Perflubron-Emulsion - A Novel Therapeutic Tool for Enhancing Microcirculation in Acute Pancreatitis
Abstracts
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Background: Microcirculatory disorders (MCD) in severe acute pancreatitis (AP) are not confined to the pancreas but can also be found in other organs (e.g. colon, liver, lungs), where they contribute to AP-associated multiple organ dysfunction syndrome (MODS). Therapy aimed at enhancing microcirculation has been shown to ameliorate MODS even when therapy is delayed to a point at which pancreatic necrosis can no longer be influenced. Thus, research on novel methods for enhancing microcirculation is of particular interest in AP. Objective: To evaluate the effect of a novel perfluorochemical oxygen carrier in AP and compare it with an established method for enhancing microcirculation, i.e. isovolemic hemodilution (HD). Method: Six hours after induction of severe AP by intraductal bile salt infusion and i.v. cerulein, 18 rats were randomized into 3 groups (6 animals each) for therapy with [SAL]: 5ml/kg normal saline i.v. (untreated controls); [HD]: isovolemic hemodilution by exchange of 8ml/kg blood for hydroxyethylstarch, or [OXY]: 5ml/kg perfluobron emulsion i.v. (3g/kg OxygentTM, Alliance Pharmaceutical Corp. San Diego). At 24 hours intravital microscopic determination of pancreatic and colonic capillary blood flow (CBF). Additional monitoring included measurement of heart rate, arterial blood pressure and blood gases, hematocrit, and urine output. Results: Hemodilution therapy significantly reduced hematocrit (33+/-2 vs. 44+/-2 % in saline-treated controls) and improved CBF in the pancreas (1.8+/-0.1 vs. 1.3+/-0.1 nl/min) and colon (1.6+/-0.1 vs. 1.3+/-0.1 nl/min). This was associated with a stabilization of cardiorespiratory parameters (RRsys 112+/-17 vs. 94+/-8 mmHg; 02 saturation 95+/-2 vs. 81+/-9%). Therapy with Oxygent had comparable beneficial effects on microcirculation and cardiorespiratory parameters (pancreatic and colonic CBF 1.7+/-0.1 nl/min; RRsys 115+/-15mmHg; 02-Sat. 96+/-2%) without reducing hematocrit (43+/-2%). Conclusion: Perfluorochemical oxygen carriers may be an option for enhancing microcirculation and stabilizing organ function in severe acute pancreatitis Further studies will evaluate whether they should be used instead of or in combination with hemodilution. |
