RESUMO
OBJECTIVE: This study was undertaken to demonstrate that gastrointestinal mucosal injury occurs during cardiopulmonary bypass in children, increasing systemic inflammatory responses, and to determine whether shen-fu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) could attenuate gastrointestinal mucosal injury and subsequent inflammatory responses. METHODS: Twenty-four children undergoing heart surgery for congenital heart defects were randomly assigned to groups C (placebo control, n = 12) and G (1.35 mg/kg ginsenosides compound intravenously before and throughout the course of cardiopulmonary bypass, n = 12). Central venous blood samples were taken before cardiopulmonary bypass and at 60 and 120 minutes after aortic declamping (reperfusion). Gastric intramucosal pH was measured by perioperative tonometry. Plasma lipid peroxidation product malondialdehyde, myocardium-specific creatine kinase isoenzyme MB activity, diamine oxidase, lipopolysaccharide, and interleukin 6 were all measured. RESULTS: Significant decrease in gastric intramucosal pH and increase in plasma diamine oxidase were seen during reperfusion in group C, accompanied by increases in plasma levels of malondialdehyde, lipopolysaccharide, interleukin 6, and creatine kinase isoenzyme MB (P < .01 vs before cardiopulmonary bypass). Shen-fu injection significantly attenuated these changes (P < .05). Consequently, fewer patients in group G (2/12) than in group C (7/12) needed postoperative inotropic support. Postoperative intensive care unit stay was shorter in group G than in group C. A tight positive correlation was seen between diamine oxidase and interleukin 6 at 60 minutes after aortic declamping and between diamine oxidase and lipopolysaccharide at 120 minutes after aortic declamping (r = 0.79, P < .0001). CONCLUSION: Ginsenosides compound may attenuate gastrointestinal injury and inhibit inflammatory response after cardiopulmonary bypass in patients with congenital heart disease.
Assuntos
Antioxidantes/uso terapêutico , Ponte Cardiopulmonar/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Gastroenteropatias/prevenção & controle , Cardiopatias Congênitas/cirurgia , Adolescente , Amina Oxidase (contendo Cobre)/sangue , Antioxidantes/farmacologia , Criança , Creatina Quinase/sangue , Creatina Quinase Forma MB , Método Duplo-Cego , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Mucosa Gástrica/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Gastroenteropatias/sangue , Gastroenteropatias/etiologia , Cardiopatias Congênitas/sangue , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Interleucina-6/sangue , Isoenzimas/sangue , Lipopolissacarídeos/sangue , Masculino , Malondialdeído/sangueRESUMO
We investigated whether propofol can inhibit tumor necrosis factor (TNF)-alpha-induced apoptosis in cultured human umbilical vein endothelial cells (HUVECs). Isolated HUVECs were cultured in Dulbecco's modified Eagle medium supplemented with 20% bovine calf serum. HUVECs in untreated and propofol control groups were cultured at 37 degrees C for 24.5 h. HUVECs in the TNF treatment groups were initially cultured for 30 min in the presence of TNF or various concentrations of propofol, respectively, which were then cultured for 24 h with the addition of TNF at 40 ng/mL in the medium. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and confirmed by electron microscopy. The antiapoptotic Bcl-2 and proapoptotic Bax protein expressions were measured by immunocytochemical analysis. TNF stimulation resulted in a reduced Bcl-2/Bax ratio and increased apoptotic index (AI: percentage of apoptotic cells) in HUVECs. Propofol, at concentrations >/=12 muM, significantly (P < 0.001) and dose-dependently attenuated TNF-induced increase in AI and decrease in Bcl-2/Bax ratio. This was accompanied by increases in nitric oxide production. There is an inverse correlation between the ratio of Bcl-2/Bax expression and AI (P = 0.0009). These results suggest that propofol, at clinical relevant concentrations, can reduce TNF-induced HUVEC apoptosis.
Assuntos
Anestésicos Intravenosos/farmacologia , Apoptose/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Genes bcl-2/fisiologia , Óxido Nítrico/fisiologia , Propofol/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais/ultraestrutura , Genes bcl-2/genética , Humanos , Marcação In Situ das Extremidades Cortadas , Óxido Nítrico/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacos , Proteína X Associada a bcl-2RESUMO
OBJECTIVE: To investigate the effect of Shen-Fu (SF) injection on gastrointestinal tract injury and its potential mechanism. METHODS: Thirty-eight patients undergoing elective open heart surgery were assigned to Group C (control group, n=18) and Group SF (n=20) randomly. In Group SF, the patients received intravenous injection of SF (0.5 ml/kg) at the beginning of the surgery followed by a continuous infusion of 100 ml SF (1.0 ml/kg) solution diluted by saline at a rate of 0.004 ml x Kg(-1) x min(-1) with a Grasby pump. The control group was injected with normal saline in the same volume. Gastric intramucosal pH (pHi), activity of blood diamine oxidase (DAO), and concentrations of blood LPS and IL-6 were measured before CPB (S0) and 1 h (S1) and 2 h (S2) after aortic declamping, respectively. RESULTS: In Group C, pHi value was significantly lower at S1 and S2 than at S0 (mean P<0.01) and blood DAO and concentrations of LPS and IL-6 were significantly higher at S1 and S2 than at S0 (mean P<0.01). In Group SF, pHi was obviously lower at S1 and S2 than at S0 (P<0.05) but LPS and IL-6 levels and DAO were higher at S0 (mean P<0.05). Blood DAO and LPS level demonstrated significant negative correlations with pHi (mean P<0.01) while LPS concentration showed a positive correlation with blood DAO (P<0.01) and IL-6 concentration (P<0.05). At S1 and S2 after aortic declamping, the levels of pHi were higher in Group SF than in Group C (mean P<0.01 ) but DAO and LPS and IL-6 levels were significantly lower in Group SF than in Group C (P<0.01). CONCLUSIONS: SF has a protective effect on gastrointestinal tract and can reduce inflammatory actions.