title: Roles of endogenous prostacyclin and thromboxane A2 in the ischemic canine heart.
abstract: The ability of the ischemic heart to release prostacyclin (PGI2) and thromboxane A2 (TXA2) was studied, together with the effects of these substances on the ischemic myocardium in open-chest dogs. We measured the plasma levels of 6-keto-PGF1 alpha and TXB2--which are stable metabolites of PGI2 and TXA2, respectively--as well as lactate and coronary venous blood flow. The dogs were divided into three groups of eight animals which received indomethacin (5 mg/kg), (E)-3-[4-l-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046) (1 mg/kg), or the vehicle. A transient increase in 6-keto-PGF1 alpha was observed in the great cardiac vein 5 min after the ligation of the left anterior descending coronary artery (LAD). TXB2 and lactate increased 30 and 15 min, respectively, after the ligation. Indomethacin prevented significant increases in 6-keto-PGF1 alpha and TXB2, but accelerated the lactate release. OKY-046 prevented significant increases in TXB2 and lactate release, but did not counteract the increase in 6-keto-PGF1 alpha. Although coronary venous flow decreased significantly 5 min after the ligation in every group, the flow returned to the preligation level 15 min after the ligation in the OKY-046 and the vehicle groups. Thus, we have demonstrated the release of PGI2 and TXA2 from the ischemic heart and suggest beneficial effects of PGI2 and of a selective inhibitor of thromboxane synthetase on the ischemic myocardium.
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D011464:Epoprostenol / Q000502:physiology*; D005260:Female; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D011460:Prostaglandins F / Q000097:blood; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000502:physiology*
chemical_list: D007773:Lactates; D011453:Prostaglandins; D011460:Prostaglandins F; D013931:Thromboxanes; D019344:Lactic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase