Local inflammatory and thrombotic responses differ in a murine model of partial and complete hindlimb ischemia/reperfusion

Mark F. Conrad, David H. Stone, Hassan Albadawi, Hong T. Hua, Fateh Entabi, Michael C. Stoner, Michael T. Watkins

Research output: Contribution to journalArticle

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Abstract

Background. These experiments were designed to quantitatively compare the patterns of tissue thrombosis, cytokine response, and tissue viability in a murine model of partial (PI) versus complete hindlimb ischemia (CI), alone or with reperfusion (RE). Methods. The control tension tourniquet was used to establish either PI or CI in the unilateral mouse hindlimb for 3 hours followed by 0, 4, and 24 hours of RE. Muscle viability, local neutrophil chemoattractant protein, interleukin 6, interleukin 1β, D-dimer, thrombin-antithrombin III complex, plasminogen activator inhibitor 1, and tissue plasminogen activator levels were measured in protein extracts for each experimental interval. Results. Tissue viability after CI and 24 hours of RE was significantly less than tissue subjected to PI and 24 hours of RE (96% ± 16 PI, 64% ± 4 CI, P = .02). The local cytokine response was initially elevated in the PI group but dissipated by 24RE. In contrast, the local cytokine response to CI alone was small but greatly increased by 24RE. The thrombotic response to PI was increased throughout ischemia/reperfusion. While thrombosis during CI alone was negligible, reperfusion led to a significant thrombotic response. Conclusions. Biochemical markers for tissue viability, thrombosis, and cytokine-mediated inflammation differ significantly in mice subjected to moderate and severe hindlimb ischemia/reperfusion. These biochemical markers may facilitate stratification of patients in clinical trials for treatment of ischemia/reperfusion injury and contribute to interpretation of their outcomes.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalSurgery
Volume138
Issue number2
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

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Hindlimb
Reperfusion
Ischemia
Tissue Survival
Cytokines
Thrombosis
Biomarkers
Tourniquets
Plasminogen Activator Inhibitor 1
Chemotactic Factors
Tissue Plasminogen Activator
Reperfusion Injury
Interleukin-1
Interleukin-6
Proteins
Neutrophils
Clinical Trials
Inflammation
Muscles

ASJC Scopus subject areas

  • Surgery

Cite this

Local inflammatory and thrombotic responses differ in a murine model of partial and complete hindlimb ischemia/reperfusion. / Conrad, Mark F.; Stone, David H.; Albadawi, Hassan; Hua, Hong T.; Entabi, Fateh; Stoner, Michael C.; Watkins, Michael T.

In: Surgery, Vol. 138, No. 2, 01.08.2005, p. 375-381.

Research output: Contribution to journalArticle

Conrad, Mark F. ; Stone, David H. ; Albadawi, Hassan ; Hua, Hong T. ; Entabi, Fateh ; Stoner, Michael C. ; Watkins, Michael T. / Local inflammatory and thrombotic responses differ in a murine model of partial and complete hindlimb ischemia/reperfusion. In: Surgery. 2005 ; Vol. 138, No. 2. pp. 375-381.
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N2 - Background. These experiments were designed to quantitatively compare the patterns of tissue thrombosis, cytokine response, and tissue viability in a murine model of partial (PI) versus complete hindlimb ischemia (CI), alone or with reperfusion (RE). Methods. The control tension tourniquet was used to establish either PI or CI in the unilateral mouse hindlimb for 3 hours followed by 0, 4, and 24 hours of RE. Muscle viability, local neutrophil chemoattractant protein, interleukin 6, interleukin 1β, D-dimer, thrombin-antithrombin III complex, plasminogen activator inhibitor 1, and tissue plasminogen activator levels were measured in protein extracts for each experimental interval. Results. Tissue viability after CI and 24 hours of RE was significantly less than tissue subjected to PI and 24 hours of RE (96% ± 16 PI, 64% ± 4 CI, P = .02). The local cytokine response was initially elevated in the PI group but dissipated by 24RE. In contrast, the local cytokine response to CI alone was small but greatly increased by 24RE. The thrombotic response to PI was increased throughout ischemia/reperfusion. While thrombosis during CI alone was negligible, reperfusion led to a significant thrombotic response. Conclusions. Biochemical markers for tissue viability, thrombosis, and cytokine-mediated inflammation differ significantly in mice subjected to moderate and severe hindlimb ischemia/reperfusion. These biochemical markers may facilitate stratification of patients in clinical trials for treatment of ischemia/reperfusion injury and contribute to interpretation of their outcomes.

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