Effect of Deferoxamine on Post-Hypoxic-Ischemic Reperfusion Injury of the Newborn Lamb Heart

Abstract

Post-hypoxic-ischemic (HI) reperfusion induces excess production of non-protein-bound iron (NPBI), leading to formation of the highly reactive hydroxyl radical. We investigated whether the iron-chelator deferoxamine (DFO) could reduce reperfusion injury and improve left ventricular (LV) function. We produced severe HI in 14 newborn lambs and measured pre-HI, upon reperfusion, 60 and 120 min after HI the following parameters: mean aortic blood pressure, total peripheral resistance, stroke volume (SV), ejection fraction (EF) and LV contractility (pre-HI, 60 and 120 min post-HI). These parameters were assessed by measuring LV pressure (tip manometer) and volume (conductance catheter), using inflow occlusion to obtain slope (E_es) and volume intercept of the end-systolic P-V relationship (V₁₀). We determined the antioxidative capacity, i.e. the ratio of ascorbic acid and dehydroascorbic acid (AA/DHAA) and malondialdehyde from coronary sinus blood at pre-HI and at 15, 60 and 120 min post-HI. Seven lambs received DFO (10 mg/kg i.v.) immediately after HI, 6 control lambs received a placebo. While neither E_es nor EF changed significantly in either group, the volume intercept V₁₀ in the DFO-treated group was significantly smaller (0.25 ± 0.03 vs. 0.70 ± 0.09, p < 0.05), whereas SV was larger (3.6 ± 0.6 vs. 2.2 ± 0.2 ml, p < 0.05) and the AA/DHAA ratio was significantly lower at 15 min post-HI (p < 0.05) providing evidence for HI damage and for the protective effect of DFO. In conclusion: post-HI treatment of the newborn lamb with DFO has a modifying effect on free radical-induced damage to the myocardium and protects myocardial performance.

Post-hypoxic cellular disintegration in glycine-preserved renal tubules is attenuated by hydroxyl radical scavengers and iron chelators

“…But our data are in line with several other reports showing protective effects of DFO both ex vivo on ischemia or reperfusion injury in isolated perfused lungs and hearts and in vivo on hemorrhagic shock-induced liver injury [33][34][35].…”

N,N,N′,N′-Tetrakis(2-pyridylmethyl)-ethylenediamine Improves Myocardial Protection against Ischemia by Modulation of Intracellular Ca2+ Homeostasis

“…Iron chelators such as deferoxamine and copper chelators such as bathocuproine and neocuproine (which is also an iron chelator) are the best studied groups so far. The cardioprotective properties of these compounds were shown in several studies both in vitro and in vivo (Ambrosio et al, 1987;Reddy et al, 1989;Appelbaum et al, 1990;Williams et al, 1991;Spencer et al, 1998;Shadid et al, 1999), but the mechanism of the protective effect is still not known.…”

The Role of Recombinant Human Erythropoietin in Lipid Peroxidation and Platelet-Activating Factor Generation in a Rat Model of Necrotizing Enterocolitis

“…Iron is an important catalyst for free oxygen radicals and lipid peroxidation reactions and we have hypothesized that administration of rhEPO mobilizes non-haem iron from the intestine and inhibits iron-catalyzed reactions. The antioxidant effect for iron chelator deferoxamine has been demonstrated in several animal models of free radical-mediated tissue injury (19,33). In addition, nutritional iron deficiency has been shown to be protective in several types of free radical-mediated injuries (3).…”