Inability of desferrioxamine to limit tissue injury in the ischaemic and reperfused rabbit heart.
The role of iron-catalysed hydroxyl radical production in development of myocardial injury was examined in an in vivo rabbit heart with regional ischaemia (45 min) and reperfusion (3 h). Open-chest anaesthetised rabbits were assigned to control (saline) or desferrioxamine-treated [30 mg/kg subcutaneously (s.c.) plus 1, 10, 20, or 100 mg/kg/h intravenously (i.v.) starting 15 min before ischaemia] groups. Haemodynamics and ECG were monitored throughout. Following reperfusion, hearts were excised and perfused in vitro with buffer. The artery was religated, and fluorescent particles were injected to delineate the ischaemic zone. Tetrazolium staining was used to define necrosis. Planimetry was performed on photographed heart slices for calculation of the size of the hearts and of the ischaemic and infarcted zones. Infarct size (as a percentage of ischaemic zone size) in control hearts was 51.2 +/- 5.8% (n = 10) and in the groups treated with desferrioxamine 1, 10, 20, and 100 mg/kg/h it was 53.1 +/- 11.7% (n = 8), 45.3 +/- 6.3% (n = 9), 65.1 +/- 10.1% (n = 6), and 52.5 +/- 9.4% (n = 7), respectively (p = NS vs. control in each instance). In addition, no antiarrhythmic effects were observed at any dose. Thus, iron-catalysed hydroxyl radical damage may not play a role in the pathogenesis of tissue injury under these conditions.
Maxwell
M P
MP
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, England.
Hearse
D J
DJ
Yellon
D M
DM
D000818:Animals; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003676:Deferoxamine / Q000494:pharmacology*; D005609:Free Radicals; D006439:Hemodynamics / Q000187:drug effects; D006878:Hydroxides / Q000096:biosynthesis; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D011817:Rabbits
D005609:Free Radicals; D006878:Hydroxides; D007502:Iron Chelating Agents; D017665:Hydroxyl Radical; D003676:Deferoxamine