Preconditioning does not prevent postischemic dysfunction in aging heart

Cattedra di Geriatria, Universita degli Studi di Napoli Federico II, Italy.

OBJECTIVES: This study was performed to investigate the effect of single or multiple brief periods of ischemia and the administration of exogenous norepinephrine before a more prolonged ischemic period and after reperfusion in adult and senescent isolated and perfused rat hearts. BACKGROUND: The mortality rate for coronary artery disease is greater in the elderly. Ischemic preconditioning has been proposed as an endogenous form of protection against ischemia-reperfusion injury. However, the role of preconditioning in aging heart is unknown. METHODS: We compared the protective effect of preconditioning transient ischemic and norepinephrine stimuli against 20 min of global normothermic ischemia and 40 min of reperfusion in isolated perfused hearts of adult (6 months old) and senescent (24 months old) rats. Norepinephrine release in coronary effluent was determined by high performance liquid chromatography. RESULTS: Final recovery of percent developed pressure was improved after single preconditioning transient ischemic and norepinephrine stimuli in adult hearts (87.7 +/- 9% and 82.3 +/- 8.7%) versus unconditioned control hearts (50.6 +/- 4.8%, p < 0.01 [mean +/-SD]). The effect of preconditioning on developed pressure recovery was not present in senescent hearts after transient ischemic stimulus (39.8 +/- 4.9% vs. 41.6 +/- 5.8%, p = NS) but was present after norepinephrine stimulus (74.3 +/- 10.5, p < 0.01). Norepinephrine release significantly increased after preconditioning transient ischemic stimulus in adult but not in senescent hearts (p < 0.01 vs. adult). Transient ischemic- and norepinephrine-induced preconditioning was blocked by alpha-adrenergic receptor antagonists in both adult and senescent hearts. Multiple transient ischemic stimuli were able to reduce postischemic dysfunction in adult but not in senescent hearts. CONCLUSIONS: Preconditioning transient ischemic stimulus significantly reduces postischemic dysfunction in adult but not in senescent hearts, whereas exogenous norepinephrine is able to mimic preconditioning in both adult and senescent hearts. Ischemic preconditioning induces an increase in norepinephrine release in adult but not in senescent hearts. Preconditioning induced by transient ischemic stimulus and norepinephrine was abolished by alpha-adrenergic receptor blockade in both adult and senescent hearts. Thus, our data demonstrate that preconditioning is absent in aging heart and is probably related to the reduction of norepinephrine release and alpha-adrenergic receptor stimulation in response to ischemic preconditioning.

This article has been cited by other articles:

				K. Boengler, R. Schulz, and G. Heusch Loss of cardioprotection with ageing Cardiovasc Res, July 15, 2009; 83(2): 247 - 261. [Abstract] [Full Text] [PDF]

				J. Frassdorf, S. De Hert, and W. Schlack Anaesthesia and myocardial ischaemia/reperfusion injury Br. J. Anaesth., July 1, 2009; 103(1): 89 - 98. [Abstract] [Full Text] [PDF]

				J. N. Peart and J. P. Headrick Clinical cardioprotection and the value of conditioning responses Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1705 - H1720. [Abstract] [Full Text] [PDF]

				P. Abete, F. Cacciatore, D. D. Morte, F. Mazzella, G. Testa, G. Galizia, D. D. Santis, G. Longobardi, N. Ferrara, and F. Rengo Joint effect of physical activity and body mass index on mortality for acute myocardial infarction in the elderly: role of preinfarction angina as equivalent of ischemic preconditioning European Journal of Cardiovascular Prevention & Rehabilitation, February 1, 2009; 16(1): 73 - 79. [Abstract] [Full Text] [PDF]

				K. Shinmura, K. Tamaki, and R. Bolli Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1 Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2348 - H2355. [Abstract] [Full Text] [PDF]

				G. Derumeaux, F. Ichinose, M. J. Raher, J. G. Morgan, T. Coman, C. Lee, J. M. Cuesta, H. Thibault, K. D. Bloch, M. H. Picard, et al. Myocardial Alterations in Senescent Mice and Effect of Exercise Training: A Strain Rate Imaging Study Circ Cardiovasc Imaging, November 1, 2008; 1(3): 227 - 234. [Abstract] [Full Text] [PDF]

				L. T. Nguyen, M. J. Rebecchi, L. C. Moore, P. S. A. Glass, P. R. Brink, and L. Liu Attenuation of Isoflurane-Induced Preconditioning and Reactive Oxygen Species Production in the Senescent Rat Heart Anesth. Analg., September 1, 2008; 107(3): 776 - 782. [Abstract] [Full Text] [PDF]

				J. D. O'Brien and S. E. Howlett Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H768 - H777. [Abstract] [Full Text] [PDF]

				J. Dow, A. Bhandari, and R. A. Kloner Ischemic Postconditioning's Benefit on Reperfusion Ventricular Arrhythmias Is Maintained in the Senescent Heart Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2008; 13(2): 141 - 148. [Abstract] [PDF]

				A. Jahangir, S. Sagar, and A. Terzic Aging and cardioprotection J Appl Physiol, December 1, 2007; 103(6): 2120 - 2128. [Abstract] [Full Text] [PDF]

				R. Bolli Preconditioning: a paradigm shift in the biology of myocardial ischemia Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H19 - H27. [Abstract] [Full Text] [PDF]

				J. Liu, S. Tsang, and T. M. Wong Testosterone Is Required for Delayed Cardioprotection and Enhanced Heat Shock Protein 70 Expression Induced by Preconditioning Endocrinology, October 1, 2006; 147(10): 4569 - 4577. [Abstract] [Full Text] [PDF]

				J. Zheng, A. Chin, I. Duignan, K.-H. Won, M. K. Hong, and J. M. Edelberg Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H525 - H530. [Abstract] [Full Text] [PDF]

				G. Kristo, Y. Yoshimura, B. J. Keith, R. M. Mentzer Jr., and R. D. Lasley Aged Rat Myocardium Exhibits Normal Adenosine Receptor-Mediated Bradycardia and Coronary Vasodilation But Increased Adenosine Agonist-Mediated Cardioprotection J Gerontol A Biol Sci Med Sci, November 1, 2005; 60(11): 1399 - 1404. [Abstract] [Full Text] [PDF]

				M. Juhaszova, C. Rabuel, D. B. Zorov, E. G. Lakatta, and S. J. Sollott Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res, May 1, 2005; 66(2): 233 - 244. [Abstract] [Full Text] [PDF]

				L. Willems, K. J. Ashton, and J. P. Headrick Adenosine-mediated cardioprotection in the aging myocardium Cardiovasc Res, May 1, 2005; 66(2): 245 - 255. [Abstract] [Full Text] [PDF]

				A. Deten, G. Marx, W. Briest, H. Christian Volz, and H.-G. Zimmer Heart function and molecular biological parameters are comparable in young adult and aged rats after chronic myocardial infarction Cardiovasc Res, May 1, 2005; 66(2): 364 - 373. [Abstract] [Full Text] [PDF]

				T. Kurotobi, H. Sato, K. Kinjo, D. Nakatani, H. Mizuno, M. Shimizu, K. Imai, A. Hirayama, K. Kodama, M. Hori, et al. Reduced collateral circulation to the infarct-related artery in elderly patients with acute myocardial infarction J. Am. Coll. Cardiol., July 7, 2004; 44(1): 28 - 34. [Abstract] [Full Text] [PDF]

				K. Przyklenk, G. Li, B. Z. Simkhovich, and R. A. Kloner Mechanisms of myocardial ischemic preconditioning are age related: PKC-{epsilon} does not play a requisite role in old rabbits J Appl Physiol, December 1, 2003; 95(6): 2563 - 2569. [Abstract] [Full Text]

				P. Abete, F. Cacciatore, N. Ferrara, C. Calabrese, D. de Santis, G. Testa, G. Galizia, S. Del Vecchio, D. Leosco, M. Condorelli, et al. Body mass index and preinfarction angina in elderly patients with acute myocardial infarction Am J Clin Nutr, October 1, 2003; 78(4): 796 - 801. [Abstract] [Full Text] [PDF]

				B. Bartling, I. Friedrich, R.-E. Silber, and A. Simm Ischemic preconditioning is not cardioprotective in senescent human myocardium Ann. Thorac. Surg., July 1, 2003; 76(1): 105 - 111. [Abstract] [Full Text] [PDF]

				M. Loubani, S. Ghosh, and M. Galinanes The aging human myocardium: tolerance to ischemia and responsiveness to ischemic preconditioning J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 143 - 147. [Abstract] [Full Text] [PDF]

				J. P Headrick, L. Willems, K. J Ashton, K. Holmgren, J. Peart, and G P. Matherne Ischaemic tolerance in aged mouse myocardium: the role of adenosine and effects of A1 adenosine receptor overexpression J. Physiol., June 15, 2003; 549(3): 823 - 833. [Abstract] [Full Text] [PDF]

				J. W. Starnes, R. P. Taylor, and Y. Park Exercise improves postischemic function in aging hearts Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H347 - H351. [Abstract] [Full Text] [PDF]

				E. o. Cosar and C. J. O'Connor Hibernation, Stunning, and Preconditioning: Historical Perspective, Current Concepts, Clinical Applications, and Future Implications Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2003; 7(2): 115 - 140. [Abstract] [PDF]

				K. Przyklenk and G. Heusch Late preconditioning against myocardial stunning: Does aspirin close the "second window" of endogenous cardioprotection? J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1195 - 1197. [Full Text] [PDF]

				R. A Kloner, M. T Speakman, and K. Przyklenk Ischemic preconditioning: a plea for rationally targeted clinical trials Cardiovasc Res, August 15, 2002; 55(3): 526 - 533. [Full Text] [PDF]

				N. J. Alkayed, T. Goyagi, H.-D. Joh, J. Klaus, D. R. Harder, R. J. Traystman, and P. D. Hurn Neuroprotection and P450 2C11 Upregulation After Experimental Transient Ischemic Attack Stroke, June 1, 2002; 33(6): 1677 - 1684. [Abstract] [Full Text] [PDF]

				P. Abete, G. Testa, N. Ferrara, D. De Santis, P. Capaccio, L. Viati, C. Calabrese, F. Cacciatore, G. Longobardi, M. Condorelli, et al. Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H1978 - H1987. [Abstract] [Full Text] [PDF]

				P. Abete, D. de Santis, M. Condorelli, C. Napoli, and F. Rengo A four-year-old rabbit cannot be considered the right model for investigating cardiac senescence J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1701 - 1701. [Full Text] [PDF]

				T.-M. Lee, S.-F. Su, T.-F. Chou, Y.-T. Lee, and C.-H. Tsai Loss of Preconditioning by Attenuated Activation of Myocardial ATP-Sensitive Potassium Channels in Elderly Patients Undergoing Coronary Angioplasty Circulation, January 22, 2002; 105(3): 334 - 340. [Abstract] [Full Text] [PDF]

				R. A. Kloner and R. B. Jennings Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications: Part 2 Circulation, December 18, 2001; 104(25): 3158 - 3167. [Abstract] [Full Text] [PDF]

				K. Przyklenk, G. Li, and P. Whittaker No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1741 - 1747. [Abstract] [Full Text] [PDF]

				P. Abete, N. Ferrara, F. Cacciatore, E. Sagnelli, M. Manzi, V. Carnovale, C. Calabrese, D. de Santis, G. Testa, G. Longobardi, et al. High level of physical activity preserves the cardioprotective effect of preinfarction angina in elderly patients J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1357 - 1365. [Abstract] [Full Text] [PDF]

				R. A. Kloner Preinfarct angina and exercise: yet another reason to stay physically active J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1366 - 1368. [Full Text] [PDF]

				Z.-K. Wu, E. Pehkonen, J. Laurikka, L. Kaukinen, E. L. Honkonen, S. Kaukinen, P. Laippala, and M. R. Tarkka The protective effects of preconditioning decline in aged patients undergoing coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., November 1, 2001; 122(5): 972 - 978. [Abstract] [Full Text] [PDF]

				D. Schulman, D. S. Latchman, and D. M. Yellon Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1630 - H1636. [Abstract] [Full Text] [PDF]

				M. L. Hamilton, Z. Guo, C. D. Fuller, H. Van Remmen, W. F. Ward, S. N. Austad, D. A. Troyer, I. Thompson, and A. Richardson A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA Nucleic Acids Res., May 15, 2001; 29(10): 2117 - 2126. [Abstract] [Full Text] [PDF]

				S. Pepe Dysfunctional ischemic preconditioning mechanisms in aging Cardiovasc Res, January 1, 2001; 49(1): 11 - 14. [Full Text] [PDF]

				M. Tani, Y. Honma, H. Hasegawa, and K. Tamaki Direct activation of mitochondrial KATP channels mimics preconditioning but protein kinase C activation is less effective in middle-aged rat hearts Cardiovasc Res, January 1, 2001; 49(1): 56 - 68. [Abstract] [Full Text] [PDF]

				P. Abete, C. Calabrese, N. Ferrara, A. Cioppa, P. Pisanelli, F. Cacciatore, G. Longobardi, C. Napoli, and F. Rengo Exercise training restores ischemic preconditioning in the aging heart J. Am. Coll. Cardiol., August 1, 2000; 36(2): 643 - 650. [Abstract] [Full Text] [PDF]

				G. Longobardi, P. Abete, N. Ferrara, A. Papa, R. Rosiello, G. Furgi, C. Calabrese, F. Cacciatore, and F. Rengo "Warm-Up" Phenomenon in Adult and Elderly Patients With Coronary Artery Disease: Further Evidence of the Loss of "Ischemic Preconditioning" in the Aging Heart J Gerontol A Biol Sci Med Sci, March 1, 2000; 55(3): M124 - M129. [Abstract] [Full Text] [PDF]

				R. L. Featherstone, D. J. Chambers, and F. J. Kelly Ischemic preconditioning enhances recovery of isolated rat lungs after hypothermic preservation Ann. Thorac. Surg., January 1, 2000; 69(1): 237 - 242. [Abstract] [Full Text] [PDF]

				M. Tani, Y. Honma, M. Takayama, H. Hasegawa, K. Shinmura, Y. Ebihara, and K. Tamaki Loss of protection by hypoxic preconditioning in aging Fischer 344 rat hearts related to myocardial glycogen content and Na+ imbalance Cardiovasc Res, March 1, 1999; 41(3): 594 - 602. [Abstract] [Full Text] [PDF]

				L. R.C Dekker Toward the heart of ischemic preconditioning Cardiovasc Res, January 1, 1998; 37(1): 14 - 20. [Full Text] [PDF]

				J.-F. Bouchard and D. Lamontagne Protection afforded by preconditioning to the diabetic heart against ischaemic injury Cardiovasc Res, January 1, 1998; 37(1): 82 - 90. [Abstract] [Full Text] [PDF]

				M. Tani, Y. Suganuma, H. Hasegawa, K. Shinmura, Y. Hayashi, X.-d. Guo, and Y. Nakamura Changes in Ischemic Tolerance and Effects of Ischemic Preconditioning in Middle-aged Rat Hearts Circulation, June 3, 1997; 95(11): 2559 - 2566. [Abstract] [Full Text]

				P. Abete, G. Testa, N. Ferrara, D. De Santis, P. Capaccio, L. Viati, C. Calabrese, F. Cacciatore, G. Longobardi, M. Condorelli, et al. Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H1978 - H1987. [Abstract] [Full Text] [PDF]