Magnesium and experimental vasospasm.
OBJECTIVE
Interest has developed in the use of magnesium (Mg++) as a neuroprotectant and antivasospastic agent. Magnesium may increase cerebral blood flow (CBF) and reduce the contraction of cerebral arteries caused by various stimuli. In this study the authors tested the hypothesis that a continuous intravenous infusion of Mg++ reduces cerebral vasospasm after experimental subarachnoid hemorrhage (SAH).


METHODS
A dose-finding study was conducted in five monkeys (Macaca fascicularis) to determine what doses of intravenous MgSO4 elevate the cerebrospinal fluid (CSF) concentrations of Mg++ to vasoactive levels and to determine what effects these doses have on the diameters of cerebral arteries, as shown angiographically. After a standard dose of MgSO4 had been selected it was then administered in a randomized, controlled, blinded study to 10 monkeys (five animals/group) with SAH, beginning on Day 0 and continuing for 7 days, at which time angiography was repeated. A 0.086-g/kg bolus of MgSO4 followed by an infusion of 0.028 g/kg/day MgSO4 significantly elevated serum and CSF levels of Mg++ (five monkeys). Magnesium sulfate significantly elevated the serum level of total Mg++ from a control value of 0.83 +/- 0.04 mmol/L to 2.42 +/- 1.01 mmol/L on Day 7 and raised the CSF level from 1.3 +/- 0.04 mmol/L to 1.76 +/- 0.14 mmol/L. There was no angiographic evidence of any effect of MgSO4 on normal cerebral arteries. After SAH, the vasospasm in the middle cerebral artery was not significantly reduced (46 +/- 8% in the MgSO4-treated group compared with 35 +/- 6% in the placebo [vehicle]-treated group, p > 0.05, unpaired t-test).


CONCLUSIONS
Magnesium sulfate did not significantly reduce cerebral vasospasm after SAH in the doses tested. An investigation of SAH is warranted mainly to test whether a benefit can be achieved by neuroprotection or by augmentation of CBF by dilation of small vessels and/or collateral pathways.
Macdonald
R Loch
RL
Section of Neurosurgery, Department of Surgery, University of Chicago Medical Center, Chicago, Illinois 60637, USA. rlmacdon@uchicago.edu
Curry
Daniel J
DJ
Aihara
Yasuo
Y
Zhang
Zhen-Du
ZD
Jahromi
Babak S
BS
Yassari
Reza
R
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008252:Macaca fascicularis; D008278:Magnesium Sulfate / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid / Q000188:drug therapy*
D018696:Neuroprotective Agents; D008278:Magnesium Sulfate