Elevated Cutaneous Leukocyte Concentration in a Rodent Model of Acute Venous Hypertension

• Published in: The Journal of surgical research 1998-01, Vol.74 (1), p.59-63
• Main Authors: Lalka, Stephen G., Unthank, Joseph L., Nixon, J.Craig
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Adhesion; Cell Count; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Hypertension - complications; Hypertension - pathology; Hypertension - physiopathology; leukocyte; Leukocytes - enzymology; Leukocytes - pathology; Ligation; Male; Medical sciences; Microcirculation - physiopathology; microvascular dysfunction; Peroxidase - metabolism; Rats; Rats, Wistar; Skin - blood supply; Skin - enzymology; Skin - pathology; Veins - physiopathology; venous hypertension; Venous Insufficiency - etiology; Venous Insufficiency - pathology; Venous Pressure
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1997.5189

Background.The pathophysiologic mechanism of the skin pathology in chronic venous insufficiency is venous hypertension (VHTN). Microvascular dysfunction involving leukocytes has recently been proposed as the primary mediator of tissue damage from VHTN. We developed a rodent model allowing the investigation of the effects of acute VHTN on tissue leukocyte 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 incisions allowed isolation of the common femoral veins and superficial epigastric 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 ligation of the cava, iliac, and femoral veins. Sham rats were identical except no venous ligation was performed. After the T-1 pressures were obtained, the distal hindlimb and forelimb skin was harvested and processed to measure myeloperoxidase (MPO) activity, an index of the number of tissue leukocytes. To evaluate the effect of arterial flow reduction known to occur with acute venous ligation, the above measurements were made in an Aortic group of rats in which the aorta was manually stenosed. 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 elevated hindlimb MPO activity (4.77 ± 0.36) vs forelimb (0.60 ± 0.39), Sham (hindlimb, 0.77 ± 0.41; forelimb, 0.10 ± 0.05), and Aortic (hindlimb, 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 associated with significantly elevated hindlimb skin MPO activity, suggesting that leukocytes may indeed be mediators of skin pathology in VHTN. This model will allow further investigation into the mechanisms of microvascular dysfunction in VHTN.