title: Thromboxane receptor blockade prevents pulmonary hypertension induced by heparin-protamine reactions in awake sheep.
abstract: We used competitive thromboxane A2-prostaglandin endoperoxide receptor blockade (SQ 30,741) as a probe to evaluate the role of thromboxane in ovine pulmonary vasoconstriction associated with protamine reversal of heparin anticoagulation. Control heparin-protamine reactions induced rapid release of thromboxane into arterial plasma (more than 1 ng/ml plasma), a 2.5-fold increase of pulmonary artery pressure, a 20% decrease of PaO2, and a 30% reduction in arterial white blood cell concentration. After giving SQ 30,741 despite similar thromboxane release into arterial plasma after heparin-protamine challenge, acute pulmonary hypertension was significantly reduced when 94% of pulmonary vascular smooth muscle thromboxane receptors were occupied with SQ 30,741 (p less than 0.01 at 1 minute after protamine versus control heparin-protamine reaction) and was completely abolished by a 10 mg/kg i.v. bolus (p less than 0.0001 at 1 minute after protamine versus control). Peripheral leukopenia was not affected by SQ 30,741 prophylaxis, but hypoxemia was prevented. We conclude that thromboxane causes pulmonary vasoconstriction in ovine heparin-protamine-induced pulmonary hypertension. Pulmonary vasoconstriction and hypoxemia can be completely prevented by thromboxane receptor blockade.
authors: Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
authors: G
authors: G
authors: Montalescot
authors: E
authors: E
authors: Lowenstein
authors: M L
authors: ML
authors: Ogletree
authors: E M
authors: EM
authors: Greene
authors: D R
authors: DR
authors: Robinson
authors: K
authors: K
authors: Hartl
authors: W M
authors: WM
authors: Zapol
mesh_terms: D000818:Animals; D003243:Consciousness; D006494:Heparin Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000517:prevention & control*; D000860:Hypoxia / Q000139:chemically induced / Q000517:prevention & control; D011479:Protamines / Q000009:adverse effects* / Q000627:therapeutic use; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D012756:Sheep; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000502:physiology / Q000627:therapeutic use
chemical_list: D006494:Heparin Antagonists; D011479:Protamines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2