AJP - Heart and Circulatory Physiology, Vol 253, Issue 6 1372-H1380, Copyright © 1987 by American Physiological Society
The iron chelator desferrioxamine attenuates postischemic ventricular dysfunction
R. Bolli, B. S. Patel, W. X. Zhu, P. G. O'Neill, C. J. Hartley, M. L. Charlat and R. Roberts
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
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.
