|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Pathology, University of Cincinnati, Cincinnati, Ohio, United States
* To whom correspondence should be addressed. E-mail: ashrafm{at}ucmail.uc.edu.
Ischemic preconditioning is the most powerful protective mechanism known against lethal ischemia. Unfortunately the protection lasts for only a few hours. Here we tested the hypothesis that the heart can be kept in preconditioned state for constant protection against ischemia. In this study we chose BMS-191095 (BMS), a highly selective opener of mitochondrial KATP channel (mitoKATP), BMS (1 mg/kg, i.p.) was administered to rats every 24 hrs till 96 hrs. In other groups, BMS plus wortmannin (WTN, 15 µg/kg, i.p.), an inhibitor of the phosphatidylinositol 3-kinase (PI-3K), or BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg, i.p.), an inhibitor of mitoKATP, or BMS plus L-NAME (30 µg/kg, i.p.), an inhibitor of nitric oxide synthase (NOS) were administered to rats. Rats were then subjected to 30 minutes LAD occlusion and 120 minutes reperfusion. Cardiac function, infarct size, pathological changes and apoptosis were assessed at the end of treatments. Saline treated hearts displayed marked contractile dysfunction and underwent pathological changes. BMS treated rats showed significant improvement in cardiac function and infarct size was significantly reduced in BMS treated hearts. However, protection by BMS was abolished by 5-HD, or WTN, or L-NAME. These data demonstrate that hearts can be chronically preconditioned and retain their ability to remain resistant against lethal ischemia and this protection is mediated by activation of mitoKATP via nitric oxide (NO) and PI3K/Akt signaling pathways.
This article has been cited by other articles:
![]() |
N. Ahmad, Y. Wang, A. K. Ali, and M. Ashraf Long-acting phosphodiesterase-5 inhibitor, tadalafil, induces sustained cardioprotection against lethal ischemic injury Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H387 - H391. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Zhao, D. Zhang, R. W. Millard, M. Ashraf, and Y. Wang Stem cell homing and angiomyogenesis in transplanted hearts are enhanced by combined intramyocardial SDF-1{alpha} delivery and endogenous cytokine signaling Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H976 - H986. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Pasha, Y. Wang, R. Sheikh, D. Zhang, T. Zhao, and M. Ashraf Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium Cardiovasc Res, January 1, 2008; 77(1): 134 - 142. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. A. Markel, P. R. Crisostomo, M. Wang, J. L. Herrmann, A. M. Abarbanell, and D. R. Meldrum Right ventricular TNF resistance during endotoxemia: the differential effects on ventricular function Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1893 - R1897. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |