Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10954296 | Journal of Molecular and Cellular Cardiology | 2005 | 7 Pages |
Abstract
Trimetazidine (TMZ) affects mitochondrial function during ischemia. Mitochondrial permeability transition is a pivotal event in cardiomyocyte death following acute ischemia. The aim of the present study was to determine whether the anti-ischemic agent TMZ might modulate mitochondrial permeability transition pore (mPTP) opening and limit lethal ischemia-reperfusion injury. Anesthetized NZW rabbits underwent 30 min of coronary artery occlusion followed by 4 hours of reperfusion. Prior to this, they underwent either no intervention (control, C), ischemic preconditioning (PC), or an IV injection of 5 mg kg-1 TMZ 10 min before ischemia (TMZ). Additional rabbits (Sham group) underwent no ischemia/reperfusion throughout the experiment. Infarct size was assessed by triphenyltetrazolium staining, and apoptosis via measurement of caspase 3 activity. Ca2+-induced mPTP opening was assessed in mitochondria isolated from ischemic myocardium. TMZ and PC significantly reduced infarct size that averaged 34 ± 4% and 21 ± 4% of the risk region respectively, versus 63±6% in controls (P < 0.005). Caspase 3 activity was reduced in both TMZ and PC groups: 37 ± 11 and 29 ± 7 respectively, versus 68 ± 9 nmol min-1 mg-1 mitochondrial protein in controls (P = 0.01 versus TMZ and PC). In controls, Ca2+ load required for mPTP opening averaged 11 ± 4 μM mg-1 mitochondrial protein versus 116±6 in shams (P < 0.0001). Pre-treatment by TMZ or PC attenuated this, with Ca2+ loads averaging 45 ± 4 and 46 ± 4 μM mg-1 mitochondrial proteins, respectively (P < 0.005 versus C). These data suggest that TMZ inhibits mPTP opening and protects the rabbit heart from prolonged ischemia-reperfusion injury.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cell Biology
Authors
Laurent Argaud, Ludovic Gomez, Odile Gateau-Roesch, Elisabeth Couture-Lepetit, Joseph Loufouat, Dominique Robert, Michel Ovize,