Enoxaparin Does Not Ameliorate Limb Ischemia-Reperfusion Injury

Thomas A. Abbruzzese, Hassan Albadawi, Jeanwan Kang, Virendra I. Patel, Jin Hyung Yoo, Glenn M. LaMuraglia, Michael T. Watkins

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: Since low molecular weight heparin has greater bioavailability and sustained serum levels in vivo than unfractionated heparin, it has been used to supplant unfractionated heparin to achieve therapeutic anticoagulation in humans. These studies were designed to determine whether treatment with enoxaparin could protect murine skeletal muscle from ischemia reperfusion injury. Methods: C57BL6 mice were divided into four groups. Sham control animals underwent 90 min of anesthesia alone. All other groups underwent 90 min of unilateral hindlimb ischemia. At the onset of reperfusion, animals received either normal saline (control and saline) or 4 mg/kg of enoxaparin subcutaneously twice daily. Groups were followed for 24 or 48 h reperfusion. Hindlimb skeletal muscle blood flow was measured by laser Doppler, and muscle was removed for histological and protein analysis. Tissue thrombosis was evaluated by thrombin antithrombin III (TAT III), local inflammation by measurement of proinflammatory cytokines (macrophage inflammatory protein-2: MIP-2, monocyte chemoattractant protein-1: MCP-1), and neutrophil infiltration by myeloperoxidase (MPO) using enzyme-linked immunosorbent assay. Plasma levels of Factor Xa were measured during reperfusion to confirm therapeutic levels of anticoagulation. Comparisons were calculated using analysis of variance. Results: At 24 h reperfusion, there was increased expression of MIP-2, MCP-1, MPO, and TAT III in saline and enoxaparin treated mice compared with control (*P < 0.05). By 48 h reperfusion, all parameters measured remained greater than control except for the enoxaparin treated mice whose TAT III levels were significantly less than untreated mice (P < 0.05). Despite documented therapeutic anticoagulation and decreased levels of markers of thrombosis in enoxaparin treated mice, there was no difference in tissue cytokines, inflammatory markers, degree of muscle fiber injury (31% ± 8% versus 30% ± 5%) or muscle flow between ischemia-reperfusion groups (2447 ± 141 versus 2475 ± 74 flux units) at 48 h reperfusion. Conclusions: Post hoc administration of enoxaparin did not affect local tissue thrombosis, inflammatory markers, or muscle necrosis. This suggests that despite its potent in vivo activity, enoxaparin did not modulate skeletal muscle injury, thrombosis, or inflammatory following ischemia reperfusion. enoxaparin may not be useful in mediating skeletal muscle injury when administered in a clinically relevant scenario.

Original languageEnglish (US)
Pages (from-to)260-266
Number of pages7
JournalJournal of Surgical Research
Volume147
Issue number2
DOIs
StatePublished - Jun 15 2008
Externally publishedYes

Fingerprint

Enoxaparin
Reperfusion Injury
Reperfusion
Extremities
Antithrombin III
Skeletal Muscle
Thrombosis
Thrombin
Muscles
Ischemia
Hindlimb
Peroxidase
Heparin
Wounds and Injuries
Chemokine CXCL2
Cytokines
Factor Xa
Neutrophil Infiltration
Chemokine CCL2
Low Molecular Weight Heparin

Keywords

  • cytokines
  • heparin
  • ischemia
  • reperfusion
  • skeletal muscle

ASJC Scopus subject areas

  • Surgery

Cite this

Abbruzzese, T. A., Albadawi, H., Kang, J., Patel, V. I., Yoo, J. H., LaMuraglia, G. M., & Watkins, M. T. (2008). Enoxaparin Does Not Ameliorate Limb Ischemia-Reperfusion Injury. Journal of Surgical Research, 147(2), 260-266. https://doi.org/10.1016/j.jss.2008.03.024

Enoxaparin Does Not Ameliorate Limb Ischemia-Reperfusion Injury. / Abbruzzese, Thomas A.; Albadawi, Hassan; Kang, Jeanwan; Patel, Virendra I.; Yoo, Jin Hyung; LaMuraglia, Glenn M.; Watkins, Michael T.

In: Journal of Surgical Research, Vol. 147, No. 2, 15.06.2008, p. 260-266.

Research output: Contribution to journalArticle

Abbruzzese, TA, Albadawi, H, Kang, J, Patel, VI, Yoo, JH, LaMuraglia, GM & Watkins, MT 2008, 'Enoxaparin Does Not Ameliorate Limb Ischemia-Reperfusion Injury', Journal of Surgical Research, vol. 147, no. 2, pp. 260-266. https://doi.org/10.1016/j.jss.2008.03.024
Abbruzzese, Thomas A. ; Albadawi, Hassan ; Kang, Jeanwan ; Patel, Virendra I. ; Yoo, Jin Hyung ; LaMuraglia, Glenn M. ; Watkins, Michael T. / Enoxaparin Does Not Ameliorate Limb Ischemia-Reperfusion Injury. In: Journal of Surgical Research. 2008 ; Vol. 147, No. 2. pp. 260-266.
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AU - Yoo, Jin Hyung

AU - LaMuraglia, Glenn M.

AU - Watkins, Michael T.

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