Local inflammatory and thrombotic responses differ in a murine model of partial and complete hindlimb ischemia/reperfusion.
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 1beta, 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.
Conrad
Mark F
MF
Division of Vascular and Endovascular Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and the VA Boston Healthcare System, 02114, USA.
Stone
David H
DH
Albadawi
Hassan
H
Hua
Hong T
HT
Entabi
Fateh
F
Stoner
Michael C
MC
Watkins
Michael T
MT
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000098:blood supply; D020127:Recovery of Function; D015424:Reperfusion; D015427:Reperfusion Injury / Q000276:immunology* / Q000503:physiopathology*; D013927:Thrombosis / Q000276:immunology* / Q000503:physiopathology*; D014111:Tourniquets
D016207:Cytokines