Journal of Applied Physiology, Vol 73, Issue 6 2604-2607, Copyright © 1992 by American Physiological Society
Role of platelet-activating factor in the ovine heparin-protamine reaction
G. Montalescot, J. M. Huerta, P. Braquet and W. M. Zapol
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
Platelet-activating factor (PAF) infusion into sheep, as well as protamine
reversal of heparin anticoagulation, causes thromboxane release into
plasma, pulmonary hypertension, hypoxemia, and leukopenia. We investigated
the possible role of PAF in the heparin-protamine reaction. Intravenous
protamine was administered to neutralize heparin anticoagulation in five
awake sheep and caused an increase of mean pulmonary arterial pressure from
16.6 +/- 1 (SE) mmHg at base-line to 47 +/- 9 mmHg at 1 min after protamine
injection (P < 0.01) because of a 4.5-fold increase of pulmonary
vascular resistance. This neutralization reaction induced a 25% reduction
of circulating leukocyte count and arterial PO2. Undetectable blood levels
of PAF were measured by bioassay and high-performance liquid chromatography
during these heparin-protamine reactions. Infusion of BN 52021 (20 mg/kg),
a PAF receptor antagonist, before rechallenging the same sheep with heparin
and then protamine did not reduce the level of peak pulmonary hypertension
or the degree of hypoxemia and leukopenia. We conclude that the leukopenia
and thromboxane-mediated pulmonary vasoconstriction occurring after rapid
intravascular formation of heparin-protamine complexes in sheep are not due
to the release of PAF.
