Improvement of Impaired Microcirculation and Tissue Oxygenation by Hemodilution with Hydroxyethyl Starch plus Cell-Free Hemoglobin in Acute Porcine Pancreatitis

Abstract

Aims: To avoid the progression from mild edematous acute pancreatitis (AP) to the severe necrotizing form, one therapeutic option is to improve pancreatic microcirculation and tissue oxygenation. The aim of the study was to evaluate the influence of improved rheology (isovolemic hemodilution) plus enhanced oxygen supply (bovine hemoglobin HBOC-301) on pancreatic microcirculation, tissue oxygenation and survival in severe acute experimental pancreatitis. Methods: Severe AP was induced in 39 pigs (25–30 kg BW) by stimulation with intravenous administration of cerulein plus a pressure- and volume-controlled 10-min intraductal infusion of glycodeoxycholic acid. Seventy-five minutes after induction of AP, animals were randomized and hemodiluted isovolemically (PAOP constant) with either 10% hydroxyethyl starch (HES) 200,000/0.5 plus HBOC-301 (+0.6 g/dl plasmatic hemoglobin; Oxyglobin^®, Biopure, Cambridge, Mass., USA), or 10% HES 200,000/0.5, or Ringer’s solution to a hematocrit of 15%. Hemodynamics, oxygen transport parameters, pancreatic microcirculation and tissue oxygen tension were evaluated over 6 h. Then the abdomen was closed, animals were extubated and observed for 6 days. After that, the surviving animals were sacrificed and specimens were taken from the pancreas. The histopathologic findings were scored by two blinded pathologists who quantified acinar necrosis, fat necrosis, inflammation and edema. Results: Isovolemic hemodilution with HES plus HBOC-301 reduced mortality and preserved pancreatic microcirculation compared with Ringer’s solution, but was not significantly different from hemodilution with HES alone. Only treatment with HES plus HBOC-301 normalized pancreatic tissue oxygen tension compared with IHD with HES or Ringer’s solution alone. Conclusions: IHD with HES plus HBOC-301 as a combination of rheologic and O₂-delivering therapy may represent a novel therapeutic option for treatment of AP.