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Capillary pericytes mediate coronary no-reflow after myocardial ischaemia
Fergus M O'Farrell1, Svetlana Mastitskaya1, Matthew Hammond-Haley1
1Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
Insights
Cardiac pericytes constrict coronary capillaries after ischemia, reducing blood flow. Adenosine treatment relaxed these pericytes, improving microvascular perfusion in ischemic heart disease.
Area of Science:
- Cardiovascular Biology
- Microcirculation Research
- Ischemic Heart Disease Pathophysiology
Background:
- Reduced coronary microvascular perfusion, known as the 'no-reflow' phenomenon, persists after restoring blood flow in blocked arteries, worsening outcomes in ischemic heart disease.
- In the brain, post-stroke 'no-reflow' is linked to capillary constriction by contractile pericytes.
Purpose of the Study:
- To investigate the role of cardiac pericytes in the post-ischemic 'no-reflow' phenomenon in the heart.
- To determine if pericyte constriction contributes to reduced microvascular blood flow after cardiac ischemia.
- To evaluate the therapeutic potential of pericyte relaxation in improving perfusion.
Main Methods:
- Inducing transient coronary artery occlusion followed by reperfusion in a rat model.
- Quantifying capillary blockage, pericyte association, and changes in capillary diameter.
- Measuring perfused blood volume in the affected cardiac region.
- Administering adenosine, a pericyte relaxant, and assessing its effects on capillary diameter and perfusion.
Main Results:
- Cardiac ischemia and reperfusion resulted in 40% capillary blockage and halved perfused blood volume.
- Capillary blockages were strongly associated with pericytes, which reduced capillary diameter by 37%.
- Adenosine administration increased capillary diameter by 21%, reduced capillary block by 25%, and increased perfusion volume by 57%.
Conclusions:
- Cardiac pericytes actively constrict coronary capillaries, contributing to reduced microvascular blood flow after ischemia, even when the main artery is reopened.
- Cardiac pericytes represent a novel therapeutic target for improving microvascular perfusion in ischemic heart disease.
Abstract:
After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affected region. Capillary blockages colocalised strongly with pericytes, where capillary diameter was reduced by 37%. The pericyte relaxant adenosine increased capillary diameter by 21% at pericyte somata, decreased capillary block by 25% and increased perfusion volume by 57%. Thus, cardiac pericytes constrict coronary capillaries and reduce microvascular blood flow after ischaemia, despite re-opening of the culprit artery. Cardiac pericytes are therefore a novel therapeutic target in ischaemic heart disease.
