EXPERIMENTAL STUDY
No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits
Karin Przyklenk, PhD, FACC*,a,
Guohu Li, MDa and
Peter Whittaker, PhDa
a Heart Institute, Good Samaritan Hospital and the Department of Medicine, Section of Cardiology, University of Southern California, Los Angeles, California, USA
Manuscript received March 9, 2001;
revised manuscript received July 17, 2001,
accepted August 13, 2001.
* Reprint requests and correspondence: Dr. Karin Przyklenk, Heart Institute/Research, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles, California 90017-2395 USA
karinp{at}dnamail.com
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 ( 2 years old) and old (4 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 (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.
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Abbreviations and Acronyms
| | AN | = area of necrosis | | ANCOVA | = analysis of covariance | | ANOVA | = analysis of variance | | AR | = area at risk of infarction | | dP/dtmax | = peak positive LV dP/dt | | LV | = left ventricular | | LV dP/dt | = first derivative of LV pressure | | MI | = myocardial infarction | | NE | = norepinephrine | | PC | = preconditioning |
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