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

OBJECTIVES We tested the hypothesis that cardioprotection with ischemic preconditioning (PC) is lost in the aging, or senescent, heart. BACKGROUND Although infarct size reduction with PC has been documented in virtually all models, a purported exception to this paradigm is the aging heart, the population in which cardioprotection is most relevant. However, no previous studies have assessed the concept of an age-associated loss in the efficacy of PC in an in vivo model of acute myocardial infarction in which definitive hallmarks of cardiovascular aging were demonstrated and a reduction 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 studied: adult (4 to 6 months old), middle-aged (not, vert, similar2 years old) and old (not, vert, similar4 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 hallmarks of cardiovascular aging (progressive myocyte hypertrophy, increased myocardial fibrosis and attenuated responsiveness to beta-adrenergic stimulation). 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 middle-aged and old rabbits exhibited all three archetypal indexes of cardiovascular aging, a comparable (not, vert, similar50%) 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.