Coronary constrictor effect of stroma-free hemoglobin solutions

Area of Science:

• Cardiovascular Physiology
• Hemoglobin Therapeutics

Background:

• Stroma-free hemoglobin (SFH) is explored as a blood substitute.
• Potential side effects, including vasoconstriction, require investigation.

Purpose of the Study:

• To investigate the coronary vasoconstrictor effect of human SFH.
• To determine if this effect is related to oxygen delivery.

Main Methods:

• Isolated rabbit hearts perfused with buffer or blood.
• Dose-response studies with varying SFH concentrations.
• Experiments with carboxyhemoglobin and methemoglobin formation.
• Testing of modified SFH preparations.

Main Results:

• SFH caused dose-dependent increases in coronary perfusion pressure.
• Vasoconstrictor effect was observed with both buffer and blood perfusion.
• Methemoglobin formation reduced the vasoconstrictor activity.
• Modified SFH (polymerized, pyridoxalated) exhibited reduced constrictor effects.
• The effect was species-dependent, with less activity in rat and guinea pig hearts.

Conclusions:

• Stroma-free hemoglobin solutions exert a significant coronary vasoconstrictor effect.
• This vasoconstriction is independent of oxygen delivery capacity.
• SFH modifications can mitigate the vasoconstrictor activity, offering insights for developing safer hemoglobin-based oxygen carriers.