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, R. Roberts

Research output: Contribution to journalArticlepeer-review

Abstract

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 < 0.005) at 1 h, 6 ± 3 vs. -2 ± 3% (P < 0.05) at 2 h, 5 ± 3 vs. -6 ± 2% (P < 0.005) at 3 h, and 6 ± 2% (P < 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.

Original languageEnglish (US)
Pages (from-to)22/6
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume253
Issue number6
StatePublished - 1987

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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