Role of endogenous prostacyclin in myocardial blood flow regulation distal to a severe coronary stenosis.
To test the hypothesis that endogenous prostacyclin is required to maintain reduced arteriolar tone distal to a severe coronary arterial stenosis under basal conditions and during challenge with a vasoconstrictor eicosanoid such as thromboxane A2 10 closed chest, domestic swine were prepared with an artificial stenosis, which reduced the luminal diameter of the left anterior descending coronary artery by 80%. Haemodynamic variables, regional myocardial blood flow (microsphere method), and lactate metabolism were measured at control (1); after infusion of U46619 (thromboxane A2 mimetic) distal to the stenosis at 1 microgram.min-1 for 10 min and 5 micrograms.min-1 for 10 min; at control (2); after indomethacin infusion distal to the stenosis; and after repeat infusion of U46619. At the end of the study the animal hearts were removed and their coronary vessels harvested for in vitro determination of prostacyclin (PGI2) production. Regional myocardial blood flow in all layers of the heart distal to the stenosis did not change compared with control during the initial 1 microgram.min-1 dose of U46619 but was reduced significantly after the 5 micrograms.min-1 dose (approximately 20% vs control). Distal zone flow (all layers) returned to baseline at control (2) and remained unchanged after indomethacin infusion. Although distal zone flows were reduced significantly in response to the second 5 micrograms.min-1 dose, the reduction in each layer after indomethacin was comparable to that observed with the 5 micrograms.min-1 dose before indomethacin infusion. Finally, the in vitro production of PGI2 by coronary vessels was considerably impaired by indomethacin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Ruocco
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Brown University Program in Medicine, Rhode Island Hospital, Providence 02903.
Most
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Sasken
H
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Steiner
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Gewirtz
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D011464:Epoprostenol / Q000378:metabolism / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D007773:Lactates; D011450:Prostaglandin Endoperoxides, Synthetic; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol