Hepatic perfusion changes in mice livers with developing colorectal cancer metastases.
OBJECTIVE
To evaluate whether intrahepatic flow alterations occur during formation of hepatic colorectal cancer metastases and to identify possible causes of these alterations.


METHODS
Intravital imaging of exteriorized livers was performed in 72 live mice. Three groups of mice were studied: a sham-operated control group (n = 24), a group with nonmetastasizing subcutaneous gliomas (n = 24), and a group with developing hepatic CX-1 colon cancer metastases (n = 24). Microvascular flow parameters, leukocyte-endothelial interactions, and wall shear stress were directly measured in hepatic sinusoids and postsinusoidal venules at 2-day intervals prior to and during the development of metastases. The Kruskal-Wallis test was used initially to test for overall equality of medians in each data group. Single posttest comparisons of independent samples were performed with the Mann-Whitney test, with an overall statistical significance of .05.


RESULTS
Prior to the development of visible colorectal cancer metastases, significant (P <.05) reductions occurred in sinusoidal and postsinusoidal flow and wall shear rates, coupled with increased leukocyte rolling and adherence. With tumor growth, flow was further compromised in 92% of tumors larger than 0.5 mm in diameter by extrinsic compression of sinusoids and portal venules and narrowing caused by adherent leukocytes.


CONCLUSIONS
Significant intrahepatic flow alterations occur in mouse livers prior to growth of visible metastases and provide a rational explanation for elevation in the Doppler perfusion index that occurs prior to tumor formation.
Kruskal
Jonathan B
JB
Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 1 Deaconess Rd, West Campus 302B, Boston, MA 02215, USA. jkruskal@bidmc.harvard.edu
Thomas
Peter
P
Kane
Robert A
RA
Goldberg
S Nahum
SN
D000818:Animals; D002450:Cell Communication; D015179:Colorectal Neoplasms / Q000473:pathology*; D042783:Endothelial Cells / Q000502:physiology; D006439:Hemodynamics; D007962:Leukocytes / Q000502:physiology; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000098:blood supply* / Q000503:physiopathology / Q000556:secondary*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012039:Regional Blood Flow