Roles of endogenous prostacyclin and thromboxane A2 in the ischemic canine heart.
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.
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*
D007773:Lactates; D011453:Prostaglandins; D011460:Prostaglandins F; D013931:Thromboxanes; D019344:Lactic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase