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Benefits of various dextrans after delayed therapy in necrotizing pancreatitis of the rat

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Abstract

Objective

Ultrahigh-molecular dextran (500 000 DA) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancreatitis. This study should clarify the following: (a) are dextrans still effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is their effect influenced by the dextran concentration or by the addition of hypertonic saline?

Animals and interventions

Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bile-salt infusion and intravenous hyperstimulation. After 3 h, animals were assigned to one of seven groups (n=10 per group) receiving either Ringer solution or different dextrans (10%) including 70 000 Da (DEX-70), 160 000 Da (DEX-160), 300 000 Da (DEX-300) or 500 000 Da (DEX-500). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combination with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given at 24 ml/kg and all dextrans at 8 ml/kg.

Measurements and results

Trypsinogen activation peptides (TAP) were quantified in ascites and acinar necrosis after death or sacrifice at 9 h. As an index of less pathological trypsinogen activation, the mean TAP levels in ascites were significatly lower in DEX-70 and DEX-160 compared to Ringer controls (p<0.05,t-test). Furthermore, the amount of acinar necrosis was significantly lower in all dextran groups except the HHS-70 in comparison with Ringer controls (p<0.01,t-test). Finally, mortality was significantly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p<0.03, Fisher's Exact test). There was a similar trend in all other groups except the HHS-70.

Conclusions

Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentration of dextran are of secondary importance for these beneficial effects.

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Authors and Affiliations

  1. Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany

    H. G. Hotz, H. J. Buhr, C. Herfarth, E. Klar, J. Schmidt, K. Huch & K. Mithöfer

  2. Department of Pathology, University of Heidelberg, Heidelberg, Germany

    H. P. Sinn

  3. Department of Surgery, Massachusetts General Hospital, Boston, MA, USA

    A. L. Warshaw

Authors
  1. H. G. Hotz
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  2. H. J. Buhr
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  3. C. Herfarth
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  4. E. Klar
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  5. J. Schmidt
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  6. K. Huch
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  7. K. Mithöfer
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  8. H. P. Sinn
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  9. A. L. Warshaw
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Supported by Deutsche Forschungsgemeinschaft no. Schm 781/2-1+2

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Hotz, H.G., Buhr, H.J., Herfarth, C. et al. Benefits of various dextrans after delayed therapy in necrotizing pancreatitis of the rat. Intensive Care Med 22, 1207–1213 (1996). https://doi.org/10.1007/BF01709338

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  • DOI: https://doi.org/10.1007/BF01709338

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