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Coronary constrictor effect of stroma-free hemoglobin solutions
Insights
Stroma-free hemoglobin (SFH) solutions cause coronary vasoconstriction in isolated hearts, independent of oxygen delivery. Modified SFH formulations show reduced constrictor effects, suggesting potential for safer hemoglobin-based oxygen carriers.
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.
Abstract:
A coronary vasoconstrictor effect of human stroma-free hemoglobin (SFH) was identified in isolated rabbit hearts perfused with Krebs-Henseleit buffer or whole rabbit blood at a constant coronary flow rate. In buffer-perfused hearts, SFH in concentrations of 5 to 200 mg/dl produced dose-related increases of coronary perfusion pressure. At a concentration of 150 mg/dl, SFH, equilibrated with CO to form carboxyhemoglobin, caused an increase in perfusion pressure (55 +/- 7 mmHg), similar to that observed with oxyhemoglobin (57 +/- 6 mmHg); addition of potassium ferricyanide to form methemoglobin reduced the increase of perfusion pressure to 34 +/- 5 mmHg (P less than 0.05). The vasoconstrictor activity could not be eliminated by dialyzing against the perfusion buffer. Human SFH prepared by different methods had similar vasoconstrictor activity. Rabbit SFH and human SFH were equi-effective in the rabbit heart. Less constrictor activity of SFH was evident in rat and guinea pig heart. Polymerized, pyridoxalated SFH had greatly reduced constrictor effect compared with unmodified or pyridoxalated tetramer SFH. In blood-perfused hearts, increasing plasma hemoglobin to 1.6 +/- 0.1 g/dl, without changing total hemoglobin or arterial O2 content, increased coronary perfusion pressure by 36 +/- 13 mmHg (P less than 0.05). We conclude that stroma-free hemoglobin solutions exert a coronary vasoconstrictor effect that is unrelated to O2 delivery.