Magnesium Therapy for Subarachnoid Hemorrhage Induced Cerebral Vasospasm as Assessed by In Vitro Studies on the Porcine Carotid Artery
Background: Mg2+ has been used therapeutically in the treatment of eclampsia and it has recently become a novel avenue in the treatment of stroke because it can relax vascular smooth muscle. Currently there is a clinical trial, on going in England, involving Mg2+ administration to stroke patients. But relatively little is known regarding the function or mechanism of Mg2+ treatment following subarachnoid hemorrhage (SAH). We therefore set out to determine if Mg2+ could be used to prevent or reverse the in vitro vasospasm caused by the CSF from vasospastic (SAH) patients. Methods: Oxygen consumption and isometric force measurements of the isolated porcine carotid artery were used to assess the functional and metabolic responses of the vascular smooth muscle following stimulation by CSF from SAH patients with cerebral vasospasm. We used a method of exposing the vascular smooth muscle to 12 mM MgCl2 for 1 hour to increase intracellular magnesium. This method has been shown to increase intracellular Mg2+ to levels reached with two to three days of Mg2+ therapy. Results: CSF from SAH patients with vasospasm will cause vasospasm when applied to vessels in vitro. Following this in vitro vasospasm, Mg2+ caused a dose dependant decrease in tension (relaxation) following exposure to CSF from vasospasm patients. Exposure of vessels to 12 mM Mg2+ normalized the rate of relaxation in the presence of CSF from SAH patients was normalized (2.70±0.71 Nm-2s-1 in the presence of CSF; 15.8±4.20 Nm-2s-1 with CSF and Mg2+; and 16.1±4.85 Nm-2s-1without CSF). Mg2. significantly (P≤0.05) decreased the rate of oxygen consumption observed when stimulated by CSF (0.70±0.03 μmol O2 min-1g-1 with CSF alone and 0.46±0.08 μmol O2 min-1g1 with CSF and Mg2+). Conclusion: These results suggest that Mg2+ is a potent vasodilator that helps to normalize contractile behavior and metabolism of the porcine carotid artery exposed to the CSF of SAH patients with vasospasm. Therefore, Mg2+ therapy is a possible avenue for treating patients with cerebral vasospasm by causing a relaxation of vascular smooth muscle.