Surgery
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We previously demonstrated that therapy with a new endothelin A receptor antagonist (ET-RA) significantly reduced mortality rates in severe acute pancreatitis (AP) in the rat without attenuating local signs of disease severity (intrapancreatic protease activation, acinar cell necrosis). This raised the question as to why ET-RA was so effective. The purpose of this study was to assess the effect of ET-RA on microcirculation (particularly capillary permeability) within and outside of the pancreas on intravascular fluid loss and extravascular fluid sequestration and on distant organ function. ⋯ Improved microcirculation and stabilized capillary permeability in ET-RA-treated animals together with reduced intravascular fluid loss and extravascular fluid sequestration and improved renal and pulmonary function (1) may explain improved survival in this model, (2) support the hypothesis that systemic disease sequelae significantly contribute to outcome in AP, and (3) suggest that ET-RA may be a promising therapeutic tool in AP because it counteracts microcirculatory disorders that contribute to pancreatitis-associated organ dysfunction even when therapy is delayed to a point at which pancreatic injury may no longer be influenced.