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Reduction of prostacyclin synthesis as a possible cause of transient flow reduction in a partially constricted canine coronary artery

1984; Elsevier BV; Volume: 16; Issue: 12 Linguagem: Inglês

10.1016/s0022-2828(84)80040-1

1095-8584

Michihiko Tada, Kimio Esumi, Masakazu Yamagishi, Tsunehiko Kuzuya, Hisao Matsuda, Hiroshi Abe, Yasumi Uchida, Satoru Murao,

Acute Myocardial Infarction Research

Coronary blood flow decreases cyclically in a partially occluded coronary artery of anesthetized dogs. Spontaneous aggregation and deaggregation of platelet plugs in the constricted artery have been indicated to be responsible for this phenomenon. A current hypothesis is that platelet aggregation may be determined by a balance between proaggregatory platelet product, thromboxane A2 (TXA2), and antiaggregatory substance, prostacyclin (PGI2). To elucidate the relationship between the cyclical reduction of coronary flow (CRCF) and metabolic alterations of TXA2 and PGI2, we attempted to determine the plasma levels of their stable catabolites, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α), in the coronary circulation of 69 dogs. Of 40 cases, 20 cases exhibited CRCF accompanying a significant increase in TXB2 in the coronary sinus (CS) (P<0.05) and constant levels of 6-keto-PGF1α in the CS and aorta (Ao). Another 20 cases did not exhibit CRCF that accompanied a marked increase in 6-keto-PGF1α (P<0.05) with virtually no change in TXB2 in the CS and Ao. A higher dose of indomethacin (10 mg/kg, i.v.) was capable of evoking CRCF in cases not exhibiting CRCF spontaneously. Under these conditions, a significant decrease in 6-keto-PGF1α was seen both in the CS and Ao compared with lower doses of indomethacin (1 to 3 mg/kg, P<0.01), that produced less pronounced reduction of 6-keto-PGF1α without CRCF. Intravenous infusion of PGI2 (0.1 μg/kg/min.) completely abolished spontaneously and indomethacin-induced CRCF with a marked elevation of 6-keto-PGF1α in the CS and Ao. Although OKY-1580, a TXA2 synthetase inhibitor, relieved spontaneously-evoked CRCF with a marked increase in 6-keto-PGF1α and a slight reduction of TXB2, indomethacin-induced CRCF was not abolished by this agent. These results are consistent with the hypothesis that the reduction of endogenous PGI2 synthesis in the vascular wall is related to the occurrence of CRCF after partial constriction of coronary artery and indomethacin. Coronary blood flow decreases cyclically in a partially occluded coronary artery of anesthetized dogs. Spontaneous aggregation and deaggregation of platelet plugs in the constricted artery have been indicated to be responsible for this phenomenon. A current hypothesis is that platelet aggregation may be determined by a balance between proaggregatory platelet product, thromboxane A2 (TXA2), and antiaggregatory substance, prostacyclin (PGI2). To elucidate the relationship between the cyclical reduction of coronary flow (CRCF) and metabolic alterations of TXA2 and PGI2, we attempted to determine the plasma levels of their stable catabolites, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α), in the coronary circulation of 69 dogs. Of 40 cases, 20 cases exhibited CRCF accompanying a significant increase in TXB2 in the coronary sinus (CS) (P<0.05) and constant levels of 6-keto-PGF1α in the CS and aorta (Ao). Another 20 cases did not exhibit CRCF that accompanied a marked increase in 6-keto-PGF1α (P<0.05) with virtually no change in TXB2 in the CS and Ao. A higher dose of indomethacin (10 mg/kg, i.v.) was capable of evoking CRCF in cases not exhibiting CRCF spontaneously. Under these conditions, a significant decrease in 6-keto-PGF1α was seen both in the CS and Ao compared with lower doses of indomethacin (1 to 3 mg/kg, P<0.01), that produced less pronounced reduction of 6-keto-PGF1α without CRCF. Intravenous infusion of PGI2 (0.1 μg/kg/min.) completely abolished spontaneously and indomethacin-induced CRCF with a marked elevation of 6-keto-PGF1α in the CS and Ao. Although OKY-1580, a TXA2 synthetase inhibitor, relieved spontaneously-evoked CRCF with a marked increase in 6-keto-PGF1α and a slight reduction of TXB2, indomethacin-induced CRCF was not abolished by this agent. These results are consistent with the hypothesis that the reduction of endogenous PGI2 synthesis in the vascular wall is related to the occurrence of CRCF after partial constriction of coronary artery and indomethacin.