Effect of FTY720 treatment on postischemic pancreatic microhemodynamics

Abstract

CD4+ T cells contribute to disturbances of pancreatic microcirculation after cold and even after warm ischemia/reperfusion (I/R). The aim of this study was to investigate a possible protective role of FTY720 (fingolimod) in this setting. In an in vivo model (42 Wistar rats), ischemia of the pancreas was induced for 60 minutes under anesthesia with xylazin/ketanest. Sham-operated (SO) (I), untreated ischemic (II), and treatment group with FTY720 pre-treatment (1 mg/kg body weight i.v.) (III) were investigated. The effect of FTY720 on I/R injury was assessed by in vivo microscopy 30-90 minutes after reperfusion and by measurement of serum lipase. In the untreated ischemic group (II), capillary constriction to 85.3 ± 6.3% of SO diameters and a reduction of functional capillary density to 67% was found. After 30 minutes of reperfusion, the number of T cells in capillaries was increased (165.7%; P < .05 vs I). FTY720 pretreatment reduced this number to 54.2% of SO (P < .05 vs II). Likewise, the number of adherent leukocytes in capillaries (145.4 ± 11.2% of SO) was reduced in group III (109.3 ± 11.4%; P < .05 vs II), leading to an improvement in functional capillary density in the treatment group (98.2 ± 2% of SO; P < .05 vs II). According to improved microcirculation, lipase values were reduced in the therapy group (P < .05). In conclusion, FTY720 ameliorates the microcirculatory and biochemical manifestations of pancreatic I/R injury by preventing T-cell infiltration.