Adverse effects of prostacyclin used to perfuse isolated lung lobes.
To test the hypothesis that preservation of circulating platelets would prolong the function of an isolated perfused canine lung lobe, prostacyclin (PGI2) was added to the perfusate. Platelet count in heparinized controls (n = 7) fell to 44,500 platelets/mm3, lower than 136,000 platelets/mm3 seen with 1 microgram/min PGI2 (n = 7, P less than 0.005). Surprisingly, with PGI2, thromboxane B2 (TXB2) the stable product of thromboxane A2 (TXA2), rose from 0.07 to 0.25 ng/ml, a level higher than controls (P less than 0.005). PGI2, in comparison to controls, also led to higher pulmonary arterial pressure, an increase in lobe weight, an increase in wet weight-dry weight ratio, an increase in physiological shunt, and a decrease in compliance (P less than 0.005). Further, with PGI2 there was hemorrhagic edema. Infusion of the PGI2 hydrolysis product 6-keto-prostaglandin F1 alpha (n = 2) led to results similar to controls. Adverse PGI2 effects were eliminated by pretreatment with ibuprofen (12.5 mg/kg, n = 5) or an antiplatelet antibody (n = 6). Infusion of PGI2 into a lobar pulmonary artery of an intact animal was without effect on the lung (n = 2). These results show that platelets exposed to a foreign surface will aggregate and be lost from the circulation. PGI2 prevents platelet loss but not the synthesis of TXA2. This vasoconstrictor is likely to be the cause of pulmonary hypertension and hemorrhagic pulmonary edema.
D015121:6-Ketoprostaglandin F1 alpha / Q000009:adverse effects / Q000032:analysis; D000818:Animals; D001696:Biomechanical Phenomena; D004285:Dogs; D011464:Epoprostenol / Q000009:adverse effects*; D007052:Ibuprofen / Q000494:pharmacology; D008168:Lung / Q000032:analysis / Q000187:drug effects*; D010477:Perfusion; D010976:Platelet Count; D011453:Prostaglandins / Q000009:adverse effects*; D013929:Thromboxane B2 / Q000032:analysis
D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007052:Ibuprofen