title: Determinants of the Efficacy of Cardiac Ischemic Preconditioning: A Systematic Review and Meta-Analysis of Animal Studies.
abstract: BACKGROUND
  Ischemic preconditioning (IPC) of the heart is a protective strategy in which a brief ischemic stimulus immediately before a lethal ischemic episode potently limits infarct size. Although very promising in animal models of myocardial infarction, IPC has not yet been successfully translated to benefit for patients.
  
  
  OBJECTIVE
  To appraise all preclinical evidence on IPC for myocardial infarction and identify factors hampering translation.
  
  
  RESULTS
  Using systematic review and meta-analysis, we identified 503 animal studies reporting infarct size data from 785 comparisons between IPC-treated and control animals. Overall, IPC reduced myocardial infarction by 24.6% [95%CI 23.5, 25.6]. Subgroup analysis showed that IPC efficacy was reduced in comorbid animals and non-rodents. Efficacy was highest in studies using 2-3 IPC cycles applied <45 minutes before myocardial infarction. Local and remote IPC were equally effective. Reporting of study quality indicators was low: randomization, blinding and a sample size calculation were reported in 49%, 11% and 2% of publications, respectively.
  
  
  CONCLUSIONS
  Translation of IPC to the clinical setting may be hampered by the observed differences between the animals used in preclinical IPC studies and the patient population, regarding comorbidity, sex and age. Furthermore, the IPC protocols currently used in clinical trials could be optimized in terms of timing and the number of ischemic cycles applied. In order to inform future clinical trials successfully, future preclinical studies on IPC should aim to maximize both internal and external validity, since poor methodological quality may limit the value of the preclinical evidence.
authors.affiliation: Systematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Kimberley E
authors.initials: KE
authors.lastname: Wever
authors.affiliation: Systematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Carlijn R
authors.initials: CR
authors.lastname: Hooijmans
authors.affiliation: Department of Internal Medicine and Dept. of Pharmacology-Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Niels P
authors.initials: NP
authors.lastname: Riksen
authors.affiliation: Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Sterenborg
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Sena
authors.affiliation: Systematic Review Centre for Laboratory animal Experimentation (SYRCLE), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Merel
authors.initials: M
authors.lastname: Ritskes-Hoitinga
authors.affiliation: Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michiel C
authors.initials: MC
authors.lastname: Warlé
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*