Effect of deferoxamine on post-hypoxic-ischemic reperfusion injury of the newborn lamb heart

Post-hypoxic-ischemic (HI) reperfusion induces excess production of non-pro tein-bound iron (NPBI), leading to formation of the highly reactive hydroxy l radical. We investigated whether the iron-chelator deferoxamine (DFO) cou ld reduce reperfusion injury and improve left ventricular (LV) function. We produced severe HI in 14 newborn lambs and measured pre-HI, upon reperfusi on, 60 and 120 min after HI the following parameters: mean aortic blood pre ssure, 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 (conduct ance catheter), using inflow occlusion to obtain slope (E-es) and volume in tercept of the end-systolic P-V relationship (V-10). We determined the anti oxidative capacity, i.e. the ratio of ascorbic acid and dehydroascorbic aci d (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.) immedi ately after HI, 6 control lambs received a placebo. While neither E-es nor EF changed significantly in either group, the volume intercept V-10 in the DFO-treated group was significantly smaller (0.25 +/- 0.03 vs. 0.70 +/- 0.0 9, 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 modifyi ng effect on free radical-induced damage to the myocardium and protects myo cardial performance.