The iron chelator desferrioxamine attenuates postischemic ventricular dysfunction.
Recent evidence suggests that postischemic myocardial dysfunction ("stunning") may be mediated by oxygen free radicals, but the mechanism by which they produce myocellular damage remains unknown. Since iron catalyzes formation of hydroxyl radicals (HO.) as well as HO.-initiated lipid peroxidation, we explored the potential role of this metal in the pathogenesis of myocardial stunning. Open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received the iron chelator desferrioxamine intravenously (10 mg/kg over 45 min beginning 30 min before occlusion, then 1.7 mg.kg-1.h-1 throughout REP, n = 19) or normal saline (n = 17). Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. After REP, however, recovery of contractile function (expressed as percent systolic thickening) as considerably greater in desferrioxamine-treated compared with control dogs: 5 +/- 3 (mean +/- SE) vs. -3 +/- 2% (P less than 0.05) at 1 h, 6 +/- 3 vs. -2 +/- 3% (P less than 0.05) at 2 h, 5 +/- 3 vs. -6 +/- 2% (P less than 0.005) at 3 h, and 6 +/- 3 vs. -6 +/- 2% (P less than 0.002) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that iron-catalyzed reactions (possibly HO. generation) play a significant role in myocardial stunning after a brief episode of reversible regional ischemia.
Bolli
R
R
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Patel
B S
BS
Zhu
W X
WX
O'Neill
P G
PG
Hartley
C J
CJ
Charlat
M L
ML
Roberts
R
R
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels; D003676:Deferoxamine / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005609:Free Radicals; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics; D007501:Iron / Q000502:physiology; D008026:Ligation; D008297:Male; D011188:Potassium / Q000097:blood; D012039:Regional Blood Flow
D005609:Free Radicals; D007501:Iron; D003676:Deferoxamine; D011188:Potassium