In prospective randomized study we will block the key mediator that leads to cardiopulmonary collapse when heparin anticoagulation is reversed by protamine. In recent prospective study of 925 patients undergoing cardiac surgery at Massachusetts General Hospital we found 14 patients (1.5%) developed acute transient pulmonary hypertension associated with markedly increased blood thromboxane levels (a powerful eicosanoid pulmonary vasoconstrictor). When severe, this reaction can cause shock, bronchoconstriction and death. Our prior animal and clinical studies have probed the biochemical pathways of this adverse drug interaction, and identified a key point to block the reaction. In a pilot clinical study we will examine a thromboxane receptor blocker to learn if ie is sufficiently safe for use at cardiac surgery. Then we will test the competitive thromboxane receptor inhibitor for is ability to block this reaction in a prospective randomized study of 1250 patients undergoing heart surgery.
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