Effect of penehyclidine hydrochloride on patients with acute lung injury and its mechanisms

Objective： To assess the effects of penehyclidine hydrochloride on patients with acute lung injury （ALI）, to observe the expression of Toll-like receptor 4 （TLR4） on the peripheral monocytes of ALI patients and changes of inflammatory ＆ anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI.Methods： Forty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group （P group, n=21） and conventional treatment group （control group, C group, n=24）. Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride （1 mg, im, q. 12 h） in addition.The TLR4 expression of 20 healthy volunteers were detected.The clinical effect, average length of stay in ICU and hospital,values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h.Results： The general conditions of the two groups were improved gradually and PaO2 increased progressively.Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased （P＜0.05）. The improvement in P group was obviously greater than that in C group （P＜0.05）. The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU （t=3.485, P＜0.01）. The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers （P＜0.01）. It decreased significantly at 24 h （t=2.032, P＜0.05） and 48 h （t=3.620, P＜0.01）and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome （ARDS）. The incidence of ARDS was 23.8% in P group and 29.17% in C group at 24 h.Until148 h, there were other two patients developing ARDS in control group. Serum IL-l, IL-8 and TNF-α expressions reduced after 24 h in both groups. The reduction in P group was more obvious than that in C group （P＜0.05）. IL-13 increased gradually from 0 h to 24 h, and decreased slightly at 48 h, which showed no difference between two groups （t=1.028, P＞0.05）.Conclusions： Penehyclidine hydrochloride improves the arterial oxygen pressure, down-regulates the expression of TLR4 and restrains the inflammatory cytokines in the downstream of TLR4 signaling pathway. It prevents the development of ALI and can be considered as an important drug in ALI treatment.     

Moderate hypothermia attenuates lung in flammation inlipopolysaccharide- induced acute lung injury in rats

Objective To investigate the role of moderate h.vpothennia in the lung inflammation of rat acute lung injury induced by lipopolysaccharide(LPS). Methods A rat model of acute lung injury (ALl) was established by in-tin-tracheal instillation of lipopolysaccharide ( 1.5 mg/kg, 0.5 ml) at 16 h after LPS ( 1.0 mg/kg) intraperitoneal adrninis-tmtion. Thirty-four male Sprague Dawley rats were randomly divided into four groups: control group, receiving saline only;LPS group, receiving LPS; hypothennia group, treated with hypothennia without LPS; LPS hypothennia group, treated with LPS and cooled to 32.5℃-33.0℃ as PaO2/FiO2. was below 300 mmHg. Hemodynamics and blood gases were record-ed every hour throughout the study. Rats were killed 4 h after ALl, and lung lavage was performed to measure the tumor ne-crosis factor α(TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) concentrations in bronchoalveolar lavage fluid (BALF) by using enzyme-linked immunosorbent assay (ELISA). Results PaO2/FiO2 was significantly decreased and PaCO2 was increased in the LPS group as compared to their baseline values( P＜0.01). Treatment with hypothermia inhib-ited the increase in PaCO2( P＜0.05) but had no effect on PaO2/FiO2 in the presence of LPS. The administration of LPS significantly increased the concentrations of TNF-α, IL-6 and IL-10 in BALF as compared to the control experiment( P＜0.05, P＜0.01 ). Moderate hypothermia reduced the expressions of TNF-α and IL-6 ( P＜0.01 ) but had no effect on the production of IL-10 ( P＞0.05). Conclusion Moderate hypothermia significantly inhibits proinflammatory cytokine ex-pressions in lipopolysaccharide-induced acute lung injury.     

不同剂量6%HES 130/0.4容量治疗对失血性休克大鼠肺损伤的影响

Objective To evaluate the effects of volume therapy with different doses of 6% hydroxyethyl starch 130/0.4 (6% HES 130/0.4) on lung injury in a rat model of hemonhagic shock.Methods Twenty-four male SD rats weighing 220-300 g were randomly divided into 4 groups ( n = 6 each) : group I sham operation (group S); group II Ringer's solution (group RS); group HI and IV 2 HES groups (group H1, H2 ). The animals were anesthetized with intraperitoneal 1% sodium pentobarbital 45 ing/kg. Right common carotid artery (CCA) and left femoral vein were cannulated for blood letting, MAP monitoring, fluid administration and blood sampling. Hemonhagic shock was induced by withdrawing blood from right CCA in group II , III and IV . MAP was reduced to 35-45 mmHg which was maintained for 90 min. In group RS, hemorrhagic shock was resuscitated with Ringer's solution 3 times of the volume of blood withdrawn, while group H1 and H2 received HES 33 and 50 ml/kg respectively and Ringer' s solution (the total volume was equal to 3 times of the volume of blood removed) . Arterial blood samples were taken before blood letting (T0 , baseline), and at 2, 3 h after volume therapy (T1,2) for blood gas analysis and PaO2/FiO2 was calculated. The animals were then sacrificed by exsanguination and the lungs were immediately removed for microscopic examination and determination of protein concentration in broncho-alveolar lavage fuid (BALF), W/D lung weight ratio and TNF-α, IL-1 β and IL-10 contents in the lung.Results TNF-α, IL-1β and IL-10 content in the lung, protein concentration in BALF and W/D ratio were significantly higher in group RS, H1 and H2, while PaO2/FiO2 was significantly lower at T,2 in group RS and at T2 in group H2 than in group S (P < 0.05). TNF-α and IL-1β contents in the lung, protein concentration in BALF and W/D ratio were significantly lower in group H1 and H2 , while PaO2/FiO2 was significantly higher at T,i2 in group H1 and at T1 in group H2 than in group RS (P <0.05) . PaO2/FiO2 at T2 and IL-10 content in the lung were significantly lower in group H2 than in group H, ( P < 0.05) . The lung damage was significantly ameliorated in group H1 and H2 especially in group H, as compared with group RS. Conclusion Volume therapy with 6% HES 130/0.4 33 or 50 ml/kg can attenuate lung injury in a rat model of hemorrhagic shock and the efficacy of 33 ml/kg is better.     

盐酸戊乙奎醚对大鼠胸部撞击致急性肺损伤及肺组织Toll样受体4表达的影响

目的 探讨盐酸戊乙奎醚对大鼠胸部撞击致急性肺损伤及肺组织Toll样受体4(TLR4)表达的影响.方法 健康雄性SD大鼠96只,体重250～300 g,采用随机数字表法,将大鼠随机分为3组(n=32):对照组(C组)只麻醉,不制备模型;肺损伤组(ALI组);盐酸戊乙奎醚组(PHcD组)模型制备后即刻,腹腔注射盐酸戊乙奎醚2 mg/kg.砝码(300g)于95 cm高处自由落体撞击大鼠心前区以制备急性肺损伤模型.于模型制备后2、8、12和24h时取8只大鼠,取动脉血样,测定血清TNF-α浓度.于模型制备后8 h取8只大鼠,取动脉血样,行动脉血气分析,随后处死大鼠,取肺组织观察病理学结果,测定干/湿重比(W/D比)、髓过氧化物酶(MPO)活性和TLR4表达水平.结果 与c组比较,ALI组和PHCD组pH值和PaO2下降,PaCO2、乳酸浓度、肺组织MPO活性、W/D比及TLR4表达和血清TNF-α浓度升高(P＜0.01);与ALI组比较,PHcD组pH值和PaO2升高,PaCO2、乳酸浓度、肺组织MPO活性、W/D比及TLR4表达和血清TNF-α浓度降低(P＜0.05).PHcD组肺组织病理性损伤较ALI组减轻.结论 盐酸戊乙奎醚可减轻大鼠胸部撞击诱发的急性肺损伤,其机制与下调肺组织TLR4表达,降低炎性反应有关.

Abstract：

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) on acute lung injury (ALI) induced by blunt chest trauma and Toll-like receptor 4 (TLR4) expression in the lung tissues in rats.Methods Ninety-six male SD rats weighing 250-300 g were randomly divided into 3 groups ( n = 32 each):control group (group C), ALI group and PHCD group. ALI was induced by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs in anesthetized rats according to the method described by Raghavendran et al. PHCD 2 mg/kg was injected intraperitoneally immediately after ALI was induced in group PHCD. Eight rats were selected at 2, 8, 12 and 24 h after ALI was induced, and arterial blood samples were collected for determination of the serum TNF-α concentration. Eight rats were selected at 8 h after ALI was induced, arterial blood samples collected for blood gas analysis and then the rats sacrificed. The lungs were immediately removed for determination of W/D lung weight ratio, myeloperoxidase (MPO) activity and TLR4 expression, and microscopic examination. Results The pH value and PaO2 were significantly lower, and the PaCO2, lactic acid level, MPO activity, W/D ratio, TLR4 expression and serum TNF-α concentration higher in groups ALI and PHCD than in group C (P ＜ 0.01 ). The pH value and PaO2 were significantly higher, and the PaCO2, lactic acid level, MPO activity, W/D ratio, TLR4 expression and serum TNF-α concentration lower in group PHCD than in group ALI ( P ＜ 0.05). The lung histopathologic damage was significantly ameliorated in PHCD group as compared with ALI group. Conclusion PHCD can protect the lungs against blunt chest trauma-induced ALI, and the down-regulation of TLR4 expression in lung tissues and reduction of inflammatory response are involved in the mechanism.     

不同剂量6%HES 130/0.4容量治疗对失血性休克大鼠肺损伤的影响

Objective To evaluate the effects of volume therapy with different doses of 6% hydroxyethyl starch 130/0.4 (6% HES 130/0.4) on lung injury in a rat model of hemonhagic shock.Methods Twenty-four male SD rats weighing 220-300 g were randomly divided into 4 groups ( n = 6 each) : group I sham operation (group S); group II Ringer's solution (group RS); group HI and IV 2 HES groups (group H1, H2 ). The animals were anesthetized with intraperitoneal 1% sodium pentobarbital 45 ing/kg. Right common carotid artery (CCA) and left femoral vein were cannulated for blood letting, MAP monitoring, fluid administration and blood sampling. Hemonhagic shock was induced by withdrawing blood from right CCA in group II , III and IV . MAP was reduced to 35-45 mmHg which was maintained for 90 min. In group RS, hemorrhagic shock was resuscitated with Ringer's solution 3 times of the volume of blood withdrawn, while group H1 and H2 received HES 33 and 50 ml/kg respectively and Ringer' s solution (the total volume was equal to 3 times of the volume of blood removed) . Arterial blood samples were taken before blood letting (T0 , baseline), and at 2, 3 h after volume therapy (T1,2) for blood gas analysis and PaO2/FiO2 was calculated. The animals were then sacrificed by exsanguination and the lungs were immediately removed for microscopic examination and determination of protein concentration in broncho-alveolar lavage fuid (BALF), W/D lung weight ratio and TNF-α, IL-1 β and IL-10 contents in the lung.Results TNF-α, IL-1β and IL-10 content in the lung, protein concentration in BALF and W/D ratio were significantly higher in group RS, H1 and H2, while PaO2/FiO2 was significantly lower at T,2 in group RS and at T2 in group H2 than in group S (P < 0.05). TNF-α and IL-1β contents in the lung, protein concentration in BALF and W/D ratio were significantly lower in group H1 and H2 , while PaO2/FiO2 was significantly higher at T,i2 in group H1 and at T1 in group H2 than in group RS (P <0.05) . PaO2/FiO2 at T2 and IL-10 content in the lung were significantly lower in group H2 than in group H, ( P < 0.05) . The lung damage was significantly ameliorated in group H1 and H2 especially in group H, as compared with group RS. Conclusion Volume therapy with 6% HES 130/0.4 33 or 50 ml/kg can attenuate lung injury in a rat model of hemorrhagic shock and the efficacy of 33 ml/kg is better.     

吸入一氧化碳对大鼠脑死亡致肺损伤的影响

Objective To investigate the effects of carbon monoxide (CO) inhalation on lung injury induced by brain death (BD) in rats. Methods Adult male Wistar rats weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg, tracheostomized and mechanically ventilated (VT 10 ml/kg, RR 50 bpm, PEEP 2 cm H2O). A balloon-tip catheter was placed in the cranium. Twenty-four rats in which Fogarty catheter was successfully placed in the cranium without complication were randomly divided into 3 groups ( n = 8 each) : group I sham operation (group S) ; group II BD and group Ⅲ BDCO. BD was induced by increase in intracranial pressure produced by inflating the balloon at the tip of the catheter. In group S the balloon of the catheter was not inflated. The animals inhaled 40% O2 for 150 min. In group BD, BD was induced and confirmed at 30 min after inflation of the balloon. Then 40% O2 was inhaled for 120 min. In group BDCO, 40% O2 and 0.025% CO were inhaled for 120 min after BD was confirmed at 30 min after balloon inflation. At the end of the experiment the animals were killed. Arterial blood samples were obtained for blood gas analysis before anesthesia (basline), immediately after confirmation of BD, and at 30, 60, 90 and 120 min of CO inhalation. Blood was collected for determination of plasma TNF-α, IL-6 and IL-10 concentrations at 120 min of CO inhalation. The lungs were obtained for determination of W/D lung weight ratio, and MPO activity in the lung tissue and microscopic examination. Lung injury scores were calculated. Results PaO2/FiO2 was stable during the 150 min in group S. Brain death significantly decreased PaO2/FiO2 at 30 min after balloon inflation. PaO2/FiO2 was gradually decreasing during the 120 min in group BD. CO inhalation prevented PaO2/FiO2 from decreasing further. W/D lung weight ratio and MPO activity were significantly higher in group BD than in group S and BDCO. The lung injury score (1 = normal, 4= severely injured) and plasma TNF-αα IL-6 and IL-10 concentrations were significantly higher in group BD than in group S. CO inhalation ameliorated the BD-induced lung injury and attenuated the increase in plasma TNF-a and IL-6 concentration. Plasma IL-10 concentration was significantly higher in group BDCO than in group BD. Conclusion CO inhalation can ameliorate acute lung injury induced by BD through decreasing the local and systemic inflammatory response.     

吸入一氧化碳对大鼠脑死亡致肺损伤的影响

Objective To investigate the effects of carbon monoxide (CO) inhalation on lung injury induced by brain death (BD) in rats. Methods Adult male Wistar rats weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg, tracheostomized and mechanically ventilated (VT 10 ml/kg, RR 50 bpm, PEEP 2 cm H2O). A balloon-tip catheter was placed in the cranium. Twenty-four rats in which Fogarty catheter was successfully placed in the cranium without complication were randomly divided into 3 groups ( n = 8 each) : group I sham operation (group S) ; group II BD and group Ⅲ BDCO. BD was induced by increase in intracranial pressure produced by inflating the balloon at the tip of the catheter. In group S the balloon of the catheter was not inflated. The animals inhaled 40% O2 for 150 min. In group BD, BD was induced and confirmed at 30 min after inflation of the balloon. Then 40% O2 was inhaled for 120 min. In group BDCO, 40% O2 and 0.025% CO were inhaled for 120 min after BD was confirmed at 30 min after balloon inflation. At the end of the experiment the animals were killed. Arterial blood samples were obtained for blood gas analysis before anesthesia (basline), immediately after confirmation of BD, and at 30, 60, 90 and 120 min of CO inhalation. Blood was collected for determination of plasma TNF-α, IL-6 and IL-10 concentrations at 120 min of CO inhalation. The lungs were obtained for determination of W/D lung weight ratio, and MPO activity in the lung tissue and microscopic examination. Lung injury scores were calculated. Results PaO2/FiO2 was stable during the 150 min in group S. Brain death significantly decreased PaO2/FiO2 at 30 min after balloon inflation. PaO2/FiO2 was gradually decreasing during the 120 min in group BD. CO inhalation prevented PaO2/FiO2 from decreasing further. W/D lung weight ratio and MPO activity were significantly higher in group BD than in group S and BDCO. The lung injury score (1 = normal, 4= severely injured) and plasma TNF-αα IL-6 and IL-10 concentrations were significantly higher in group BD than in group S. CO inhalation ameliorated the BD-induced lung injury and attenuated the increase in plasma TNF-a and IL-6 concentration. Plasma IL-10 concentration was significantly higher in group BDCO than in group BD. Conclusion CO inhalation can ameliorate acute lung injury induced by BD through decreasing the local and systemic inflammatory response.     

吸入一氧化碳对大鼠脑死亡致肺损伤的影响

Objective To investigate the effects of carbon monoxide (CO) inhalation on lung injury induced by brain death (BD) in rats. Methods Adult male Wistar rats weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg, tracheostomized and mechanically ventilated (VT 10 ml/kg, RR 50 bpm, PEEP 2 cm H2O). A balloon-tip catheter was placed in the cranium. Twenty-four rats in which Fogarty catheter was successfully placed in the cranium without complication were randomly divided into 3 groups ( n = 8 each) : group I sham operation (group S) ; group II BD and group Ⅲ BDCO. BD was induced by increase in intracranial pressure produced by inflating the balloon at the tip of the catheter. In group S the balloon of the catheter was not inflated. The animals inhaled 40% O2 for 150 min. In group BD, BD was induced and confirmed at 30 min after inflation of the balloon. Then 40% O2 was inhaled for 120 min. In group BDCO, 40% O2 and 0.025% CO were inhaled for 120 min after BD was confirmed at 30 min after balloon inflation. At the end of the experiment the animals were killed. Arterial blood samples were obtained for blood gas analysis before anesthesia (basline), immediately after confirmation of BD, and at 30, 60, 90 and 120 min of CO inhalation. Blood was collected for determination of plasma TNF-α, IL-6 and IL-10 concentrations at 120 min of CO inhalation. The lungs were obtained for determination of W/D lung weight ratio, and MPO activity in the lung tissue and microscopic examination. Lung injury scores were calculated. Results PaO2/FiO2 was stable during the 150 min in group S. Brain death significantly decreased PaO2/FiO2 at 30 min after balloon inflation. PaO2/FiO2 was gradually decreasing during the 120 min in group BD. CO inhalation prevented PaO2/FiO2 from decreasing further. W/D lung weight ratio and MPO activity were significantly higher in group BD than in group S and BDCO. The lung injury score (1 = normal, 4= severely injured) and plasma TNF-αα IL-6 and IL-10 concentrations were significantly higher in group BD than in group S. CO inhalation ameliorated the BD-induced lung injury and attenuated the increase in plasma TNF-a and IL-6 concentration. Plasma IL-10 concentration was significantly higher in group BDCO than in group BD. Conclusion CO inhalation can ameliorate acute lung injury induced by BD through decreasing the local and systemic inflammatory response.     

吸入一氧化碳对大鼠脑死亡致肺损伤的影响

Objective To investigate the effects of carbon monoxide (CO) inhalation on lung injury induced by brain death (BD) in rats. Methods Adult male Wistar rats weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg, tracheostomized and mechanically ventilated (VT 10 ml/kg, RR 50 bpm, PEEP 2 cm H2O). A balloon-tip catheter was placed in the cranium. Twenty-four rats in which Fogarty catheter was successfully placed in the cranium without complication were randomly divided into 3 groups ( n = 8 each) : group I sham operation (group S) ; group II BD and group Ⅲ BDCO. BD was induced by increase in intracranial pressure produced by inflating the balloon at the tip of the catheter. In group S the balloon of the catheter was not inflated. The animals inhaled 40% O2 for 150 min. In group BD, BD was induced and confirmed at 30 min after inflation of the balloon. Then 40% O2 was inhaled for 120 min. In group BDCO, 40% O2 and 0.025% CO were inhaled for 120 min after BD was confirmed at 30 min after balloon inflation. At the end of the experiment the animals were killed. Arterial blood samples were obtained for blood gas analysis before anesthesia (basline), immediately after confirmation of BD, and at 30, 60, 90 and 120 min of CO inhalation. Blood was collected for determination of plasma TNF-α, IL-6 and IL-10 concentrations at 120 min of CO inhalation. The lungs were obtained for determination of W/D lung weight ratio, and MPO activity in the lung tissue and microscopic examination. Lung injury scores were calculated. Results PaO2/FiO2 was stable during the 150 min in group S. Brain death significantly decreased PaO2/FiO2 at 30 min after balloon inflation. PaO2/FiO2 was gradually decreasing during the 120 min in group BD. CO inhalation prevented PaO2/FiO2 from decreasing further. W/D lung weight ratio and MPO activity were significantly higher in group BD than in group S and BDCO. The lung injury score (1 = normal, 4= severely injured) and plasma TNF-αα IL-6 and IL-10 concentrations were significantly higher in group BD than in group S. CO inhalation ameliorated the BD-induced lung injury and attenuated the increase in plasma TNF-a and IL-6 concentration. Plasma IL-10 concentration was significantly higher in group BDCO than in group BD. Conclusion CO inhalation can ameliorate acute lung injury induced by BD through decreasing the local and systemic inflammatory response.     

吸入一氧化碳对大鼠脑死亡致肺损伤的影响

Objective To investigate the effects of carbon monoxide (CO) inhalation on lung injury induced by brain death (BD) in rats. Methods Adult male Wistar rats weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg, tracheostomized and mechanically ventilated (VT 10 ml/kg, RR 50 bpm, PEEP 2 cm H2O). A balloon-tip catheter was placed in the cranium. Twenty-four rats in which Fogarty catheter was successfully placed in the cranium without complication were randomly divided into 3 groups ( n = 8 each) : group I sham operation (group S) ; group II BD and group Ⅲ BDCO. BD was induced by increase in intracranial pressure produced by inflating the balloon at the tip of the catheter. In group S the balloon of the catheter was not inflated. The animals inhaled 40% O2 for 150 min. In group BD, BD was induced and confirmed at 30 min after inflation of the balloon. Then 40% O2 was inhaled for 120 min. In group BDCO, 40% O2 and 0.025% CO were inhaled for 120 min after BD was confirmed at 30 min after balloon inflation. At the end of the experiment the animals were killed. Arterial blood samples were obtained for blood gas analysis before anesthesia (basline), immediately after confirmation of BD, and at 30, 60, 90 and 120 min of CO inhalation. Blood was collected for determination of plasma TNF-α, IL-6 and IL-10 concentrations at 120 min of CO inhalation. The lungs were obtained for determination of W/D lung weight ratio, and MPO activity in the lung tissue and microscopic examination. Lung injury scores were calculated. Results PaO2/FiO2 was stable during the 150 min in group S. Brain death significantly decreased PaO2/FiO2 at 30 min after balloon inflation. PaO2/FiO2 was gradually decreasing during the 120 min in group BD. CO inhalation prevented PaO2/FiO2 from decreasing further. W/D lung weight ratio and MPO activity were significantly higher in group BD than in group S and BDCO. The lung injury score (1 = normal, 4= severely injured) and plasma TNF-αα IL-6 and IL-10 concentrations were significantly higher in group BD than in group S. CO inhalation ameliorated the BD-induced lung injury and attenuated the increase in plasma TNF-a and IL-6 concentration. Plasma IL-10 concentration was significantly higher in group BDCO than in group BD. Conclusion CO inhalation can ameliorate acute lung injury induced by BD through decreasing the local and systemic inflammatory response.     

Role of nitric oxide in treatment of acute lung injury after surgery with extracorporeal circulation

Postoperative acute lung injury (ALI) compromises oxygen transfer across alveolar-capillary membrane with consecutive hypoxia, one of its indicators being reduction of oxygenation index PaO2/FiO2 below 40 kPa (300 mm Hg). Management of ALI includes different procedures like mechanical lung ventilation (MLV), drugs and others. One of the new possibilities for treatment of ALI is nitric oxide (NO) inhalation. The aim of this prospective study was to examine the role of NO inhalation in treatment of ALI. 14 patients with ALI developed immediately after operation with extracorporeal circulation (ECC) were included in the study. Group A (n = 8) inhaled NO and group B (n = 6) did not inhale NO during treatment of ALI. All other therapeutic measures were the same in both groups. The groups were similar in relation to demographic data, type of surgery and duration of ECC. PaO2/FiO2 was calculated before operation (T1), immediately after surgery (T2) and after lung recovery, when the need for MLV stopped (T3). The duration of MLV was also registered. PaO2/FiO2 (kPa) in referent times was in group A 54.9 +/- 1.6, 33.8 +/- 1.2 and 46.2 +/- 0.8 and in group B 52.2 +/- 1.1, 33.5 +/- 1.5 and 47.3 +/- 0.9, respectively. There was a statistically significant decrease of PaO2/FiO2 in T2 and T3 vs T1 in both groups (p < 0.05), while the difference between the groups was not statistically significant. The duration of MLV (h) in group B (28.5 +/- 1.6) was statistically significantly shorter than in group A (63.1 +/- 8.7) (p < 0.01). According to the results of this study we conclude that NO inhalation during ALI after surgery with ECC significantly reduces the duration of MVL and improves pulmonary recovery.     

原位肝移植术后急性肺损伤的研究进展

急性肺损伤(acute lung injury,ALI)是原位肝移植术(orthotopic liver transplant,OLT)后常见的并发症,是术后医院时间延长及死亡率增加的重要原因.ALI的诊断标准是氧合指数(分氧压/吸氧浓度)<300,肺小动脉楔压<18 mm Hg,X先示肺部浸润征.ALI可发展成为急性呼吸窘迫综合征(acute respiratory distress syndrome,ARPS),其诊断除氧合指数<200外,其他与ALI相同,此文对OLT术后ALI的发生,临床因素及机制作一综述.     

肝移植术后患者并发急性肺损伤与术中氧代谢的关系

目的 研究肝移植术后患者并发急性肺损伤(ALI)与术中氧代谢的关系.方法 择期行肝移植术的终末期肝病患者62例,年龄29～63岁,体重48～76 kg,ASA Ⅲ或Ⅳ级.于麻醉诱导后(T1)、无肝期前10 min(T2)、无肝期25 min(T3)、新肝期30 min(T4)及术毕(T5)时,采集桡动脉血和混合静脉血进行血气分析,计算动脉血氧含量(CaO2)、混合静脉血氧含量(C(v)O2)、动脉-混合静脉血氧含量差(Ca-(v)O2)、氧供指数(DO2I)、氧耗指数(VO2I)、氧摄取率(ERO2)和通气.血流灌注指数(VQI).根据术后14 d内是否发生ALI分为2组:ALI组和非ALI组.两组氧代谢指标与术后ALI发生与否进行logistic回归分析.结果 与T1时相比,T2,4,5时P(v)O2升高,T3时降低,T2-5时CaO2、C(v)O2升高,T3时Ca-(v)O2升高,T2,4,5时DO2I、VO2I升高,ERO2降低,T3时VQI降低,氧合指数T3时降低,T4时升高(P<0.05).与非ALI组相比,ALI组T4,5时CaO2、C(v)O2和DO2I降低,T1,2,4,5时PaO2降低(P＜0.05).logistic回归分析结果示T4时PaO2和T5时CaO2与术后发生ALI有关(P<0.05).结论 肝移植术后患者并发ALI可能与新肝期氧代谢异常有关.     

Evaluation of the oxygenation ratio as long-term prognostic marker after lung transplantation

OBJECTIVE: We hypothesized that the arterial blood gas oxygen tension/fraction of inspired oxygen ratio (PaO2/FiO2) would prove to be useful as a mortality marker after lung transplantation (LT). The aims of this study were to define the prevalence of various ranges of PaO2/FiO2 during the first 24 hours after LT and to evaluate which measurement using the PaO2/FiO2 best correlates with mortality. METHODS: A retrospective study was performed that included all patients who underwent LT from 1997 to 2005. We collected PaO2/FiO2 ratios at 0, 12, and 24 hours after admission to the intensive care unit (ICU). We classified the 132 patients in 5 groups, based on PaO2/FiO2 (Group 1, PaO2/FiO2 <100; Group 2, PaO2/FiO2 100-199; Group 3, PaO2/FiO2 200-299; Group 4, PaO2/FiO2 300-399; Group 5, PaO2/FiO2 >or=400). The correlation between PaO2/FiO2 and mortality was studied using Cox regression. RESULTS: Cox regression analysis showed that PaO2/FiO2 at 0 and 12 hours after admission to the ICU were not useful mortality markers. However, the PaO2/FiO2 at 24 hours after admission to the ICU was a useful long-term prognostic marker. PaO2/FiO2 >100 (groups 2, 3, 4, and 5) at 24 hours was significantly associated with less mortality when a lower PaO2/FiO2 was the reference (hazard Ratio: 0.08, 0.02, 0.05, and 0.02, respectively). On multivariate analysis PaO2/FiO2 >or=100 (groups 2, 3, 4, and 5) at 24 hours was significantly associated with less mortality when a lower PaO2/FiO2 was the reference (hazard ratio: 0.07, 0.003, 0.01, and 0.005, respectively). CONCLUSIONS: A value of PaO2/FiO2 >100 mm Hg 24 hours after admission to the ICU is associated with a lower mortality.     

肝移植术后患者早期呼吸机脱机延迟的术前及术中危险因素

目的 分析肝移植术后患者早期呼吸机脱机延迟的术前及术中危险因素.方法 2004年9月至2006年8月212例肝移植术患者,其中男性152例,女性60例,年龄22～69岁.术中常规麻醉管理,按输血原则输入血制品,并维持平均动脉压不低于60 mm Hg.记录16个术前变量和7个术中变量.术后24 h按第1次拔除气管导管时间分为正常脱机组和脱机延迟组.结果 两组间9个术前变量[分别为年龄＞64岁、PaO2＜75 mm Hg、胸膜渗出、Ⅲ级以上肝性脑病、合并自发性细菌性腹膜炎、晚期肝病模型(MELD)评分、血清白蛋白、腹水≥20 ml/kg和中度门肺高压]及5个术中变量[RBC输入量、新鲜冰冻血浆输入量、晶体液输入量、胶体液输入量和尿量＜1 ml·kg-1·h-1]差异有统计学意义(P＜0.05或0.01).logistic回归分析显示,5个术前变量(年龄＞64岁、PaO2＜75 mm Hg、Ⅲ级以上肝性脑病、MELD评分和中度门肺高压)及2个术中变量(RBC输入量和尿量＜1 ml·kg-1·h-1)与术后脱机延迟存在相关性(P＜0.05或0.01).结论 5个术前变量(年龄＞64岁、术前PaO2＜75 mm Hg、Ⅲ级以上肝性脑病、MELD评分和中度门肺高压)及2个术中变量(RBC输入量和尿量＜1 ml·kg-1·h-1)是肝移植术后患者早期脱机延迟的危险因素.     

Effects of different intramedullary stabilizing procedures of the femur on lung function in polytrauma]

We investigated the effects of primary (< 24 h) intramedullary femoral nailing on lung function and pulmonary hemodynamics in multiple trauma patients. The standard procedure following reaming of the medullary canal (AFN) was compared with a new procedure using a small, solid nail without prior reaming (UFN). Pulmonary hemodynamics were determined using a pulmonary artery catheter. Global lung function was assessed by means of the oxygenation ratio (PaO2/FiO2). Concentrations of elastase and the platelet count as a general parameter of the clinical course were determined from central venous blood during and 3 days after surgery. The lung function was stable in UFN patients (n = 6), but decreased significantly in AFN patients (n = 10) from 353 +/- 24 (PaO2/FiO2 preoperative) to 260 +/- 28 (PaO2/FiO2 postoperative) and did not improve until 48 h later. Pulmonary artery pressure (Pap) remained within normal limits in UFN patients, whereas in AFN patients Pap increased from 27.4 +/- 3 mm Hg (preoperative) to 37 +/- 3 mm Hg during reaming and did not normalize until 1 h after insertion of the nail. The platelet count remained unchanged in UFN patients and dropped in AFN patients from 143 +/- 25 x 1000 cells/ml blood (preoperative) to 87.5 +/- 15 x 1000 cells/ml blood 2 days after surgery. Our measurements did not show an increase in central venous triglycerides in the AFN group, probably because bone marrow does not become immediately soluble. There was no significant difference between the increase of elactase levels in the two groups. The femoral nailing procedure with reaming in multiple trauma patients involves a potential risk to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

乌司他丁对主动脉夹层术后急性肺损伤治疗效果的研究

目的:探讨乌司他丁对主动脉夹层术后急性肺损伤(ALI)的治疗作用.方法:将2009年与2010年主动脉夹层术后出现ALI的18例和21例患者分别设为常规治疗组和乌司他丁治疗组.针对ALI,常规治疗组给予常规治疗,乌司他丁治疗组在常规治疗基础上应用乌司他丁300 kU+生理盐水100 ml静脉滴注,每日1次,连用3 d....     

肝移植术后急性肺损伤的治疗策略

目的探讨肝移植术后急性肺损伤（ALI）的治疗方法和策略。方法肝移植术后合并Au患者18例,于术后早期给予预防感染、限液、减少炎症反应的措施,并积极纠正低氧血症。于出现低氧血症3h内经提高吸氧浓度不能纠正低氧者,给予肺复张结合肺保护通气策略,即给予吸气压力25cmH2O呼气未正压（及PEEP）17cmH2O通气2min,扩张已萎陷实变的肺泡,随后逐步降低PEEP至压力-容积曲线低位转折点（Pinf）以上2cmH：O处,预防肺泡闭塞,保持肺泡复张。结果18例患者经综合治疗及肺复张后氧分压、氧饱和度及吸氧分数均有明显改善,除1例肺部严重感染患者肺复张后吸氧分数仅上升40％,余17例均对肺复张反应良好,吸氧分数上升＞50％。复张后平均氧分压上升68mmHg,平均氧饱和度上升9．5％,平均吸氧分数上升104．7％,改善的氧合可维持2—24h。肺复张结合肺保护通气策略纠正低氧血症的有效率为94．4％,18例Au患者均成功脱机拔管,康复出院。患者对肺复张的耐受性佳,无明显并发症。结论肝移植术后Au需及时诊断和综合治疗,肺复张结合肺保护通气策略是治疗肝移植术后Au或ARDS的安全有效措施。