Protection by cyclosporine A against normothermic liver ischemia-reperfusion in pigs

BACKGROUND: Cyclosporine A (CYA) is primarily utilized as an immunosuppressant, but its mechanisms of action (including decreased neutrophilic free radical production and stabilization of mitochondrial and lysosomal membranes) may have beneficial effects in ischemia and reperfusion (IR) injury. This study was undertaken to examine the effect of CYA pretreatment on porcine liver histopathologic changes and enzymatic release caused by ischemia and reperfusion. MATERIALS AND METHODS: CYA was administered orally for 4 days prior to surgery in two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion. RESULTS: Significant decreases in AST levels compared to controls were seen in high dose CYA pigs at the end of ischemia and at 30-min intervals during the reperfusion period. Controls exhibited necrotic hepatocytes and severe inflammatory cell infiltration, while high dose CYA animals demonstrated mild inflammatory cell infiltrates. Controls had decreased survival--20% did not survive reperfusion. CONCLUSIONS: This study indicates that CYA may be useful in decreasing initial damage resulting from warm hepatic IR injury.     

Postprandial glucose, insulin, free fatty acid and growth hormone responses in children consuming all the day's protein in one meal

BLOOD GLUCOSE, INSULIN (IRI), growth hormone, and plasma free fatty acids (FFA) were determined in six children consuming a diet of uneven distribution of protein relative to energy (study period). Preprandial and postprandial samples surrounding the 8 AM protein-free feeding and the 3 PM feeding containing all the day's protein were compared with values obtained in the same children similarly sampled while consuming an isonitrogenous isoenergetic diet of even protein distribution (control period). After the 8 AM feeding during the study period there was a mean maximal rise of blood glucose at 30 min of 51 mg/dl compared with a rise of 16 mg/dl during the control period. Glucose remained significantly elevated above fasting values at 120 min during the study but not the control period. IRI response after the 8 AM feeding was significantly greater and suppression of FFA was more marked during the study than during the control period. Glucose concentration 30 min after the 3 PM feeding was significantly lower during the study period than during the control period. A peak value occurred at 60 min during the study period which was equal to the 30 min peak control value. Despite the slower elevation of blood glucose during the study period, IRI rose at 30 min, possibly related to a larger influx of amino acids from the protein-containing meal. FFA rose at 30 and 60 min and were then suppressed by the slowly rising blood glucose. Growth hormone after both meals while consuming both diets was variable but considered normal. The qualitative changes in glucose-IRI-FFA responses were for the most part attributable to differences in the test meals and suggested little long-term adaptation to the uneven protein distribution diet.