Application of the bovine hemoglobin solution HBOC-301 with and without isovolemic hemodilution reduces the histopathologic damage in acute severe pancreatitis in swine

Introduction

Severe acute pancreatitis (AP) remains associated with a high mortality. In experimental AP the application of the bovine hemoglobin solution HBOC-301 with and without IHD was able to normalize pancreatic tissue oxygen tension [1, 2]. The aim of this study was to evaluate the therapeutic approach of volume therapy with HES plus HBOC-301 with and without IHD with regard to the histologic damage and survival time in pigs suffering from AP.

Methods

After approval of the local animal ethics committee 33 pigs were anesthetized (FIO2: 0.3). AP was induced by combination of cerulein and glucodeoxycholic acid. After induction of AP animals were randomized and either isovolemicly hemodiluted with 10% HES 200,000/0.5 plus HBOC-301 (+0.6 g/dl plasmatic Hb; Oxyglobin, Biopure, USA) (IHD + HBOC group) or received volume replacement without IHD with HES plus HBOC-301 (+0.6 g/dl plasmatic Hb) (HBOC group), or were hemodiluted with Ringer's solution (IHD RINGER group) to a hematocrit (Hct) of 15%. Six hours after therapy all animals were extubated, and killed after 6 days at the latest. Two 5 μm slices from the specimens of the pancreas were examined in a blinded manner using a light microscope. The histopathologic findings were scored as previously described quantifying acinar necrosis, fat necrosis, inflammation and edema on a scale from 0 to 3 points [3]. The total score was the sum of the median of two tissue areas (maximum value 24). Statistical analyses: Kruskal–Wallis and Mann–Whitney U test (P < 0.05).

Results

The histopathologic tissue damage (Table 1) was higher in the IHD RINGER group in comparison with the IHD + HBOC group and the HBOC group. The survival rate at the end of the observation period was higher in the IHD + HBOC group (10/11) and the HBOC group (8/11) in comparison with the IHD RINGER group (2/11) (P < 0.001).

Table 1 Histopathologic score (range 0–24) of two areas from the pancreas

Implications

In a former experiment application of HBOC-301 with and without IHD normalized pancreatic tissue oxygen tensions [1]. The higher tpO₂ is now reflected by less tissue damage and a better outcome. The application of HBOC-301 deserves further analysis to assess its potential in the clinical treatment of AP.