Apigenin Reduces NF-κB and Subsequent Cytokine Production as Protective Effect in a Rodent Animal Model of Lung Ischemia-Reperfusion Injury.

PURPOSE: Lung ischemia-reperfusion injury (LIRI) can complicate lung transplantation or cardiac surgery with cardiopulmonary bypass, increasing morbidity and mortality. In LIRI, pro-inflammatory cytokines are activated, reactive oxygen species are generated and nuclear factor-κB (NF-κB) is up-regulated, altering lung mechanics. We tested the effect of the flavonoid apigenin on a rodent model of LIRI. METHODS: Thirty-seven Wistar rats were subjected to LIRI with or without a single or double dose of apigenin. Induction of LIRI involved sternotomy and clamping of either the left lung hilum or the pulmonary artery alone for 30 min, followed by 60 min of reperfusion. Control groups consisted of LIRI plus NaCl, a sham group and a baseline group. At the end of the experiments, both lungs were analyzed by RT-PCR, Western blot, and light microscopy. RESULTS: In placebos, the expression levels of pro-inflammatory markers were increased in both lungs significantly, whereas NF-κB was markedly up-regulated. Administration of apigenin reduced the activation of NF-κB and the expression of TNFα, iNOS, and IL-6. These effects were observed in total lung ischemia. Histology showed greater hemorrhage and exudation in the pulmonary periphery of all groups, whereby damage was practically absent in the central lung regions of the apigenin animals. A second dose of apigenin did not outclass a single one. CONCLUSIONS: We conclude that apigenin given intraperitoneally can reduce activation of NF-κB and also attenuate the expression of TNFα, IL-6, and iNOS in a surgical model of LIRI. The surgical procedure itself can induce significant damage to the lungs.

Treatment of cardiovascular implantable electronic device infection with daptomycin.

We describe a case of 83-year-old man who was admitted to our department for treatment of recurrent device-pocket infections. Our report shows that in a case of high-risk patient with a complicated cardiac implantable electric devices infection involving multidrug-resistent gram-positive pathogen, the application of daptomycin in combination with staged surgical therapy can be efficient and safe.

Treatment of gram-positive deep sternal wound infections in cardiac surgery--experiences with daptomycin.

The reported incidence of deep sternal wound infection (DSWI) after cardiac surgery is 0.4-5% with Staphylococcus aureus being the most common pathogen isolated from infected wound sternotomies and bacteraemic blood cultures. This infection is associated with a higher morbidity and mortality than other known aetiologies. Little is reported about the optimal antibiotic management. The aim of the study is to quantify the application of daptomycin treatment of DSWI due to gram-positive organisms post cardiac surgery. We performed an observational analysis in 23 cases of post sternotomy DSWI with gram-positive organisms February 2009 and September 2010. When the wound appeared viable and the microbiological cultures were negative, the technique of chest closure was individualised to the patient. The incidence of DSWI was 1.46%. The mean dose of daptomycin application was 4.4 ± 0.9 mg/kg/d and the average duration of the daptomycin application was 14.47 ± 7.33 days. In 89% of the patients VAC therapy was used. The duration from daptomycin application to sternal closure was 18 ± 13.9 days. The parameters of infection including, fibrinogen (p = 0.03), white blood cell count (p = 0.001) and C-reactive protein (p = 0.0001) were significantly reduced after daptomycin application. We had no mortality and wound healing was successfully achieved in all patients. Treatment of DSWI due to gram-positive organisms with a daptomycin-containing antibiotic regimen is safe, effective and promotes immediate improvement of local wound conditions.Based on these observations, daptomycin may offer a new treatment option for expediting surgical management of DSWI after cardiac surgery.