ABSTRACT
The goal of this study was to characterize acute neuronal injury in a novel nonhuman primate (NHP) ischemic stroke model by using multiple outcome measures. Silk sutures were inserted into the M1 segment of the middle cerebral artery of rhesus macaques to achieve permanent occlusion of the vessel. The sutures were introduced via the femoral artery by using endovascular microcatheterization techniques. Within hours after middle cerebral artery occlusion (MCAO), infarction was detectable by using diffusion-weighted MRI imaging. The infarcts expanded by 24 h after MCAO and then were detectable on T2-weighted images. The infarcts seen by MRI were consistent with neuronal injury demonstrated histologically. Neurobehavioral function after MCAO was determined by using 2 neurologic testing scales. Neurologic assessments indicated that impairment after ischemia was limited to motor function in the contralateral arm; other neurologic and behavioral parameters were largely unaffected. We also used microarrays to examine gene expression profiles in peripheral blood mononuclear cells after MCAO-induced ischemia. Several genes were altered in a time-dependent manner after MCAO, suggesting that this ischemia model may be suitable for identifying blood biomarkers associated with the presence and severity of ischemia. This NHP stroke model likely will facilitate the elucidation of mechanisms associated with acute neuronal injury after ischemia. In addition, the ability to identify candidate blood biomarkers in NHP after ischemia may prompt the development of new strategies for the diagnosis and treatment of ischemic stroke in humans.
Subject(s)
Disease Models, Animal , Infarction, Middle Cerebral Artery/blood , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/pathology , Psychomotor Disorders/pathology , Stroke/pathology , Animals , Blotting, Western , Catheterization , Cytokines/metabolism , Diagnostic Techniques, Neurological , Enzyme-Linked Immunosorbent Assay , Gene Expression Profiling , Histological Techniques , Leukocytes, Mononuclear/metabolism , Macaca mulatta , Magnetic Resonance Imaging , Microarray Analysis , Neurons/pathology , Psychomotor Disorders/etiology , Stroke/bloodABSTRACT
BACKGROUND: The original guidelines for using ondansetron recommending its administration prior to induction of anesthesia have been questioned. METHOD: In an effort to determine the most effective timing of ondansetron administration to prevent postoperative nausea and vomiting (PONV), a prospective, randomized, double-blind study was performed. Patients undergoing ambulatory plastic surgery procedures estimated to last two hours or more and who had at least two risk factors for PONV (female gender, non-smoker, previous history of PONV and postoperative opioids) participated in the study. General anesthesia for all patients followed the same standard institutional protocol and all patients received dexamethasone 4 mg intravenously at the start of surgery. The control group (n = 188) received 4 mg of ondansetron intravenously prior to the induction of anesthesia. The study group (n = 184) received 4 mg of ondansetron intravenously 30 minutes prior to completion of the surgery. The incidence of PONV during the early (0-2 hours) and delayed (2-24 hours) postoperative periods was recorded. RESULTS: No significant difference was found between the groups regarding early postoperative nausea or vomiting (p > 0.05). However, a significant difference (p < 0.05) was noted in both late postoperative nausea (control: 30% vs. study group: 20%) and late postoperative vomiting (control: 17% vs. study group: 8%). CONCLUSION: This clinical study indicates that when performing prolonged surgical procedures, late administration of ondansetron (within 30 minutes prior to completing the surgery) is significantly more effective in the prevention of late PONV than when administered prior to the induction of anesthesia.
