Pulmonary hypertensive effect of heparin and protamine interaction: evidence for thromboxane B2 release from the lung.

The characteristic pulmonary hypertensive effect of the heparin and protamine interaction has been studied in the isolated pig lung preparation using sequential autologous blood perfusate and dextran perfusate. A significant (p less than 0.001) increase in pulmonary artery pressure at constant flow was seen in 10 of 14 dextran and 12 of 15 blood perfusions. The average increase for dextran was 112 percent and for blood, 109 percent. Antihistamines did not inhibit the response. However, this was abolished in all 11 animals treated with aspirin. In 11 intact swine, thromboxane B2 blood levels increased significantly (p less than 0.01) from 0.46 +/- 0.38 ng/dl to 2.97 +/- 1.5 ng/dl. Thus, pulmonary hypertension associated with protamine reversal of heparinization is associated with prostaglandin release from the lung, and this does not require mediation of platelets or leukocytes.