| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
2 Electron Microscopy Core Facility, Harvard Medical School, Boston, MA, USA
3 Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: james_mccully{at}hms.harvard.edu.
Previously, we have shown that the pharmacological opening of the mitochondrial ATPsensitive potassium channels with diazoxide (DZX) enhances the cardioprotection afforded by magnesium-supplemented potassium (K/Mg) cardioplegia. To determine the mechanisms involved in the cardioprotection afforded by K/Mg+DZX cardioplegia, rabbit hearts (n=24) were subjected to isolated Langendorff perfusion. Control hearts were perfused for 75 min. Global Ischemia (GI) hearts were subjected to 30 min. equilibrium, 30 min. global ischemia and 15 min. reperfusion. K/Mg and K/Mg+DZX cardioplegia hearts received either K/Mg or K/Mg+DZX for 5 minutes prior to global ischemia and reperfusion. Tissue was harvested for mitochondrial isolation and transmission electron microscopy (TEM). Mitochondrial structure, area, matrix volume, calcium and oxygen consumption were determined. TEM demonstrated that GI mitochondria were damaged and that K/Mg and K/Mg+DZX preserved mitochondrial structure. TEM and light scattering demonstrated separately that mitochondrial matrix and cristae area and matrix volume were significantly increased following global ischemia and reperfusion with GI > K/Mg+DZX > K/Mg hearts (p<0.05 vs. Control). Mitochondrial free calcium was significantly increased in GI and K/Mg hearts. K/Mg+DZX significantly decreased mitochondrial calcium accumulation (p<0.05 vs. GI and K/Mg). State 3 oxygen consumption and respiratory control index (RCI) in malate (complex I substrate) and succinate (complex II substrate) energized mitochondria were significantly decreased (p<0.05 vs. Control) in GI and K/Mg+DZX groups. These data indicate that the enhanced cardioprotection afforded by K/Mg+DZX cardioplegia occurs through the preservation of mitochondrial structure and the significant decrease in mitochondrial free calcium accumulation and mitochondrial state 3 oxygen consumption.
This article has been cited by other articles:
|
|
 |
|
  S. E. McAllister, H. Ashrafpour, N. Cahoon, N. Huang, M. A. Moses, P. C. Neligan, C. R. Forrest, J. E. Lipa, and C. Y. Pang Postconditioning for salvage of ischemic skeletal muscle from reperfusion injury: efficacy and mechanism Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R681 - R689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Oka, L. Wang, W. Mi, and C. A. Caldarone Inhibition of mitochondrial remodeling by cyclosporine A preserves myocardial performance in a neonatal rabbit model of cardioplegic arrest J. Thorac. Cardiovasc. Surg., March 1, 2008; 135(3): 585 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Pamenter, D. S.-H. Shin, M. Cooray, and L. T. Buck Mitochondrial ATP-sensitive K+ channels regulate NMDAR activity in the cortex of the anoxic western painted turtle J. Physiol., February 15, 2008; 586(4): 1043 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Oka, L. Wang, W. Mi, W. Zhu, O. Honjo, and C. A. Caldarone Cyclosporine A prevents apoptosis-related mitochondrial dysfunction after neonatal cardioplegic arrest J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Hadzimichalis, S. S. Baliga, R. Golfetti, K. M. Jaques, B. L. Firestein, and G. F. Merrill Acetaminophen-mediated cardioprotection via inhibition of the mitochondrial permeability transition pore-induced apoptotic pathway Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3348 - H3355. [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]
|
|
|
|
|
|
J. D. McCully, Y. Toyoda, H. Wakiyama, A. J. Rousou, R. A. Parker, and S. Levitsky Age- and gender-related differences in ischemia/reperfusion injury and cardioprotection: effects of diazoxide. Ann. Thorac. Surg., July 1, 2006; 82(1): 117 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-q. Zhu, U. Simonis, G. Cecchini, H.-z. Zhou, L. Li, J. R. Teerlink, and J. S. Karliner Comparison of Pyrroloquinoline Quinone and/or Metoprolol on Myocardial Infarct Size and Mitochondrial Damage in a Rat Model of Ischemia/Reperfusion Injury Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2006; 11(2): 119 - 128. [Abstract] [PDF]
|
|
|
|
|
|
L. Wang, C. Kinnear, J. M. Hammel, W. Zhu, Z. Hua, W. Mi, and C. A. Caldarone Preservation of Mitochondrial Structure and Function After Cardioplegic Arrest in the Neonate Using a Selective Mitochondrial K(ATP) Channel Opener. Ann. Thorac. Surg., May 1, 2006; 81(5): 1817 - 1823. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
