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

Abstract

UNLABELLED:

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 (Ees) 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 Ees 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.

• Authors: M Shadid, F Van Bel, P Steendijk, C A Dorrepaal, R Moison, E T Van Der Velde, J Baan
• Journal: Biology of the neonate (Biol Neonate) Vol. 75 Issue 4 Pg. 239-49 ( 1999) ISSN: 0006-3126 [Print] Switzerland
• PMID: 10026372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Malondialdehyde
• Deferoxamine
• Ascorbic Acid
• Dehydroascorbic Acid

Topics

• Animals
• Animals, Newborn (physiology)
• Ascorbic Acid (blood)
• Chelating Agents (pharmacology)
• Deferoxamine (pharmacology)
• Dehydroascorbic Acid (blood)
• Female
• Heart (drug effects, physiopathology)
• Hypoxia (physiopathology)
• Male
• Malondialdehyde (blood)
• Myocardial Ischemia (physiopathology)
• Myocardial Reperfusion Injury (physiopathology)
• Myocardium (metabolism)
• Oxidation-Reduction
• Sheep