Differential necrosis despite similar perfusion in mouse strains after ischemia.
BACKGROUND
Numerous mouse models have been used to study the tissue response to ischemia, but multiple technical differences make comparisons difficult. We have comprehensively characterized the mouse hind limb ischemia model and determined how different genetic backgrounds of mice affect recovery.


METHODS
Severity of tissue necrosis and restoration of perfusion after femoral artery excision or femoral artery transection, using five different surgical procedures, were evaluated using laser Doppler imaging in a mouse model of hind limb ischemia. Severity of necrosis was concurrently measured using a five-point scale.


RESULTS
Significant differences were observed depending upon the surgical procedure used to initiate ischemia as well as the strain of mouse used. First, a progressively delayed and incomplete recovery of vascular perfusion occurred in relation to the anatomical position and extent of the arterial defect. Second, among mouse strains, the severity of tissue necrosis varied despite similar restoration of perfusion. Thus, DBA/1J mice had significantly increased severity and incidence of tissue loss as compared with either C57Bl/6J (P = 0.01) or BALB/c (P = 0.01) mice. Finally, contrary to previous reports, T-cell-mediated immune events did not modify ischemia-induced hind limb perfusion and necrosis as responses in nude mice were not different than controls on either BALB/c or C57Bl/6J backgrounds.


CONCLUSIONS
Surgical approach, mouse strain, and measures of hind limb perfusion and tissue injury are crucial considerations in the study of ischemia. Understanding how different genetic backgrounds in mice can affect necrosis may provide insights into the diverse healing responses observed in humans.
Shireman
Paula K
PK
The South Texas Veterans Health Care System, San Antonio, Texas 78229, USA. shireman@uthscsa.edu
Quinones
Marlon P
MP
D000792:Angiography; D000818:Animals; D003097:Collateral Circulation; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000601:surgery; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009336:Necrosis; D010477:Perfusion; D012720:Severity of Illness Index; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014463:Ultrasonography