Effects of octreotide pretreatment in experimental acute pancreatitis.

BACKGROUND: Severity of systemic lesions and mortality of experimental acute pancreatitis (AP) are reduced after pancreatic enzyme content reduction induced by cerulein administration. Octreotide has been used both prophylatically and therapeutically in AP. The possible effects of octreotide on pancreatic enzyme content and its influence on pulmonary lesions of experimental AP were assessed in this study. METHODS: Wistar male rats were divided in two branches: BRANCH I - Animals divided into three groups: Group Sa (n = 10) intravenous saline infusion; Group Ce (n = 10) intravenous cerulein infusion, (0.133 micro g/kg(-1).h(-1)) and Group Oc (n = 10) SC octreotide (10 micro g/kg(-1)). Trypsin, elastase and amylase pancreatic contents as well as serum amylase were determined thereafter in all three groups; BRANCH II - Rats treated as in branch I, were submitted to sodium taurocholate AP (Groups Sa+AP, Ce+AP and Oc+AP). Two hours thereafter amylase and TAP assays were performed in serum, ascites and pancreatic tissue in eight animals of each group. Pulmonary histology was studied by morphometry 24 h after AP in the remaining animals. RESULTS: Increased serum amylase and pancreatic enzyme contents were observed in octreotide-treated animals when compared to animals receiving saline or cerulein. After AP increases of serum and ascitic fluid amylase and of pancreatic TAP were observed in octreotide pre-treated animals when compared to saline and cerulein groups. Pulmonary interstitial and alveolar edema after AP was significantly increased in rats receiving octreotide as compared to the cerulein group. CONCLUSION: Octreotide administration acutely increases the enzymatic content of the pancreas and thus may have a potential deleterious influence in the evolution of AP.

Lesäo hepatica na pancreatite aguda experimental: influencia da reduçäo da reserva enzimatica do pancreas / Evaluation of hepatic lesion of experimental acute pancreatitis: influence of pancreatic enzyme reduction

A pancreatite aguda (PA) produz alteracoes morfologicas e funcionais no figado. A administraçäo de doses baixas de ceruleina diminui o conteudo enzimatico do pancreas. O objetivo do presente estudo foi estudar o efeito da reduçäo do conteudo enzimatico do pancreas na funçäo mitocondrial hepatica. Ratos machos Wistar foram submetidos a PA atraves de injeçäo retrograda intraductal de taurocolato de sodio a 5 por cento com e sem infusäo de ceruleina (0,133 ug/Kg/h) durante tres horas : Grupo I (GI): sem reducao enzimatica do pancreas, com induçäo de PA, GRUPO II (GII): com reduçäo enzimática do pancreas, com induçäo de PA, GRUPO III (GIII): com reduçäo enzimatica do pancreas, sem induçäo de PA, GRUPO IV (GIV): sem reduçäo enzimatica do pancreas, sem induçäo de PA (Controle). Após duas horas da inducao da PA os animais foram sacrificados e os figados retirados para avaliaçäo da funçäo mitocondrial hepatica, determinada polarograficamente com eletrodo de Clark, medindo-se o consumo de oxigenio na ausência de ADP (S4-Basal) e na presença de ADP (S-3 Ativado), utilizando-se succinato de potassio como substrato. Os conteudos de tripsina, amilase e proteinas totais no liquido ascitico foram determinados. Após duas horas da induçäo da PA observamos aumento significativo no estado 4 da respiraçäo (41 por cento) e diminuiçäo do RCR e da relaçäo ADP/O nos animais do GI (PA sem ceruleina) quando comparados com os animais do GII (PA com ceruleina) (p<0,05). O conteudo de amilase (A) e tripsina (T) no liquido ascitico mostraram-se diminuidos nos animais do GII (A=80 +- 10 U/ml, T= 9,75 +- 1,25 U/ml), quando comparados com os animais do GI que nao receberam ceruleina ( A= 231 +- 24 U/ml, T = 40,32 +- 5,19 U/ml) (p<0,001). Infusäo somente de ceruleina (GIII) näo alterou a funçäo mitocondrial hepatica. Estes achados sugerem que a reduçäo do conteudo enzimatico do pancreas através de infusäo de ceruleina atenua a disfunçäo mitocondrial hepatica na PA experimental evidenciada por desacoplamento da oxigenaçäo fosforilativa

Reduction of pancreatic enzyme content and mortality in experimental acute pancreatitis in rats.

A previous report has shown that undernutrition reduces the mortality of acute experimental pancreatitis probably by decreasing pancreatic enzyme content. Cerulein in physiological doses reduces the enzyme content of the pancreas without any harmful effect on the organ. The aim of the present study was to asses the effect of acute reduction of pancreatic enzyme content on the outcome of acute pancreatitis. Two groups of male Wistar rats weighing 230-250 g were studied: group I, 12-h fasted animals, and group II, ad libitum-fed animals who received cerulein at the inframaximal dose (0.2 microgram kg-1 h-1) for 2 h. Cerulein administration resulted in the reduction of the pancreatic contents of chymotrypsinogen (71%), trypsinogen (55%), proelastase (60%), amylase (62%) and cathepsin B (45%) (P < 0.05). However, no significant reduction in pancreatic phospholipase content was observed. Acute pancreatitis was induced in group I after 12-h fasting and in group II at the end of cerulein infusion by retrograde injection o 0.5 ml of 2.5% Na+ taurocholate into the pancreatic duct. Ascites volume and the degree of histologically observed lesions were similar in both groups, but 72-h mortality was 56% in the control group (10/ 18) and 23% (5/22) in the cerulein group (P < 0.05). We speculate that the reduction of pancreatic enzyme content may exert its beneficial effect in acute pancreatitis by decreasing the quantity of pancreatic enzymes reaching the circulation and consequently their pathogenic effects.

Reduction of pancreatic enzyme content and mortality in experimental acute pancreatitis in rats

A previous report has shwon that undernutrition reduces the mortality of acute experimental pancreatitis probably by decreasing pancreatic enzyme content of the pancreas without any harmful effect on the organ. The aim of the present study was to assess the effect of acute reduction of pancreatic enzyme content on the outcome of acute pancreatitis. Two groups of males Wistar rats weighing 230-250 g were studied: group I, 12-h fasted animals, and group II, add libitum-fed animals who received cerulein at the inframaximal dose (0.2 µg kg-1h-1) for 2 h. Cerulein adminsitration resulted in the reduction of the pancreatic contents of chymotrypsinogen (71 percent), trypsinogen (55 percent), proelastase (60 percent), amylase (62 percent) and cathepsin B (45 percent) (P<0.05). However, no significant reduction in pancreatic phospholipase content was observed. Acute pancreatitis wass induced in group I after 12-h fasting and in group II at the end of cerulein infusion by retrograde injection of 0.5 ml of 2.5 percent Na+ taurocholate into the pancreatic duct. Ascites volume and the degree of histologically observed lesions were similar in both groups, but 72-h mortality was 56 percent in the control group (10/18) and 23 percent (5/22) in the cerulein group (P<0.05). We speculate that the reduction of pancreatic enzyme content may exert its beneficial effect in acute pancreatitis by decreasing the quantity of pancreatic enzymes reaching the circulation and consequently their pathogenic effects

Modelo simplificado de inducao de pancreatite aguda experimental com uso de dose supramaxima de ceruleina / Simplified model of produced experimental acute pancreatitis with use of supra-maximal dosis of cerulein

A administracao de ceruleina tanto por via endovenosa como intraperitonial, tem sido extensivamente utilizada para inducao de pancreatite aguda experimental. Com objetivo de se testar uma nova metodologia de inducao de pancreatite aguda, que fosse de facil e rapida execucao, assim como de boa reprodutibilidade , 40 ratos Wistar foram distribuidos em quatro grupos: GRUPO I - animais que receberam infusao continua de ceruleina (15µ/Kg) GRUPO II - animais que receberam infusao continua e salina GRUPO III - animais submetidos a duas injecoes (SC+CV) de ceruleina (40µ/Kg) GRUPO IV - animais submetidos a duas injecoes (SC+CV) de salina. Apos a realizacao de dosagens bioquimicas, nao houve diferenca estatisticamente significativa entre os grupos I e II nas concentracoes teciduaias de tripsionogenio, quimiotripsinogenio, proelastase , catepsina e tambem amilase serica; ocorrendo diferenca somente entre os valores de porcentagem de agua no tecido pancreatico...

Efeito protetor da depelecao de enzimas pancreaticas na evolucao da pancreatite aguda: estudo experimental em ratos / Protective effect of the reduction of pancreatic enzymes in the acute pancreatitis evolution: experimental study in rats

A reducao da concentracao de enzimas no parenquima pancreatico pode reduzir a gravidade da pancreatite aguda. Para testar esta possibilidade foram estudados 116 ratos da raca Wistar distribuidos em 4 grupos: Grupo I - ratos em jejum que recebiam doses supramaximas de ceruleina (8µg/Kg). Grupo II - ratos controles em jejum. Grupo III - ratos com alimentacao normal que recebiam doses fisiologicas de ceruleina (0,4 µg/Kg). Grupo IV - ratos controles com alimentacao normal. Observou-se reducao de 60 por cento do conteudo enzimatico do pancreas nos ratos do grupo I e tambem de 60 por cento nos ratos do grupo III, porem observou-se elevacao de catepsina B no grupo I. A mortalidade, apos inducao de pancreatite aguda pela injecao intraductal de acido taurocolico, foi de 60 por cento no grupo I, 56 por cento no grupo II, 23 por cento no grupo III e 34 por cento no grupo IV. Estes resultados sugerem que a gravidade da pancreatite aguda depende de um lado do conteudo de enzimas do pancreas e de outro da ativacao de catepsina.

Radionuclide evaluation of enterogastric reflux using caerulein to stimulate biliary excretion

O refluxo biliar desempenha um importante papel na patogenia da esofagite, gastrite e úlcera gástrica. Recentemente, um método utilizando radioisótopos tem sido empregado como o mais fisiológico na avaliaçäo desta condiçäo. No presente artigo, estudou-se o refluxo enterogástrico, empregando o Tc-99m DISIDA em 37 pacientes em várias situaçöes, a saber: esofagite de refluxo, úlcera péptica, ressecçöes gástricas, vagotomia gástrica proximal e colecistite crônica calculosa. Em 19 pacientes, o esvaziamento vesicular foi estimulado com uma dieta hipercalórica altamente concentrada e nos restantes com a injeçäo endovenosa de 5 ng/kg (14 casos) ou 50 ng/kg de ceruleína. Os resultados obtidos sugerem que a injeçäo endovenosa de ceruleína nas doses de 5 ou 50 ng/kg está associada com refluxo enterogástrico significativo

Colecistograma ultra-sonográfico com ceruletide intramuscular / Ultrasonographic cholecystogran with intramuscular ceruletide

Foram estudados 13 pacientes, com idades de 19 a 30 anos (média 24,4), sete do sexo feminino e seis do masculino, sem afecçäo orgânica digestiva alta demonstrável, submetidos a exame ultra-sonográfico da vesícula biliar em jejum e 20 minutos após 300 ng/kg de ceruletide IM, sem administraçäo prévia de contraste iodado. Os cálculos volumétricos demonstraram resposta motora vesícular com esvaziamento de 67,27% + ou - 18,65, aos 20 minutos, em relaçäo aos volumes vesiculares de jejum de 18,00 ml + ou - 4,99. Näo foram detectados sinais de lesöes orgânicas e de esforço anormal de contraçäo vesicular à ultra-sonografia ou efeitos colaterais decorrentes da aplicaçäo intramuscular de ceruletide