Endogenous cardioprotection by ischaemic postconditioning and remote conditioning.
Persistent myocardial ischaemia causes cell death if not rescued by early reperfusion. Millions of years in nature's laboratory have evolved protective responses that 'condition' the heart (and other tissues) to adapt to stressors, and these responses are applicable to the relatively new societal stress of myocardial ischaemia and reperfusion injury. Conditioning can be applied before (preconditioning), during (perconditioning), or after (postconditioning) the ischaemic stressor by imposing short periods of non-lethal ischaemia separated by brief periods of reperfusion. This conditioning protects multiple cell types and induces or rebalances a number of physiological and molecular pathways that ultimately attenuate necrosis and apoptosis. The seemingly disparate pathways may converge directly or indirectly on the mitochondria as a final effector, but other pathways not affecting mitochondria broaden the mechanisms of cardioprotection. The potential downsides of imposing even brief ischaemia directly on the heart somewhat tempered the enthusiasm for applying conditioning stimuli to the heart, but this hurdle was surmounted by applying ischaemia to remote organs and tissues in pre-, per-, and postconditioning. Although the clinical translation of remote per- and postconditioning has been rapid compared with classical preconditioning, there are numerous basic questions that require further investigation, and wider adoption awaits large-scale randomized clinical trials. Pharmacological mimetics may provide another important therapeutic approach by which to treat evolving myocardial infarction.
Department of Surgery, Emory University School of Medicine, Atlanta, GA 30308-2225, USA.
Weiwei
W
Shi
Jakob
J
Vinten-Johansen
D017209:Apoptosis / Q000502:physiology; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods*; D019194:Ischemic Preconditioning / Q000379:methods*; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D017202:Myocardial Ischemia / Q000378:metabolism / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore