Improvement of postischemic myocardial function and metabolism induced by administration of deferoxamine at the time of reflow: The role of iron in the pathogenesis of reperfusion injury

G. Ambrosio, J. L. Zweier, W. E. Jacobus, M. L. Weisfeldt, J. T. Flaherty

Research output: Contribution to journalArticlepeer-review

Abstract

Reperfusion of ischemic myocardium has been postulated to result in a specific oxygen radical-mediated component of tissue injury. In a previous study we demonstrated improved recovery of ventricular function and metabolism when the superoxide radical scavenger superoxide dismutase was administered at the time of postischemic reflow. Studies in vitro, however, have suggested that superoxide toxicity might be mediated via the generation of more reactive hydroxyl radicals in an iron-catalyzed reaction. The present study was designed to test the hypothesis that myocardial reperfusion injury might be reduced by administration of the iron chelator deferoxamine at the time of reflow, most likely by preventing hydroxy radical formation. Sixteen isolated Langendorff rabbit hearts, perfused within the bore of a superconducting magnet, were subjected to 30 min of normothermic (37°C) total global ischemia followed by 45 min of reperfusion. At reflow eight treated hearts received a 10 ml bolus containing 50 μmol of deferoxamine followed by an infusion of 11 μmol/min for the first 15 min of reflow. The hearts were then perfused with standard perfusate for an additional 30 min. Eight untreated control hearts received a similar bolus of perfusate followed by 45 min of standard reperfusion. Serial 5 min 31P nuclear magnetic resonance spectra were recorded. Myocardial phosphocreatine (PCr) content fell to 5% to 7% of control during ischemia in both groups of hearts. Deferoxamine-treated hearts recovered 99 ± 10% of control PCr content, while untreatd hearts recovered 60 ± 16% (p < .05). Intracellular pH fell to 5.9 during ischemia in both groups, before showing more rapid and complete recovery in treated hearts (p < .01). Recovery of developed pressure reached 70 ± 6% of control in treated hearts compared with 35 ± 10% in untreated hearts (p < .05). Iron content of the perfusate was 7 μM, and by electron paramagentic resonance spectroscopy was in the form of Fe3+-EDTA complexes. In the effluent of treated hearts iron was in the form of Fe3+-deferoxamine chelates. In summary, administration of the iron chelator deferoxamine at the time of postischemic reflow results in greater recovery of myocardial function and energy metabolism, which supports the hypothesis that iron plays an important role in the pathogenesis of reperfusion injury.

Original languageEnglish (US)
Pages (from-to)906-915
Number of pages10
JournalCirculation
Volume76
Issue number4
DOIs
StatePublished - 1987

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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