Ischaemic conditioning: pitfalls on the path to clinical translation

Area of Science:

• Cardiology
• Translational Medicine
• Cardioprotection

Background:

• Myocardial ischemia-reperfusion injury is a significant clinical challenge.
• Ischaemic conditioning, including postconditioning and remote conditioning, demonstrates potent cardioprotective effects in preclinical studies.
• Despite strong preclinical data, clinical translation of ischaemic conditioning has faced significant hurdles, leading to disappointing trial outcomes.

Purpose of the Study:

• To review the challenges hindering the clinical translation of ischaemic conditioning.
• To identify key areas for improvement in the application of cardioprotective strategies.
• To provide insights into optimizing future clinical trials for ischaemic conditioning.

Main Methods:

• Literature review focusing on preclinical and clinical studies of ischaemic conditioning.
• Analysis of factors contributing to heterogeneity in clinical trial outcomes.
• Discussion of appropriate preclinical models for facilitating clinical translation.

Main Results:

• Preclinical evidence strongly supports the cardioprotective efficacy of ischaemic conditioning.
• Clinical trials have exhibited significant heterogeneity, failing to consistently confirm benefits.
• Meta-analyses have not yet validated the efficacy suggested by preclinical research.

Conclusions:

• The successful clinical translation of ischaemic conditioning is stalled by issues in study design and preclinical model selection.
• Refining clinical study designs and choosing appropriate preclinical models are crucial for advancing this cardioprotective therapy.
• Addressing these translational pitfalls is essential to realize the therapeutic potential of ischaemic conditioning for myocardial infarction.