RESUMO
BACKGROUND: To reduce surgical stress, fentanyl is frequently used for neurosurgical procedure where focal and/or global ischemia may occur. However, the effect of fentanyl on the cytokine level during ischemia/reperfusion is still uncertain. The goal of this study was to evaluate the effect of fentanyl infusion on the proinflammatory cytokine, TNF-alpha and IL-1beta, levels during global cerebral ischemia/reperfusion (I/R) in rats using the intracerebral microdialysis technique. METHODS: Forty male S-D rats weighing 280 320 g were randomly assigned to four groups. Group 1: no fentanyl infusion and only I/R, Group 2: 1.5 ng/ml of fentanyl infusion during I/R, Group 3: 3.0 ng/ml of fentanyl infusion during I/R (n = 10 in each group). Rats were anesthetized with a intraperitoneal injection of pentobarbital (50 mg/kg), intubated and ventilated with room air using an animal ventilator. Two femoral arteries and one femoral vein were cannulated with PE-50 tubing for hemorrhagic hypotension, drug infusion and hydration. Both carotid arteries were dissected and a sling was placed for brain ischemia. The head was fixed on a stereotaxic device and a small burrhole was made for probe insertion. A CMA-12 probe was inserted into the left hippocampal CA-1 region according to the guidelines. Artificial CSF was run from the inserted microdialysis probe and infused with or without fentanyl at 3 microliter/min using a microinjection syringe pump during I/R. Ischemia was induced by clamping the carotid arteries while hemorrhagic hypotension for 17 min via the femoral artery and reperfusion were accomplished by the unclamping of the sling and reinfusing the blood via the femoral artery. Nasopharyngeal and rectal temperatures were maintained within the normal range during the whole procedure. After 2 hours of stabilization, the microdialysate was collected every 17 min just before (control) and during I/R and stored at 80oC until analysis using HPLC. RESULTS: During global I/R, TNF-alpha and IL-1 beta significantly increased at reperfusion (R5) compared to the control value (P < 0.05). However, in both cases of fentanyl infusion, TNF-alpha and IL-1 beta did not increase compared to the control value. CONCLUSIONS: Fentanyl inhibited the increase of proinflammatory cytokine TNF-alpha and IL-1 beta levels during global cerebral ischemia/reperfusion in rats.