Loss of Cardioprotection With Ischemic Preconditioning in Aging Hearts: Role of Sirtuin 1?

• Published in: Journal of cardiovascular pharmacology and therapeutics Vol. 18; no. 1; pp. 46 - 53
• Main Authors: Adam, Tasneem, Sharp, Stephanie, Opie, Lionel H., Lecour, Sandrine
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2013
• Subjects: Aging - physiology; Animals; Ischemic Preconditioning, Myocardial; Male; Myocardial Reperfusion Injury - prevention & control; Rats; Rats, Long-Evans; Sirtuin 1 - physiology; ischemic preconditioning; cardioprotection; Sirtuin 1; age
• ISSN: 1074-2484; 1940-4034
• DOI: 10.1177/1074248412458723

The effectiveness of ischemic preconditioning (IPC) to protect the heart against ischemia/reperfusion injury (IRI) declines with age. The deacetylase protein sirtuin 1 (Sirt 1) confers myriad functions including longevity and cardioprotection against IRI. As such, Sirt 1 may be a potential candidate to explain the protective effect of IPC. We aim to explore the role of Sirt 1 in the loss of the cardioprotective effect of IPC with age. Isolated hearts from young (9 weeks) and older (12-18 months) Long-Evans rats were subjected to 30 minutes of global ischemia and 60 minutes of reperfusion. Preconditioning stimuli were applied with either 2 cycles of 5-minute ischemia/reperfusion or with the potent Sirt 1 agonist resveratrol (RSV, 10 µmol/L) for 15 minutes followed by a 10-minute washout before the sustained ischemia. Both IPC and RSV significantly enhanced the functional recovery of young hearts by 168% (P < .001 vs control) and 65% (P < .01 vs control), respectively, and concomitantly reduced the infarct size by 65% and 45%, but the effect was blunted in older hearts. Administration of the selective Sirt 1 inhibitor III to young hearts did not alter the protective effect of IPC. Following ischemia/reperfusion, higher Sirt 1 deacetylase activity was detected in older hearts compared to young hearts (0.48 ± 0.13 arbitrary units [AU] vs 0.17 ± 0.03 AU, P < .01) and IPC did not alter Sirt 1 deacetylase activity. In conclusion, although Sirt 1 deacetylase activity is increased with age during ischemia/reperfusion, our data suggest that the loss of the cardioprotective effect of IPC in older animals is likely to be independent of Sirt 1.