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Objective To explore the effects of multidrug resistance-associated protein 4 (MRP4) inhibition on pulmonary vascular endothelial barrier dysfunction in septic rats.Methods Sixty Sprague Dawley rats were randomly (random number) divided into three groups:sham-operated group,sepsis group,and sepsis plus MRP4 inhibitor treatment group,with 20 rats in each group.Sepsis was induced by cecal ligation and puncture.MRP4 inhibitor MK571 (20 mg/kg) was administrated by intraperitoneal injection 30 minutes before induction of sepsis.Twenty-four later,serum interlukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels were measured by enzyme-linked immunosorbent assay.Lung injury was assessed by histopathological examination.Lung vascular permeability was evaluated by quantitation of Evans blue dye extravasation from vascular space to lung parenchyma.Results Compared with sham group,serum IL-6 and TNF-α levels were significantly higher in sepsis group.In addition,lung injury and lung vascular permeability were elevated in sepsis group compared to sham group.Importantly,MRP4 inhibitor treatment significantly decreased serum IL-6 and TNF-α levels,improved lung injury and reduced lung vascular permeability in septic rats.Conclusions Inhibition of MRP4 protects against pulmonary vascular endothelial barrier dysfunction in septic rats.
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Objective To compare the myocardial damage in patients with severe valvular heart disease undergoing open heart surgery under propofol and sevoflurane combined anesthesia.Methods Thirty-two patients with severe heart valvular disease undergoing open heart surgery were randomized into 3 groups:midazolam group (group M,n =8),propofol group (group P,n =12) and sevoflurane group (group S,n =12).Midazolam 1-5 mg,vecuronium 0.15 mg/kg and fentanyl 10-20 μg/kg were injected intravenously in group M.Propofol 1-2 mg/kg,vecuronium 0.15 mg/kg and fentanyl 10 μg/kg were injected intravenously in group P.In group S,the patients inhaled sevoflurane until the eyelash reflex disappeared,the end-tidal concentration of sevoflurane was 0.5 ％-2.0％,and vecuronium 0.15 mg/kg and fentanyl 10μg/kg were injected intravenously.The patients were mechanically ventilated after tracheal intubation.Anesthesia was maintained with iv infusion of midazolam 0.1 mg· kg-1 · h-1,fentanyl 0.2 μg· kg-1 · min-1,and vecuronium 0.12 mg· kg-1 · h-1 in group M,with iv infusion of propofol 150 μg· kg-1 · min-1 and fentanyl μg· kg-1 · min-1 in group P,or with inhalation of 0.5％-2.0％sevoflurane in group S.CPB was established routinely.The concentration of sevoflurane was 0.5 ％-1.0％ during CPB.Venous blood samples were collected before anesthesia (T1),at 20 min and 2 h after aortic unclamping (T2,3),and at 24 h after operation (T4) for determination of the levels of plasma lactic dehydrogenase (LDH),creatine kinase (CK),creatine kinase MB (CK-MB),cardiac troponin Ⅰ (cTnⅠ),superoxide dismutase (SOD)and tumor necrosis factor (TNF)-α.Myocardial tissues were taken at T2 for determination of heme oxygenase-1 (HO-1) expression and for examination of the myocardial ultrastructure.Results Compared with group M,the levels of plasma LDH,CK-MB,and CK were significantly decreased at T2-4,the levels of plasma SOD and cTnⅠ were significantly increased at T2,3,and the expression of HO-1 was up-regulated at T2 in groups P and S,and the levels of plasma TNF-α were significantly decreased at T2-4 in group P and at T2,3 in group S (P ＜ 0.05).The pathologic changes induced by I/R were less severe in groups P and S than in group M.Conclusion Both propofol and sevoflurane can attenuate the myocardial damage in patients with severe valvular heart disease undergoing open heart surgery and the effects are comparable.