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Updated: Jul 29, 2026

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Complement and polymorphonuclear leukocyte activation each play a role in determining myocardial ischemia-reperfusion
T Atsuumi1, H Yaoita, T Shichishima
1First Department of Internal Medicine, Fukushima Medical University, Japan.
Insights
Cobra venom factor (CVF) activates immune cells, but its effect on heart injury depends on complement and polymorphonuclear leukocytes (PMNs). Both factors are crucial in determining myocardial infarct size after ischemia.
Area of Science:
- Cardiovascular Research
- Immunology
- Inflammation Biology
Background:
- Cobra venom factor (CVF) is known to activate complement and polymorphonuclear leukocytes (PMNs).
- The sequential effects of complement activation/depletion and PMN activation/deactivation by CVF offer a model to study their roles in myocardial injury.
- Understanding the interplay between complement and PMNs is crucial for mitigating ischemia-reperfusion injury.
Purpose of the Study:
- To investigate the individual and combined effects of complement and PMNs on myocardial infarct size (IS) using CVF-induced sequential changes.
- To determine whether complement depletion or PMN modulation influences IS during myocardial ischemia-reperfusion.
- To assess the role of myeloperoxidase (MPO) activity in the context of complement and PMN status on IS.
Main Methods:
- Rats were treated with CVF and/or anti-PMN antibodies to modulate complement and PMN levels.
- Myocardial ischemia was induced by coronary artery occlusion followed by reperfusion.
- Myocardial infarct size (IS) and myeloperoxidase (MPO) activity in the infarct area were quantified.
Main Results:
- CVF treatment led to transient PMN activation followed by complement depletion and PMN deactivation.
- Both CVF and anti-PMNs reduced MPO activity and IS.
- Complement depletion by CVF, despite PMN activation, failed to reduce IS, indicating a complex role.
Conclusions:
- Complement and PMN status independently influence myocardial infarct size.
- Ischemic reperfusion injury can occur even with low myocardial MPO activity, highlighting the importance of PMN and complement dynamics.
- Targeting both complement and PMNs may be necessary for effective treatment of myocardial ischemia-reperfusion injury.
Abstract:
Cobra venom factor (CVF) transiently activates polymorphonuclear leukocytes (PMN) by complement activation, followed by rapid complement depletion and gradual reversal of PMN activation. Utilizing these sequential changes caused by CVF, the individual and combined effects of complement and PMNs on myocardial infarct size (IS) were investigated. Rats were treated with CVF, and/or anti-PMNs. Complement was depleted, but circulating PMNs were being activated at 4h after CVF administration, and at 36h after, complement was depleted, but PMNs were in a near basal condition. Under anesthesia, the rats had a 30-min coronary occlusion followed by 6h of reperfusion. The IS was assessed by tetrazolium staining. CVF, as well as anti-PMNs, reduced myeloperoxidase (MPO) activity in the risk area and the reduced MPO resulted in a reduced IS, which was also the effect of anti-PMNs, but complement depletion by CVF, during which circulating PMNs were activated, failed to reduce the IS despite low MPO activity. These results suggest that complement and the condition of PMNs each play a role in determining the IS, and ischemic reperfusion injury might be produced even by relatively low myocardial MPO activity.
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