TY - JOUR
T1 - Local inflammatory and thrombotic responses differ in a murine model of partial and complete hindlimb ischemia/reperfusion
AU - Conrad, Mark F.
AU - Stone, David H.
AU - Albadawi, Hassan
AU - Hua, Hong T.
AU - Entabi, Fateh
AU - Stoner, Michael C.
AU - Watkins, Michael T.
N1 - Funding Information:
Supported by a Merit Award from the Research Service of the Veterans Administration, the VA- Department of Defense Combat Casualty Care Project; the Department of Surgery, American Diabetes Association; and the Division of Vascular and Endovascular Surgery, Massachusetts General Hospital.
PY - 2005/8
Y1 - 2005/8
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.
AB - 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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U2 - 10.1016/j.surg.2005.06.005
DO - 10.1016/j.surg.2005.06.005
M3 - Article
C2 - 16153450
AN - SCOPUS:24344469684
SN - 0039-6060
VL - 138
SP - 375
EP - 381
JO - Surgery
JF - Surgery
IS - 2
ER -