Thromboxane receptor blockade prevents pulmonary hypertension induced by heparin-protamine reactions in awake sheep.
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.
Montalescot
G
G
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
Lowenstein
E
E
Ogletree
M L
ML
Greene
E M
EM
Robinson
D R
DR
Hartl
K
K
Zapol
W M
WM
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
D006494:Heparin Antagonists; D011479:Protamines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2