The effects of a high dose of ascorbate on ischemia-reperfusion-induced mitochondrial dysfunction in canine hearts.
The cardioprotective effects of a high dose of ascorbate on ischemia-reperfusion-induced myocardial damage were investigated using open chest anesthetized dogs. Two-hour occlusion of the left anterior descending coronary artery (LAD) induced mitochondrial dysfunction with a depletion of mitochondrial glutathione (GSH) concentration. Two-hour LAD occlusion followed by 1-h reperfusion worsened the ischemia-induced mitochondrial dysfunction together with a marked depletion of mitochondrial GSH concentration. Ascorbate reduced the mitochondrial dysfunction and prevented the depletion of mitochondrial GSH concentration after 2-h LAD occlusion and 1-h reperfusion. Activities of mitochondrial glutathione peroxidase and glutathione reductase did not change significantly in each group. Administration of ascorbate also prevented reperfusion arrhythmias without affecting blood pressure or heart rate. These results suggest that coronary reperfusion induces mitochondrial dysfunction and a depletion of mitochondrial GSH concentration, and that a high dose of ascorbate prevents reperfusion damage.
Nishinaka
Y
Y
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Sugiyama
S
S
Yokota
M
M
Saito
H
H
Ozawa
T
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001205:Ascorbic Acid / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*
D005609:Free Radicals; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D001205:Ascorbic Acid