A porcine model of acute quadriplegic myopathy: a feasibility study

Authors

  • H. Norman,

    1. 1Department of Clinical Neurophysiology, Uppsala University, Sweden,2Center for Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA,3Intensive Care Unit, Division of Surgery, Ulleval University Hospital, Oslo, Norwayand 4Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
    Search for more papers by this author
  • 1 K. Kandala,

    1. 1Department of Clinical Neurophysiology, Uppsala University, Sweden,2Center for Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA,3Intensive Care Unit, Division of Surgery, Ulleval University Hospital, Oslo, Norwayand 4Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
    Search for more papers by this author
  • 2 R. Kolluri,

    1. 1Department of Clinical Neurophysiology, Uppsala University, Sweden,2Center for Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA,3Intensive Care Unit, Division of Surgery, Ulleval University Hospital, Oslo, Norwayand 4Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
    Search for more papers by this author
  • 2 H. Zackrisson,

    1. 1Department of Clinical Neurophysiology, Uppsala University, Sweden,2Center for Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA,3Intensive Care Unit, Division of Surgery, Ulleval University Hospital, Oslo, Norwayand 4Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
    Search for more papers by this author
  • 3 J. Nordquist,

    1. 1Department of Clinical Neurophysiology, Uppsala University, Sweden,2Center for Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA,3Intensive Care Unit, Division of Surgery, Ulleval University Hospital, Oslo, Norwayand 4Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
    Search for more papers by this author
  • 1 S. Walther,

    1. 1Department of Clinical Neurophysiology, Uppsala University, Sweden,2Center for Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA,3Intensive Care Unit, Division of Surgery, Ulleval University Hospital, Oslo, Norwayand 4Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
    Search for more papers by this author
  • 3 L. I. Eriksson,

    1. 1Department of Clinical Neurophysiology, Uppsala University, Sweden,2Center for Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA,3Intensive Care Unit, Division of Surgery, Ulleval University Hospital, Oslo, Norwayand 4Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
    Search for more papers by this author
  • and 4 L. Larsson 1,2

    Corresponding author
    1. 1Department of Clinical Neurophysiology, Uppsala University, Sweden,2Center for Developmental and Health Genetics, Pennsylvania State University, University Park, PA, USA,3Intensive Care Unit, Division of Surgery, Ulleval University Hospital, Oslo, Norwayand 4Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden
    Search for more papers by this author

Lars Larsson
Department of Clinical Neurophysiology
Uppsala University Hospital
SE 751 85 Uppsala
Sweden
e-mail: lars.larsson@neurofys.uu.se

Abstract

Background:  The mechanisms underlying acute quadriplegic myopathy (AQM) are poorly understood, partly as a result of the fact that patients are generally diagnosed at a late stage of the disease. Accordingly, there is a need for relevant experimental animal models aimed at identifying underlying mechanisms.

Methods:  Pigs were mechanically ventilated and exposed to various combinations of agents, i.e. pharmacological neuromuscular blockade, corticosteroids and/or sepsis, for a period of 5 days. Electromyography and myofibrillar protein and mRNA expression were analysed using sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE), confocal microscopy, histochemistry and real-time polymerase chain reaction (PCR).

Results:  A decreased compound muscle action potential, normal motor nerve conduction velocities, and intact sensory nerve function were observed. Messenger RNA expression, determined by real-time PCR, of the myofibrillar proteins myosin and actin decreased in spinal and cranial nerve innervated muscles, suggesting that the loss of myosin observed in AQM patients is not solely the result of myofibrillar protein degradation.

Conclusion:  The present porcine AQM model demonstrated findings largely in accordance with results previously reported in patients and offers a feasible approach to future mechanistic studies aimed at identifying underlying mechanisms and developing improved diagnostic tests and intervention strategies.

Ancillary