Evidence for lack of importance of oxygen free radicals in Escherichia coli endotoxemia in dogs.

Reactive oxygen species have been proposed as pathophysiological factors responsible for the hypodynamic circulatory response to gram-negative endotoxin. To test this hypothesis, we examined the cardiorespiratory effects of mechanistically different oxygen free radical scavenging agents during Escherichia coli endotoxemia in beagle dogs. Pentobarbital-anesthetized dogs were instrumented for repeated sampling of cardiorespiratory, hematologic, and tissue blood flow (radiolabeled 15-micron microspheres) indexes. Four groups were studied: 1) time-matched control dogs (n = 6); 2) dogs receiving only endotoxin (1.5 mg/kg; n = 6); 3) dogs receiving endotoxin and combination therapy with allopurinol (150 mg/kg) plus superoxide dismutase (5 mg/kg) and catalase (5 mg/kg; n = 6); and 4) dogs receiving endotoxin and deferoxamine (30 mg/kg; n = 5). Measured variables in control dogs were constant during the 4-h study, whereas endotoxin-injected dogs consistently demonstrated the following: 1) maintained reductions in blood pressure (greater than 45%), left ventricular systolic pressure (greater than 43%), left ventricular maximum rate of pressure development (+/- dP/dtmax) (greater than 41%), cardiac index (greater than 33%), and blood flow in all sampled tissues except liver and skeletal muscle; 2) transient tachypnea, bradycardia, and arterial acidosis; and 3) persistent neutropenia and hemoconcentration. Neither of the free radical scavenging protocols significantly improved measured variables during endotoxemia (P greater than 0.05). This lack of efficacy suggests that superoxide anion, hydrogen peroxide, and hydroxyl radical may lack primary pathophysiological importance during the development of E. coli endotoxicosis in intact dogs.