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Updated: Aug 14, 2026
NADH Fluorescence Imaging of Isolated Biventricular Working Rabbit Hearts
Published on: July 24, 2012
Flow-independent myocardial ischemia induced by endothelin-1: an NADH fluorescence analysis
Soushin Inoue1, Shingo Hori, Takeshi Adachi
1Cardiopulmonary Division, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Insights
Endothelin-1 (ET-1) causes greater myocardial ischemia than coronary stenosis by affecting myocytes and constricting coronary microcirculation, leading to transmural ischemia.
Area of Science:
- Cardiovascular Physiology
- Ischemic Heart Disease Research
Background:
- Endothelin-1 (ET-1) is recognized for inducing myocardial ischemia.
- The precise mechanisms underlying ET-1-induced ischemia, particularly beyond simple vasoconstriction, require further elucidation.
Purpose of the Study:
- To characterize myocardial ischemia following intracoronary endothelin-1 administration.
- To compare ET-1-induced ischemia with ischemia generated by coronary stenosis.
Main Methods:
- Intracoronary administration of ET-1 or coronary stenosis in canine left anterior descending coronary arteries.
- Rapid heart cross-sectioning and freeze-clamping within 120 ms.
- NADH fluorescence photography to quantify the ischemic area (%IA).
Main Results:
- Endothelin-1 resulted in a significantly larger ischemic area (%IA) compared to coronary stenosis (66% vs. 18%).
- ET-1 induced transmural ischemia, whereas stenosis caused subendocardial ischemia.
- ET-1 increased coronary arterial resistance, particularly in the subepicardial region, and affected microcirculation.
Conclusions:
- Endothelin-1 induces more extensive myocardial ischemia than coronary stenosis.
- The mechanism involves both pro-ischemic effects on myocytes and vasoconstriction of coronary microcirculation.
- ET-1's impact on ischemia is predominantly observed in the subepicardial region.
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.