title: Flow-independent myocardial ischemia induced by endothelin-1: an NADH fluorescence analysis.
abstract: The endothelin-1 (ET-1) is known to cause myocardial ischemia; however, whether this effect is entirely dependent on vasoconstriction is uncertain. The aim of this study was to characterize the myocardial ischemia after the intracoronary administration of endothelin-1, and compare it with that induced by coronary stenosis. In the left anterior descending coronary artery of 15 dogs, a mild inflow reduction (30%) was produced for 10 minutes using intracoronary endothelin-1 (46 +/- 33 pmol/min) or coronary stenosis. The hearts were rapidly cross-sectioned at short axial plane and freeze-clamped within 120 milliseconds using a specially developed device to visualize and quantify the area of ischemia (%IA) with NADH fluorescence photography. The %IA was larger in the endothelin-1 group than in the stenosis group (66 +/- 23 versus 18 +/- 18, P = 0.0005); furthermore, the ischemia was transmural in the ET-1 group, but limited to subendocardium in the stenosis group. ET-1 increased the coronary arterial resistance especially in subepicardial region and produced smaller ischemic foci in microcirculation. The mechanism of larger ischemia produced by ET-1 might depend on pro-ischemic effects on myocytes and vasoconstriction of the coronary microcirculation, predominantly in the subepicardium in vivo.
authors.affiliation: Cardiopulmonary Division, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Soushin
authors.initials: S
authors.lastname: Inoue
authors.forename: Shingo
authors.initials: S
authors.lastname: Hori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Adachi
authors.forename: Koji
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Shingo
authors.initials: S
authors.lastname: Kyotani
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
authors.forename: Hidezo
authors.initials: H
authors.lastname: Mori
authors.forename: Hiroe
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Aikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D019332:Endothelin-1 / Q000633:toxicity*; D005453:Fluorescence; D006439:Hemodynamics / Q000187:drug effects; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000503:physiopathology; D009243:NAD / Q000032:analysis*
chemical_list: D019332:Endothelin-1; D009243:NAD