Hypoxia-Ischemia (HI) Alters the Relationship Between Plasma and Brain Extracellular Fluid (ECF) Magnesium Concentration ([Mg]) † 1727

We have shown that increases in plasma [Mg] ([Mg]_pl) increases brain ECF[Mg] ([Mg]_ECF) during normoxia, (Ped. Res. 39: 374A, 1996). The effects of HI on [Mg]_pl and its entry into brain are unclear. This study determined the effects of HI on the uptake and clearance rate and maximal [Mg] in plasma and brain ECF by comparing 6 HI miniswine (HI, 5.5±3 days, x±SD) to 7 nomoxic animals (Nx, 4±2 days). A 1 cm loop-type microdialysis probe was inserted into the superficial cerebral cortex for measurement of brain [Mg]_ECF. After a control period, 275 mg/kg MgSO₄ was administered i.v. for 30 min followed by 100 mg/kg for 30 min. HI and Nx miniswine differed only during the last 15 min of Mg infusion, when HI was induced (FiO₂=.08, bilateral carotid occlusion, hypotension). For Nx, [Mg]_pl increased from 0.57±0.21 mM at control to 5.71±1.08mM at 30 min and 5.38±1.08mM at 60 min of Mg infusion. For HI, [Mg]_pl increased from 0.48±0.11mM at control to 6.40±1.08mM at 30 min and 8.90±1.44mM at 60 min of infusion(p<.0001 group-time interaction). T_1/2uptake (time to achieve ½ maximal [Mg]_pl) was faster for Nx(12.9±1.7min,Nx vs 19.6±2.2min,HI respectively, p<.0001). Following infusion [Mg]_pl decreased to similar values at 300 min in both groups (1.87±0.96mM, Nx vs 2.18±0.56mM, HI). T_1/2clearance(time to achieve a 50% decrease in maximal[Mg]_pl) did not differ between groups. For [Mg]_ECF, values for Nx increased from 0.21±0.06mM at control to a maximum of 0.38±0.14mM. Similarly, for HI, [Mg]_ECF increased from 0.23±0.11mM at control to a maximum of 0.39±0.13mM. There were no group differences in T_1/2 uptake and T_1/2clearance for [Mg]_ECF, but the ratio of[Mg]_ECF/[Mg]plat 60 min of infusion was greater for Nx(0.076±0.025 Nx vs 0.042±0.010 HI, p=.009). Conclusion HI results in higher [Mg]_pl during and after Mg infusion and may reflect decreased renal perfusion. The lower [Mg]_ECF/[Mg]_pl ratio for HI suggests that entry of Mg into the brain is limited relative to normoxia; decreased Mg delivery, and/or transporter saturation may contribute to this observation.