Evaluation of inflammatory cytokines as prognostic markers in experimental acute pancreatitis in rats

Background: Early evaluation of the severity of acute pancreatitis requires measurements of many variables. Clinical parameters as well as CT scan have traditionally been used as predictors of severity, and complications. None of them however can predict the outcome early and reliably. Inflammatory cytokines were shown to play an important role in the inflammatory cascade, which occurs early in the course of the disease. The aim of the present study is to evaluate the predictive value of plasma interleukin-6 (IL-6) and interleukin-1 (IL-1) levels in experimental pancreatitis in rats. Methods: Male wistar rats were anesthetized and pancreatitis was induced by intraparenchymal injection of 5% (group 2) and 10% (group 3) sodium taurocholate (TC), resulting in 2 distinct groups of severity. In sham controls (group 1), saline was injected into the pancreas in the same fashion. Blood samples were obtained before and 2, 4, 24, and 96 hours after the induction of pancreatitis and plasma amylase, lipase, LDH, IL-1 and IL-6 levels were measured. Mortality was recorded every 8 hours. Pancreatitis severity was also assessed by histopathology. Results: Four hours after pancreatitis induction, plasma amylase, lipase and LDH levels were markedly increased in the pancreatitis groups. In the sham control group, moderate increases were also observed. No consistent significant difference in amylase, lipase or LDH levels was observed between the groups. At 2 hours from pancreatitis induction, IL-6 levels increased mildly in-groups 1 and 2, and decreased to the baseline levels at 24 hours. In-group 3, the increase in IL-6 levels was significantly higher then in-groups 1 and 2 (p=0.029 and 0.036 respectively), and correlated well with pancreatitis severity as defined by pathology (p=0.01) and mortality rates (p=0.037). No difference in IL-1 levels was observed at 2,4 and 24 hours from induction. At 96 hours IL-1 levels were higher in group 3 then in groups 1 and 2 (p=0.037). Conclusion: IL-6 plasma levels correlated well with the severity of the disease as reflected by the mortality rates and pathological score. IL-6 levels may be a reliable predictor of severity and mortality in acute pancreatitis. This marker can be used as early as 2 hours and up to 24 hours from the beginning of the inflammatory process. IL-1 levels at 96 hours also correlated with pathology, but were not found to predict outcome at the early phases of the disease.

The effect of the somatostatin analogue octreotide on experimental intestinal obstruction in rats

Background: Somatostatin has an inhibitory effect on the endocrine and exocrine secretions of the gut. It may have a beneficial effect in the conservative treatment of intestinal obstruction. The aim of the present study is to investigate the effect of octreotide in mechanical intestinal obstruction in rats. Method: Intestinal obstruction was induced in rats by ligation of a segment of the distal ileum. Animals were treated with the somatostatin analogue octreotide (n=16), or saline (n=16). Eight rats were operated but their intestine was not ligated (n=8) serving as sham controls. Forty eight hours after the operation, the animals were operated upon again and blood samples from the femoral vein were tested for electrolytes, urea, glucose, lactic acid, amylase, ph and bicarbonate. Portal vein blood samples were also obtained and tested for lactic acid and amylase. Results: Intestinal obstruction resulted, after 48 hours, in severe dilatation of bowel loops. A significant increase in plasma levels of urea, amylase and lactic acid was observed. Plasma pH decreased. In blood samples from the portal vein, a significant increase in lactic acid was observed, indicating metabolic acidosis, probably secondary to bowel ischemia. Octreotide treatment, resulted in less acidosis, with concomitant lower urea and lactic acid levels in the plasma and especially in the portal vein. Conclusion: Octreotide treatment may have a beneficial effect in the conservative treatment of selected cases of intestinal obstruction.

Objetivo: A somatostatina tem efeito inibidor nas secrees endcrina e excrina do intestino. Poderß ter efeito benfico no tratamento conservador da obstruo intestinal. O objetivo do presente estudo investigar o efeito do octreotide na obstruo mecnica do intestino delgado de ratos. Mtodo: A obstruo intestinal foi induzida em ratos pela ligadura do segmento distal do ileum. Os animais foram tratados com somatostatina anßloga octreotide (n=16) ou com soluo salina (n=16). Oito ratos foram operados mas o intestino delgado no foi ligado (n=8) servindo como o grupo sham. Quarenta oito horas aps a operao os animais foram re-operados e submetidos a colheita de sangue da veia femoral a fim de verificar os eletrlitos, uria, glicose, ßcido lßtico, amilase, pH e bicarbonato. Obteve-se tambm amostra de sangue da veia porta para verificar os nveis de ßcido lßtico e amilase. Resultados: Aps 48 horas de obstruo houve intensa dilatao das alas intestinais. Observou-se aumento significante dos nveis plasmßticos de uria, amilase e ßcido lßtico. Diminuiu o pH plasmßtico. Observou-se aumento do ßcido lßtico no sangue portal, indicando acidose metablica, provavelmente secundßria a isquemia intestinal. O tratamento com octreotide resultou em menos acidose, com nveis baixos de uria e ßcido lßtico no plasma, e especialmente na veia porta. Concluso: O emprego de octreotide pode ter efeito benfico no tratamento conservador de casos selecionados de obstruo intestinal.

Effect of the somatostatin analogue octreotide (SMS201-995) on portal and mesenteric blood flow in rats

Várias investigaçöes revelaram que a somatostatina e análogas baixam o fluxo sanguíneo esplâncnico e portal em cirróticos e em modelos experimentais de hipertensäo portal. Tem sido experimentado habitualmente no tratamento de varizes sangrantes. O mecanismo pelo qual o hormônio age permanece obscuro. No presente estudo investigou-se o efeito da açäo prolongada do octreotide, somatostatina análoga, no fluxo sanguíneo mesentérico e portal, em ratos sadios. A administraçäo intravenosa do octreotide näo teve efeito significante na circulaçäo esplânic. Em alguns animais registrou-se, após a infusäo inicial da droga, queda pequena no fluxo venoso portal. Infusöes adicionais näo alteraram o fluxo portal. O fluxo sangüíneo mesentérico superior permaneceu inalterado. Conclui-se que o octreotide näo influiu na circulaçäo espâncnica, em ratos sadios, e que novos estudos se fazem necessários para explicar os seus efeitos em modelos de hipertensäo portal