Effect of fluid resuscitation with and without endothelin A receptor blockade on hemoconcentration and organ function in experimental pancreatitis

Background: Intravascular fluid loss contributes to pancreatitis-associated multiple organ dysfunction and is thus a major target for therapy in this life-threatening disease. Aim: To evaluate intravascular fluid loss and ext ravascular fluid sequestration together with cardiorespiratory and renal fu nction in a well-established rat model of severe acute pancreatitis (AP) an d to investigate the effect of fluid resuscitation with and without endothe lin receptor A blockade on these parameters. Method: Induction of AP in rat s by a standardized bile salt infusion into the pancreatic duct and intrave nous cerulein hyperstimulation. Six hours after AP induction, animals were randomized into 4 groups to receive (1) no therapy; (2) 4 ml/kg/h Ringer's lactate (RL) i.v.; (3) 8 ml/kg/h RL i.v., or (4)4 ml/kg/h RL plus an endoth elin receptor antagonist. Target parameters measured before and after AP in duction and during the 24-hour observation period included: mean arterial b lood pressure, heart rate, hematocrit, arterial blood gases, urine producti on, ascites and pleural effusions. Results: After 6 h, all animals presente d with severe hemoconcentration (hematocrit >57%) and oliguria (<0.5 ml/6 h ). Cardiorespiratory parameters were within the normal range. Up to 12 h af ter AP induction, animals without therapy had an increased hematocrit and o liguria and developed metabolic acidosis. Animals receiving fluid resuscita tion had a significant drop in hematocrit and maintained compensated blood gas values. A significant increase in urine production was only observed in animals given 8 mg/kg/h RL. Between 12 and 24 h, urine production signific antly increased with fluid resuscitation and respiratory parameters stabili zed except for animals treated with 8 ml/kg/h RL which developed arterial h ypoxia and hypercapnia. Conclusions: Intravascular fluid loss and extravasc ular fluid sequestration together with decreased urine production character ize the early phase of this model of severe AP. Massive fluid resuscitation necessary for increasing urine output may lead to respiratory distress. Re duction of intravascular fluid loss by endothelin receptor blockade is asso ciated with improved renal and respiratory function. Copyright (C) 2000 S. Karger AG. Basel.