Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2017; 23(9): 1576-1585
Published online Mar 7, 2017. doi: 10.3748/wjg.v23.i9.1576
Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure
Karolin Thiel, Wilfried Klingert, Kathrin Klingert, Matthias H Morgalla, Martin U Schuhmann, Pamela Leckie, Yalda Sharifi, Nathan A Davies, Rajiv Jalan, Andreas Peter, Christian Grasshoff, Alfred Königsrainer, Martin Schenk, Christian Thiel
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany
Kathrin Klingert, Christian Grasshoff, Department of Anaesthesiology, Tuebingen University Hospital, Tuebingen 72076, Germany
Matthias H Morgalla, Martin U Schuhmann, Department of Neurosurgery, Tuebingen University Hospital, Tuebingen 72076, Germany
Pamela Leckie, Yalda Sharifi, Nathan A Davies, Rajiv Jalan, Institute for Liver and Digestive Health, University College London, London NW3 2PF, United Kingdom
Andreas Peter, Division of Endocrinology, Diabetology, Angiology, Nephrology, Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine, Tuebingen University Hospital, Tuebingen 72076, Germany
Author contributions: Thiel K, Klingert W, Klingert K, Morgalla MH, Schuhmann MU, Leckie P, Sharifi Y, Schenk M and Thiel C performed the animal experiments; Thiel K, Davies NA, Jalan R, Schenk M and Thiel C designed the study and coordinated the study group; Morgalla MH and Schuhmann MU contributed to the neurosurgical part of the experimental setting; Klingert K and Grasshoff C provided advice for the standardized intensive care therapy; Thiel K, Davies NA, Grasshoff C, Schenk M and Thiel C drafted the manuscript; Klingert W, Peter A and Königsrainer A helped to draft the manuscript and participated in its design; Klingert W and Schenk M carried out the biochemical and statistical analysis; Peter A supervised all biochemical and laboratory measurements; all authors read and approved the final manuscript.
Supported by TÜFF Programm, 2341-0-0.
Institutional review board statement: The study was reviewed and approved by the institutional review board for animal experiments Regierungspräsidium Tuebingen, Germany.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the institutional review board for animal experiments, Regierungspräsidium Tuebingen, Germany, approval code C3/09.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at christian.thiel@med.uni-tuebingen.de.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Christian Thiel, MD, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Hoppe-Seyler Strasse 3, Tuebingen 72076, Germany. christian.thiel@med.uni-tuebingen.de
Telephone: +49-7071-2982968 Fax: +49-7071-294943
Received: December 9, 2016
Peer-review started: December 9, 2016
First decision: January 10, 2017
Revised: January 24, 2017
Accepted: February 16, 2017
Article in press: February 17, 2017
Published online: March 7, 2017
Processing time: 87 Days and 8.2 Hours
Abstract
AIM

To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose.

METHODS

Eight pigs underwent a midline laparotomy following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study. Portal blood flow, hemodynamic and ventilation parameters were continuously recorded. Laboratory parameters were analysed every eight hours. Liver biopsies were sampled every 24 h following intoxication and upon autopsy.

RESULTS

Acute liver failure (ALF) occurred after 28 ± 5 h resulted in multiple organ failure and death despite maximal support after further 21 ± 1 h (study end). Portal blood flow (baseline 1100 ± 156 mL/min) increased to a maximum flow of 1873 ± 175 mL/min at manifestation of ALF, which was significantly elevated (P < 0.01). Immediately after peaking, portal flow declined rapidly to 283 ± 135 mL/min at study end. Thrombocyte values (baseline 307 × 103/µL ± 34 × 103/µL) of intoxicated animals declined slowly to values of 145 × 103/µL ± 46 × 103/µL when liver failure occurred. Subsequent appearance of severe thrombocytopenia in liver failure resulted in values of 11 × 103/µL ± 3 × 103/µL preceding fatality within few hours which was significant (P > 0.01).

CONCLUSION

Declining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model.

Keywords: Acetaminophen intoxication; Acute liver failure; Portal blood flow; Thrombocytopenia; Animal model; Porcine model

Core tip: It still remains difficult to predict the outcome in patients with acute liver failure (ALF). Therefore we aimed to investigate the clinical course of portal blood flow (PBF) and changes in thrombocyte count in a porcine model of acetaminophen induced ALF. At manifestation of ALF, PBF increased maximally, followed by a rapidly decline until death due to multiple organ failure. In addition, thrombocytes values declined slowly at the onset of ALF. In the early ALF course, a second decline appeared 8 h after ALF escalating to a more severe thrombocytopenia after 16 h in ALF preceding fatality within few hours.