Effects of FTY720 pretreatment on ventilator-induced lung injury in rats / 中华急诊医学杂志

Objective To study the effects of FTY720 pretreatment on ventilator-induced lung injury (VILI) in rats in order to explore the role of sphingosine-l-phosphate receptor 1 (S1PR1).Methods Forty healthy adult male SD rats weighing 300-350 g were randomly (randlom number) divided into 4 groups (n=10 each):group CV (conventional tidal volume VT =8 mL/kg),group HV (high tidal volume VT =40 mL/kg),group HF and group HFW.The rats in group HF received intra-gastric administration of FTY720 10 mg · kg-1 · d-1 for 7 days,while additional dose of W146 (S1PR1 antagonist) 1 mg · kg-1 · d-1 was administrated in group HFW before high tidal volume ventilation.After 4-hour mechanical ventilation,arterial blood samples were obtained for blood gas analysis before the animals were sacrificed.The lungs were harvested for histopathologic observation.Apoptosis rate in lung tissue was determined with flow cytometry.W/D lung weight ratio,pulmonary permeability index (PPI),total protein,and TNF-α,IL-1β in bronchoaveolar lavage fluid (BALF) were measured.All data were analyzed by oneway analysis of variance (ANOVA),The intergroup comparisons were analyzed by the least-significantdifference (LSD) test by using SPSS version 20.0 software.Differences were considered statistically significant if P ＜ 0.05.Results Compared with group CV,the level of PaO2 [(73.6 ± 8.9) vs.(50.5 ± 6.0)] was decreased,the levels of W/D [(3.12 ± 0.27) vs.(5.12 ± 0.56)],PPI [(0.08 ±0.03) vs.(0.30 ± 0.06)],apoptosis rate [(10.6 ±2.9) vs.(48.5±6.7)],total protein [(5.8 ±2.1) vs.(15.4±5.6)] and TNF-α [(24.3±5.7) vs.(108.4±16.0)] andIL-1β [(90.6±14.1) vs.(338.5 ± 44.3)] were increased in group HV (P ＜ 0.05).Compare with group HV,PaO2 [(50.5 ± 6.0) vs.(65.9±10.3)] was increased,W/D[(5.12±0.56)vs.(3.85±0.37)],PPI[(0.30± 0.06)vs.(0.14±0.03)],apoptosis rate [(48.5 ±6.7)vs.(25.6 ±5.3)],total protein [(15.4±5.6) vs.(8.9±2.5)],TNF-cα [(108.4±16.0) vs.(75.6±10.3)] andIL-1β [(338.5 ±44.3) vs.(188.9 ±33.8)] in BALF were decreased in group HF (P ＜0.05).PaO2 [(50.5±6.0) vs.(59.7±7.8)] was higher,W/D[(5.12±0.56) vs.(4.44±0.30)],PPI [(0.30±0.06)vs.(0.19±0.09)] andIL-1β[(338.5-±44.3) vs.(246.8±24.6)] levels were lower in group HFW than those in group HF There were no significant differences in apoptosis rate[(48.5±6.7)vs.(41.3±6.8)],totalprotein[(15.4±5.6)vs.(10.4±2.7)] and TNF-α level [(108.4 ± 16.0) vs.(97.5 ± 10.3)] between HFW group and HF group (P ＞ 0.05).Compare with group CV,The histopathologic damage of lung tissue was obvious in group HV and group HFW,it was attenuated by pretreatment with FTY720 in group HF.Conclusions FTTY720 pretreatment provides protective effects against ventilation-induced lung injury in rats,and S1PR1 may mediate the protection through reducing apoptosis rate and inflammatory reaction.

Role of cyclooxygenase-2 in ventilator-induced lung injury in rats / 中华麻醉学杂志

Objective To evaluate the role of cyclooxygenase-2 (COX-2) in ventilator-induced lung injury in rats.Methods Thirty healthy adult male Sprague-Dawley rats,aged 3.0-3.5 months,weighing 300-350 g,were randomly divided into 3 groups (n =10 each) using a random number table:traditional tidal volume group (group T,VT =8 ml/kg),large tidal volume group (group L,VT =40 ml/kg) and NS398 (selective COX-2 inhibitor,VT =40 ml/kg) group (group N).In group N,8 mg/kg NS398 (in 2 ml of 10％ dimethyl sulfoxide) was injected intraperitoneally at 1 h before ventilation,while dimethyl sulfoxide 2 ml was administrated instead of NS398 in T and L groups.After 4 h of mechanical ventilation,arterial blood samples were obtained for blood gas analysis and PaO2 was recorded.The animals were sacrificed and lungs removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio) and concentrations of total protein,intercellular adhesion molecule-1 (ICAM-1),tumor necrosis factor-alpha (TNF-α),NO and 6-keto-prostaglandin F1alpha (6-keto-PGF1 α) in bronchoaveolar lavage fluid (BALF).Pulmonary permeability index (PPI) and TXB2/6-keto-PGF1 α ratio were calculated.Results Compared with group T,PaO2 was significantly decreased,W/D ratio and PPI were increased,the total protein,ICAM-1,TNF-α and NO levels and TXB2/6-keto-PGF1 α ratio in BALF were increased in group L(P ＜ 0.05).PaO2 was significantly higher,W/D ratio and PPI were lower,and total protein,ICAM-1,TNF-α and NO levels and TXB2/6-keto-PGF1 α ratio in BALF were lower in group NS than in group L (P ＜ 0.05).The damage to lung tissues was severe in group L,and obviously alleviated in group N.Conclusion COX-2 is involved in ventilator-induced lung injury in rats.

Role of vascular endothelial active facters in gas exchange impairment induced by tourniquet and the effect of shenmai injection / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Shenmai injection on vascular endothelial active facters nitric oxide (NO) and endothelin-1 (ET-1), and pulmonary gas exchange induced by tourniquet deflation in patients undergoing lower extremity surgery.</p><p><b>METHOD</b>Twenty-six patients scheduled for unilateral lower extremity surgery were randomly divided into 2 groups: control group (group C, n = 14) and Shenmai injection group (group SM, n = 12). All the patients agreed to a combined spinal-epidural anesthesia at the L2-L3 interspace and a radial artery catheter was placed for sampling. Patients in group SM were injected Shenmai injection 0.6 mL x kg(-1) and physiological saline 100 mL, while patients in group C were injected equal volume of normal saline instead 15 min before tourniquet inflation. Blood samples which were used for blood gas analysis and measurement of nitric oxide (NO) and endothelin-1 (ET-1) were taken before tourniquet inflation (T0, baseline) and 30 min (T1), 2 h (T2), 6 h (T3), 24 h (T4) after tourniquet deflation.</p><p><b>RESULT</b>Compared with the baseline values at T0, in group C at T3 P(a) O2 and the levels of NO were significantly decreased, while P(A-a) DO2 and the levels of ET-1 at T3 were significantly increased (P < 0.05 or P < 0.01), in group SM, the levels of NO at T3 were significantly decreased (P < 0.05). Compared with group C, the changes of P(a)O2, P(A-a) DO2, NO and ET-1 were significantly mitigated in group SM.</p><p><b>CONCLUSION</b>The concentrations of NO and ET-1 is connected with the pulmonary gas exchange impairment induced by tourniquet application. Shenmai injection can improve the pulmonary gas exchange based on rising the level of NO, reducing the level of ET-1.</p>

Effect of methylene blue on oxygen metabolism in patients with septic shock / 中华麻醉学杂志

Objective To investigate the effect of methylene blue (MB) on oxygen metabolism in patients with septic shock. MethodsForty ASA Ⅱ or Ⅲ patients with septic shock aged 38-64 yr weighing 48-75 kg undergoing emergency surgery were randomly divided into 2 groups ( n = 20 each): group Ⅰ norepinephrine (group NE) and group Ⅱ MB. The patients were unpremedicated. Anesthesia was induced with midazolam, etomidate,sufentanil and vecuronium and maintained with inhalation of 0.5％-1.5％ sevoflurane and intermittent iv boluses of sufentanil and vecuronium. The patients were mechanically ventilated after tracheal intubation. PETCO2 was maintained at 35-45 mm Hg. During operation MB was infused at 0.5-1.0 mg·kg-1·h-1 in group MB and NE at 0.5-2.0 μg· kg-1 · min-1 in group NE respectively to maintain hemodynamic stability. Radial artery was cannulated and connected with Vigileo cardiac output monitor. Right internal jugular vein was cannulated for CVP monitoring.HR, SvO2, MAP, CVP, SV and CI were continuously monitored. Arterial and central venous blood samples were collected simultaneously before induction of anesthesia (T0, baseline), immediately before (T1) and at 30, 60 and 90 min after skin incision (T2-4) and at the end of operation (T5) . Blood gas analysis was performed. O2 consumption index (VO2I), O2 delivery index (DO2I) and O2 extraction rate (ERO2) were calculated. Blood lactate concentration was measured. Results MAP, HR, CVP, SVRI, DO2I, VO2I and ERO2 were significantly higher,while CI and blood lactate concentration lower during operation (T2-5) in group MB than in group NE. MAP, HR,CVP, SVRI, VO2I, DO2I, and ERO2 were significantly higher, while CI and blood lactate concentration were lower during operation (T2-5) as compared with the baseline values at T0 in group MB. In group NE there were no significant change in MAP, HR, CVP and DO2I during operation (T2-5 ) as compared with the baseline at T0. ConclusionIntravenous infusion of MB at 0.5-1.0 mg·kg-1·h-1 during operation may improve hemodynamics and oxygen metabolism in patients with septic shock.

Clinical study on total intravenous anesthesia with sufentanil-profofol given by target-controlled infusion in neurosurgical operations / 中国临床药理学与治疗学

0.05).At the T1,T3,T4,T7 time point,changes of the MAP and HR were more stable in TCI group than those in control group.The awakening time and extubation time in TCI group was obviously shorter in than that in control group.The OAAS scores after extubation were higher and the VRS scores 30 min after extubation were lower in TCI group than those in control group(P

Effect of MAPK inhibition on the hypoxia hypercapnia-induced pulmonary vasoconstriction / 中国病理生理杂志

AIM:To investigate isometric force displacement in isolated rat main pulmonary artery rings and right main branch pulmonary artery(second pulmonary artery)rings during hypoxia hypercapnia and the role of mitogen activated protein kinase(MAPK).METHODS:The main pulmonary artery rings were dissected from the male Sprague-Dawley rats and were randomly divided into control group and hypoxia hypercapnia group.The second pulmonary artery rings were also randomly divided into control group,hypoxia hypercapnia group,DMSO incubation group,U0126 incubation group and SB203580 incubation group.The tension changes of pulmonary artery rings were monitored in vitro.RESULTS:Under normoxia conditions,there was no statistically significant change between main pulmonary artery rings and second pulmonary artery rings.A biphasic pulmonary artery contractile response to hypoxia hypercapnia in the second pulmonary artery rings was observed instead of a sharp and transient increase in the main pulmonary artery tension.Both p38 MAPK inhibitor SB203580 and ERK1/2 inhibitor U0126 significantly attenuated the delayed,but not early,contractile phase of the biphasic pulmonary artery contraction.CONCLUSION:Acute hypoxia hypercapnia causes a biphasic pulmonary artery contractile response in the second pulmonary artery,and p38 MAPK and ERK1/2 may be two key mediators in the process.