![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication January 3, 2006.
Revised February 3, 2006.
Accepted for publication February 6, 2006.
Trimetazidine (TMZ), an anti-ischemic metabolic drug, is used to treat chest pain (angina pectoris). We hypothesized that derivatives of TMZ with antioxidant functions may improve the cardiac dysfunction caused by ischemia/reperfusion (I/R) above that observed with TMZ alone. Isolated rat hearts, perfused with Krebs-Henseleit buffer according to the Langendorff method, were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Trimetazidine, TMZ-NH (TMZ modified with a pyrroline moiety) or TMZ-
NH (TMZ-NH with a phenyl substitute) were infused (50 µM) for 1 min before the onset of ischemia. Untreated (control) hearts at the end of 45 min of reperfusion showed a significant decrease in the recovery of coronary flow (42%), left-ventricular-developed pressure (22%) and rate-pressure product (25%) as compared to pre-ischemic baseline values. The I/R hearts also showed markedly increased lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the coronary effluent, significant myocardial infarction (46% of risk area), and activation of Akt, ERK, and p38 MAPK. Pretreatment of hearts with TMZ-NH or TMZ-NH showed significantly enhanced the recovery of heart function and decreased infarct size. The I/R-induced activation of Akt was further enhanced by TMZ-NH. The present study demonstrated that TMZ-NH and TMZ-NH significantly protected hearts against I/R-mediated cardiac dysfunction and injury. The protective effect of the TMZ derivatives could be due to the combined effects of antioxidant and anti-ischemic activities as well as enhanced pro-survival Akt activity.
Key words:
Ischemia-reperfusion injury, anti-ischemic, heart, nitroxide, oxidative stress, trimetazidine
This article has been cited by other articles:
|
|
 |
|
  R. Mandal, V. K. Kutala, M. Khan, I. K. Mohan, S. Varadharaj, A. Sridhar, C. A. Carnes, T. Kalai, K. Hideg, and P. Kuppusamy N-Hydroxy-pyrroline Modification of Verapamil Exhibits Antioxidant Protection of the Heart against Ischemia/Reperfusion-Induced Cardiac Dysfunction without Compromising Its Calcium Antagonistic Activity J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 119 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Wang, C. Zaragoza, and W. Holman Sodium-Hydrogen Exchange Inhibition and {beta}-Blockade Additively Decrease Infarct Size Ann. Thorac. Surg., March 1, 2007; 83(3): 1121 - 1127. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
