Sporadic cases of inexplicable noncardiogenic pulmonary edema occur after operations requiring total cardiopulmonary bypass (CPB). Prostaglandins, such as thromboxane (Tx) A2, have been implicated in this form of pulmonary pathology in many clinical and experimental settings. Because Tx generation has been demonstrated in association with ischemia of solid organs, we postulated that total CPB, which decreases pulmonary tissue perfusion and oxygenation, would stimulate local Tx synthesis. Total CPB was examined in 7 sheep. The level of TxB2 (a stable metabolite of the active, unstable A2) was measured in the left and right atria before, during, and after 105 minutes of total CPB. Significant increases in TxB2 concentrations occurred in the left atrium compared with the right (p < 0.05) during CPB. Immediately after reperfusion, both the left atrial and right atrial TxB2 concentrations increased significantly over the baseline values (p < 0.05), but this increase and the atrial gradient were rapidly abolished with continued pulmonary perfusion. To determine the effect of extracorporeal circulation without significant (< 30%) alteration in pulmonary perfusion, we evaluated the effect of partial CPB in 5 sheep. Increased TxB2 concentrations were noted at 15 and 30 minutes after the onset of partial CPB (left atrium increased significantly over baseline; p < 0.05), but this elevation spontaneously diminished to insignificance after 15 and 30 additional minutes of extracorporeal circulation. These data establish that total CPB stimulates Tx generation in the lung, and although the effect of partial CPB is transient, that of total CPB is progressive and abolished by reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)