Effect of platelet depletion on lung vasoconstriction in heparin-protamine reactions

• Published in: Journal of applied physiology (1985) Vol. 66; no. 5; p. 2344
• Main Authors: Montalescot, G, Kreil, E, Lynch, K, Greene, E M, Torres, A, Carvalho, A, Fitzgibbon, C, Robinson, D R, Lowenstein, E, Zapol, W M
• Format: Journal Article
• Language: English
• Published: United States 01.05.1989
• Subjects: Animals; Blood Platelets - physiology; Cardiac Output - drug effects; Hemodynamics - drug effects; Heparin - pharmacology; Leukocyte Count; Platelet Aggregation - drug effects; Platelet Count - drug effects; Protamines - pharmacology; Pulmonary Circulation - drug effects; Sheep; Thrombin - physiology; Thromboxane B2 - blood; Vascular Resistance - drug effects; Vasoconstriction - drug effects
• ISSN: 8750-7587
• DOI: 10.1152/jappl.1989.66.5.2344

In six awake sheep the control heparin-protamine reaction was associated with a 150-fold rise in arterial plasma thromboxane B2 (TxB2) levels, a 4.5-fold increase in pulmonary vascular resistance, a 20% decrease in cardiac output, a 30% decrease in arterial PO2, and a 30% reduction in arterial white blood cell concentrations. Depletion of 99% of circulating platelets by antibodies did not prevent either acute and severe pulmonary hypertension or increased plasma TxB2 levels induced by heparin-protamine administration. We produced sheep platelet aggregation in vitro with bovine thrombin and measured marked TxB2 release (36.3 +/- 16.3 ng/10(9) platelets). In contrast, neither heparin, protamine, nor heparin-protamine complexes over a 10,000-fold range of concentrations induced platelet aggregation and release of thromboxane in vitro. Therefore sheep platelets are not the source of thromboxane production associated with acute pulmonary hypertension during the heparin-protamine reaction, and other cells must produce the thromboxane.