2-4-dinitrophenylhydrazine and Ischemia

4-Hydroxynonenal (HNE) as an indicator of lipid peroxidation was determined in rat jejunal mucosa. HNE was extracted as the dinitrophenylhydrazone derivative from the tissue, partially separated from other carbonyl compounds by thin-layer chromatography and measured by HPLC. During reperfusion of the small intestine following an ischemic period of 60 minutes a marked increase of the tissue concentration of HNE was observed. The mucosal HNE level passed a maximum value of 3.0 +/- 0.5 microM 10 min after the onset of reperfusion in comparison with 0.7 +/- 0.2 microM as initial value. The increased tissue level of the highly cytotoxic 4-hydroxyalkenal is suggested to be involved in the reperfusion induced morphological and biochemical changes of the small intestine.

Topics: Aldehydes; Animals; Chromatography, High Pressure Liquid; Glutathione; Glutathione Disulfide; Hypoxanthine; Hypoxanthines; Intestine, Small; Ischemia; Jejunum; Lipid Peroxidation; Male; Phenylhydrazines; Rats; Rats, Wistar; Reperfusion; Thiobarbituric Acid Reactive Substances

1. The burst of damaging oxygen free-radicals at the time of reperfusion is one of the crucial factors affecting skin flap survival after an ischaemic interval. In these experiments the efficacy of the antioxidant and free-radical scavenger N-acetylcysteine in improving the survival of ischaemic rabbit epigastric skin flaps was tested. 2. At the time of reperfusion flaps were given: (1) balanced salt solution by intravenous whole-body administration, (2) N-acetylcysteine (200 mg/kg) by intravenous whole-body administration, (3) balanced salt solution by intra-arterial infusion into the flap, (4) N-acetylcysteine (20 mg/kg) by intra-arterial infusion into the flap, or (5) N-acetylcysteine (200 mg/kg) by intra-arterial infusion into the flap. Flap survival at 1 week, and tissue levels of parameters related to free-radical production, blood levels of thromboxane B2 and peripheral resistance during reperfusion were determined. 3. Compared with controls (groups 1 and 3) which had flap survival rates (expressed as percentage surface area surviving) of 27.1% and 31.6%, respectively. N-acetylcysteine treatment in group 2 (55.2%) and group 4 (51.9%) resulted in significant (P less than 0.05) improvements in flap survival. The survival rate in group 5 (37.7%) was not significantly better than that of the controls. 4. N-Acetylcysteine significantly reduced parameters related to free-radical production in the skin flap after 30 min of reperfusion, determined as tissue levels of malonyldialdehyde and protein oxidation products. There was also a significant decrease in peripheral resistance when low-dose N-acetylcysteine (group 4) was infused intra-arterially into the flap.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetylcysteine; Animals; Antioxidants; Disease Models, Animal; Free Radical Scavengers; Graft Survival; Ischemia; Malondialdehyde; Phenylhydrazines; Rabbits; Reperfusion Injury; Skin; Surgical Flaps; Thromboxane B2; Vascular Resistance