Effects of distal embolization on the timing of platelet and inflammatory cell activation in interventional coronary no-reflow
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Updated: Jun 12, 2026
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Published on: March 15, 2022
Thierry Charron1, Ronen Jaffe, Amit Segev
1Roy and Ann Foss Interventional Cardiology Research Program, University Health Network, University of Toronto, and Department of Hematology, St. Michael's Hospital, Toronto, Ontario, Canada.
Insights
Distal embolization triggers inflammation and platelet activation before coronary no-reflow occurs. These interactions between white blood cells and platelets are key to no-reflow development and potential therapeutic targets.
Area of Science:
- Cardiovascular Research
- Interventional Cardiology
- Inflammation and Immunology
Background:
- Percutaneous coronary intervention (PCI) can lead to myocardial hypoperfusion, known as no-reflow.
- Distal coronary embolization is a suspected initiator of no-reflow.
- Understanding the early inflammatory and platelet responses is crucial.
Purpose of the Study:
- To investigate the effects of distal embolization on inflammation and platelet activation.
- To determine the timing of these responses relative to no-reflow onset.
- To utilize an experimental model of coronary no-reflow.
Main Methods:
- A no-reflow model was created in Yorkshire pigs using polystyrene microsphere injections.
- Control pigs received saline infusions.
- Coronary sinus blood was analyzed via flow cytometry for white blood cell and platelet activation markers, and TNF-alpha.
Main Results:
- No-reflow was achieved after a specific microsphere dose.
- Distal embolization significantly increased polymorphonuclear-platelet and monocyte-platelet aggregates, and TNF-alpha levels before no-reflow.
- Annexin A5 also showed a significant increase prior to no-reflow.
Conclusions:
- Inflammatory and coagulation pathways activate before angiographic no-reflow following embolization.
- These findings are not due to instrumentation.
- WBC-platelet interactions are critical in no-reflow pathogenesis and represent therapeutic targets.
Introduction:
Myocardial hypoperfusion following percutaneous coronary intervention, termed "no-reflow", may be initiated by distal coronary embolization. This study examined the effects of distal embolization on the extent and timing of inflammation and platelet activation in an experimental model of coronary no-reflow.
Material And Methods:
A no-reflow model was established in 9 Yorkshire pigs by injecting incremental doses of biologically inert polystyrene microspheres into the left anterior descending artery every 20 minutes via a transit catheter. A control group included 3 pigs that received corresponding intra-coronary boluses of normal saline. At predefined time points, coronary sinus blood samples were drawn and immediately analyzed by flow cytometry analysis for a panel of white blood cell and platelet activation markers, and the inflammatory cytokine TNFalpha.
Results:
No-reflow was achieved after delivery of 1,169,000+/-303,000 (range: 680,000 to 2,600,000) microspheres. In the distal embolization group, there were significant increases above baseline values in polymorphonuclear-platelet aggregates (146%-218%), in monocyte-platelet aggregates (51%-94%) and in TNFalpha levels (54%-84%) at multiple time points prior to no- reflow (15% cumulative dose and higher). For Annexin A5, there was a significant increase at 52% of cumulative dose (177% above baseline). Controls only showed one significant increase above baseline value for polymorphonuclear-platelet aggregates at the time of the last injection.
Conclusions:
Widespread activation of interacting inflammatory and coagulation pathways following microsphere embolization occurred prior to the onset of angiographic no-reflow. This activation pattern cannot be attributed to prolonged coronary sinus instrumentation. Interactions between white blood cells (polymorphonuclears and monocytes) and platelets likely play an important role in the pathogenesis of no-reflow following distal embolization and may represent important therapeutic targets.
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