Involvement of neutrophils in ischemia-reperfusion injury of inguinal island skin flaps in rats.

Increased production of oxygen free radicals and infiltration of neutrophils into tissue subjected to ischemia-reperfusion have emphasized that neutrophils play a direct role in the development of injury. The present study was designed to elucidate the effect of FK506, a new immunosuppressive drug, on 11 hours of complete ischemia and reperfusion of the inguinal island skin flaps in rats. Group 1 (n = 10) control animals underwent ischemia and reperfusion and no treatment. Group 2 (n = 10) animals received FK 506 0.3 mg/kg/day, and group 3 (n = 9) animals received 0.5 mg/kg/day intramuscularly for 3 days before the ischemia. The effect of the drug was evaluated by measuring flap survival and tissue malondialdehyde content and myeloperoxidase activity and also by histopathologic examination of the skin specimens taken at the 1st and 24th hour after reperfusion. The survival of flaps controlled for 7 days was found to be significantly improved in group 2 (65.0 +/- 10.93 percent) and group 3 (93 +/- 6.25 percent) when compared with the control group (14 +/- 10.12 percent) (p < 0.04 and p < 0.0001). The tissue contents of malondialdehyde and activities of myeloperoxidase were significantly lower in groups 2 and 3 than in the control group. Three days of pretreatment with FK506 significantly reduced neutrophil infiltration in groups treated with either of the doses. These results showed that neutrophils play an important role in island flap survival associated with ischemia-reperfusion injury. Increased neutrophil infiltration was found related with increased levels of malondialdehyde and myeloperoxidase. Flap necrosis and the increase in malondialdehyde, myeloperoxidase, and neutrophil infiltration were improved by FK506 pretreatment, a neutrophil modulating agent.

The effect of intestinal transit time on bacterial translocation.

Increase in intraluminal bacterial count, disruption of the mucosal integrity, changes in intestinal immunity and transit time are the factors involved in bacterial translocation. The relationship between intestinal transit time, intra luminal bacterial count and translocation rate were investigated in 40 Wistar-albino rats. The study was conducted in 4 groups with 10 animals in each. Group I (controls): saline + laboratory chow, Group II: saline + oral total parenteral nutrition (TPN) solution, Group III: morphine sulfate (MS) + oral TPN solution, Group IV: neostigmine bromide (NB) + oral TPN solution. Intestinal transit time was measured by using Indium111-labeled diethylene triamine pentaacetic acid (DTPA). It was prolonged in the MS-treated group and shortened in the NB-treated group (p < 0.01). The frequency of bacterial translocation was 60% in the oral TPN solution group, 100% in the MS-treated group, 20% in the NB-treated group and 10% in controls. Bacterial counts in duodenum, jejunum, ileum and caecum were significantly increased (p < 0.001) in the MS-treated group and decreased (p < 0.05) in the NB-treated group in comparison with the control group. In conclusion, the prolongation of intestinal transit time increased the intraluminal bacterial count and augmented bacterial translocation. The decrease in intestinal transit time had a converse effect.

Involvement of neutrophils in ischemic injury. I. Biochemical and histopathological investigation of the effect of FK506 on dorsal skin flaps in rats.

The purpose of this study was to investigate the role of neutrophils in ischemic tissue injury and the possible inhibition by pretreatment with FK506, a neutrophilic modulating agent. A dorsal caudally based skin flap (3 x 9 cm) was used as an ischemic injury model in experimental groups. Prior to flap elevation, FK506 at doses of 0.3 mg per kilogram (group 2), 0.5 mg per kilogram (group 3), and 1.0 mg per kilogram (group 4) was given for 3 days intramuscularly. The relationship among neutrophil accumulation (histopathologically), myeloperoxidase (MPO) activity, malondialdehyde (MDA) content (biochemically) of the flap tissue, and flap survival were studied. Skin flaps showed reduced necrosis in the FK506-treated groups (p < 0.08, p < 0.0001, and p < 0.0001 respectively). The increase in accumulation of neutrophils, and MDA and MPO levels (which were induced by ischemia) observed 1 and 24 hours after flap elevation was diminished by FK506 pretreatment. The increased neutrophilic infiltration, and raised tissue MDA content and MPO activity revealed involvement of both free radical production and neutrophils in ischemia. This injury was decreased by FK506, probably by inhibition of neutrophilic chemotaxis, infiltration, and releasing factors.

Neutrophil-mediated injury in ischemic skin flaps: amelioration of ischemic injury by cyclosporine in the rat.

The role of neutrophils, their presence, and their degree of infiltration was examined in ischemic skin flaps. In a rat model, caudally based dorsal flaps were studied and neutrophils were manipulated by giving cyclosporine at two different doses (15 and 30 mg per kilogram), administrated either for 5 days as a pretreatment or 15 minutes before flap elevation. The presence of neutrophils and lymphocytes in both intravascular and extravascular space was assessed at 15, 30, and 60 minutes by skin biopsies, taken after elevation of the flap, by direct quantitative counting under the light microscope. The correlation between the counts and localization of the neutrophils, but not the lymphocytes, and the percentage of necrosis showed an early and definite role of neutrophils on skin flap survival during ischemic insult. Cyclosporine-treated flaps showed a 24% to 37% increase in viability when compared to control flaps. These data suggest that neutrophils, probably their interactions and/or products, play an important role in ischemic flap survival, and cyclosporine A is able to inhibit neutrophil accumulation and sequestration.

Neu-Laxova syndrome: report of a case from Turkey.

We describe a case of Neu-Laxova syndrome in a newborn female who was born at full-term to consanguineous Turkish parents. The pathological and radiological features are described.