EXPERIMENTAL FAT-EMBOLISM INDUCES URINE 2,3-DINOR-6-KETOPROSTAGLANDINF1-ALPHA AND 11-DEHYDROTHROMBOXANE B-2 EXCRETION IN PIGS

Objective: To evaluate the in vivo production of prostacyclin and thro mboxane A(2) during the initial phase of experimental fat embolism as assessed, respectively, by determinations of urine 2,3-dinor-6-ketopro staglandin F-1 alpha and 11-dehydrothromboxane B-2 excretion. Design: Randomized, controlled trial. Setting: Animal laboratory, Subjects: Tw enty seven domestic pigs, weighing 24 to 31 kg. Interventions: All pig s were anesthetized and mechanically ventilated during the experiment, Eighteen pigs were subjected to an intracaval infusion of 10% allogen eic bone marrow suspension at a dose of 100 mg/kg over 5 mins. Nine pi gs received only bone marrow suspension (fat embolism group). Nine pig s were given an intravenous bolus of aspirin (300 mg) 1 hr before the bone marrow suspension infusion. After the induction of fat embolism, intravenous aspirin was administered at a dose of 150 mg/hr for 2 hrs (aspirin treated group). Nine pigs were infused with saline (control g roup). Measurements and Main Results: In the fat embolism group, cardi ac index decreased within 30 mins, while mean arterial pressure remain ed unchanged, Central Venous pressure and pulmonary artery occlusion p ressure remained relatively stable over time in the animals with fat e mbolism, Mean pulmonary arterial pressure and pulmonary Vascular resis tance increased immediately after the bone marrow suspension infusion from 23 +/- 0.8 (SEM) to 34 +/- 1.3 mm Hg and from 305 +/- 28 to 585 /- 45 dyne.sec/cm(5), respectively; these variables remained increased throughout the study period. Simultaneously, pulmonary shunt in the f at embolism group increased persistently from the baseline of 12.3 +/- 2.8%, and reached its maximum of 26.1 +/- 4.8% at the end of the expe riment. Instant and gradual decreases in Pao(2) (from 95 +/- 4 to 67 /- 5 torr [12.6 +/- 0.5 to 8.9 +/- 0.7 kPa]), hemoglobin oxygen satura tion (from 97.2 +/- 0.4 to 91.8 +/- 1.8%), and oxygen delivery (from 1 6.3 +/- 1.0 to 12.6 +/- 0.4 mL/min/kg) were observed in the fat emboli sm group. In the bone marrow suspension-infused animals, urine 2,3-din or-6-ketoprostaglandin F-1 alpha excretion increased transiently from 451 +/- 63 up to 1466 +/- 499 pg/mu mol creatinine, while urine 11-deh ydrothromboxane B-2 excretion increased transiently from 385 +/- 36 up to 2307 +/- 685 pg/mu mol creatinine. In the aspirin-treated animals, urinary excretion of these prostanoid metabolites was reduced by 81% and 88%, respectively. The changes in mean pulmonary arterial pressure and Pao(2) were ameliorated, and the alterations in pulmonary shunt a nd Sao(2) were abolished in the animals with aspirin treatment. Conclu sions: Pulmonary hypertension, increased pulmonary vascular tone, and increased pulmonary shunt are hallmarks of the present fat embolism mo del. These hemodynamic responses may, at least partly, be related to t he changed balance between prostacyclin and thromboxane A(2) productio n.