Ischemic preconditioning: fact or fantasy?
Fifteen years ago, an experimental effort to magnify a myocardial infarction, with preinfarction episodes of transient ischemia, proved paradoxically protective. In the ensuing years, surgeons have learned to discriminate a biochemical/metabolic/functional spectrum of cardiac states ranging from healthy myocardium to "stunned" or "hibernating" heart to the modes of "apoptotic" or "necrotic" cardiomyocyte death. It is now clear that "protective cardiac preconditioning" influences all of these cardiac states. The cellular mechanisms of preconditioning (PC) are now sufficiently understood to permit clinical application. Ligation of adrenergic, adenosine, bradykinin or opioid receptors involves signaling via both tyrosine and calcium-dependent protein kinases (PKC), which activate mitochondrial ATP-dependent potassium channels. Subsequently, the release of oxygen radicals induces nuclear translocation of transcriptional regulators, which transform the cardiomyocyte into a more resilient cell. Although preconditioning was initially recognized as protecting only against infarction, PC also limits postischemic dysrhythmias and enhances contractile function. Phase I (safety) and phase II (efficacy) clinical trials now persuasively support pharmacological preconditioning as a safe mode of preventing postcardiac surgical complications. Indeed, preconditioning is currently being proposed as adjunctive to hypothermic perfusates in protecting against the obligate organ ischemia during transplantation.
Raeburn
Christopher D
CD
Department of Surgery, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box C-305, Denver, CO 80262, USA.
Zimmerman
Michael A
MA
Arya
Jyoti
J
Barsness
Katherine
K
Harken
Alden H
AH
D000818:Animals; D003097:Collateral Circulation / Q000502:physiology; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy