Small Animal Models of Hemorrhagic Shock–Induced Liver Dysfunction

Inge Bauer1, Michael Bauer1

1 University of the Saarland, Homburg, Germany
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 14.3
DOI:  10.1002/0471140856.tx1403s11
Online Posting Date:  May, 2002
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


Blood loss and ensuing circulatory failure continues to be the leading cause of death between the ages of 1 and 45 in most western countries. Hepatocellular dysfunction is a key feature of the pathophysiological sequelae of trauma/hemorrhage in patients surviving the first hours and hemorrhagic hypotension has been widely used as a model for indirect liver injury in the critically ill. This unit describes a low‐flow ischemia model of the liver due to hemorrhagic hypotension that can be used to produce a reproducible and graded injury to the pericentral region of the acinus, which is critical for metabolism of xenobiotics. This protocol allows for measurement of cardiac output and regional flow.

PDF or HTML at Wiley Online Library

Table of Contents

  • Basic Protocol 1: Inducing Hemorrhagic Shock
  • Support Protocol 1: Measurement of Cardiac Output and Regional Flow
  • Support Protocol 2: Coating of Polyethylene Tubing with TDMAC
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
PDF or HTML at Wiley Online Library


Basic Protocol 1: Inducing Hemorrhagic Shock

  • Male Sprague‐Dawley rats (≥250 g body weight)
  • Sodium pentobarbital
  • Disinfectant
  • Ringers solution; (see recipe)
  • Citrate‐phosphate‐dextrose solution; aseptically filtered (see recipe): suggested anticoagulant/whole blood ratio is 1.4:10; store at 4° to 8°C
  • Animal clippers
  • Heating pad
  • Rectal temperature probe (e.g., Thermistor 8402‐20, Cole‐Parmer Instrument)
  • Sterile surgical instruments
  • Polyethylene tubing (0.58‐mm i.d., 0.96‐mm o.d.; Intramedic PE 50, Becton Dickinson Primary Care Diagnostics), TDMAC coated (see protocol 3)
  • Pressure transducer and data acquisition system
  • 5‐ml sterile disposable syringes

Support Protocol 1: Measurement of Cardiac Output and Regional Flow

  • 2% (w/w) solution (∼1000 USP U/ml) TDMAC‐heparin (tridodecylmethylammonium heparinate; Polysciences)
  • Source of constant nitrogen flow
PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
   Bauer, M., Pannen, B.H.J., Bauer, I., Herzog, C., Wanner, G.A., Hanselmann, R., Zhang, J.X., Clemens, M.G., and Larsen, R. 1996. Evidence for a functional link between stress response and vascular control in hepatic portal circulation. Am. J. Physiol., 271:G929‐G935
   Chaudry, I.H., Wang, P., Singh, G., Hauptman, J.G., and Ayala, A. 1993 Rat and mouse models of hypovolemic‐traumatic shock. In Pathophysiology of Shock, Sepsis, and Organ Failure (G. Schlag and H. Redl, eds.) pp. 371‐383. Springer New York.
   Clemens, M.G. and Zhang, J.X. 1999. Regulation of sinusoidal perfusion: In vivo methodology and control by endothelins. Semin. Liver Dis. 19:383‐396
   D'Almeida, M.S., Cailmail, S., and Lebrec, D. 1996. Validation of transit‐time ultrasound flow probes to directly measure portal blood flow in conscious rats. Am. J. Physiol. 271:H2701‐H2709.
   Hauptman, J.G., DeJong, G.K., Blasko, K.A., and Chaudry, I.H. 1989. Measurement of hepatocellular function, cardiac output, effective blood volume and oxygen saturation in the rat. Am. J. Physiol. 257:R439‐R444.
   Hawker, F. 1991. Liver dysfunction in critical illness. Anaesth.Intensive Care 19:165‐181
   Penfield, W.G. 1919. The treatment of severe and progressive hemorrhage by intravenous injections. Am. J. Physiol. 48:121‐132
   Van Oosterhout, M.F., Prinzen, F.W., Sakurada, S., Glenny, R.W., and Hales, J.R. 1998. Fluorescent microspheres are superior to radioactive microspheres in chronic blood flow measurements. Am.J. Physiol. 275:H110‐H115.
PDF or HTML at Wiley Online Library