Increased hindlimb leukocyte concentration in a chronic rodent model of venous hypertension.
BACKGROUND
The pathophysiologic mechanism for tissue damage in chronic venous insufficiency (CVI) is venous hypertension (VH), the primary mediator behind leukocyte trapping in tissues. We developed a new rodent model of chronic hindlimb VH to allow testing of the microvascular dysfunction that occurs in clinical CVI.


METHODS
Hindlimb VH was created in adult rats ( approximately 350 g, male, Wistar) by ligation of the inferior vena cava, bilateral common iliac veins, and bilateral common femoral veins. In a sham group, a loose tie was placed around the same vessels. One week later, pressure catheters were placed in the right common carotid artery, right internal jugular vein (forelimb), and right superficial epigastric vein (hindlimb). Measurements were taken 15 min later, to allow for stabilization. Bilateral forelimb and hindlimb skin specimens were harvested. The myeloperoxidase (MPO) assay, an indicator of tissue leukocyte trapping, was performed using a well-described, standard technique.


RESULTS
In the chronic rats (n = 8), the hindlimb pressures (12.6 +/- 3.2 mm Hg) were significantly elevated (P < 0.05) when compared to forelimb pressures (1.75 +/- 0.71) and to chronic sham rat (n = 6) hindlimb (3.3 +/- 1.2) pressures. There was a significant (P < 0.05) elevation of MPO activity in hindlimbs of the chronic group (32.9 +/- 13.9 units) when compared to forelimbs (17 +/- 11.3) and sham hindlimbs (18 +/- 10.2).


CONCLUSIONS
In our chronic model, as in clinical studies and previous acute investigations, we have demonstrated, using an MPO assay, an increase in the amount of cutaneous leukocytes in the hindlimbs with chronic VH but not in experimental forelimbs or sham hindlimbs or forelimbs.
Hahn
T L
TL
Peripheral Vascular Surgery Section, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA.
Unthank
J L
JL
Lalka
S G
SG
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005268:Femoral Vein; D006614:Hindlimb / Q000098:blood supply*; D006973:Hypertension / Q000209:etiology / Q000473:pathology*; D007084:Iliac Vein; D007958:Leukocyte Count; D008026:Ligation; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014682:Vena Cava, Inferior; D014689:Venous Insufficiency / Q000209:etiology / Q000503:physiopathology*; D014690:Venous Pressure
D009195:Peroxidase