Abstract P317: Methylene Blue Preserve The Microcirculation And Reduces Death In Rats Inflammation Models

Abstract

Introduction: Sepsis is a serious medical condition in response that occurs when the body responds to an infection in an exaggerated way, causing a widespread inflammation that can lead to damage in multiple organs and systems of the body. Sepsis mortality is high, and new and old drugs are being studied to help maintain hemodynamic stability as methylene blue (MB). MB has been used to increase the blood pressure in sepsis showing to be efficient in rebalancing circulatory integrity in physiological patterns. We sought to investigate methylene blue treatment in the sepsis survival rate and mesenteric microcirculation preservation. Methods: Male Hannover rats from University of São Paulo (USP)were treated by intravenous bolus with MB (4 mg/kg) or saline. Mild sepsis was induced by CLp with 4 holes, moderate sepsis with 10 holes, and severe sepsis with 20 holes in the cecum using a 16-gauge needle. The rats survival was observed during 9 days after surgery and expressed as the percentage of animals surviving by the log-rank test (X2, chi-square). Intravital microscopy was performed to evaluate the integrity of the mesenteric microcirculation by analyzing the leukocyte rolling and adhesion by lipopolysaccharide(LPS) sepsis model. LPS was administered intraperitoneal and treatment with intravenously MB by femoral vein. Rolling and adhesion were quantified by intravital microscopy in rats that received treatment with MB or saline. Results: MB treatment improved survival rate in severe sepsis. Severe sepsis groups with MB had a survival rate of30% (p=0.02). MB treatment did not change survival rate in the mild and moderate sepsis groups. The rats that received LPS showed an improvement of leukocyte adhesion and rolling in mesenteric vessels compared with the saline group. Rats that received only MB had similar results to the saline group. Although, when rats received LPS and were treated with MB (after or before LPS), the leukocytes adhered and rolled in the mesentery diminished significantly (p< 0,001)similarly to the saline group. Conclusion: Our data suggest that MB was able to increase survival in the severe sepsis and might be a beneficial drug for the protection of microcirculation. Funding: FAPESP, CAPES, FAEPA.