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 heparin-protamine 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 F1 alpha, 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.
Konstadt
S N
SN
Mount Sinai School of Medicine, New York, NY 10029.
Thys
D M
DM
Kong
D
D
Mindich
B P
BP
Watkins
W D
WD
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D011464:Epoprostenol / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D011479:Protamines / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D011479:Protamines; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D006493:Heparin; D011464:Epoprostenol