underwent sham operation. One hundred eighty minutes after completion of hypoxia and ischemia, the brains were obtained and frozen. Na+,K+-ATPase activity was measured in the P-2 fraction of cortical tissue. Na+,K+-ATPase activity was 35.1 +/- 7.4, 42.0 +/- 7.6, and 40.7 +/- 1.4 mu mol inorganic phosphate/mg protein per hour in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p < 0.05: DFO versus PLAC). ECBA was 11.2 +/- 6.1, 14.8 +/- 4.8, and 17.5 +/- .0.5 mu V in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p = 0.06: DFO versus PLAC). Na+,K+-ATPase activity correlated with ECBA at 180 mill of reperfusion (r = 0.85, p < 0,001). We conclude that Na+,K+-ATPase activity of cortical brain tissue was higher in DFO-treated lambs compared with PLAC-treated animals during the early reperfusion phase after severe hypoxia-ischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a positive relationship was found between Na+,K+-ATPase activity and ECBA.