No loss in the in vivo efficacy of ischemic preconditioning in middle-agedand old rabbits

OBJECTIVES We tested the hypothesis that cardioprotection with ischemic pre conditioning (PC) is lost in the aging, or senescent, heart. BACKGROUND Although infarct size reduction with PC has been documented in v irtually all models, a purported exception to this paradigm is the aging he art, the population in which cardioprotection is most relevant. However, no previous studies have assessed the concept of an age-associated loss in th e efficacy of PC in an in vivo model of acute myocardial infarction in whic h definitive hallmarks of cardiovascular aging were demonstrated and a redu ction of infarct size, the "gold standard" of PC, served as the primary end point. METHODS Using the in vivo rabbit model, three cohorts of animals were studi ed: adult (4 to 6 months old), middle-aged (similar to2 years old) and old (similar to4 years old) rabbits. Within each cohort we assessed: 1) infarct size (measured by tetrazolium staining and expressed as percent myocardium at risk) in control and PC groups; and 2) morphologic and functional hallm arks of cardiovascular aging (progressive myocyte hypertrophy, increased my ocardial fibrosis and attenuated responsiveness to beta-adrenergic stimulat ion). RESULTS In adult animals, infarct size was significantly smaller in the PC group than in the control group (29 4% vs. 57 2%; p < 0.01). Although middl e-aged and old rabbits exhibited all three archetypal indexes of cardiovasc ular aging, a comparable (similar to 50%) reduction in infarct size with PC was evident in both cohorts. CONCLUSIONS These data provide the first in vivo evidence that infarct size reduction with PC is not precluded by increased cardiovascular age, per se . (C) 2001 by the American College of Cardiology.