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Updated: Feb 22, 2026
Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats
Published on: June 28, 2019
Changes in vasodilation following myocardial ischemia/reperfusion in rats
Sarah Brøgger Kristiansen1, Majid Sheykhzade2, Lars Edvinsson3
1Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Rigshospitalet-Glostrup, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Insights
Myocardial ischemia/reperfusion (I/R) reduces nitric oxide (NO) dependent vasodilation, specifically ADPβS signaling. However, hydrogen peroxide (H2O2) mediated EDH-type dilation offers some compensation, alongside reduced CGRP response, impacting recovery after I/R.
Area of Science:
- Cardiovascular Research
- Endothelial Function
- Myocardial Ischemia/Reperfusion Injury
Background:
- Coronary artery blockage, often from arteriosclerosis, causes acute myocardial infarction.
- Percutaneous coronary intervention (PCI) can be lifesaving but reperfusion may worsen cellular damage.
- Endothelial changes are implicated in exacerbated outcomes following reperfusion injury.
Purpose of the Study:
- To compare endothelial-dependent and independent vasodilation after experimental myocardial ischemia/reperfusion (I/R).
Main Methods:
- Utilized a rat model of myocardial ischemia followed by 24 hours of reperfusion.
- Investigated vascular responses using a wire myograph.
- Assessed endothelial function through agonist-induced vasodilation.
Main Results:
- Nitric oxide (NO) dependent relaxation to carbachol was unaffected by I/R.
- NO dependent ADPβS signaling was significantly reduced post-I/R.
- An H2O2-dependent EDH-type dilation emerged post-I/R.
- Calcitonin gene-related peptide (CGRP) induced vasodilation was diminished.
Conclusions:
- I/R impairs NO dependent ADPβS induced dilation.
- Released H2O2 partially compensates via EDH-type mechanisms.
- Reduced vasodilation, including loss of CGRP response, contributes to exacerbated I/R damage.
Background:
Blockage of a coronary artery, usually caused by arteriosclerosis, can lead to life threatening acute myocardial infarction. Opening with PCI (percutaneous coronary intervention), may be lifesaving, but reperfusion might exacerbate the cellular damage, and changes in the endothelium are believed to be involved in this worsened outcome.
Aim:
The aim of the present study was to compare endothelial dependent and independent vasodilatory effect after experimental myocardial ischemia/reperfusion (I/R).
Methods:
A well-established rat model of myocardial ischemia with 24 h of reperfusion was applied, followed by a study in a wire myograph.
Results:
Endothelial NO dependent relaxation in response to carbachol, was sensitive to arterial depolarization, and was unaffected by I/R. In contrast, endothelial NO dependent ADPβS signalling, which was not sensitive to arterial depolarization, was significantly reduced after I/R. Following I/R, an H2O2 dependent EDH induced dilation appears in response to both of the above agonists. In addition, calcitonin gene-related peptide (CGRP) induced vasodilation was reduced.
Conclusion:
These data show that NO dependent ADPβS induced dilation is reduced after I/R. However, there is some compensation by released H2O2 causing an EDH. Combined with a loss of maximal dilation in response to CGRP, the reduced vasodilation could be an important factor in understanding the exacerbated damage after I/R.
