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Continuous infusion of pyridoxalated hemoglobin polyoxyethylene conjugate in hyperdynamic septic sheep
H G Bone1, S R Fischer, P J Schenarts
1Department of Anesthesiology and Intensive Care Medicine, Westfälische-Wilhelms-Universität, Münster, Germany.
Abstract:
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 infusion of live Pseudomonas aeruginosa bacteria for 48 h. Animals that survived the first 24 h of sepsis (n=12) were randomly assigned either to a treatment group that received 20 mg x kg(-1) x h(-1) pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) for 20 h or to a control group 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 mmHg above the MAP before starting PHP (p < .05). MAP in the control group did not change significantly from 24 h to 48 h of sepsis. No differences in regional blood flow were seen between groups. Bacterial counts in the spleen and kidney were lower in the treatment group than in the control group. Continuous low-dose infusion of PHP can normalize systemic vascular resistance and MAP for long periods without deterioration of regional blood flow or bacterial clearance.
Insights
Modified hemoglobin (PHP) infusion normalized blood pressure in sheep with hyperdynamic sepsis. This treatment maintained mean arterial pressure and improved bacterial clearance without affecting regional blood flow.
Area of Science:
- Cardiovascular Physiology
- Sepsis Pathophysiology
- Hemoglobin Therapeutics
Background:
- Cell-free hemoglobin solutions can scavenge nitric oxide, leading to increased mean arterial pressure (MAP).
- Hyperdynamic sepsis is characterized by vasodilation and decreased MAP.
- The potential of modified hemoglobin to counteract these effects requires investigation.
Purpose of the Study:
- To investigate the effects of continuous low-dose pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) infusion during ovine hyperdynamic sepsis.
- To assess PHP's impact on mean arterial pressure (MAP), systemic vascular resistance, regional blood flow, and bacterial clearance.
Main Methods:
- Ovine model of hyperdynamic sepsis induced by continuous Pseudomonas aeruginosa infusion for 48 hours.
- Survivors (n=12) were randomized to receive either PHP (20 mg x kg(-1) x h(-1)) or vehicle infusion for 20 hours.
- MAP, systemic vascular resistance, regional blood flow, and bacterial counts in spleen and kidney were monitored.
Main Results:
- PHP infusion significantly increased MAP by 12.7+/-1.7 mmHg within 4 hours and maintained this elevation (12.4+/-2.1 mmHg) after 20 hours.
- MAP in the control group showed no significant change during the study period.
- PHP treatment led to lower bacterial counts in the spleen and kidney compared to controls, with no observed differences in regional blood flow.
Conclusions:
- Continuous low-dose PHP infusion effectively normalized systemic vascular resistance and MAP in ovine hyperdynamic sepsis.
- PHP treatment sustained these hemodynamic improvements for extended periods.
- The therapeutic approach did not compromise regional blood flow or bacterial clearance, suggesting a potential treatment for sepsis-induced hypotension.