Age-dependent differences in the relationship between plasma and brain extracellular fluid concentrations of magnesium after MgSO4 infusions in miniswine.

Abstract

Magnesium is a potential neuroprotective agent in the treatment of head injury and ischemia whose efficacy is likely determined by increases in brain extracellular fluid (ECF) magnesium, which in turn depends on its concentration in plasma. The objectives of this study were to: 1) examine the effects of increasing plasma magnesium concentration ([Mg]plasma) to 4-6 mM on brain ECF magnesium concentration ([Mg]ECF) and 2) determine whether maturational changes occur in the transfer of magnesium into brain ECF for newborn and more mature (approximately 1 month old) miniswine. Increases in [Mg]plasma by systemic administration of MgSO4 resulted in similar maximal elevations in brain [Mg]ECF for both age groups (193+/-76% versus 253+/-106% of control for newborn and 1-month-old miniswine, respectively). Calculations of half-lives (t1/2) for the increase and decrease in magnesium concentration (t1/2 uptake and t1/2 clearance) were used to characterize magnesium kinetics in plasma and brain ECF. Plasma magnesium uptake was shorter in 1-month-old (t1/2 = 11.1+/-0.9 min) compared with newborns (12.9+/-1.7 min, p < 0.05). The faster increase in [Mg]plasma probably contributed to a faster uptake of brain [Mg]ECF in 1-month-old compared with newborn swine (t1/2 uptake = 27.9+/-12.8 versus 46.0+/-20.9 min, respectively, p < 0.05). Although plasma magnesium clearance was shorter in 1-month-old swine compared with newborn (t1/2 = 34.3+/-7.0 versus 74.7+/-33.7 min, respectively, p < 0.05), the clearance of magnesium from the brain ECF was similar for each age group. Reductions in blood pressure and heart rate occurred during hypermagnesemia and were similar in each age group. This study shows that acute elevations in [Mg]plasma to 4-6 mM result in similar relative increases in brain [Mg]ECF for both newborn and 1-month-old miniswine. However, there are maturational differences, as demonstrated by the faster rate of magnesium uptake into the ECF observed in the older miniswine.