Chronic pharmacological preconditioning against ischemia.
Despite decades of research and thousands of experimental publications, acute preconditioning strategies have yet to be implemented in clinical practice. While some have attributed this to a failure of the experimental studies to mimic the clinical environment, others have suggested that acute preconditioning strategies themselves may possess physiological limitations. In particular, there is evidence to suggest a reduced efficacy of acute preconditioning in the aged heart and in disease states, such as diabetes, hypertension, hyperlipidemia, and atherosclerosis. In addition, pharmacologic agent commonly used in clinical practice, such as sulfonylureas and non-steroidal anti-inflammatory agents may interfere with acute preconditioning signaling pathways. Such considerations may preclude the translation of acute preconditioning strategies to the clinical setting. This has led some to shift attention to alternate strategies of cardioprotection, one such strategy being the possibility of generating a prolonged state of cardioprotection. Although preliminary, studies to date have suggested that sustained preconditioning strategies may not be associated with the same drawbacks as acute preconditioning. Further, cardioprotective signaling pathways that elicit the sustained preconditioning response may be distinct from acute signaling pathways, which permit pharmacologic targeting of these pathways in the future. Additionally, sustained preconditioning strategies may be clinically applicable in the setting of acute myocardial infarction, a setting where acute preconditioning strategies are inherently limited. This review will briefly discuss the current data regarding sustained preconditioning strategies, including those in humans, and discuss the goal of future studies in this setting.
Division of Cardiology, Mount Sinai Hospital, Toronto, Canada.
Mary Clare
MC
Luca
Andrew
A
Liuni
Selina
S
Muxel
Thomas
T
Münzel
Sandro
S
Forconi
Tommaso
T
Gori
John D
JD
Parker
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019157:Ischemic Preconditioning, Myocardial / Q000009:adverse effects / Q000379:methods*; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D013552:Swine
D002316:Cardiotonic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C058394:2-chloro-N(6)cyclopentyladenosine; D009020:Morphine; D052247:Nitric Oxide Synthase Type II; D005996:Nitroglycerin; D000241:Adenosine