THROMBOXANE RECEPTOR STIMULATION-INHIBITION AND PERFUSION REDISTRIBUTION AFTER ACUTE LUNG INJURY

Perfusion redistribution (PR) after acute oleic acid (OA) lung injury may be the result of changes in the tissue concentration ratio of thro mboxane (Tx) and prostacyclin (A. H. Stephenson et al. J. Appl. Physio l. 73: 2126-2134, 1992). We tested this hypothesis by determining whet her the Tx mimetic U-46619 would mimic PR caused by cyclooxygenase inh ibition with meclofenamate and whether the Tx receptor antagonist ONO- 3708 would inhibit PR even in the presence of meclofenamate. Measureme nts of regional pulmonary blood flow (PBF) and lung water concentratio n were made with the nuclear medicine imaging technique of positron em ission tomography. Measurements were made at baseline and 2 h after OA . At baseline, the spatial distribution of PBF was similar in all expe rimental groups. Two hours after OA, fractional PBF was reduced to the edematous lung in all groups given OA, but the magnitude of change wa s greater in those groups receiving meclofenamate or U-46619 compared with the change in the group given OA only. Thus, although the Tx mime tic produced the same amount of PR as meclofenamate, Tx inhibition did not prevent PR after meclofenamate. Therefore, the ratio of Tx to pro stacyclin per se is not the critical determinant of PR.