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Challenges facing the clinical translation of cardioprotection: 35 years after the discovery of ischemic preconditioning

Journal

VASCULAR PHARMACOLOGY
Volume 144, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2022.106995

Keywords

Cardioprotection; Co-morbidities; Diabetes; Inflammation; Microvascular injury; Remote conditioning

Funding

  1. Beneficenza San Paolo [B/2021/0159]
  2. COST (European Cooperation in Science and Technology) [CA16225]

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Since the introduction of coronary reperfusion in the late 1970s, the translation of successful animal experiments on cardioprotection into clinical practice has been disappointing. Animal experiments are often lacking the risk factors, co-morbidities and co-medications characteristic of acute myocardial infarction patients. The long-term effects of additional cardioprotection, particularly regarding vessel protection, repair, inflammation, remodeling, and mortality, are not well-studied. Species differences, co-morbidities, vascular damage, inflammatory processes, and co-medications often limit the reproducibility and robustness of experimental studies. Future studies should focus on interventions with reliable preclinical data and recruit patients who have the potential to benefit from further cardioprotection.
Since coronary reperfusion was introduced into clinical practice in the late 1970s, the further translation of several successful animal experiments on cardioprotection into clinical practice has been disappointing to date. Animal experiments are often performed on young, healthy animals lacking the risk factors, co-morbidities and co-medications characteristic of acute myocardial infarction patients. Many hopes were kindled in 1986 when ischemic preconditioning was discovered. However, it is not yet known how long ischemia can last and what is the best modality for additional cardioprotection through conditioning to obtain benefits. There is a lack of experimental studies on the long-term effects of additional cardioprotection, in addition to the reduction in infarct size; in particular, there is a lack of studies on vessel protection, repair, inflammation, remodeling, and mortality. The reproducibility and robustness of experimental studies are often limited by species differences, the role of co-morbidities, vascular damage, inflammatory processes, and co-medications, which are not adequately considered. In particular, inflammatory processes, including NLRP3 inflammasome, play an important role in the long-term effects. Future studies should focus on interventions/agents with robust preclinical data and should recruit patients who truly have the potential to benefit from further cardioprotection. Here we focus on the main mechanisms and targets of cardioprotection during remote conditioning and their alteration by one of the most common co-morbidities, namely diabetes, in which microvascular lesions and inflammatory processes play extremely important roles.

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