Mesenchymal stem cell attenuates neutrophil-predominant inflammation and acute lung injury in an in vivo rat model of ventilator-induced lung injury.

BACKGROUND: Subsequent neutrophil (polymorphonuclear neutrophil [PMN])-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI), and mesenchymal stem cell (MSC) can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair of VILI. However, whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown. This study aimed to test whether MSC intervention could attenuate the PMN-predominate inflammatory in the mechanical VILI. METHODS: Sprague-Dawley rats were ventilated for 2 hours with large tidal volume (20 mL/kg). MSCs were given before or after ventilation. The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation, and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation. RESULTS: Mechanical ventilation (MV) caused significant lung injury reflected by increasing in PMN pulmonary sequestration, inflammatory chemokines (tumor necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein 2) in the bronchoalveolar lavage fluid, and injury score of the lung tissue. These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity, production of radical oxygen series. MSC intervention especially pretreatment attenuated subsequent lung injury, systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation. CONCLUSIONS: MV causes profound lung injury and PMN-predominate inflammatory responses. The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.

[Effect of continuous hemofiltration for treatment of multiple organ dysfunction syndrome after acute myocardial infarction in elderly patients].

OBJECTIVE: To study the effect of continuous hemofiltration (CH) on the prognosis of multiple organ dysfunction syndrome (MODS) after acute myocardial infarction (AMI) in elderly patients. METHODS: Thirty-four elderly patients with MODS after AMI admitted to intensive care unit (ICU) were grouped into continuous hemofiltration (CH) group and non-CH (NCH) group. The Acute Physiology and Chronic Health Evaluation (APACHEII) scores and Marshall scores were assessed upon admission in ICU and 7 days after the admission. The mortality rates of the patients within 28 and 90 days after admission to ICU were calculated, and the changes in APACHEII scores and Marshall scores were compared between the two groups. RESULTS: The APACHEII scores and Marshall scores showed no significant difference between the two upon admission to the ICU, but significantly decreased in CH group 7 days after the admission (P<0.05 and P<0.01 respectively). The APACHEII scores increased significantly in NCH group (P<0.01) 7 days after the admission while the Marshall scores remained unchanged (P>0.05). The overall mortality rates at 28 and 90 days were 41.18% and 61.76%, respectively. A significant difference was noted in the mortality rate at 28 days between the two groups (P<0.05), but not in the rate at 90 days (P>0.05). CONCLUSION: CH can improve the organic functions and the short-term outcome of elderly patients with MODS after AMI, but has no positive effect on their long-term outcomes.

Serum and lung endothelin-1 increased in a canine model of ventilator-induced lung injury.

BACKGROUND: Nitric oxide (NO) plays an important role in acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and in ventilator-induced lung injury (VILI). A change in the balance of endothelin-1 (ET-1) and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model. METHODS: Models of oleic acid induced ALI were established in dogs; these models were then randomized into three groups undergone different tidal volume (VT) mechanical ventilation, which included a VT6 group (VT equaled to 6 ml/kg body weight, positive end expiratory pressure (PEEP) equaled to 10 cmH2O, n = 6), a VT10 group (VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH2O, n = 4) and a VT20 group (VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH2O, n = 6) for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial. RESULTS: PaO2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALI models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation (P < 0.05) while the serum NO levels were similar in the three groups (all P > 0.05). There was no significant difference in serum ratio of ET-1/NO between any two out of three groups (P > 0.05), although there was a significant positive relationship between serum ET-1 and serum NO (r = 0.80, P < 0.01). The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group (both P < 0.05) while there was no significant difference in lung NO levels between two groups (P > 0.05). In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation (P < 0.05) as there was a significant positive relationship between ET-1 and NO in the lung (r = 0.54, P < 0.05). CONCLUSIONS: The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.

[Effect of mechanical ventilation with different tidal volume on small intestine in dogs suffering from acute lung injury].

OBJECTIVE: To compare the effect of different tidal volume (VT) on intestinal tissue in oleic acid-induced acute lung injury (ALI) dogs undergoing mechanical ventilation (MV). METHODS: ALI was induced with oleic acid in dogs. While all of them were undergoing MV, they were randomized into two groups: low VT group (n=6), with VT 6 ml/kg, positive end-expiratory pressure (PEEP) 10 cm H2O (1 cm H2O= 0.098 kPa), and large VT group (n=6), with VT 20 ml/kg, PEEP 10 cm H2O. MV with different VT was maintained for 6 hours. After 6 hours, dogs were sacrificed by exsanguination. Pathological changes in small bowel tissues were observed with hematoxylin and eosin (HE) staining, and cellular apoptosis detected with terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) in situ apoptosis determination. RESULTS: After 6-hour MV, the degree of flatulence was severe in the large VT group, but no flatulence was observed in the low VT group. Bowel injury score was lower in the low VT group than in large VT group [(3.17+/-0.75) scores vs. (2.00+/-0.89) scores]. There was significant difference between two groups (P<0.01). Apoptosis-positive cells were rare in the small bowel tissues in both groups. CONCLUSION: MV with large VT can induce bowel dysfunction, in contrast low VT MV does not produce small bowel dysfunction.

[Clinical value of the model for end-stage liver disease score in predicting the prognosis of liver transplantation in patients with end-stage liver disease].

OBJECTIVE: To assess the value of the model for end-stage liver disease (MELD) in predicting the early-stage outcome of liver transplantation in patients with end-stage liver disease. METHODS: The MELD scores of 87 liver transplantation recipients with end-stage liver disease were calculated, and their early-stage complications and mortality were analyzed. RESULTS: The incidence of severe complications was 20.7%; in these recipients, with the 28-day and 3-month survival rates of 89.7%; and 88.5%;, respectively. The mean MELD scores showed significant differences between the complication-free group and survival group (14.6 vs 12.9, P<0.05), and also between the complication group and death group (21.6 vs 29.4, P<0.05). Compared to patients with MELD no greater than 15, patients with MELD between 16 and 24 showed significantly increased complication rate but had comparable survival rate (P>0.05); but in patients with MELD no less than 25, the survival rate was significantly decreased with also increased complication rate. CONCLUSIONS: A higher MELD score before liver transplantation is associated with greater likeliness of early-stage complication rate and mortality. High MELD score (over 25) can be a useful index in predicting severe complications and death in patients undergoing liver transplantation.