Inhibition of thromboxane A2 production does not improve post-ischemic brain hypoperfusion in the dog.
In a canine model of global brain ischemia, six dogs received a selective thromboxane A2 synthetase inhibitor, UK 38,485 (dazmagrel) before the ischemic event; six received a saline placebo. Cerebral blood flow (CBF), systolic and diastolic arterial pressure, cardiac output, pH, PaCO2, PaO2, and arterial and jugular-vein thromboxane B2 (a stable metabolite of thromboxane A2) and 6-keto PGF1 alpha (a stable metabolite of prostacyclin) were measured at baseline, after release of aortic and venae caval occlusion and at intervals up to 120 min thereafter. Treated animals showed nearly complete post-ischemic inhibition of thromboxane B2 production; control animals showed increases in jugular venous thromboxane B2. Arterial and jugular venous levels of 6-keto PGF1 alpha were significantly higher in treated animals at most post-ischemic intervals. CBF in both groups was similar to baseline values at time 0, then declined similarly in both groups by 30 min to approximately equal to 35% of baseline values where it remained thereafter. There were no significant differences in other variables at any interval. We conclude that inhibition of thromboxane A2 production does not alter post-ischemic brain hypoperfusion.
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004285:Dogs; D011464:Epoprostenol / Q000378:metabolism; D007093:Imidazoles / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors
D007093:Imidazoles; C039242:dazmegrel; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase