111 - Early Administration of an NO Spin Trap Shortens the Survival and Reduces NO Production in Septic- Shocked Rat

Abstract

The role of nitric oxide (NO) in shock depends on its evolution. It seems that an early NO increment compensates for systemic vasoconstriction whereas a late massive production participates in vasoplegia. NO spin traps are used to form short life time adducts with NO, and evidence for NO by electron paramagnetic resonance. The goal of this study was to evaluate the early administration of sodium diethyldithiocarbamate (DETC, an NO spin trap) on survival and NO production in septic shock. Septic shock was induced in Male Wistar rats through the iv administration of lipopolysaccharide (LPS, 5 mg/Kg). To assess their survival the animals were divided into two groups (n=6) which were treated at exactly the same time as the LPS with either: 1) Isotonic saline solution (ISS, 600 µl ip, and 600 µl sc) or 2) DETC (500 mg/Kg, diluted in 600 µl of ISS, ip) and iron citrate complex (iron sulfate and sodium citrate diluted in 600 µl of ISS, sc). Survival times were recorded and differences evaluated by the Mantel Cox Test. Two more groups (the same treatments as above) were used to measure NO2/NO3 ions (indirect NO measurement, modified Griess reaction) in arterial blood samples (1ml, replaced with 3ml of Hartman solution) before (time 0) and after (1, 2 and 6 h) LPS. The animals were sacrificed by anesthesia overdose after the last blood sample was taken. Differences were evaluated by two way ANOVA testing. Survival was significantly shorter (p=0.01) and NO2/NO3 concentration was significantly smaller (p This study was supported by CONACYT 216184 and 225115 Grants.