Flow-independent myocardial ischemia induced by endothelin-1: an NADH fluorescence analysis.
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.
Inoue
Soushin
S
Cardiopulmonary Division, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Hori
Shingo
S
Adachi
Takeshi
T
Miyazaki
Koji
K
Kyotani
Shingo
S
Fukuda
Keiichi
K
Mori
Hidezo
H
Nakazawa
Hiroe
H
Aikawa
Naoki
N
Ogawa
Satoshi
S
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*
D019332:Endothelin-1; D009243:NAD