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.

Effects of FTY720 pretreatment on lung injury induced by limb ischemia-reperfusion in rats / 中华麻醉学杂志

Objective To evaluate the effects of FTY720 pretreatment on lung injury induced by limb ischemia-reperfusion (I/R) in rats.Methods Thirty healthy male Sprague-Dawley rats,weighing 230-260 g,were divided into 3 groups (n=10 each) using a random number table:sham operation group (group S),I/R group and FTY720 group (group F).Bilateral hind limb I/R was induced by applying rubber band tourniquet high around each thigh for 3 h followed by 3 h of reperfusion.FTY720 was given by intragastric gavage at 3 mg · kg-1 · d-1 for 7 consecutive days before I/R in group F,while the equal volume of normal saline was given instead in group I/R.At the end of reperfusion,blood samples were collected from the carotid artery for blood gas analysis,and oxygenation index (OI) was calculated.The rats were then sacrificed and lungs removed for examination of pathological changes (with light microscope) and for determination of apoptosis rate (using flow cytometry) and expression of CCAAT/enhancer-binding protein homologous protein (CHOP),caspase-12,c-Jun N-terminal kinase (JNK),Bcl-2 and Bax protein in lung tissues (using Western blot).Bax/Bcl-2 ratio was calculated.Results Compared with group S,OI was significantly decreased in group I/R,and apoptosis rate was increased,the expression of CHOP,caspase-12,JNK and Bax protein was up-regulated,and the expression of Bcl-2 was down-regulated,and Bax/Bcl-2 ratio was increased in I/R and F groups (P＜0.05).Compared with group I/R,OI was significantly increased,apoptosis rate was decreased,the expression of caspase-12,CHOP,Bax and JNK protein was down-regulated,and the expression of Bcl-2 was up-regulated,and Bax/Bcl-2 ratio was decreased in group F (P＜0.05).The pathological changes of lungs were significantly attenuated in group F as compared with group I/R.Conclusion FTY720 pretreatment can attenuate lung injury induced by limb I/R in rats,and the mechanism may be related to inhibition of endoplasmic reticulum stress-related cell apoptosis.

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 non-invasive ischemic preconditioning on nitric oxide/endothelin-1 imbalance and gas exchange impairment following limb ischemia reperfusion: a clinical study / 中国病理生理杂志

AIM: To investigate the effects of non-invasive ischemic preconditioning on nitric oxide (NO)/endothelin-1 (ET-1) imbalance and gas exchange impairment following limb ischemia reperfusion in patients undergoing unilateral lower extremity surgery with tourniquet. METHODS: Twenty-seven patients aged 25-65 years, whose tourniquets duration varied from 1 h to 1.5 h and matched American Society of Anesthesiologists Physical Status Ⅰ-Ⅱ, were randomized into two groups: a control group (n=14) and a ischemic preconditioning group (IPC group, n=13) in which patients received three cycles of 5 min of ischemia/5 min of reperfusion before tourniquet inflation. Radial arterial blood gas, plasma malondialdehyde (MDA) and NO, serum ET-1 and interleukin-6 (IL-6) were measured just before tourniquet inflation(T_0), 1 h after inflation(T_1), and 0.5 h(T_2), 2 h(T_3), 6 h(T_4), 24 h(T_5) after tourniquet deflation. Meanwhile NO/ET-1 ratio, alveolar-arterial oxygen gradient (P_(A-a)DO_2) and intrapulmonary shunt (Qs/Qt) were calculated. RESULTS: In control group, arterial partial pressure of oxygen (PaO_2) were decreased, while P_(A-a)DO_2 and Qs/Qt were increased significantly at T_4 compared to the baselines at T_0 (P<0.01). Plasma NO levels and NO/ET-1 ratios decreased gradually after tourniquets deflation and statistical significances were observed at T_3 (P<0.01) with a valley at T_4 (P<0.01) and recovered to baselines at T_5. Serum ET-1, IL-6 and plasma MDA began to increase remarkably after T_3 (P<0.05 or P<0.01), peaked at T_4 and dropped slightly at T_5. The changes above-mentioned could be well attenuated by the application of IPC (P<0.05 or P<0.01) except PaO_2 (P>0.05). CONCLUSION: Clinical application of unilateral tourniquet within safe time limit (1.5 h) may lead to limb ischemia reperfusion and further pulmonary gas exchange impairment, which could be partially attenuated by the application of IPC via alleviating NO/ET-1 imbalance.

Effect of nitroglycerin-induced hypotension on cognitive function after endoscopic sinus surgery under isoflurane anesthesia in eldedy patients / 中华麻醉学杂志

Objective To evaluate the effect of nitroglycerin (NTG)-induced hypotension on cognitive function after endoscopic sinus surgery performed under isoflurane anesthesia in elderly patients.Methods Forty ASAⅠ or Ⅱ patients aged 65-85 yr weighing 40-75 ks undergoing endoscopic nasal sinus surgery for chronic sinusitis under isoflurane anesthesia were randomly divided into 2 groups(n=20 each):control group(group C) and controlled hypotension group(group H).Anesthesia was maintained with isoflurane inhalation in both groups.In group H controlled hypotension was induced and maintained with continuous iv infusion of NTG at function was assessed 1 day before(baseline)and at 6,12,24 and 72h after surgery using Minimental State examination (MMSE) and scored.Results The MMSE scores were significantly decreased after surgery from 6h to 24h in both groups and were significantly lower in group H than in group C.There was no significant difference in MMSE scores between the 2 groups at 72h after surgery.The incidence of cognitive deficit was significantly higher in group H(55%) than in group C(25%).Conclusion Controlled hypotension induced by NTG may aggravate transient cognitive deficit after isoflurane anesthesia in elderly patients.

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.

Effect and significance of Shenmai injection on value of vascular endothelial active factors of heart valve replacement patients / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of Shenmai injection on the value of vascular endothelial active factors nitric oxide (NO), endothelin-1 (ET-1) of patients undergoing heart valve rveplacement and cardiac pulmonary bypass (CPB).</p><p><b>METHOD</b>Thirty patients of cardiac valve replacement undergoing open heart surgery under cardiopulmonary bypass (CPB) were randomized single-blind method divided into Shenmai injection group (SM) and control group (C) with 15 cases each. Shenmai injection group (SM) were injected Shenmai injection 0.6 mL x kg(-1) added to physiological saline 250 mL after anaesthesia before CPB, the control control group were injected only physiological saline 250 mL at the same time. Blood samples were taken before induction of anesthesia and at 0.5, 2, 6, 24 hours after terminating CPB. To calculate P(A-a) DO2 and respiratory indexs (RI) by blood gas analysis, nitric oxide (NO) and endothelin-1 (ET-1) ET-1 were measured. At the same time, the time of CPB and artery blockage were recorded.</p><p><b>RESULT</b>There was no statistical significance before operation between 2 groups to every blood index. After CPB, P(A-a) DO2 , RI and ET-1 was higher than pre-operation after CPB (P < 0.05). But P(A-a) DO2, RI and ET-I of Shenmai group were lower than control group evidently at every point after CPB (P < 0.05 or P < 0.01). The concentrations of NO were reduced obveiously after CPB (P < 0.05), but in shenmai group, the range of descent was lower than control group (P < 0.01 or P < 0.05).</p><p><b>CONCLUSION</b>The concentrations of NO and ET-1 is connected with the lung injury after CPB. Through rise the level of NO and reduce the level of ET-1, Shenmai injection can alleviate the lung injury in some degree after CPB and improve pulmonary oxygenation function.</p>