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Updated: Sep 26, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice
Edith Hochhauser1, Shaye Kivity, Daniel Offen
1Cardiac Research Laboratory, Department of Cardiothoracic Surgery, Tel Aviv University, Israel. hochhaus@post.tau.ac.il
Abstract:
The role of the proapototic Bax gene in ischemia-reperfusion (I/R) injury was studied in three groups of mice: homozygotic knockout mice lacking the Bax gene (Bax(-/-)), heterozygotic mice (Bax(+/-)), and wild-type mice (Bax(+/+)). Isolated hearts were subjected to ischemia (30 min, 37 degrees C) and then to 120 min of reperfusion. The left ventricular developed force of Bax-deficient vs. Bax(+/+) hearts at stabilization and at 120 min of reperfusion was 1,411 +/- 177 vs. 1,161 +/- 137 mg and 485 +/- 69 vs. 306 +/- 68 mg, respectively. Superior cardiac function of Bax(-/-) hearts after I/R was accompanied by a decrease in creatine kinase release, caspase 3 activity, irreversible ischemic injury, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cardiomyocytes. Electron microscopic evaluation revealed reduced damage to mitochondria and the nuclear chromatin structure in Bax-deficient mice. In the Bax(+/-) hearts, the damage markers were moderate. The superior tolerance of Bax knockout hearts to I/R injury recommends this gene as a potential target for therapeutic intervention in patients with severe and intractable myocardial ischemia.
Insights
Mice lacking the Bax gene showed improved heart function after ischemia-reperfusion injury. This suggests the Bax gene is a potential therapeutic target for myocardial ischemia.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cell Death Pathways
Background:
- Ischemia-reperfusion (I/R) injury is a significant cause of heart damage.
- The proapoptotic Bax gene's role in I/R injury is not fully understood.
Purpose of the Study:
- To investigate the function of the Bax gene in myocardial I/R injury.
- To evaluate the therapeutic potential of targeting the Bax gene.
Main Methods:
- Comparison of cardiac function in Bax knockout (Bax(-/-)), heterozygotic (Bax(+/-)), and wild-type (Bax(+/+)) mice subjected to I/R.
- Assessment of biochemical markers (creatine kinase, caspase 3 activity) and cell death (TUNEL assay).
- Mitochondrial and nuclear structure evaluation using electron microscopy.
Main Results:
- Bax(-/-) hearts exhibited superior cardiac function and reduced injury markers post-I/R compared to wild-type.
- Decreased creatine kinase release, caspase 3 activity, and TUNEL-positive cells were observed in Bax-deficient hearts.
- Mitochondrial and nuclear damage was significantly reduced in Bax knockout mice.
Conclusions:
- The proapoptotic Bax gene exacerbates I/R injury in the heart.
- Bax deficiency confers significant protection against myocardial I/R injury.
- Targeting the Bax gene represents a promising therapeutic strategy for myocardial ischemia.
