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Circulation, Vol 84, 350-356, Copyright © 1991 by American Heart Association
GS Liu, J Thornton, DM Van Winkle, AW Stanley, RA Olsson and JM Downey
BACKGROUND. Preconditioning (5 minutes of ischemia followed by 10 minutes
of recovery) renders the heart very resistant to infarction from subsequent
ischemia. This study tests whether adenosine receptors might mediate
preconditioning protection. METHODS AND RESULTS. We examined the effect on
infarct size of pretreatment with either of two adenosine receptor
antagonists in both control and preconditioned in situ rabbit hearts.
Hearts underwent 30 minutes of regional ischemia plus 3 hours of
reperfusion, and infarct size was measured with tetrazolium. Infarct size
averaged 39% of the zone at risk in controls but only 8% in preconditioned
hearts. Preconditioned and nonpreconditioned hearts receiving either
blocker had infarcts not different in size from the controls. A 5-minute
intracoronary infusion of adenosine was as effective as 5 minutes of
ischemia in protecting parabiotically perfused isolated hearts against
infarction from a 45- minute ischemic insult. Similarly, intracoronary
infusion of N6-1- (phenyl-2R-isopropyl)adenosine, an A1-selective adenosine
receptor agonist, at a dose that delayed conduction but did not dilate the
coronary vessels, also limited infarct size. The protection disappeared
when we reduced the coronary concentration of drug by intravenous infusion
of adenosine, indicating that cardiac rather than peripheral receptors were
involved in the protection. CONCLUSIONS. We conclude that adenosine
released during the preconditioning occlusion stimulates cardiac A1
receptors, which leaves the heart protected against infarction even after
the adenosine has been withdrawn.
ARTICLES
Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart
Department of Medical Physiology, University of South Alabama, Mobile 36688.
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 H. Wasir, A. Bhan, S. K. Choudhary, R. Sharma, S. Chauhan, and P. Venugopal Pretreatment of human myocardium with adenosine Eur. J. Cardiothorac. Surg., January 1, 2001; 19(1): 41 - 46. [Abstract] [Full Text] [PDF]
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G.-Y. Wang, S. Wu, J.-M. Pei, X.-C. Yu, and T.-M. Wong {kappa}- but not {delta}-opioid receptors mediate effects of ischemic preconditioning on both infarct and arrhythmia in rats Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H384 - H391. [Abstract] [Full Text] [PDF]
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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]
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S. P. Bell, M. N. Sack, A. Patel, L. H. Opie, and D. M. Yellon Delta opioid receptor stimulation mimics ischemic preconditioning in human heart muscle J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2296 - 2302. [Abstract] [Full Text] [PDF]
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J. Feng, H. Li, and E. R. Rosenkranz Bradykinin protects the rabbit heart after cardioplegic ischemia via NO-dependent pathways Ann. Thorac. Surg., December 1, 2000; 70(6): 2119 - 2124. [Abstract] [Full Text] [PDF]
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D. Merkus, D. W. Stepp, D. W. Jones, Y. Nishikawa, and W. M. Chilian Adenosine preconditions against endothelin-induced constriction of coronary arterioles Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2593 - H2597. [Abstract] [Full Text] [PDF]
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Y. Toyoda, I. Friehs, R. A. Parker, S. Levitsky, and J. D. McCully Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2694 - H2703. [Abstract] [Full Text] [PDF]
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 F L. Pasini, P. Capecchi, and T Di Perri Adenosine and chronic ischemia of the lower limbs Vascular Medicine, November 1, 2000; 5(4): 243 - 250. [Abstract] [PDF]
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T. Yoshida, R. M. Engelman, D. T. Engelman, J. A. Rousou, N. Maulik, M. Sato, G. T. Elliott, and D. K. Das Preconditioning of swine heart with monophosphoryl lipid A improves myocardial preservation Ann. Thorac. Surg., September 1, 2000; 70(3): 895 - 900. [Abstract] [Full Text] [PDF]
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R. R. Morrison, R. Jones, A. M. Byford, A. R. Stell, J. Peart, J. P. Headrick, and G. P. Matherne Transgenic overexpression of cardiac A1 adenosine receptors mimics ischemic preconditioning Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1071 - H1078. [Abstract] [Full Text] [PDF]
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E. J. Tanhehco, K. Yasojima, P. L. McGeer, E. G. McGeer, and B. R. Lucchesi Preconditioning reduces myocardial complement gene expression in vivo Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1157 - H1165. [Abstract] [Full Text] [PDF]
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T. Zhao, L. Xi, J. Chelliah, J. E. Levasseur, and R. C. Kukreja Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A1 Receptors : Evidence From Gene-Knockout Mice Circulation, August 22, 2000; 102(8): 902 - 907. [Abstract] [Full Text] [PDF]
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M. Kitakaze, K. Node, H. Asanuma, S. Takashima, Y. Sakata, M. Asakura, S. Sanada, Y. Shinozaki, H. Mori, T. Kuzuya, et al. Protein Tyrosine Kinase Is Not Involved in the Infarct Size-Limiting Effect of Ischemic Preconditioning in Canine Hearts Circ. Res., August 18, 2000; 87(4): 303 - 308. [Abstract] [Full Text] [PDF]
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T. Sato, N. Sasaki, B. O'Rourke, and E. Marban Adenosine Primes the Opening of Mitochondrial ATP-Sensitive Potassium Channels : A Key Step in Ischemic Preconditioning? Circulation, August 15, 2000; 102(7): 800 - 805. [Abstract] [Full Text] [PDF]
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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]
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A. E. Saltman, I. B. Krukenkamp, G. R. Gaudette, H. Horimoto, and S. Levitsky Pharmacological preconditioning with the adenosine triphosphate-sensitive potassium channel opener pinacidil Ann. Thorac. Surg., August 1, 2000; 70(2): 595 - 601. [Abstract] [Full Text] [PDF]
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 R. A. Hopper, C. R. Forrest, H. Xu, A. Zhong, W. He, J. Rutka, P. Neligan, and C. Y. Pang Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279(2): R666 - R676. [Abstract] [Full Text] [PDF]
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J. W. Mockridge, A. Punn, D. S. Latchman, M. S. Marber, and R. J. Heads PKC-dependent delayed metabolic preconditioning is independent of transient MAPK activation Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H492 - H501. [Abstract] [Full Text] [PDF]
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T. Miki, T. Miura, A. Tsuchida, A. Nakano, T. Hasegawa, T. Fukuma, and K. Shimamoto Cardioprotective Mechanism of Ischemic Preconditioning Is Impaired by Postinfarct Ventricular Remodeling Through Angiotensin II Type 1 Receptor Activation Circulation, July 25, 2000; 102(4): 458 - 463. [Abstract] [Full Text] [PDF]
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