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N-acetylcysteine Protects Striated Muscle in a Model of Compartment Syndrome

  • Basic Research
  • Basic Research
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

To avoid ischemic necrosis, compartment syndrome is a surgical emergency treated with decompression once identified. A potentially lethal, oxidant-driven reperfusion injury occurs after decompression. N-acetylcysteine is an antioxidant with the potential to attenuate the reperfusion injury.

Questions/purposes

We asked whether N-acetylcysteine could preserve striated muscle contractility and modify neutrophil infiltration and activation after simulated compartment syndrome release.

Materials and Methods

Fifty-seven rats were randomized to control, simulated compartment syndrome, and simulated compartment syndrome plus N-acetylcysteine groups. We isolated the rodent cremaster muscle on its neurovascular pedicle and placed it in a pressure chamber. Chamber pressure was elevated above critical closing pressure for 3 hours to simulate compartment syndrome. Experiments were concluded at three times: 1 hour, 24 hours, and 7 days after decompression of compartment syndrome. We assessed twitch and tetanic contractile function and tissue myeloperoxidase activity. Ten additional rats were randomized to control and N-acetylcysteine administration after which neutrophil respiratory burst activity was assessed.

Results

The simulated compartment syndrome decreased muscle contractility and increased muscle tissue myeloperoxidase activity compared with controls. Treatment with N-acetylcysteine preserved twitch and tetanic contractility. N-acetylcysteine did not alter neutrophil infiltration (myeloperoxidase activity) acutely but did reduce infiltration at 24 hours, even when given after decompression. N-acetylcysteine reduced neutrophil respiratory burst activity.

Conclusion

N-acetylcysteine administration before or after simulated compartment syndrome preserved striated muscle contractility, apparently by attenuating neutrophil activation and the resultant oxidant injury.

Clinical Relevance

Our data suggest a potential role for N-acetylcysteine in the attenuation of muscle injury after release of compartment syndrome and possibly in the prophylaxis of compartment syndrome.

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Authors and Affiliations

  1. Department of Orthopaedics, Galway University Hospitals, Newcastle Road, Galway, Ireland

    Stephen R. Kearns FRCS (Tr&Orth) & David E. O’Briain IMRCS

  2. Department of Pathology, Beaumont Hospital, Dublin, Ireland

    Katherine M. Sheehan MD

  3. Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland

    Cathal Kelly FRCSI (Gen) & David Bouchier-Hayes FRCSI

Authors
  1. Stephen R. Kearns FRCS (Tr&Orth)
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  2. David E. O’Briain IMRCS
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  3. Katherine M. Sheehan MD
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  4. Cathal Kelly FRCSI (Gen)
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  5. David Bouchier-Hayes FRCSI
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Correspondence to Stephen R. Kearns FRCS (Tr&Orth).

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed in the Royal College of Surgeons in Ireland and Beaumont Hospital.

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Kearns, S.R., O’Briain, D.E., Sheehan, K.M. et al. N-acetylcysteine Protects Striated Muscle in a Model of Compartment Syndrome. Clin Orthop Relat Res 468, 2251–2259 (2010). https://doi.org/10.1007/s11999-010-1287-7

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  • DOI: https://doi.org/10.1007/s11999-010-1287-7

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