Novel vasodilatory effect of intracisternal injection of magnesium sulfate solution on spastic cerebral arteries in the canine two-hemorrhage model of subarachnoid hemorrhage.

OBJECT: The extracellular Mg++ has a vasodilatory effect on the cerebral artery. The present study investigated the effect of intracisternal injection of MgSO4 solution on cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH). METHODS: Subarachnoid hemorrhage was induced in 10 beagles using the two-hemorrhage model. Angiography of the vertebrobasilar artery was performed on Day 1 (baseline values before SAH) and on Day 7 (during cerebral vasospasm after induced SAH) before and after intracisternal injection of 0.5 ml/kg of 15 mmol/L MgSO4 solution into the cerebellomedullary cistern. RESULTS: The cerebrospinal fluid Mg++ concentration was significantly increased to 3.15 +/- 1.14 mEq/L after intracisternal injection from the preinjection value (1.45 +/- 0.09 mEq/L; p < 0.01). The diameters of the basilar artery, vertebral artery, and superior cerebellar artery on Day 7 were significantly decreased to 58.0 +/- 10.9%, 71.0 +/- 10.1%, and 60.9 +/- 13.8%, respectively, of their baseline diameters on Day 1 (p < 0.01). After intracisternal injection of MgSO4, these diameters significantly increased to 73.8 +/- 14.3%, 83.0 +/- 14.8%, and 74.1 +/- 13.5%, respectively (p < 0.01). CONCLUSIONS: Intracisternal injection of MgSO4 solution causes significant dilation of spastic cerebral arteries in the canine two-hemorrhage model of SAH.

Magnesium and experimental vasospasm.

OBJECT: 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.

Antinociceptive potentiation and attenuation of tolerance by intrathecal co-infusion of magnesium sulfate and morphine in rats.

UNLABELLED: N-methyl-D-aspartate (NMDA) antagonists, such as MK801, delay the development of morphine tolerance. Magnesium, a noncompetitive NMDA antagonist, reduces postoperative morphine requirements. The present study was designed to evaluate the effects of intrathecal co-administration of magnesium sulfate with morphine on antinociceptive potentiation, tolerance, and naloxone-induced withdrawal signs. Magnesium sulfate (40-60 microg/h) co-administration for 7 days, similar to MK801 (10 nmol/h), prevented the decline in antinociceptive response compared with morphine (20 nmol/h). Magnesium sulfate (60 microg/h) produced no antinociception, but co-infused with morphine (1 nmol/h), it resulted in potentiated antinociception compared with morphine throughout the 7-day period. Probe morphine doses after 7-day infusions demonstrated a significantly greater 50% effective dose value for morphine 1 nmol/h (109.7 nmol) compared with saline (10.9 nmol), magnesium sulfate 60 microg/h (10.9 nmol), and magnesium sulfate 60 microg/h plus morphine 1 nmol/h (11.2 nmol), which indicates that magnesium had delayed morphine tolerance. Morphine withdrawal signs after naloxone administration were not altered by the co-infusion of magnesium sulfate. Cerebrospinal fluid magnesium levels after intrathecal magnesium sulfate (60 microg/h) for 2 days increased from 17.0 +/- 1.0 microg/mL to 41.4 +/- 23.6 microg/mL, although serum levels were unchanged. This study demonstrates antinociceptive potentiation and delay in the development of morphine tolerance by the intrathecal coinfusion of magnesium sulfate and morphine in the rat. IMPLICATIONS: The addition of magnesium sulfate, an N-methyl-D-aspartate antagonist, to morphine in an intrathecal infusion provided better analgesia than morphine alone in normal rats. These results suggest that intrathecal administration of magnesium sulfate may be a useful adjunct to spinal morphine analgesia.

Cerebrospinal fluid passage of intravenous magnesium sulfate in neurosurgical patients.

Increasing evidence suggests a neuroprotective potential of magnesium sulfate (MgSO4). Only limited information about the passage of MgSO4 to the cerebrospinal fluid (CSF) is available in neurosurgical patients. However, with regard to the clinical relevance of magnesium's neuroprotective properties, quantitative data about its CSF passage are needed. The present study aims to assess the amount and the time course of magnesium's CSF passage in neurosurgical patients. To this end, 20 patients undergoing general anesthesia for neurosurgery and needing CSF drainage were included. Patients received an i.v. bolus of 60 mg/kg MgSO4. The increase in plasma and CSF magnesium concentration were measured 30, 90, and 240 min after the end of the MgSO4 infusion. These values were compared with the baseline levels taken before the start of the MgSO4 infusion. Thus, each patient served as his or her own control. Values are expressed as means +/- SD. The plasma magnesium levels were measured as follows: baseline, 0.74 +/- 0.12 mM; at 30 min, 1.24 +/- 0.1 mM (p < 0.01); at 90 min, 0.95 +/- 0.15 mM (p < 0.01), and at 240 min, 0.82 +/- 0.14 mM (p < 0.05). The CSF magnesium levels were measured as follows: baseline, 0.95 +/- 0.11 mM; at 30 min, 1.00 +/- 0.15 mM (NS); at 90 min, 1.10 +/- 0.17 mM (p < 0.01); and at 240 min, 1.13 +/- 0.19 mM (p < 0.001). We concluded that a bolus of 60 mg/kg of MgSO4 leads at least after 90 min to a significant increase in the CSF magnesium concentration. Moreover, the increase in plasma and CSF magnesium concentration is not parallel. Thus, plasma magnesium concentration cannot be used to predict the changes in CSF concentrations.

Peripheral magnesium sulfate enters the brain and increases the threshold for hippocampal seizures in rats.

OBJECTIVES: Our objectives were to determine whether magnesium sulfate crosses the blood-brain barrier and whether it has central anticonvulsant action. STUDY DESIGN: In experiment 1 34 female Long-Evans rats were divided into six groups: control (n = 7); single magnesium sulfate injection and evaluation after 20 minutes in 3 conditions: normal rats (n = 7), sham-operated animals (n = 5), and after electrical stimulation by hippocampal electrode (n = 5); single injection and evaluation after 2 hours (n = 5); and prolonged (2 hours) serum magnesium elevation (n = 5). Serum, cerebrospinal fluid, and specific brain areas were analyzed for magnesium concentrations. In experiment 2 threshold for electrical seizure was measured in eight rats before and after intraperitoneal injections of magnesium sulfate versus saline solution. RESULTS: In experiment 1 there was a significant correlation between blood and cerebrospinal fluid magnesium concentrations (r = 0.80, p < 0.0001). Magnesium concentrations were increased in the cortex and hippocampus, with the largest changes occurring after two hours of sustained serum magnesium concentrations (p < 0.01). Induction of hippocampal seizure activity resulted in further elevations in cerebrospinal fluid magnesium concentrations but did not change brain concentrations. In experiment 2 magnesium sulfate increased the electrical threshold required to induce seizures by 34% (p = 0.01). CONCLUSIONS: Magnesium sulfate enters the cerebrospinal fluid and brain and has a central anticonvulsant effect.