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Effects of Nitric Oxide Donor SIN-1 on Oxygen Availability and Regional Blood Flow During Endotoxic Shock

Haibo Zhang, MD, PhD; Peter Rogiers, MD; Gilberto Friedman, MD; Jean-Charles Preiser, MD; Herbert Spapen, MD; Wim A. Buurman, PhD; Jean-Louis Vincent, MD, PhD
Arch Surg. 1996;131(7):767-774. doi:10.1001/archsurg.1996.01430190089022.
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Background:  An excessive release of nitric oxide (NO) has been incriminated in the circulatory disturbances of septic shock.

Objective:  To study the effects of an NO donor, 3-morpholinosydnonimine (SIN-1), on oxygen availability and regional blood flow during endotoxic shock to see if a beneficial effect of NO synthase inhibitors in septic shock could be conclusively demonstrated.

Materials and Methods:  In 14 anesthetized and mechanically ventilated dogs, global invasive hemodynamic monitoring was completed and ultrasonic flow probes were placed around the superior mesenteric, left renal, and left femoral arteries for simultaneous measurements of regional blood flow. All dogs received Escherichia 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 combination of saline with SIN-1 at successive doses of 1, 2, and 4 μg/kg per minute.

Results:  Neither systemic nor pulmonary arterial pressures were influenced by SIN-1. Cardiac index, stroke index, and left ventricular 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 concentrations of tumor necrosis factor were not significantly influenced. At the end of the SIN-1 infusion, the administration of 5 mg/kg of methylene 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 cardiac index and superior mesenteric blood flow without deleterious effects on arterial pressure in this model of endotoxic shock. These findings support the hypothesis that NO is essential to maintain organ blood flow even during endotoxic shock.Arch Surg. 1996;131:767-774


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