Effect of zinc pretreatment on pulmonary endothelial cells in vitro and pulmonary function in a porcine model of endotoxemia

• Published in: The Journal of surgical research Vol. 123; no. 2; pp. 251 - 256
• Main Authors: Krones, Carsten Johannes, Klosterhalfen, Bernd, Butz, Nick, Hoelzl, Friedrich, Junge, Karsten, Stumpf, Michael, Peiper, Christian, Klinge, Uwe, Schumpelick, Volker
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2005; Elsevier
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Disease Models, Animal; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endotoxemia - drug therapy; Endotoxemia - metabolism; extravascular lung water; Female; General aspects; heat shock response; Heat-Shock Response - drug effects; HSP70 Heat-Shock Proteins - metabolism; In Vitro Techniques; intrapulmonary shunt; Medical sciences; Pulmonary Artery - cytology; pulmonary function; septic shock; Sus scrofa; Zinc - pharmacology; zinc endotoxemia; zinc endotoxemia; pulmonary function; septic shock; heat shock response; intrapulmonary shunt; extravascular lung water; Water; Endothelial cell; Lung; Sepsis syndrome; Lung function; Surgery; Heat shock protein; Pretreatment; Ungulata; Endotoxemia; Shunt; In vitro; Zinc; Pig; Infection; Medicine; Vertebrata; Mammalia; Animal; Models; Artiodactyla
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2004.08.024

During endotoxemia, the systemic inflammatory response often leads to severe pulmonary damages. Destruction of endothelial cells, interstitial edema, and interstitial alveolitis depress pulmonary circulation and raise extravascular lung water and intrapulmonary shunt. As protective effects of zinc are described in vitro as well as in vivo, this study investigates its impact on septic porcine pulmonary endothelial monolayers as well as on the pulmonary function of endotoxemic pigs. Cell culture: Endothelial cells were incubated with ascending doses of zinc and pooled with septic plasma. Cellular damage, metabolism, and proliferation were measured by vital stain, XTT-assay, and BrDU-ELISA. HSP70 was visualized by immunohistochemistry. Animal study: We used an established porcine model. Twenty-four hours before endotoxemia (intravenous infusion of 1.0 μg/kg Escherichia coli endotoxin WO111:B4), each animal received an intravenous pretreatment. Group I ( n = 3): saline pretreatment, group II ( n = 5): zinc pretreatment (5 mg/kg elementary zinc). Monitoring included blood gas analysis and the thermal dye dilution technique. In vitro, zinc leads to significantly altered rates of viable cells, metabolism, and proliferation with the strongest cell-protective effect at moderate concentrations of 1 μg/ml Zn 2+. This correlates with a qualitatively increased expression of HSP70. In vivo, the zinc pretreatment before LPS-induced endotoxemia grossly improves all measured hemodynamic and pulmonary parameters. Zinc pretreatment of endotoxemia decreases cellular damages in vitro and improved pulmonary function in vivo. This could be mediated by the heat shock response. Further studies, particularly concerning the dose-effect relationship and the underlying mode of action, are mandatory.