Pyridoxalated hemoglobin polyoxyethylene conjugate reverses hyperdynamic circulation in septic sheep

Abstract

We investigated the effects of modified hemoglobin on regional blood flow and function of different organs during hyperdynamic sepsis. Fourteen sheep were surgically prepared for the study. After a 5-day recovery period, a continuous infusion of live Pseudomonas aeruginosa bacteria was begun and maintained for 48 h. At 24 h, after a hyperdynamic circulation had developed, the animals were randomly assigned to two groups: 1) a treatment group ( n = 7) that received an infusion with 100 mg/kg pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) over 30 min and 2) a control group ( n = 7) that received only the vehicle. PHP infusion increased mean arterial pressure from 86 ± 2.8 to 101.8 ± 3.5 mmHg ( P < 0.05) and systemic vascular resistance index from 769 ± 42.1 to 1,087 ± 56.8 dyn ⋅ s ⋅ m2⋅ cm−5( P < 0.05). PHP infusion did not decrease regional blood flow, measured with fluorescent microspheres, below the baseline values in any of the analyzed tissues. None of the investigated blood chemistry variables showed any changes indicative of impaired organ function after PHP infusion. In our model of ovine sepsis we found no side effects after PHP infusion that would limit the use of PHP as a nitric oxide scavenger in sepsis.