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Updated: May 17, 2026
Model of Ischemia and Reperfusion Injury in Rabbits
Published on: November 3, 2023
Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective Peptide
Robert A Kloner1, Sharon L Hale, Wangde Dai
1Heart Institute of Good Samaritan Hospital, University of Southern California, Los Angeles (R.A.K., S.H., W.D.) ; Keck School of Medicine, Division of Cardiovascular Medicine, University of Southern California, Los Angeles (R.A.K., W.D.).
Background:
Manifestations of reperfusion injury include myocyte death leading to infarction, contractile dysfunction, and vascular injury characterized by the "no-reflow" phenomenon. Mitochondria-produced reactive oxygen species are believed to be centrally involved in each of these aspects of reperfusion injury, although currently no therapies reduce reperfusion injury by targeting mitochondria specifically.
Methods And Results:
We investigated the cardioprotective effects of a mitochondria-targeted peptide, Bendavia (Stealth Peptides), across a spectrum of experimental cardiac ischemia/reperfusion models. Postischemic administration of Bendavia reduced infarct size in an in vivo sheep model by 15% (P=0.02) and in an ex vivo guinea pig model by 38% to 42% (P<0.05). In an in vivo rabbit model, the extent of coronary no-reflow was assessed with Thioflavin S staining and was significantly smaller in the Bendavia group for any given ischemic risk area than in the control group (P=0.0085). Myocardial uptake of Bendavia was ≈25% per minute, and uptake remained consistent throughout reperfusion. Postischemic recovery of cardiac hemodynamics was not influenced by Bendavia in any of the models studied. Isolated myocytes exposed to hypoxia/reoxygenation showed improved survival when treated with Bendavia. This protection appeared to be mediated by lowered reactive oxygen species-mediated cell death during reoxygenation, associated with sustainment of mitochondrial membrane potential in Bendavia-treated myocytes.
Conclusions:
Postischemic administration of Bendavia protected against reperfusion injury in several distinct models of injury. These data suggest that Bendavia is a mitochondria-targeted therapy that reduces reperfusion injury by maintaining mitochondrial energetics and suppressing cellular reactive oxygen species levels. (J Am Heart Assoc. 2012;1:e001644 doi: 10.1161/JAHA.112.001644.).
Insights
Bendavia, a novel mitochondria-targeted peptide, effectively reduces reperfusion injury and infarct size in cardiac models. This peptide protects heart cells by maintaining mitochondrial function and lowering reactive oxygen species levels.
Area of Science:
- Cardiovascular Science
- Mitochondrial Biology
- Pharmacology
Background:
- Reperfusion injury causes myocyte death, contractile dysfunction, and no-reflow phenomenon.
- Mitochondria-derived reactive oxygen species (ROS) are key contributors to reperfusion injury.
- Current therapies do not specifically target mitochondria to reduce reperfusion injury.
Purpose of the Study:
- To investigate the cardioprotective effects of Bendavia, a mitochondria-targeted peptide, in experimental cardiac ischemia/reperfusion (I/R) models.
- To assess Bendavia's impact on infarct size, no-reflow phenomenon, and myocyte survival.
- To elucidate the mechanism of Bendavia's protective effects, focusing on mitochondrial energetics and ROS levels.
Main Methods:
- Bendavia administered post-ischemia in vivo sheep, ex vivo guinea pig, and in vivo rabbit cardiac I/R models.
- Infarct size quantified, and coronary no-reflow assessed using Thioflavin S staining.
- Myocardial uptake of Bendavia measured; isolated myocytes exposed to hypoxia/reoxygenation with Bendavia treatment.
Main Results:
- Bendavia reduced infarct size by 15% in sheep (P=0.02) and 38-42% in guinea pigs (P<0.05).
- Significantly smaller coronary no-reflow area observed in Bendavia-treated rabbits (P=0.0085).
- Bendavia-treated myocytes showed improved survival, sustained mitochondrial membrane potential, and reduced ROS-mediated cell death.
Conclusions:
- Postischemic Bendavia administration demonstrates protective effects against reperfusion injury across multiple models.
- Bendavia acts as a mitochondria-targeted therapy, preserving mitochondrial energetics and suppressing cellular ROS.
- These findings support Bendavia's potential as a novel therapeutic agent for reducing cardiac reperfusion injury.
