EFFECTS OF METHYLENE-BLUE ON OXYGEN AVAILABILITY AND REGIONAL BLOOD-FLOW DURING ENDOTOXIC-SHOCK

Objective: We hypothesized that methylene blue, by inhibiting the acti vation of soluble guanylate cyclase mediated by nitric oxide, may reve rse systemic hypotension, enhance myocardial function, and improve per ipheral distribution of blood flow during endotoxic shock. Design: Ran domized, controlled, acute intervention study. Setting: University int ensive care laboratory. Subjects: Twenty-one healthy, anesthetized, mo ngrel dogs, weighing 26 +/- 4 kg. Interventions: Groups 1 (n = 7) and 2 (n = 7) received endotoxin (2 mg/kg iv) alone combined with increasi ng doses of 2.5, 5, 10, and 20 mg/kg iv of methylene blue. Each dose w as administrated for 30 mins with a free interval of 30 mins. Group 3 (n = 7) served as a control group, receiving the same doses of methyle ne blue in the absence of endotoxin. All animals were given normal sal ine to keep cardiac filling pressures constant. Blood flow probes were placed around the superior mesenteric, renal, and femoral arteries to measure regional blood flow by ultrasonic technique. Data were collec ted every 30 mins during the study. Measurements and Main Results: Aft er endotoxemia, methylene blue increased systemic and pulmonary arteri al pressure and vascular resistances in a dose-dependent manner up to 10 mg/kg, but had no effect on cardiac index. At the highest dose, met hylene blue decreased arterial pressure and systemic vascular resistan ce. At doses of methylene blue of less than or equal to 10 mg/kg, mese nteric and femoral blood artery flow increased. At the highest dose of 20 mg/kg, femoral artery blood flow further increased, but mesenteric blood flow decreased. Renal artery blood flow was unaffected by methy lene blue. In the absence of endotoxin, methylene blue at doses of 2.5 or 5 mg/kg did not alter mean arterial pressure, but reduced cardiac index, indicating an increase in systemic vascular resistance. In cont rast, the higher doses of 10 or 20 mg/kg of methylene blue decreased m ean arterial pressure and systemic vascular resistance. However, pulmo nary arterial pressure and pulmonary vascular resistance increased in a dose-dependent manner. Mesenteric and renal artery blood flow decrea sed but femoral blood flow increased. As in the presence of endotoxin, methylene blue induced dose-related increases in oxygen uptake and ox ygen extraction ratio, but did not alter oxygen delivery. Methylene bl ue largely attenuated the endotoxin-induced increase in plasma nitrite concentrations. Conclusions: Low and moderate doses of methylene blue can significantly increase arterial blood pressure but not cardiac in dex during endotoxic shock. Methylene blue infusion may selectively in crease mesenteric blood flow. High doses of methylene blue can worsen systemic hypotension, myocardial depression, and pulmonary hypertensio n after endotoxemia.