Related Experiment Video
Updated: Jul 29, 2026

06:11
Model of Ischemia and Reperfusion Injury in Rabbits
Published on: November 3, 2023
Reperfusion induces myocardial apoptotic cell death
Z Q Zhao1, M Nakamura, N P Wang
1Department of Surgery, Emory University School of Medicine, Atlanta, GA 30365-2225, USA.
Cardiovascular Research
|March 23, 2000
Summary
Myocardial apoptosis is primarily induced by reperfusion, not permanent ischemia. Reperfusion injury involves Bcl-2 family proteins and polymorphonuclear neutrophil accumulation, contributing to cell death.
Area of Science:
- Cardiovascular Research
- Cellular Biology
- Pathology
Background:
- Ischemia and reperfusion (I/R) injury is a critical factor in cardiovascular diseases.
- Understanding the mechanisms of cell death, including apoptosis, during I/R is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate if apoptosis occurs during ischemia (I) and reperfusion (R).
- To determine if I/R-induced apoptosis correlates with changes in Bcl-2 and Bax protein expression.
Main Methods:
- Open-chest dogs underwent either permanent ischemia (PI) or 60 minutes of ischemia followed by 6 hours of reperfusion (I/R).
- Apoptosis was assessed using DNA laddering and the TUNEL assay.
- Bcl-2 and Bax expression levels were analyzed by Western blot.
- Polymorphonuclear neutrophil (PMN) accumulation was quantified via immunohistochemistry and myeloperoxidase activity.
Main Results:
- Permanent ischemia (PI) did not induce significant apoptosis, with minimal TUNEL-positive cells and no DNA laddering.
- Ischemia/reperfusion (I/R) significantly increased TUNEL-positive cells and DNA laddering, indicating apoptosis primarily occurs during reperfusion.
- I/R led to decreased Bcl-2 and increased Bax expression, suggesting the Bcl-2 family's involvement.
- PMN accumulation was significantly higher in the I/R group and correlated with the number of apoptotic cells.
Conclusions:
- Apoptosis, alongside necrosis, is a key cell death mechanism following I/R, but not permanent ischemia.
- The Bcl-2 family proteins likely play a role in early reperfusion-induced myocardial apoptosis.
- Polymorphonuclear neutrophil infiltration may contribute to the development of apoptosis during I/R injury.
Related Concept Videos
Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Necrosis
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...

