Anatomical and physiological characterization of a novel porcine model for varicose veins

Abstract

Varicose veins constitute a significant financial and social burden. Despite being well documented since Hippocrates, there is still a lack of understanding concerning both the underlying pathogenesis and the rationale of treatments of varicose veins. The management of varicose veins is marked by confusion and debate, which could benefit from well-designed experiments in a suitable animal model. Especially as the current available therapies for the treatment of varicose veins is limited by their high recurrence rates. While studying neointimal hyperplasia in arterial ends of common femoral AVF created in pig models we, at the Department of Surgery in Dunedin Hospital, observed that the pigs also developed progressive enlargement and tortuosity of the superficial veins over the medial aspect the thigh and groin. These changes in superficial veins developed into what appeared to be an extensive network of varicose veins. This novel finding has not been described to the same extent in other animal models of venous disease. Consequently, the aim of this thesis is to further characterize a porcine model of varicose veins. Eleven female domesticated large white Duroc cross pigs, aged 13-14 weeks and weights 25.1- 35 kg, were used in this research project (control pigs [n=2], surgery animals [n=9]). The first animal was used to assist in the characterisation the normal anatomy of pigs’ hind limb, the nominal saphenous vein and its relations and the sapheno- femoral junction. Each of the remaining animals had a right common femoral side to side arteriovenous fistula (AVF) fashioned by a vascular surgeon. Post-operatively the animals were assessed to document of macroscopic changes of venous vasculature, characterise the physiological changes that occur within the superficial venous system and to document any histological changes in the vessel wall. Venous hypertension was demonstrated within the superficial varicosities, 23±11.4 mmHg at the mid point of the study, and 20±8.3 mmHg at termination, while in the control it was 4.5± 3.5 mmHg. In all but one pig with an AVF there was variation in pressure, associated with the cardiac cycle. The flow velocities also demonstrated a degree of pulsatility. Overall there was both an intra-vessel and inter-animal heterogeneity to the vessel walls changes seen in the veins sampled. Finding which were consistently seen included: variable neointimal formation, medial hypertrophy, fragmentation of the medial and adventitial elastic tissue, and medial and mural atrophy. Areas of greatest intimal thickness were associated with disruption of the internal elastic lamina. A variety of valvular defects were also observed with the specimens including bilateral and unilateral elongation of cusps, and valve cusp tearing. In conclusion we describe a stable and chronic porcine AVF model of venous insufficiency, which is simple to create and closely replicates the human condition of venous insufficiency and superficial varicose veins. The formation of an AVF between the femoral vessels leads to the progressive loss of venous valve competence and the development of superficial varicosities, which demonstrated elements consistent with the human disease including venous reflux and hypertension and pathological remodeling of the vein wall. The mechanism by which these varicosities are formed appears to be a combination of retrograde flow accompanied by increased pressures within the superficial veins. With further characterisation and refinement, including assessment of ambulatory venous pressures in particular the model may contribute to both the quantitative and qualitative evaluation of the underlying disease process, including its initial onset.