Cardioprotection via adaptation to hypoxia: expanding the timeline and targets?

摘要: Substantial effort and resources throughout the past fourdecades have been devoted to investigation of novelparadigms limit damage caused heart bymyocardial ischemia and, more recently, spectrum oflethal ischemia–reperfusion injury. The scope thisintellectual financial investment is underscored by thefact that, as December 2010, than 9,600 publica-tions cited in PubMed include term ‘cardioprotection’as a key word.A milestone field cardioprotection was pro-vided 1986 Murry et al. [14], who demonstrated thattransient exposure stressful stimulus (i.e.,antecedent ‘preconditioning’ ischemia) marshaled pro-found, endogenous cardioprotective response renderedthe myocardium resistant subsequent sustained ische-mic insult. Although this observation was, at time,considered remarkable viewed with some skepticism,the phenomenon via adaptation tostress has corroborated host studies andexpanded from initial paradigm ischemic precondi-tioning encompass multiple triggers including remoteischemia or ‘preconditioning distance’ [18, 27], mildhypothermia hyperthermia [12, 23, 25, 29], endotoxinand endotoxin analogs [19, 30, 31], endoplasmic reticulumstress [17] many others. There are, however, twoimportant caveats reduction infarct size achievedwith preconditioning other stressors: theprotective are considered delay (rather thanpreclude) cardiomyocyte death, efficacy achievedwhen applied pretreatment (beforeischemia) or, instances, during seconds–minutes reperfusion. That is: myocardial salvage istypically not obtained setting permanent coronaryocclusion, strategies generallyineffective when administered hours–days following reliefof ischemia.In current issue Basic Research Cardiology,Xuand colleagues [28] report that prolonged ratsto intermittent hypobaric hypoxia (IHH: barometric pres-sure 404 mmHg PO