ELEVATED CUTANEOUS LEUKOCYTE CONCENTRATION IN A RODENT MODEL OF ACUTEVENOUS HYPERTENSION

Background. The pathophysiologic mechanism of the skin pathology in ch ronic venous insufficiency is venous hypertension (VHTN). Microvascula r dysfunction involving leukocytes has recently been proposed as the p rimary mediator of tissue damage from VHTN. We developed a rodent mode l allowing the investigation of the effects of acute VHTN on tissue le ukocyte concentration. Materials and methods. Under general anesthesia , adult male rats underwent transperitoneal isolation of the inferior vena cava and the common iliac veins and arteries, Bilateral thigh inc isions allowed isolation of the common femoral veins and superficial e pigastric veins (SEV: distal branch of the femoral vein in the thigh). Pressure in the SEV and flow in the iliac artery were measured before (T-Pre), immediately after (T-0), and for 135 min (T-1) after ligatio n of the cava, iliac, and femoral veins. Sham rats were identical exce pt no venous ligation was performed. After the T-1 pressures were obta ined, the distal hindlimb and forelimb skin was harvested and processe d to measure myeloperoxidase (MPO) activity, an index of the number of tissue leukocytes. To evaluate the effect of arterial how reduction k nown to occur with acute venous ligation, the above measurements were made in an Aortic group of rats in which the aorta was manually stenos ed. Results. This venous ligation technique resulted in a significant (P < 0.05) and sustained rise in venous pressure (T-Pre, 9.91 +/- 0.94 and T-1, 26.22 +/- 2.15). Hypertensive rats had significantly elevate d hindlimb MPO activity (4.77 +/- 0.36) vs forelimb (0.60 +/- 0.39), S ham (hindlimb, 0.77 +/- 0.41; forelimb, 0.10 +/- 0.05), and Aortic (hi ndlimb, 0.96 +/- 0.38; forelimb, 0.58 +/- 0.11) controls. Conclusions. Acute VHTN was successfully created by venous ligation in this newly developed rat model. VHTN, but not arterial flow reduction, was associ ated with significantly elevated hindlimb skin MPO activity, suggestin g that leukocytes may indeed be mediators of skin pathology in VHTN. T his model will allow further investigation into the mechanisms of micr ovascular dysfunction in VHTN. (C) 1998 Academic Press.