Collateral capillary arterialization following arteriolar ligation in murine skeletal muscle.
OBJECTIVE
Chronic and acute ischemic diseases-peripheral artery disease, coronary artery disease, stroke-result in tissue damage unless blood flow is maintained or restored in a timely manner. Mice of different strains recover from arteriolar ligation (by increasing collateral blood flow) at different speeds. We quantify the spatio-temporal patterns of microvascular network remodeling following arteriolar ligation in different mouse strains to better understand inter-individual variability.


METHODS
Whole-muscle spinotrapezius microvascular networks of mouse strains C57Bl/6, Balb/c and CD1 were imaged using confocal microscopy following ligation of feeding arterioles.


RESULTS
Baseline arteriolar structures of C57Bl/6 and Balb/c mice feature heavily ramified arcades and unconnected dendritic trees, respectively. This network angioarchitecture identifies ischemia-protected and ischemia-vulnerable tissues; unlike C57Bl/6, downstream capillary perfusion in Balb/c spinotrapezius is lost following ligation. Perfusion recovery requires arterialization (expansion and investment of mural cells) of a subset of capillaries forming a new low-resistance collateral pathway between arteriolar trees. Outbred CD1 exhibit either Balb/c-like or C57Bl/6-like spinotrapezius angioarchitecture, predictive of response to arteriolar ligation.


CONCLUSIONS
This collateral capillary arterialization process may explain the reported longer time required for blood flow recovery in Balb/c hindlimb ischemia, as low-resistance blood flow pathways along capillary conduits must be formed ("arterialization") before reperfusion.
Mac Gabhann
Feilim
F
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. feilim@jhu.edu
Peirce
Shayn M
SM
D000818:Animals; D001160:Arterioles / Q000254:growth & development / Q000473:pathology; D002196:Capillaries / Q000254:growth & development / Q000473:pathology; D003097:Collateral Circulation; D004195:Disease Models, Animal; D005260:Female; D007511:Ischemia / Q000473:pathology*; D008026:Ligation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply*; D015424:Reperfusion; D013045:Species Specificity