Related Experiment Video
Updated: May 3, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Cardioprotection Through Mitochondrial Modulation: A Systematic Review of Pharmacological Interventions in Animal
Trissha Ybanez1, Joshua Ingles2, Eugene Du Toit3
1School of Pharmacy and Medical Science, Griffith University, Southport, QLD, 4217, Australia. trissha.ybanez@griffithuni.edu.au.
Purpose:
Myocardial reperfusion following ischaemia paradoxically exacerbates mitochondrial and thus cardiac dysfunction. Although various treatment strategies have been utilised to prevent irreversible myocardial injury, translation to positive clinical trial outcomes has been unsuccessful. This systematic review aimed to evaluate pharmacological interventions in animal models of ischaemia-reperfusion (I/R), with emphasis on cardiac and cell death outcomes and direct assessment of mitochondrial bioenergetics.
Methods:
Search terms were entered into PubMed, Scopus, Embase and Web of Science. Screening, data extraction and quality assessment of papers were conducted according to the inclusion and exclusion criteria selected for this study. Eighteen papers from a total of 1571 studies were included. These studies investigated 15 drugs of interest in animals subjected to either in vivo or ex vivo I/R. Mitochondrial function parameters were assessed by measuring either mitochondrial respiration and/or enzyme activity, with 4 of these also assessing electron transport chain protein expression.
Results:
Pharmaceuticals preserved mitochondrial respiratory capacity by directly targeting the electron transport chain complexes or indirectly via proteins involved in canonical cardioprotective pathways. This led to improved post-ischaemic cardiac function and reductions in markers of cellular injury and myocardial infarction.
Conclusion:
Multi-targeted manipulation of components of mitochondrial signalling and function evidently reduces I/R injury. Quality assessment of most papers revealed an unclear risk of bias due to inadequate reporting of study parameters. Clear and consistent reporting of study outcomes, specifically mitochondrial bioenergetics across all experimental stages, is essential to enhance the translational potential of mitoprotective compounds in the clinical treatment of I/R.
Insights
Pharmacological interventions targeting mitochondria improve cardiac function after ischaemia-reperfusion injury. This systematic review highlights the potential of these drugs, emphasizing consistent reporting for clinical translation.
Area of Science:
- Cardiovascular Research
- Mitochondrial Biology
- Pharmacology
Background:
- Myocardial reperfusion paradoxically worsens cardiac dysfunction post-ischaemia.
- Current treatments for irreversible myocardial injury lack clinical success.
- Mitochondrial dysfunction is a key factor in ischaemia-reperfusion (I/R) injury.
Purpose of the Study:
- To systematically review pharmacological interventions in animal models of I/R.
- To evaluate effects on cardiac function, cell death, and mitochondrial bioenergetics.
- To identify strategies for mitigating I/R-induced myocardial damage.
Main Methods:
- Systematic literature search of PubMed, Scopus, Embase, and Web of Science.
- Inclusion of 18 studies investigating 15 drugs in animal I/R models.
- Assessment of mitochondrial respiration, enzyme activity, and electron transport chain proteins.
Main Results:
- Drugs preserved mitochondrial respiratory capacity by targeting electron transport chain complexes.
- Interventions improved post-ischaemic cardiac function.
- Reduced markers of cellular injury and myocardial infarction were observed.
Conclusions:
- Targeting mitochondrial signalling and function effectively reduces I/R injury.
- Inconsistent reporting and unclear risk of bias in studies limit translational potential.
- Standardized reporting of mitochondrial bioenergetics is crucial for clinical application of mitoprotective compounds.
Related Concept Videos
01:25Cardiopulmonary Resuscitation IV: Pharmacological Management
01:29Cardiomyopathy V: Interprofessional Care