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.