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 +,K⁺-ATPase activity was measured in the P₂ fraction of cortical tissue. Na⁺,K⁺-ATPase activity was 35.1 ± 7.4, 42.0 ± 7.6, and 40.7 ± 1.4 μmol 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 μV 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 min 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 hypoxiaischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a positive relationship was found between Na⁺,K⁺-ATPase activity and ECBA.