Nafamostat mesilate on the course of acute pancreatitis. Protective effect on peritoneal permeability and relation with supervening pulmonary distress
| Autor: | De Hua Chui, K Suzuki, E Fesce, Francesco Marotta, Gaetano Idéo, Indira Rezakovic |
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| Předmět: |
Male
medicine.medical_specialty Pancreatic disease medicine.medical_treatment Pharmacology Guanidines Permeability Rats Sprague-Dawley Endocrinology Ascites medicine Animals Protease Inhibitors Saline Respiratory distress business.industry Peritoneal fluid Gastroenterology Dextrans medicine.disease Surgery Benzamidines Rats Nafamostat Oncology Pancreatitis Phospholipases Acute Disease Acute pancreatitis medicine.symptom Peritoneum business Respiratory Insufficiency Fluorescein-5-isothiocyanate |
| Zdroj: | Europe PubMed Central |
| Popis: | Three hundred sixty Sprague-Dawley rats were allocated into four groups, according to different content of a 24-h i.v. infusion performed 1 h after intrabiliary injection of enterokinase/sodium taurocholate to induce acute pancreatitis (AP): (1) Saline; (2) 5 micrograms/kg/h nafamostat mesilate (FUT-175); (3) 10 micrograms/kg/h FUT-175; and (4) 25 micrograms/kg/h FUT-175. Peritoneal fluid was removed and exchanged with 1 mL 3.33 M fluorescein-isothiocyanate-conjugated (FITC) dextrans of 4000-40,000 Dalton. Serial blood samples were withdrawn and examined for FITC-dextrans, phospholipase A2 (PLA2), blood gases, amylase, and lipase. As compared to control (55%), FUT-175 brought about a lower (5 micrograms/kg/h: 25%) or no mortality (10 and 25 micrograms/kg/h), and a milder histological and biochemical evidence of AP. Untreated animals with PLA2 values over two times the standard deviation showed a respiratory distress. Further, unlike group 1, FUT-175 doses as low as 5 micrograms/kg prevented the increase in peritoneal permeability to small-size molecules (up to 20,000 Dalton). In a second experiment under the same drug protocol, 1000 U/mL of PLA2 and 2 mL of pancreatitis ascites were instilled ip. Peritoneal permeability to FITC-dextrans up to 30,000 Dalton and to PLA2 significantly increased in the saline group and in the 5 micrograms/kg FUT-175 group. However, 10 micrograms/kg and 25 micrograms/kg FUT-175 doses prevented such phenomenon. In conclusion, FUT-175 proves to be a potent antiprotease molecule with a biochemical activity also against PLA2 in vivo and prevents significant transperitoneal-blood access of pancreatic enzymes. |
| Databáze: | OpenAIRE |
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