EFFECTS OF NITRIC-OXIDE DONOR SIN-1 ON OXYGEN AVAILABILITY AND REGIONAL BLOOD-FLOW DURING ENDOTOXIC-SHOCK

Background: An excessive release of nitric oxide (NO) has been incrimi nated in the circulatory disturbances of septic shock. Objective: To s tudy the effects of an NO donor, 3-morpholinosydnonimine (SIN-1), on o xygen availability and regional blood flow during endotoxic shock to s ee if a beneficial effect of NO synthase inhibitors in septic shock co uld be conclusively demonstrated. Materials and Methods: In 14 anesthe tized and mechanically ventilated dogs, global invasive hemodynamic mo nitoring was completed and ultrasonic flow probes were placed around t he superior mesenteric, left renal, and left femoral arteries for simu ltaneous measurements of regional blood flow. All dogs received Escher ichia coli endotoxin, 2 mg/kg. A control group (n=7) was administered saline at 20 mL/kg per hour, and a SIN-1 group (n=7) was given a combi nation of saline with SIN-1 at successive doses of 1, 2, and 4 mu g/kg per minute. Results: Neither systemic nor pulmonary arterial pressure s were influenced by SIN-1. Cardiac index, stroke index, and left vent ricular stroke work index did increase at low to moderate doses of SIN -1 but tended to decrease at the highest dose. Systemic and pulmonary vascular resistances decreased. Fractional blood flow increased in the mesenteric bed at all doses used, was not influenced in the renal bed , but decreased in the femoral bed at the highest dose. Oxygen-derived variables were similar in the 2 groups. Blood lactate and plasma conc entrations of tumor necrosis factor were not significantly influenced. At the end of the SIN-1 infusion, the administration of 5 mg/kg of me thylene blue increased arterial pressure, pulmonary arterial pressure, and systemic and pulmonary vascular resistances but decreased cardiac index and regional blood flow.Conclusions: The administration of low to moderate doses of the NO donor SIN-1 can significantly increase car diac index and superior mesenteric blood flow without deleterious effe cts on arterial pressure in this model of endotoxic shock. These findi ngs support the hypothesis that NO is essential to maintain organ bloo d flow even during endotoxic shock.