Methylene blue as a potential intervention in sepsis: Effects on survival and microcirculation in rat models of sepsis

Abstract

Sepsis is a life-threatening condition characterized by systemic inflammation and microcirculatory dysfunction. Methylene blue (MB), a compound with known antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study aimed to investigate the effects of MB on survival rates and the preservation of mesenteric microcirculation in a rat model of endotoxemia. A total of 36 rats underwent cecal ligation and puncture (CLP) surgery to induce varying degrees of sepsis: mild (4 perforations), moderate (10 perforations), and severe (20 perforations). Animals received intravenous treatment with either MB (4 mg/kg) or saline. Survival was monitored for ten days. Additionally, intravital microscopy was used to assess leukocyte rolling and adhesion in mesenteric vessels following lipopolysaccharide (LPS)-induced sepsis. The experimental groups included saline, LPS + saline, MB + saline, LPS + MB, and MB + LPS. MB treatment significantly improved survival in the severe sepsis group, with a 30 % survival rate at ten days (p = 0.02, 95 % CI: 0.12–0.48), whereas all animals in the severe sepsis + saline group died within nine days. No significant survival benefit was observed in the mild and moderate sepsis groups (mild sepsis: p = 0.45, 95 % CI: 0.08–0.34; moderate sepsis: p = 0.32, 95 % CI: 0.15–0.51). In the LPS-induced model, treatment with both LPS and MB significantly reduced leukocyte rolling and adhesion (p < 0.001, 95 % CI: 0.45–0.75 for rolling; p < 0.03, 95 % CI: 0.30–0.60 for adhesion), with values comparable to those of the control group. In contrast, MB alone had no effect on leukocyte rolling or adhesion.In summary, MB significantly improved survival in severe sepsis and inhibited leukocyte migration in mesenteric vessels. These findings suggest that MB may protect the microcirculation and enhance survival under severe septic conditions, representing a promising therapeutic approach for sepsis management.