| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Havard Medical School, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: james_mccully{at}hms.harvard.edu.
Necrosis and apoptosis differentially contribute to myocardial injury. Determination of the contribution of these processes in ischemia/reperfusion injury would allow for the preservation of myocardial tissue. Necrosis and apoptosis were investigated in Langendorff perfused rabbit hearts (n=47) subjected to 0, 5, 10, 15, 20, 25, 30 min. global ischemia (GI-) and 120 min reperfusion. Myocardial injury was determined by TTC staining, TUNEL, bax, bcl2, PARP cleavage, caspase -3,-8,-9 cleavage and activity, Fas-ligand (FasL) and Fas activated death domain (FADD). The contribution of apoptosis was determined separately (n=42) using irreversible caspase-3,-8,-9 inhibitors. RESULTS: LVPDP and systolic shortening (SS) were significantly decreased and infarct size and TUNEL positive cells were significantly increased (p<0.05 vs. Control) at GI-20, GI-25 and GI-30. Pro-apoptotic bax, PARP cleavage and caspase- 3,-9 cleavage and activity were apparent at GI 5 to GI-30. Fas, FADD, caspase-8 cleavage and activity were unaltered. Irreversible inhibition of caspase-3,-9 activity significantly decreased (p<0.05) infarct size at GI-25 and GI-30 but had no effect on LVPDP or SS. CONCLUSION: Myocardial injury results from a significant increase in both necrosis and apoptosis (p<0.05 vs. Control) evident by TUNEL, TTC staining and caspase activity at GI-20. Intrinsic pro-apoptotic activation is evident early during ischemia but does not significantly contribute to infarct size prior to GI-25. The contribution of necrosis to infarct size at GI-20, GI-25 and GI-30 is significantly greater than that of apoptosis. Apoptosis is significantly decreased by caspase inhibition during early reperfusion but this protection does not improve immediate post-ischemic functional recovery.
This article has been cited by other articles:
|
|
 |
|
  J. D. McCully, M. K. Bhasin, C. Daly, M. C. Guerrero, S. Dillon, T. A. Liberman, D. B. Cowan, J. D. Mably, F. X. McGowan, and S. Levitsky Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart Physiol Genomics, July 9, 2009; 38(2): 125 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. McCully, D. B. Cowan, C. A. Pacak, I. K. Toumpoulis, H. Dayalan, and S. Levitsky Injection of isolated mitochondria during early reperfusion for cardioprotection Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H94 - H105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Hsieh, H. Wakiyama, S. Levitsky, and J. D. McCully Cardioplegia and Diazoxide Modulate STAT3 Activation and DNA Binding Ann. Thorac. Surg., October 1, 2007; 84(4): 1272 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. McCully, A. J. Rousou, R. A. Parker, and S. Levitsky Age- and Gender-Related Differences in Mitochondrial Oxygen Consumption and Calcium With Cardioplegia and Diazoxide Ann. Thorac. Surg., March 1, 2007; 83(3): 1102 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Taylor, M. E. Olsen, and J. W. Starnes Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H601 - H607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Tansey, K. F. Kwaku, P. E. Hammer, D. B. Cowan, M. Federman, S. Levitsky, and J. D. McCully Reduction and redistribution of gap and adherens junction proteins after ischemia and reperfusion. Ann. Thorac. Surg., October 1, 2006; 82(4): 1472 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Malmberg, T. Vahasilta, A. Saraste, V. Kyto, J. Kiss, E. Kentala, M. Kallajoki, and T. Savunen Cardiomyocyte apoptosis and duration of aortic clamping in pig model of open heart surgery. Eur. J. Cardiothorac. Surg., September 1, 2006; 30(3): 480 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Toth, J. R. Jeffers, P. Nickson, J.-Y. Min, J. P. Morgan, G. P. Zambetti, and P. Erhardt Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H52 - H60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huang, K. Nakamura, Y. Ito, T. Uzuka, M. Morikawa, S. Hirai, K. Tomihara, T. Tanaka, Y. Masuta, K. Ishii, et al. Bcl-xL Gene Transfer Inhibits Bax Translocation and Prolongs Cardiac Cold Preservation Time in Rats Circulation, July 5, 2005; 112(1): 76 - 83. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
