(Circulation. 1997;96:1598-1604.)
© 1997 American Heart Association, Inc.
Articles |
Ischemic Preconditioning Decreases Apoptosis in Rat Hearts In Vivo
From the Cardiovascular Research Institute, Department of Medicine (Cardiology Division) (C.A.P., D.P., R.E.S., C.L.W.) and Department of Pathology (P.C.U.), University of California, San Francisco.
Background Previous studies have demonstrated that ischemic preconditioning prevents lethal cell injury and, as a consequence, limits infarct size in rat heart. Although both apoptosis and necrosis have been shown to contribute to myocardial cell death after myocardial ischemia and reperfusion, the ability of ischemic preconditioning to prevent programmed cell death remains unknown.
Methods and Results To test the hypothesis that ischemic preconditioning reduces irreversible ischemic injury in part by decreasing apoptosis, rats that underwent ischemic preconditioning and controls were subjected to 30 minutes of left coronary artery occlusion followed by 180 minutes of reperfusion. Ischemic preconditioning was achieved by five 5-minute cycles of ischemia, each followed by 5 minutes of reperfusion. Infarct size, determined by dual staining with triphenyltetrazolium chloride and phthalocyanine blue dye, was significantly reduced in preconditioned compared with nonpreconditioned rats (11.4±1.4% versus 58.7±1.4%; n=20 in each group; P<.001; infarct size/risk area). Genomic DNA from preconditioned hearts showed little or no oligonucleosome-sized fragments (200-bp multiples), whereas genomic DNA from nonpreconditioned hearts showed a typical nucleosome fragmentation. The TUNEL assay localized fewer and sparsely stained nuclei within the infarct zone of ischemic preconditioned hearts compared with nonpreconditioned hearts. Consistent with these findings, the number of cytosolic histone–associated low-molecular-weight DNA fragments was significantly decreased in preconditioned hearts compared with controls (0.17±0.02 versus 1.07±0.09 U; n=10 in each group; P<.001; absorbance 405 nm/490 nm).
Conclusions This study suggests that ischemic preconditioning reduces irreversible ischemic injury in part by decreasing apoptosis after prolonged ischemia and reperfusion.
Key Words: apoptosis • ischemia • myocardial infarction • reperfusion
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|
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|
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|
|
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|
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|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
|
|
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|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
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|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
S. Pepe Dysfunctional ischemic preconditioning mechanisms in aging Cardiovasc Res, January 1, 2001; 49(1): 11 - 14. [Full Text] [PDF]
|
|
|
|
 |
|
 B. O'Rourke Myocardial KATP Channels in Preconditioning Circ. Res., November 10, 2000; 87(10): 845 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Taimor Cardiac gap junctions: good or bad? Cardiovasc Res, October 1, 2000; 48(1): 8 - 10. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
H. Yaoita, K. Ogawa, K. Maehara, and Y. Maruyama Apoptosis in relevant clinical situations: contribution of apoptosis in myocardial infarction Cardiovasc Res, February 1, 2000; 45(3): 630 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
Z.-Q. Zhao, M. Nakamura, N.-P. Wang, J. N. Wilcox, S. Shearer, R. S. Ronson, R. A. Guyton, and J. Vinten-Johansen Reperfusion induces myocardial apoptotic cell death Cardiovasc Res, February 1, 2000; 45(3): 651 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakamura, N.-P. Wang, Z.-Q. Zhao, J. N Wilcox, V. Thourani, R. A Guyton, and J. Vinten-Johansen Preconditioning decreases Bax expression, PMN accumulation and apoptosis in reperfused rat heart Cardiovasc Res, February 1, 2000; 45(3): 661 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Inserte, G. Taimor, B. Hofstaetter, D. Garcia-Dorado, and H. M. Piper Influence of simulated ischemia on apoptosis induction by oxidative stress in adult cardiomyocytes of rats Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H94 - H99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Fryer, J. T. Eells, A. K. Hsu, M. M. Henry, and G. J. Gross Ischemic preconditioning in rats: role of mitochondrial KATP channel in preservation of mitochondrial function Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H305 - H312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sato Signaling in Late Preconditioning : Involvement of Mitochondrial KATP Channels Circ. Res., December 3, 1999; 85(12): 1113 - 1114. [Full Text] [PDF]
|
|
|
|
|
|
E. Takashi, Y. Wang, and M. Ashraf Activation of Mitochondrial KATP Channel Elicits Late Preconditioning Against Myocardial Infarction via Protein Kinase C Signaling Pathway Circ. Res., December 3, 1999; 85(12): 1146 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A Piot, J.-F. Martini, S. K Bui, and C. L Wolfe Ischemic preconditioning attenuates ischemia/reperfusion-induced activation of caspases and subsequent cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo Cardiovasc Res, December 1, 1999; 44(3): 536 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.A. Cook and P.A. Poole-Wilson Cardiac myocyte apoptosis Eur. Heart J., November 2, 1999; 20(22): 1619 - 1629. [PDF]
|
|
|
|
|
|
T. Okamura, T. Miura, H. Iwamoto, K. Shirakawa, S. Kawamura, Y. Ikeda, M. Iwatate, and M. Matsuzaki Ischemic preconditioning attenuates apoptosis through protein kinase C in rat hearts Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1997 - H2001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Baghelai, L. J. Graham, A. S. Wechsler, and E. R. Jakoi Phenylephrine induces delayed cardioprotection against necrosis without amelioration of stunning Ann. Thorac. Surg., October 1, 1999; 68(4): 1219 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-S. V. Chen, S. C. Body, and S. K. Shernan Myocardial Preconditioning: Characteristics, Mechanisms, and Clinical Applications Seminars in Cardiothoracic and Vascular Anesthesia, July 1, 1999; 3(2): 85 - 97. [Abstract] [PDF]
|
|
|
|
|
|
N.-P. Wang, B. L. Bufkin, M. Nakamura, Z.-Q. Zhao, J. N. Wilcox, K. O. Hewan-Lowe, R. A. Guyton, and J. Vinten-Johansen Ischemic preconditioning reduces neutrophil accumulation and myocardial apoptosis Ann. Thorac. Surg., June 1, 1999; 67(6): 1689 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Baghelai, L. J. Graham, A. S. Wechsler, and E. R. Jakoi DELAYED MYOCARDIAL PRECONDITIONING BY {{alpha}}1-ADRENOCEPTORS INVOLVES INHIBITION OF APOPTOSIS J. Thorac. Cardiovasc. Surg., May 1, 1999; 117(5): 980 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A Woodcock, S. J Matkovich, and O. Binah Ins(1,4,5)P3 and cardiac dysfunction Cardiovasc Res, November 1, 1998; 40(2): 251 - 256. [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Meldrum Tumor necrosis factor in the heart Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1998; 274(3): R577 - R595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-H. Ning, S.-H. Chen, C.-S. Xu, L. Li, L. Y. Yao, K. Qian, J. J. Krueger, O. M. Hyyti, and M. A. Portman Molecular Biology of Thermoregulation: Selected Contribution: Hypothermic protection of the ischemic heart via alterations in apoptotic pathways as assessed by gene array analysis J Appl Physiol, May 1, 2002; 92(5): 2200 - 2207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chen, H. He, S. Zhan, S. Krajewski, J. C. Reed, and R. A. Gottlieb Bid Is Cleaved by Calpain to an Active Fragment in Vitro and during Myocardial Ischemia/Reperfusion J. Biol. Chem., August 10, 2001; 276(33): 30724 - 30728. [Abstract] [Full Text] [PDF]
|
|