Journal
BASIC RESEARCH IN CARDIOLOGY
Volume 111, Issue 4, Pages -Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-016-0558-1
Keywords
Ischaemia; Reperfusion; Injury; Infarction; Pre-clinical; Basic research; Clinical trials; Ischaemic; Preconditioning; Postconditioning; Conditioning; RISK pathway; SAFE pathway; p2y12; Opiates; Asprin; Beta blockers; Statins; Metoprolol; Cyclosporine; CABG; Valve replacement; Cardiac surgery; Mitochondrial transition pore; Necrosis; Apoptosis; Necroptosis; Autophagy; Pyroptosis; DNA
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Funding
- British Heart Foundation [PG/15/52/31598, PG/09/106/28142] Funding Source: researchfish
- Medical Research Council [MR/K002066/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10164] Funding Source: researchfish
- Novo Nordisk Fonden [NNF13OC0007447] Funding Source: researchfish
- Rosetrees Trust [M565, M274] Funding Source: researchfish
- MRC [MR/K002066/1] Funding Source: UKRI
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In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality. Nonetheless, despite these improvements, cardiovascular disease and ischaemic heart disease in particular, remain the leading cause of death and a significant cause of long-term morbidity (with a concomitant increase in the incidence of heart failure) worldwide. The need for effective cardioprotective strategies has never been so pressing. However, despite unequivocal evidence of the existence of ischaemia/reperfusion in animal models providing a robust rationale for study in man, recent phase 3 clinical trials studying a variety of cardioprotective strategies in cardiac surgery and acute ST-elevation myocardial infarction have provided mixed results. The investigators meeting at the Hatter Cardiovascular Institute workshop describe the challenge of translating strong pre-clinical data into effective clinical intervention strategies in patients in whom effective medical therapy is already altering the pathophysiology of ischaemia/reperfusion injury-and lay out a clearly defined framework for future basic and clinical research to improve the chances of successful translation of strong pre-clinical interventions in man.
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