Cell-free hemoglobin solutions can scavenge nitric oxide and therefore
increase mean arterial pressure (MAP), The present study investigated
the effects of a continuous low-dose infusion of modified hemoglobin
during ovine hyperdynamic sepsis. 13 sheep received a continuous infus
ion of live Pseudomonas aeruginosa bacteria for 48 h. Animals that sur
vived the first 24 h of sepsis (n = 12) were randomly assigned either
to a treatment group that received 20 mg.kg(-1).h(-1) pyridoxalated he
moglobin polyoxyethylene conjugate (PHP) for 20 h or to a control grou
p that received the same volume of the vehicle for 20 h, MAP increased
in the treatment group during 4 h of PHP infusion 12.7 +/- 1.7 mmHg (
p < .05) and after 20 h of PHP infusion MAP was still 12.4 +/- 2.1 mmH
g above the MAP before starting PHP (p < .05). MAP in the control grou
p did not change significantly from 24 h to 48 h of sepsis, No differe
nces in regional blood flow were seen between groups. Bacterial counts
in the spleen and kidney were lower in the treatment group than in th
e control group. Continuous low-dose infusion of PHP can normalize sys
temic vascular resistance and MAP for long periods without deteriorati
on of regional blood flow or bacterial clearance.