Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension.

Bergan JJ, Pascarella L, Schmid-Schönbein GW. Department of Surgery, University of California-San Diego, 9850 Genesee, La Jolla, CA 92037, USA.

Background: Reflux of blood through incompetent venous valves is a major cause of the venous hypertension that underlies clinical manifestations of chronic venous disease, including varicose veins, lipodermatosclerosis, and venous ulcers.

Objective: To review published literature relating to animal models in which venous hypertension has been produced and which have yielded information on the mechanisms by which venous hypertension may trigger inflammation and cause changes in the skin and venous valves.

Methods: Medline searches, with additional papers identified from reference lists in published papers.

Results: At least three types of animal model were identified that have contributed to a better understanding of the trigger mechanisms and role of inflammatory processes in chronic venous disease. These models involve venous hypertension induced either by acute venular occlusion, placement of a chronic arteriovenous fistula, or ligation of several large veins. Model results suggest that elevated venous pressure and altered flow can trigger inflammatory cascades in the vein wall and venous valves which can cause progressive valvular incompetence and eventual valvular destruction, and which are also important in the skin changes associated with venous disease. Treatment with agents that reduce oxidative stress by scavenging free radicals and that inhibit the inflammatory cascade can prevent the progressive deterioration of function in valves exposed to elevated venous pressure and can prevent the development of reflux blood flow.

Conclusion: Understanding these processes suggests potential therapeutic targets that could be effective in slowing or preventing progression, and could help promote a more positive and proactive attitude towards treatment of the underlying disease process, rather than the later manifestations of chronic venous disease.

J Vasc Surg. 2008 Jan;47(1):183-92.