Related Experiment Video
Updated: Mar 8, 2026
A Murine Model of Myocardial Ischemia-reperfusion Injury through Ligation of the Left Anterior Descending Artery
Published on: April 10, 2014
Ischemia/Reperfusion
Theodore Kalogeris1, Christopher P Baines1,2,3, Maike Krenz1,2
1Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri, USA.
Insights
Ischemia and reperfusion (I/R) injury involves complex cellular events, including ATP depletion and calcium overload. Targeting multiple pathological processes is crucial for effective therapeutic strategies against I/R damage.
Area of Science:
- Physiology
- Pathology
Background:
- Ischemic disorders like myocardial infarction and stroke are leading causes of death.
- Tissue injury severity correlates with reduced blood flow and duration of ischemia, impacting cellular ATP and pH levels.
Purpose of the Study:
- To review the multifaceted mechanisms contributing to ischemia/reperfusion (I/R) injury.
- To highlight emerging concepts and therapeutic strategies for I/R-related conditions.
Main Methods:
- Comprehensive review of existing literature on I/R injury mechanisms.
- Discussion of cellular and molecular events, including ion transport, cell volume regulation, and oxidative stress.
Main Results:
- Ischemia leads to ATP depletion, altered ion transport, and calcium overload.
- Reperfusion paradoxically exacerbates injury through reactive oxygen species, inflammation, and endoplasmic reticulum stress.
- Mitochondrial permeability transition pore opening is a key event in I/R-induced cell death.
Conclusions:
- I/R injury involves numerous interconnected pathological pathways.
- Effective therapies must target multiple deleterious events.
- Future research should utilize animal models reflecting cardiovascular disease risk factors for enhanced translational significance.
Abstract:
Ischemic disorders, such as myocardial infarction, stroke, and peripheral vascular disease, are the most common causes of debilitating disease and death in westernized cultures. The extent of tissue injury relates directly to the extent of blood flow reduction and to the length of the ischemic period, which influence the levels to which cellular ATP and intracellular pH are reduced. By impairing ATPase-dependent ion transport, ischemia causes intracellular and mitochondrial calcium levels to increase (calcium overload). Cell volume regulatory mechanisms are also disrupted by the lack of ATP, which can induce lysis of organelle and plasma membranes. Reperfusion, although required to salvage oxygen-starved tissues, produces paradoxical tissue responses that fuel the production of reactive oxygen species (oxygen paradox), sequestration of proinflammatory immunocytes in ischemic tissues, endoplasmic reticulum stress, and development of postischemic capillary no-reflow, which amplify tissue injury. These pathologic events culminate in opening of mitochondrial permeability transition pores as a common end-effector of ischemia/reperfusion (I/R)-induced cell lysis and death. Emerging concepts include the influence of the intestinal microbiome, fetal programming, epigenetic changes, and microparticles in the pathogenesis of I/R. The overall goal of this review is to describe these and other mechanisms that contribute to I/R injury. Because so many different deleterious events participate in I/R, it is clear that therapeutic approaches will be effective only when multiple pathologic processes are targeted. In addition, the translational significance of I/R research will be enhanced by much wider use of animal models that incorporate the complicating effects of risk factors for cardiovascular disease. © 2017 American Physiological Society. Compr Physiol 7:113-170, 2017.
