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.
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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)
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Chemical References |
- Chelating Agents
- Malondialdehyde
- Deferoxamine
- Ascorbic Acid
- Dehydroascorbic Acid
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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
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