Related Experiment Video
Updated: Jul 17, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Effects of rivaroxaban on myocardial mitophagy in the rat heart
Tugra Gencpinar1, Cagatay Bilen2, Baris Kemahli3
1Department of Cardiovascular Surgery, Dokuz Eylül University Faculty of Medicine, Izmir, Türkiye.
Background:
This study aims to demonstrate the efficacy of rivaroxaban's pharmacokinetic effects on myocardial mitophagy in rats by inducing apoptosis.
Methods:
In this double-blind experiment, Wistar albino male rats were randomly divided into three groups for an experimental ischemia model: the sham group (Group 1; n=7), the control group (Group 2; n=7), and the drug group (Group 3; n=7). Rivaroxaban was perorally administered with gavage at 2 mg/ kg/day for 28 days in Group 3. The heart was surgically exposed, and ischemia was achieved by compressing the vessel around the proximal part of the left anterior descending coronary artery for 10 min. The heart tissue was then transected, removed, and morphologically and immunohistochemically examined under a light microscope.
Results:
Heart sections were immunohistochemically marked with caspase 3, caspase 9, APAF1, and Bcl-2 antibodies. Group 1 was compared to the rivaroxaban-treated group, and the pathways inducing apoptosis was increased (caspase 3, caspase 9, APAF1; p<0.015, p<0.004, and p<0.01, respectively) and Bcl-2, the molecule that inhibits apoptosis, was decreased (p<0.01) in Group 3.
Conclusion:
The present study provides an evidence that the mitophagy response is less in rivaroxaban-treated rats, showing the protective effect of rivaroxaban against acute ischemia. Rivaroxaban-treated rats may have reduced cell death in cardiomyocytes during myocardial infarction and thus have reduced damage to the heart tissue caused by myocardial infarction.
Insights
Rivaroxaban treatment reduced myocardial mitophagy and apoptosis in rats experiencing acute ischemia. This suggests rivaroxaban offers a protective effect against heart tissue damage during myocardial infarction.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Cell Biology
Background:
- Myocardial infarction leads to significant heart tissue damage.
- Understanding the role of mitophagy in myocardial ischemia is crucial for developing protective strategies.
- Rivaroxaban is an anticoagulant with potential cardioprotective effects.
Purpose of the Study:
- To investigate the pharmacokinetic effects of rivaroxaban on myocardial mitophagy.
- To assess rivaroxaban's efficacy in mitigating apoptosis-induced damage in a rat model of myocardial ischemia.
Main Methods:
- A double-blind, experimental ischemia model was established in Wistar albino male rats.
- Rats were divided into sham, control, and rivaroxaban-treated groups (2 mg/kg/day for 28 days).
- Heart tissue was examined morphologically and immunohistochemically for apoptosis markers (caspase 3, 9, APAF1, Bcl-2).
Main Results:
- Rivaroxaban treatment significantly increased the expression of apoptosis-inducing pathways (caspase 3, 9, APAF1).
- The expression of Bcl-2, an apoptosis inhibitor, was significantly decreased in rivaroxaban-treated rats.
- Immunohistochemical analysis revealed a reduced mitophagy response in the rivaroxaban group.
Conclusions:
- Rivaroxaban demonstrates a protective effect against acute myocardial ischemia in rats.
- The drug appears to modulate mitophagy and apoptosis, potentially reducing cardiomyocyte death.
- These findings suggest rivaroxaban may limit heart tissue damage following myocardial infarction.
