Author + information
- Received March 9, 2001
- Revision received July 17, 2001
- Accepted August 13, 2001
- Published online November 15, 2001.
- ↵*Reprint requests and correspondence: Dr. Karin Przyklenk, Heart Institute/Research, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles, California 90017-2395 USA
We tested the hypothesis that cardioprotection with ischemic preconditioning (PC) is lost in the aging, or senescent, heart.
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.
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).
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.
These data provide the first in vivo evidence that infarct size reduction with PC is not precluded by increased cardiovascular age, per se.
☆ This study was supported by NIA RO3 Grant no. AG17758-01 to Dr. Przyklenk. Dr. Whittaker is an Established Investigator of the American Heart Association.
- Received March 9, 2001.
- Revision received July 17, 2001.
- Accepted August 13, 2001.
- American College of Cardiology