Effect of early-goal directed therapy on inflammatory response and cardiovascular oxidative stress in experimental septic shock

• Grant number: 07/04953-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2009
• End date: January 31, 2010
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luciano Cesar Pontes de Azevedo
• Grantee: Luciano Cesar Pontes de Azevedo
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Early-goal directed therapy guided by central venous oxygen saturation is considered nowadays a cornerstone in sepsis treatment. However, the precise pathophysiologic mechanisms associated with their beneficial effects are incompletely understood. The purpose of this study is to investigate the effect of early-goal directed therapy (EGDT) in hemodynamic, respiratory and metabolic variables in a sepsis model induced by fecal peritonitis. We will also study the effect of this early and aggressive resuscitation in cellular inflammatory response and cardiovascular oxidative stress. Sixteen Agroceres pigs will be anesthetized, instrumented with pulmonary and arterial catheters and submitted to sepsis by inoculation of 1.0 mg/kg fecal content in peritoneum. After shock, these animals will be randomized in two groups; Control group will be resuscitated with cristaloid solutions in order to achieve normal central venous pressure and mean arterial pressure. EGDT group will receive cristaloids and/or dobutamine in order to maintain normal blood pressure, normal central venous pressure and mixed venous oxygen saturation above 70%. The inflammatory response will be evaluated by analyzing plasmatic concentration of cytokines (IL-6, IL-10, TNF-alpha, IL-8), expression of cellular surface markers (CD11b e CD14), apoptosis assay by flow cytometry and neutrophil oxidative metabolism assay. Cardiovascular oxidative stress will be studied by assays regarding vascular and cardiac production of reactive oxygen species, quantification of myocardial glutathione content and nitric oxide metabolites, determination of SOD and NADP(H) oxidase activities and immunohistochemistry for nitrotyrosine. (AU)