Dose finding study of intravenous magnesium sulphate in transient focal cerebral ischemia in rats.
BACKGROUND
During many neurovascular procedures temporary occlusion of cerebral arteries is inevitable. Neuroprotective drugs may reduce the risk of cerebral infarction in this situation. Increasing evidence indicates neuroprotective properties of magnesium in cerebral ischemia. Previous experimental studies on the neuroprotective efficacy of magnesium-treatment in transient focal ischemia provide widely differing results using different magnesium doses and treatment-regimens. The present study was conducted to find the maximum protective dose of intravenous magnesium sulphate in a rat model of transient focal ischemia.


METHODS
45 male Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion (MCAO) by an intraluminal thread. Animals were randomly assigned to one of 4 treatment arms: (1) vehicle (2) MgSO(4) 1x0.75 mmol/kg (3) MgSO(4) 2x1 mmol/kg (4) MgSO(4) 1 mmol/kg+0.5 mmol/kg/h. Local cortical blood flow (LCBF) was continuously measured by laser-Doppler flowmetry. Functional deficits were quantified daily, infarct volumes were assessed histologically after 7 days.


RESULTS
Magnesium serum levels below 3 mmol/l were well tolerated by the animals. Above 3 mmol/l cardiodepressive effects limited neuroprotection. Total infarct volumes in groups 3 and 4 were significantly reduced by 32% and 42%, respectively, compared to controls. Postoperative neurological recovery was significantly improved in magnesium-treated groups.


CONCLUSIONS
Continuous magnesium-administration with stable serum concentrations between 2 and 3 mmol/l offered the best protection and was well tolerated. Serum concentrations above 3 mmol/l should not be exceeded. An elevation of magnesium serum levels could be useful for brain tissue protection during procedures which are prone to the risk of temporary vessel occlusion.
Westermaier
T
T
Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany. Thomas.Westermaier@med.uni-muenchen.de
Zausinger
S
S
Baethmann
A
A
Schmid-Elsaesser
R
R
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007260:Infusion Pumps; D007431:Intraoperative Complications / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D019635:Neurosurgical Procedures / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014656:Vascular Surgical Procedures / Q000009:adverse effects
D018696:Neuroprotective Agents; D008278:Magnesium Sulfate