title: Cardioprotection by Conditioning Mimetic Drugs.
abstract: BACKGROUND
  At present, ischemic heart disease (IHD) is one of the main causes of morbidity and mortality world-wide. An important insight into both IHD pathophysiology and cardioprotection was achieved in 1986 when Murry et al. described for the first time the ischemic preconditioning (IP). IP can be defined as an innate phenomenon by which brief episodes of ischemia confer protection to a tissue from a subsequent more protracted ischemic insult. Suggested mechanisms explaining IP comprise the action of circulating substances (e.g. adenosine, bradykinin, nitric oxide). These mediators are released after a prolonged ischemic stress, causing activation of molecular pathways that induce favorable posttranslational changes of proteins and adaptive modifications in genetic expression.
  
  
  OBJECTIVE
  Briefly review evidences from clinical studies on drugs that exert their effects by mimicking IP, discussing their therapeutic properties and the potential clinical employment in order to obtain cardioprotection.
  
  
  METHODS
  Literature regarding IP mimicking pharmacological agents was searched in Medline and Google Scholar. Authors reviewed relevant researches in English language including both clinical studies and reviews of clinical studies published from 1986 to 2016.
  
  
  RESULTS
  Several pharmacological agents reproducing IP protective actions have been evaluated in many clinical trials. Examined molecules include adenosine, nicorandil and atrial natriuretic peptide. Interestingly IP mimicking effects of drugs have been also analyzed perioperatively in the context of ischaemia-reperfusion heart injury. Moreover evidences suggest that also some anaesthetic drugs (especially volatile agents) are able to provide myocardial protection by inducing IP.
  
  
  CONCLUSIONS
  Drugs capable of mimicking IP exhibit a high therapeutic potential because of their properties of eliciting an effective cardioprotective signaling. Future studies should clarify the optimal doses and timing of administration of IP mimetic agents in order to favor the advent of new cardioprotective strategies beyond available reperfusive therapies.
authors.affiliation: Geriatric Rehabilitative Department of I.N.R.C.A, 63900, Fermo, Italy.
authors.forename: Elpidio
authors.initials: E
authors.lastname: Santillo
authors.forename: Monica
authors.initials: M
authors.lastname: Migale
authors.forename: Demetrio
authors.initials: D
authors.lastname: Postacchini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Balestrini
authors.forename: Raffaele Antonelli
authors.initials: RA
authors.lastname: Incalzi
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006801:Humans; D019194:Ischemic Preconditioning; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents