Ulinastatin decreases permeability of blood--brain barrier by inhibiting expression of MMP-9 and t-PA in postoperative aged rats.

Tissue-type plasminogen activator (t-PA) and matrix metalloproteinase-9 (MMP-9) have been reported to play important roles in increased permeability of blood-brain barrier (BBB) under many pathological circumstances. We have showed that Ulinastatin, a broad-spectrum serine protease inhibitor, could alleviate inflammation in the hippocampus of aged rats following partial hepatectomy. In this study, we investigate the expression and potential roles of t-PA and MMP-9 in the protective effect of Ulinastatin. We found that partial hepatectomy increased Evans blue leakage in hippocampus at day 1 and 3 postoperatively. Furthermore, surgery decreased the protein levels of claudin-5, ZO-1, and NF-kB p65 while upregulating the mRNA and protein levels of t-PA and MMP-9 in brain capillaries. All these effects caused by surgery were partially reversed by administering Ulinastatin. Our study sheds light on the roles of t-PA and MMP-9 of BBB in post-surgical neuroinflammation and postoperative cognitive dysfunction. Besides, it could also help to understand the mechanism of Ulinastatin alleviating neuroinflammation.

Comparison of neonatal tolerance to thoracoscopic and open repair of esophageal atresia with tracheoesophageal fistula.

BACKGROUND: Advances in minimally invasive surgical techniques and neonatal intensive care for neonates have allowed for repair of the neonatal esophageal atresia with tracheoesophageal fistula (EA/TEF) to be approached endoscopically. However, thoracoscopic surgery in children is still performed in only a few centers throughout the world. The aim of this study was to compare the neonatal tolerance to the thoracoscopic repair (TR) and the open repair (OR) and also to discuss anesthetic management in thoracoscopic procedure. METHODS: We performed a prospective study enrolling newborns diagnosed with EA with distal TEF (type C) receiving the repair surgery between June 2009 and January 2012 in our institution. Data collected included the newborns' gestational age and weight at the time of the operation, operative time, parameters of intraoperative mechanical ventilation, oxygenation, end-tidal carbon dioxide (ETCO2), and analysis of blood gases. Time to extubation and length of stay were also recorded. RESULTS: Intravenous induction with muscle paralysis followed by pressure-control ventilation and tracheal intubation regardless of the position of the fistula can be performed uneventfully in EA/TEF newborns with no additional airway anomalies and large, pericarinal fistulas in our experiences. The thoracoscopic approach appeared to take longer than the open approach. During the procedure of repair, hypercarbia and acidosis developed immediately 1 hour after pneumothorax in both groups. CO2 insufflation did have additional influence on the respiratory function of the newborns in the TR group; values of PaCO2 and ETCO2 were higher in the TR group but the difference did not reach statistical significance. By the end of the procedure, values of PaCO2 and ETCO2 returned to the baseline levels while pH did not, but all parameters made no difference in the two groups. Besides, time to extubation was shorter in the TR group. CONCLUSIONS: Thoracoscopic repair of EA/TEF is comparable to the open repair, and is believed to be safe and tolerable in selected patients. A wider range of neonates may be acceptable for thoracoscopic EA/TEF repair with increasing surgical experience.

[Incidence of deep venous thrombosis (DVT) in patients undergoing thoracotomy and changes of hemostasis].

OBJECTIVE: To survey the incidence of deep venous thrombosis (DVT) in high risk patients undergoing thoracotomy and observe the changes of hemostatic activity. METHODS: Fifty-two consecutive patients (ages that ranged from 35 to 79, 34 men and 18 women) with lung or esophagus cancer were enrolled into this prospective trial. The patients included underwent major thoracic surgery from February 2003 to April 2003. Bilateral lower extremity duplex ultrasonography for DVT screening was performed 3-10 days post surgery in all 52 patients and 57 matched clinic normal controls. Venous blood was collected to determine fibrinogen (FIB), D-dimer(D-D), plasminogen activator inhibitor (PAI), antithrombin (AT)i thrombin antithrombin complex (TAT), prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) immediately before surgery, the third and tenth days postoperatively. No patient had a prior thromboembotic history. Risk factors for DVT were evaluated. RESULTS: Of the 52 patients, 28 (53.8%) had an acute postoperative DVT detected in the calf. One patient died of suspected pulmonary embolism postoperatively. Plasma levels of FIB and D-D increased significantly up to 7 d after operation. AT level decreased significantly 3 d after operation and returned to normal 7 d latter. TAT increased significantly 3 d post operation and decreased to normal on day 7. PAI level was lowered 3 d after surgery, but increased significantly on day 7 compared with that on day 3. With the addition of risk factors related to thrombosis, the incidence of DVT was increased correspondingly. CONCLUSION: Of the patients undergoing major thoracic surgery,53.8% of them had a postoperative DVT by postoperative screening duplex ultrasound. In Chinese population, incidence of DVT appears to be high without prophylaxis, which is similar to other reports of westerners. These patients had a number of risk factors for the development of DVT, which include older age, overweight, hypertension, diabetes, and history of thromboembolism, etc. Prophylactic measures should be taken against postoperative venous thromboembolism in major thoracic surgery with high risk, including early mobilization, anticoagulant therapy with heparins, and intermittent pneumatic compression (IPC).

[Influence of lipopolysaccharide pretreatment on acute lung injury induced by lipopolysaccharide in rats].

OBJECTIVE: To evaluate the effect of lipopolysaccharide pretreatment on blocking the development of lipopolysaccharide (E.Coli O(55):B(5)) induced acute lung injury. The activity of nuclear factor-kappaB (NF-kappaB) in alveolar macrophages was assessed to elucidate its mechanism. METHODS: Thirty-six Wistar rats were divided into three groups: normal saline (A), lipopolysaccharide (B), lipopolysaccharide preconditioning (C). Rat model of acute lung injury was reproduced by administering intraperitoneally lipopolysaccharide in a dose of 6 mg/kg. Group A and B served as control. In the test group (group C) lipopolysaccharide was given intraperitoneally 0.5 mg/kg, 0.5 mg/kg and 1.0 mg/kg consecutively for 3 days before lipopolysaccharide challenge. Four hours after lipopolysaccharide/normal saline administration, the animals were killed. Blood gas was measured. And total protein of bronchoalveolar lavage fluid (BALF) was calculated by measuring the radioactivity of (99)Tc labeled serum albumin. Wet/dry ratios of the lungs of each group were determined. The nuclear protein of the alveolar macrophages was extracted from BALF, and the activity of NF-kappaB was assayed with electrophoretic mobility shift assay (EMSA). Microscopic examination of the lung was done. RESULTS: In group C, partial pressure of oxygen in artery (PaO(2)) was significantly higher than that in group B, and total protein content of BALF was significantly lower in group A and C than that in group B. Activity of NF-kappaB in group C was higher than group A and B. CONCLUSION: Lipopolysaccharide pretreatment can reduce the severity of acute lung injury induced by lipopolysaccharide challenge. This phenomenon may be related with change in the activity of NF-kappaB of the alveolar macrophages.