Related Experiment Video
Updated: Aug 15, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Leukocyte trafficking and myocardial reperfusion injury in ICAM-1/P-selectin-knockout mice
S A Briaud1, Z M Ding, L H Michael
1Section of Cardiovascular Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Insights
Genetic deletions of P-selectin and intercellular adhesion molecule-1 (ICAM-1) impair neutrophil trafficking after myocardial ischemia-reperfusion. However, these genetic changes did not alter infarct size in the affected heart tissue.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cellular Adhesion
Background:
- P-selectin and ICAM-1 are key molecules mediating neutrophil adhesion to the endothelium during myocardial ischemia-reperfusion injury.
- Understanding the roles of these adhesion molecules is crucial for developing therapeutic strategies against heart damage.
Purpose of the Study:
- To investigate the physiological impact of genetic deficiencies in ICAM-1 and P-selectin on neutrophil recruitment and infarct size following myocardial ischemia-reperfusion.
- To determine if blocking these adhesion pathways affects the extent of heart tissue damage.
Main Methods:
- Utilized genetically modified mice lacking ICAM-1 and P-selectin.
- Induced myocardial ischemia-reperfusion injury in both wild-type and deficient mice.
- Quantified neutrophil influx using immunohistochemistry and myeloperoxidase activity.
- Assessed infarct size as the ratio of necrotic area to the area at risk.
Main Results:
- ICAM-1/P-selectin-deficient mice exhibited significantly reduced neutrophil infiltration at 24 hours post-reperfusion compared to wild-type mice.
- No significant difference in neutrophil influx was observed at 3 hours.
- Infarct size was not significantly different between wild-type and deficient mice at 24 hours, irrespective of occlusion duration (30 min or 1 h).
Conclusions:
- Genetic deficiency of ICAM-1 and P-selectin effectively impairs neutrophil trafficking to the ischemic myocardium.
- Despite reduced neutrophil influx, the absence of ICAM-1 and P-selectin does not confer protection against infarct size in this model of myocardial ischemia-reperfusion.
Abstract:
P-selectin and intercellular adhesion molecule-1 (ICAM-1) mediate early interaction and adhesion of neutrophils to coronary endothelial cells and myocytes after myocardial ischemia and reperfusion. In the present study, we examined the physiological consequences of genetic deletions of ICAM-1 and P-selectin in mice. In wild-type mice, after 1 h of ischemia followed by reperfusion, neutrophil influx into the area of ischemia was increased by 3 h with a peak at 24 h and a decline by 72 h. ICAM-1/P-selectin-deficient mice showed a significant reduction in neutrophils by immunohistochemistry or by myeloperoxidase activity at 24 h but no significant difference at 3 h. Infarct size (area of necrosis/area at risk) assessed 24 h after reperfusion was not different between wild-type and deficient mice after 30 min and 1 h of occlusion. Mice with a deficiency in both ICAM-1 and P-selectin have impaired neutrophil trafficking without a difference in infarct size due to myocardial ischemia-reperfusion.
