Object Latest data from both experimental and clinical studies have supported the use of intravenous magnesium as a potential therapy in the setting of cerebral ischemia. according to dosing bolus and intraoperative 202475-60-3 IC50 magnesium level, those 202475-60-3 IC50 who were treated with low-dose magnesium had less cognitive decline than those treated with placebo (OR 0.09, 95% CI 0.02-0.50, p < 0.01). Those in the high-dose magnesium group demonstrated no difference from the placebo-treated group. Conclusions Low-dose intraoperative magnesium therapy protects against neurocognitive decline following CEA. Keywords: carotid endarterectomy, magnesium, neuroprotectant, stroke Magnesium is an attractive neuroprotective agent; it is widely available, inexpensive, and has a well-established safety profile. Encouraging results from both animal and clinical studies have supported the use of intravenous magnesium as a potential therapy in the setting of cerebral ischemia. Middle cerebral artery occlusion models in rodents have demonstrated that magnesium decreases infarct volume, even though abandoned to 6 hours following the onset of ischemia.12,24 Several little clinical research possess reported decreased impairment and mortality in stroke individuals treated with magnesium.13,17 These outcomes generated enthusiasm for several large scale trials. A randomized controlled study (IMAGES trial) examining the effect of intravenous magnesium administered within 12 hours of acute stroke, however, failed to show a clinically significant improvement in death or disability at 90 days. 18 It was suggested that this 12-hour time window in the IMAGES study may have been too long.25 A large ongoing clinical trial, the FAST-MAG study attempts to address this shortcoming through the administration of intravenous magnesium by paramedics, often within 120 minutes of the onset of ischemic symptoms. 19 Phase II results indicate safety and feasibility. Initial data suggest a potential role for magnesium in the setting of cerebral ischemia; however, questions regarding the precise efficacy and necessary timeline for administration remain unanswered. Heterogeneous study treatment and populations regimens LAMP1 antibody dissimilar to preclinical testing parameters have got managed to get challenging to attain therapeutic efficiency. Carotid endarterectomy medical procedures affords a distinctive paradigm where to evaluate the consequences of potential neuroprotective agencies in the placing of acute heart stroke. Although the chance of main morbidity is certainly low, refined neurocognitive decline takes place in a higher percentage of situations. Cortical ischemia supplementary to intraoperative hypoperfusion or microembolic occasions translates to scientific deficits 202475-60-3 IC50 apparent on comprehensive neurocognitive tests.3,5,6,22 Standardized neuropsychometric evaluation has demonstrated cognitive drop in 25% of sufferers undergoing CEA in the first postoperative period.9,10 Scheduled treatment administration, in conjunction with standardized perioperative clinical assessment offers a managed environment with predictable temporal associations between ischemic onset and neurologic sequelae. It really is a scientific model which allows for preischemic dosing of potential healing agents. Data produced from prior magnesium heart stroke research have got recommended that early treatment could be important to attain scientific efficiency. To this end, our CEA model provides a controlled paradigm in which to assess the benefit of elevated serum magnesium levels at the onset of an ischemic insult. Methods Study Cohort One hundred eight prospectively enrolled patients undergoing elective CEA for both symptomatic and asymptomatic carotid artery stenosis were enrolled in this institutional review boardCapproved study. All patients undergoing CEA had 60% stenosis of the operative carotid artery, and none had undergone previous ipsilateral CEA. Patients were randomly assigned to a placebo control group or to 1 of 3 intravenous magnesium protocols. Sixteen patients (6 in the treatment group and 10 in the placebo group) were excluded from analysis due to high postoperative pain levels (7 patients), patient refusal to complete testing (7), or postoperative complications (2). The postoperative complications both occurred in the placebo group and included a postoperative hemorrhage at the surgical site and a postoperative cerebrovascular accident resulting in death. Operative Procedure All sufferers received general anesthesia with schedule temperature and hemodynamic monitoring seeing that previously described. Patients going through CEA underwent constant blood circulation pressure monitoring using a radial artery catheter. An 8-route electroencephalography monitor (Neurotrac II, Moberg Medical, Inc.) was utilized during medical procedures. Fentanyl.