Thromboxane Receptor Blockade Prevents Pulmonary Hypertension Induced

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%o 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<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<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 thrombox-