Effects of dexmedetomidine hydrochloride on ERK1/2 activation in a rat model of ventilator-induced lung injury / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of dexmedetomidine hydrochloride on inflammatory lung injury and phosphorylation of extracellular regulated protein (ERK1/2) in a rat model of ventilator-induced lung injury (VILI).</p><p><b>METHODS</b>Thirty-six adult male SD rats were randomized into 3 groups (n=12) to receive a 4-h standard ventilation (group C, with tidal volume of 8 ml/kg and respiratory rate of 90/min), high-tidal volume ventilation (group H, with tidal volume of 20 ml/kg and respiratory rate of 50 /min), and high-tidal volume ventilation plus 0.5 µg·kg(-1)·h(-1) dexmedetomidine infusion (group D), with the maintenance of a positive end expiratory pressure (PEEP) of 0 cmH(2)O. After mechanical ventilation the rats were sacrificed to collect the lung lavage liquid and lung tissue to examine the pulmonary inflammatory changes and tumor necrosis factor-α (TNF-α) expression as well as the expressions of ERK1/2 and p-ERK1/2.</p><p><b>RESULTS</b>Groups H and D showed obvious lung injury and significant elevations of the total protein, WBC, MPO, TNF-α, and ERK1/2 phosphorylation as compared with those of group C. The rats in group D showed milder lung pathologies with significantly lower levels of phosphorylation of ERK1/2 and TNF-α compared with those in group H.</p><p><b>CONCLUSION</b>Dexmedetomidine can significantly attenuate VILI, decrease the production of the inflammatory molecules, and inhibit the activation of ERK1/2, demonstrating a protective effect against VILI.</p>

Effect of dexmedetomidine on patient-controlled intravenous analgesia with fentanyl in elderly patients after total hip replacement / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of a continuous infusion of low-dose dexmedetomidine on patient-controlled analgesia (PCA) with fentanyl in elderly patients after total hip replacement.</p><p><b>METHODS</b>Forty patients (ASA I-II) aged 66-81 years after total hip replacement were randomized equally into the control and test groups. The patients in the test group received continuous infusion of dexmedetomidine at the rate of 0.2 µg·kg(-1)·h(-1) from the beginning to the end of PCA with fentanyl after the surgery, while those in the control group received normal saline. The cumulative fentanyl dose, VAS pain scores and Ramsay sedation score were recorded at 0, 4, 8, 12 and 24 h after the surgery.</p><p><b>RESULTS</b>All the patients in the two groups reported good pain relief and none needed additional fentanyl. The VAS pain score was significantly lower (P<0.05 or 0.01), while the Ramsay sedation scores higher (P<0.05) in the test group than in the control group. The cumulative fentanyl dose was significantly lower in the test group (P<0.05 or 0.01). The incidence of such adverse effects as nausea and vomiting was significantly lower in the test group (P<0.05).</p><p><b>CONCLUSION</b>PCA with fentanyl combined with low-dose dexmedetomidine infusion is safe for elderly patients, and can decrease fentanyl consumption and improve the effect of PCA with fentanyl.</p>

Effects of morphine and pethidine on the expression of P-glycoprotein in mouse brain microvascular endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of morphine and pethidine on P-glycoprotein (P-gp) expression in mouse brain microvascular endothelial cells and investigate the role of nuclear factor-kappaB (NF-kappaB) signaling pathway in morphine-induced up-expression of P-gp.</p><p><b>METHODS</b>The mouse brain microvascular endothelial cell line (b.END3) was subjected to pre-incubation with NF-kappaB inhibitor PDTC (5 micromol/L) for 1 h followed by stimulation with morphine (1 microg/ml) or pethidine (1 microg/ml) for 24 h. The bEnd.3 cells were then collected for Western blotting for P-gp expression.</p><p><b>RESULTS</b>A 24-h morphine stimulation induced an up-expression of P-gp in bEnd.3 cells by almost 200%. Pethidine in similar conditions did not affect P-gp expression in the cells. PDTC, the specific inhibitor of NF-kappaB, inhibited morphine-induced up-expression of P-gp in the cells.</p><p><b>CONCLUSION</b>Morphine can induce up-expression of endogenous P-gp in mouse brain microvascular endothelial cells. NF-kappaB signaling pathway is involved in the morphine-induced up-expression of P-gp.</p>

Effect of dexmedetomidine on bispectral index and auditory evoked potential index during anesthesia with target controlled infusion of propofol and remifentanyl / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the effect of dexmedetomidine (Dex) on bispectral index (BIS) and auditory evoked potential index (AAI) during anesthesia with target controlled infusion (TCI) of propofol and remifentanyl.</p><p><b>METHODS</b>Thirty adult patients (ASA I approximate, equalsII) who were scheduled for elective thyroidectomy were monitored with BIS, AAI, ECG, blood pressure, end-tidal CO(2), and pulse oximeter before and during anesthesia. Anesthesia was induced by TCI with propofol 4 mg/L and remifentanyl 1 mu g/kg. After loss of consciousness the patients were intubated after rocuronium 0.6 mg/kg intravenous injection, remifentanyl was then infused at 0.2 microg/(kg x min)(-1) and propofol infusion (Ct) was titrated to maintain a BIS value at 50 +/- 3. At 10 min after stabilization of anesthesia the patients were randomly and double-blindly divided into 2 groups: Group D (n=15) received Dex 0.4 mu g/kg iv administered over 5 min and Group C (n=15) received equal volume of normal saline. Values of BIS, AAI, MAP, HR were recorded every 2 min within 20 min after the administration of the drugs.</p><p><b>RESULTS</b>Before anesthesia the BIS index was 90 +/- 2 in Group D and 92 +/- 2 in Group C, AAI was 81 +/- 1 in Group D and 78 +/- 1 in Group C. In anesthesia with target controlled infusion of propofol, BIS index showed a significant decrease with the i.v. administration of Dex 0.4 microg/kg, while AAI remained unchanged. In Group C, both of BIS and AAI remained unchanged after saline injection.</p><p><b>CONCLUSION</b>During propofol and remifentanyl anesthesia, after the administration of Dex, BIS value demonstrates a predominant decrease, whereas AAI shows no changes.</p>

Regulation of P38 and MKK6 on HMGB1 expression in alveolar macrophages induced by cyclic mechanical stretch / 生理学报

The aim of the present study was to investigate the role of mitogen-activated protein kinase kinase 6 (MKK6)-P38 signaling pathway in cyclic mechanical stretch-induced high mobility group box 1 protein (HMGB1) expression in alveolar macrophages. In the study, Sprague-Dawley rats were anesthetized and then sacrificed by bloodletting. The lungs were lavaged six times with prechilled PBS. Alveolar macrophages were isolated from lavage samples. Recombinant plasmids were transfected into alveolar macrophages with liposome DOTAP. Alveolar macrophages transfected with P38(AF)/pGFP and MKK6b(E)/pGFP plasmids were taken as treated groups, while the groups that transfected with pcDNA3 plasmid and pGFP plasmid served as blank transfection group and control group, respectively. All the groups were then cultured in 6-well Bioflex cell culture plates and exposed to cyclic mechanical stretch at 20% elongation using Flexercell 4000T cell stretching unit. The results showed that the transfection of MKK6b(E) led to a marked increases in P38 kinase activity compared with control group. In contrast, the transfection of P38(AF) significantly inhibited P38 kinase activity. Compared with control group, HMGB1 protein and mRNA expression in MKK6b(E) transfected cells increased markedly, while HMGB1 expression in P38(AF) transfected cells decreased markedly. These results suggest that MKK6-P38 MAPK signaling pathway regulates the expression of HMGB1 induced by cyclic mechanical stretch in alveolar macrophages.

Effect of intrathecal administration of sufentanil at different doses on bupivacaine spinal anesthesia in gynecologic laparoscopy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of sufentanil administered intrathecally at different doses on the clinical effect of bupivacaine spinal anesthesia in gynecologic laparoscopy.</p><p><b>METHODS</b>Sixty patients with ectopic pregnancy undergoing elective laparoscopy (ASA class I-II) were randomized into 4 groups (groups A, B, C and D), and received spinal anesthesia with 15 mg bupivacaine and sufentanil at 0, 2.5, 5 and 7.5 microg, respectively. When the patients complained of discomforts, showed bodily movements, had heart rate over 100 beats/min, or showed blood pressure increment by 20%, additional doses of propofol were given. The onset time of sensory block, time to Bromage scale 3 motor block, time to the highest sensory block level, time of operation and recovery from anesthesia, and the total dosages of propofol were recorded along with the sedative score and the side effects.</p><p><b>RESULTS</b>The 4 groups were comparable for age, body weight, height and operation time (range 60-65 min) (P>0.05). Both the onset time of sensory block and the time of Bromage scale 3 motor block in groups C and D were significantly shorter than those in groups A and B (P<0.05). The time of the highest sensory block in group D was shorter than that in group A (P<0.05). Compared to the group A, the dose of propofol was reduced in groups B, C, and D by 7.1%, 28.1%, and 34.8%, respectively; propofol doses in groups C and D were significantly lower than those in groups A and B (P<0.05). Pruritus associated with the spinal anesthesia occurred in 4 (26.7%), 3 (20%), and 6 (40%) cases in groups B, C and D, respectively.</p><p><b>CONCLUSIONS</b>Intrathecal sufentanil dose-dependently affect the effect of bupivacaine spinal anesthesia, and larger sufentanil dose produces better effects but more side effects. According to our results, 5.0 microg is the optimal dose for sufentanil.</p>