Absence of prostaglandin changes associated with protamine administration in patients with pulmonary hypertension

In patients with pre-existing pulmonary hypertension, severe pulmonary vasoconstriction has been observed following protamine administration. Thromboxane A₂, a potent vasoconstrictor, is capable of producing increases in pulmonary vascular resistance, and animal studies suggest that heparinprotamine complexes stimulate thromboxane A₂ synthesis. This study assessed the effect of protamine administration on hemodynamics and on plasma thromboxane A₂ and its biologic antagonist, prostacyclin, by serial measurement of the stable metabolites, thromboxane B₂ and 6-keto-prostaglandin F_1α, respectively. Ten adults with pulmonary artery hypertension undergoing elective mitral valve replacement were studied. After termination of cardiopulmonary bypass, baseline hemodynamic measurements were obtained and arterial blood for prostanoid analysis was sampled. Hemodynamic and prostanoid measurements were obtained 5, 10, 15, and 30 minutes after the protamine infusion began. Prostanoid levels were performed by double antibody radio-immunoassay. No significant hemodynamic changes occurred and no significant changes in prostanoid levels were observed. It is concluded that in patients with pulmonary hypertension, heparin-protamine complexes do not consistently raise circulating thromboxane levels, and the relationships among prostanoids, pulmonary hypertension, and systemic hypotension are still not clear.