Flow-independent myocardial ischemia induced by endothelin-1: An NADH fluorescence analysis

Soushin Inoue, Shingo Hori, Takeshi Adachi, Koji Miyazaki, Shingo Kyotani, Keiichi Fukuda, Hidezo Mori, Hiroe Nakazawa, Naoki Aikawa, Satoshi Ogawa

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)810-816
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume46
Issue number6
DOIs
Publication statusPublished - 2005 Dec 1

Keywords

  • Coronary circulation
  • Endothelin-1
  • Microcirculation
  • Myocardial ischemia
  • NADH fluorescence
  • Pro-ischemia

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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