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Pyridoxalated hemoglobin polyoxyethylene conjugate reverses hyperdynamic circulation in septic sheep
H G Bone1, P J Schenarts, S R Fischer
1Department of Anesthesiology, Westfälische-Wilhelms-Universität, Münster, Germany 48149, USA.
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.
Insights
Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) improved blood pressure and vascular resistance in a sheep sepsis model. PHP showed no adverse effects on organ function or blood flow, suggesting its potential as a nitric oxide scavenger in sepsis treatment.
Area of Science:
- Sepsis Pathophysiology
- Hemoglobin-based Oxygen Carriers
- Cardiovascular Pharmacology
Background:
- Hyperdynamic sepsis is characterized by vasodilation and decreased systemic vascular resistance.
- Nitric oxide plays a key role in the vasodilation observed during sepsis.
- Modified hemoglobin solutions are being explored for their potential therapeutic effects in sepsis.
Purpose of the Study:
- To evaluate the effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) on hemodynamics and organ function in a hyperdynamic ovine sepsis model.
- To assess the safety and efficacy of PHP as a nitric oxide scavenger in sepsis.
Main Methods:
- Ovine model of hyperdynamic sepsis induced by Pseudomonas aeruginosa infusion.
- Administration of PHP (100 mg/kg) or vehicle to septic sheep.
- Hemodynamic monitoring including mean arterial pressure and systemic vascular resistance index.
- Measurement of regional organ blood flow using fluorescent microspheres.
- Analysis of blood chemistry variables to assess organ function.
Main Results:
- PHP infusion significantly increased mean arterial pressure (P < 0.05) and systemic vascular resistance index (P < 0.05).
- PHP did not reduce regional blood flow in any analyzed tissue below baseline levels.
- No significant changes in blood chemistry indicated impaired organ function following PHP administration.
Conclusions:
- PHP effectively improved hemodynamic parameters in a hyperdynamic ovine sepsis model.
- PHP demonstrated a favorable safety profile, with no detrimental effects on organ function or blood flow.
- PHP shows promise as a therapeutic agent, potentially acting as a nitric oxide scavenger in sepsis management.