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Imaging the ovine heparin-protamine interaction with 111In-protamine
G Montalescot1, A J Fischman, H W Strauss
1Department of Anaesthesia, Massachusetts General Hospital, Boston.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|August 1, 1993
Summary
Protamine sulfate can cause dangerous pulmonary hypertension by releasing thromboxane when reversing heparin. This reaction, involving heparin-protamine complexes in sheep lungs, was not observed in rats, suggesting a role for lung macrophages.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Pulmonary Medicine
Background:
- Protamine sulfate is used to reverse heparin anticoagulation.
- This reversal can sometimes lead to severe pulmonary hypertension due to thromboxane release.
Purpose of the Study:
- To investigate the mechanism and location of protamine's interaction with heparin.
- To understand why protamine reversal of heparin causes adverse pulmonary effects in some species.
Main Methods:
- 111In-labeled protamine sulfate was administered to sheep and rats, both heparinized and unheparinized.
- Pulmonary clearance of the labeled protamine and plasma thromboxane levels were measured.
- Hemodynamic parameters and white blood cell counts were monitored.
Main Results:
- In heparinized sheep, protamine administration led to thromboxane release, pulmonary hypertension, leukopenia, and prolonged lung retention of 111In-protamine.
- Unheparinized sheep and rats showed rapid clearance of 111In-protamine without adverse pulmonary effects or thromboxane release.
- The ovine heparin-protamine reaction involves pulmonary sequestration of complexes, thromboxane release, and vasoconstriction, unlike in rats.
Conclusions:
- The ovine heparin-protamine interaction triggers pulmonary vasoconstriction and thromboxane release, linked to the sequestration of heparin-protamine complexes in the lungs.
- Interspecies differences, particularly in sheep, suggest pulmonary intravascular macrophages may be activated by these complexes, leading to adverse reactions.
- These findings highlight the specific mechanisms underlying protamine-induced pulmonary complications and species-specific responses.