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Nitric oxide inhibition attenuates systemic hypotension produced by protamine
G V Raikar1, K Hisamochi, B L Raikar
1Cardiac Surgical Research Laboratory, Mayo Clinic and Mayo Foundation, Rochester, Minn., USA.
The Journal of Thoracic and Cardiovascular Surgery
|June 1, 1996
Summary
Protamine reversal of heparin can cause hypotension, but this effect is mediated by nitric oxide release. Inhibiting nitric oxide synthesis prevents protamine-induced hypotension, suggesting a new preventive strategy.
Area of Science:
- Cardiovascular Pharmacology
- Vascular Biology
- Anesthesiology
Background:
- Protamine sulfate is used to reverse heparin anticoagulation.
- Protamine-induced hypotension may involve nitric oxide release from the endothelium.
- Direct myocardial effects of protamine require further investigation.
Purpose of the Study:
- Evaluate direct myocardial effects of protamine.
- Determine if nitric oxide inhibition prevents protamine-induced hypotension in vivo.
Main Methods:
- Isolated rabbit hearts exposed to protamine or protamine-heparin complex.
- Hemodynamic parameters measured in heparinized dogs during protamine infusion.
- Nitric oxide synthesis inhibitor (Ng-monomethyl-L-arginine) and cyclic guanosine monophosphate synthesis inhibitor (methylene blue) administered to dogs.
Main Results:
- Protamine alone caused myocardial depression in isolated rabbit hearts.
- Protamine-heparin complex did not significantly affect isolated heart function.
- Protamine infusion in dogs caused significant hypotension, decreased cardiac output, and decreased systemic vascular resistance.
- Hypotension and cardiac output reduction were blocked by Ng-monomethyl-L-arginine and methylene blue.
- Ng-monomethyl-L-arginine pretreatment prevented protamine-induced hypotension, and its effect was reversible with L-arginine.
Conclusions:
- Protamine-heparin complex does not directly depress the myocardium.
- Protamine causes in vivo hypotension mediated partly by the vascular endothelium via the nitric oxide pathway.
- Inhibition of the nitric oxide pathway offers a potential strategy to prevent protamine-induced hemodynamic complications.