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Protective effects of PARP inhibition on liver microcirculation and function after haemorrhagic shock and resuscitation in male rats

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Abstract

Objective

The aim of this study was to investigate the impact of the water-soluble poly-(ADP)-ribose-polymerase (PARP) inhibitor 5-aminoisoquinolinone (5-AIQ) on liver microcirculation and function after haemorrhagic shock and resuscitation.

Design

Controlled, randomized animal study.

Setting

University animal care facility and research laboratory.

Subject

Male Sprague–Dawley rats were subjected to haemorrhagic shock for 1 h, followed by resuscitation with shed blood and crystalloid solution for a total of 5 h.

Interventions

The PARP inhibitor 5-AIQ (3 mg/kg; n = 7) or vehicle (n = 7) was administered 5 min prior to resuscitation. Sham-operated animals without induction of shock served as controls (n = 7).

Measurements and results

Using intravital fluorescence microscopy hepatic microcirculation was assessed at baseline, end of shock phase as well as 1 h and 5 h after resuscitation. Systemic arterial blood pressure and bile flow were continuously monitored. 5-AIQ treatment attenuated shock/resuscitation-induced increase of intrahepatic leukocyte–endothelial cell interaction with a marked reduction of both sinusoidal leukostasis and venular leukocyte adherence. Moreover, nutritive perfusion was found improved, guaranteeing sufficient oxygen supply to tissue, as indicated by low NADH autofluorescence, which was not different to that in controls. Most notably, excretory liver function reached baseline level over 5 h of reperfusion in 5-AIQ-treated animals.

Conclusions

In the present setting of shock/resuscitation in male rats the PARP inhibitor 5-AIQ proved to be very effective in ameliorating compromised liver microcirculation and function. Further research has to confirm that PARP inhibition is a suitable tool in the acute treatment of patients suffering from reduced circulating blood volume and thus microcirculatory organ dysfunction.

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Acknowledgements

The study was supported by a grant from the University of Rostock (FORUN, 989021). The authors would like to thank B. Blendow, D. Butzlaff, D. Frenz and M. Nerowski, Department of Experimental Surgery, University of Rostock, for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Anaesthesiology and Intensive Care Medicine, University of Rostock, 18055, Rostock, Germany

    J. P. Roesner, D. A. Vagts, T. Iber & G. F. E. Nöldge-Schomburg

  2. Department of Experimental Surgery, Medical Faculty, University of Rostock, Schillingallee 70, 18055, Rostock, Germany

    C. Eipel & B. Vollmar

Authors
  1. J. P. Roesner
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  2. D. A. Vagts
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  3. T. Iber
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  4. C. Eipel
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  5. B. Vollmar
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  6. G. F. E. Nöldge-Schomburg
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Corresponding author

Correspondence to B. Vollmar.

Additional information

The results of this study were presented as an oral presentation at the 18th Annual Congress of the European Society of Intensive Care Medicine in Amsterdam, September 2005.

This article is discussed in the editorial available at:http://dx.doi.org/10.1007/s00134-006-0336-x

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Roesner, J.P., Vagts, D.A., Iber, T. et al. Protective effects of PARP inhibition on liver microcirculation and function after haemorrhagic shock and resuscitation in male rats. Intensive Care Med 32, 1649–1657 (2006). https://doi.org/10.1007/s00134-006-0335-y

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