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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., Materials and 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., (Copyright 1999 Academic Press.)

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.

Purpose: To evaluate the patency and hemodynamic impact of a cryopreserved allograft venous valve transplanted to the superficial femoral vein (SFV) of a canine insufficiency model aided by a distal arteriovenous fistula (dAVF)., Methods: Eight greyhounds had intravenous hemodynamic parameters measured (venous filling time [VFT], 90% of venous refilling time [VRT90], and simulated ambulatory venous pressure [AVP]) before (T0) and after complete hindlimb venous valvulotomy (T1) to produce venous insufficiency. Simultaneously, a valve-containing vein segment was harvested from the opposite SFV or external jugular vein (n = 1) and cryopreserved. Three weeks later a blood type-matched cryopreserved valve was transplanted to the insufficient SFV aided by a low-flow (n = 4) or high-flow (n = 4) dAVF. The fistula was ligated in 3 to 6 weeks, and venous indexes (T2) were obtained 3 weeks later. Analysis of variances compared the venous indexes at T0, T1, and T2 for statistical significance. Gross and histologic inspection assessed valve integrity., Results: Two valves aided by a low-flow dAVF exhibited thrombosis and scarring. The hemodynamics of the six remaining valves demonstrated normalization of the VRT90, an AVP consistent with insufficiency, and a VFT between normal and total venous insufficiency. The patent valves were normal on gross examination and by histologic examination with signs of normal external healing., Conclusions: A cryopreserved venous valve allograft transplanted to the SFV of an incompetent hindlimb partially corrects venous hemodynamics. A high-flow arteriovenous fistula most consistently preserves transplant patency.

Purpose: The objectives were to transplant a venous valve into the popliteal vein of a canine insufficiency model that would maintain long-term function and then to measure the hemodynamic benefit of such a valve., Methods: Indexes of venous valvular function, including venous filling time, 90% of venous refilling time, and simulated ambulatory venous pressure, were measured in 11 greyhounds before intervention (Control) and after hind limb venous valvulotomy, which produces chronic venous insufficiency. Three weeks later a valve-containing segment of external jugular vein was transplanted to the popliteal vein with (n = 6) or without (n = 5) a distal arteriovenous fistula. The fistula was ligated in 4 to 6 weeks. Repeat venous indexes were obtained an average of 2 weeks after the last operative intervention. Gross anatomic inspection +/- duplex scanning performed before the animals were killed were used to distinguished normal from damaged valves., Results: Four of five simple valve transplants demonstrated scarring and/or thrombosis and the average venous filling time, ambulatory venous pressure, and 90% of venous refilling time were consistent with chronic venous insufficiency and/or obstruction. One fistula failed in the six valve distal arteriovenous fistula transplants, and that valve was incompetent. Analysis of the remaining five functional valves demonstrated venous filling time consistent with chronic venous insufficiency, normalization of ambulatory venous pressure, and 90% of venous refilling time between normal, and chronic venous insufficiency. These valves appeared normal., Conclusions: Popliteal vein valve transplant anatomy is preserved by an adjunctive distal arteriovenous fistula, and a competent valve transplant improves postexercise venous hemodynamics to approach those of a normal limb.

Continued study of a chronic deep venous insufficiency (CDVI) model allows optimal comparison with the human condition. This study evaluates the model's long-term stability, its lack of observed clinical effect, and a simulated exercise study as a physiologic estimate of normal hindlimb walking. The time to maximal ankle venous pressure after standing (VFT), and to 90% of the venous refilling time after electrical stimulation, quadripedal, or hindlimb walking (VRT90), and the minimal pressure after exercise (AVP) were measured up to 10 months after CDVI model creation. The animals' intravenous resting pressure was obtained after standing stationary on all four limbs. Analysis of variance was used to determine statistical significance where indicated. VFT, AVP, and VRT90 measurements demonstrated values consistent with CDVI in animals studied up to 10 months after model creation and were statistically different from control limb values (p < or = .002, n = 8). Animals studied during quadripedal walking showed no difference in resting pressure, AVP, and VRT90 between model and control limbs (n = 5). There was no statistical difference in AVP or VRT90 measured under conditions of stimulated exercise or bipedal walking; and both conditions produced hemodynamic changes consistent with CDVI (n = 5). This animal model is a reliable long-term CDVI hemodynamic model. The normal venous hemodynamics recorded during quadripedic walking may explain the lack of clinical sequelae observed in this model. Lastly, the method of simulated exercise used in this study is a reliable test that reflects physiologic measurements obtained during bipedal walking.

This report evaluates the ability of a single competent (native or experimental) superficial femoral vein valve to correct canine hindlimb venous insufficiency. The time to maximal ankle venous pressure after standing (VFT) and to 90% of that time after exercise (VRT90), and the minimal pressure after exercise (AVP) were measured in 17 greyhounds before intervention, after only the superficial femoral vein valve remained (n = 5), and after complete lower limb venous valvulotomy (n = 17). Three weeks later, 12 dogs underwent a native (n = 4) or experimental (n = 8) autogenous venous valve transplantation. Immediately and at 3 weeks after transplantation, venous pressure measurements were obtained. The manual strip test confirmed valve competence at the time of sacrifice. Only one valve transplant became incompetent. Immediately after single superficial femoral vein valve construction, VFT, AVP, and VRT90 measurements were not significantly different from normal. Three weeks after transplantation the AVP measurements were consistent with an insufficient venous system, whereas the VRT90 measurements were between and statistically different from both the control and totally incompetent system (p less than 0.05). After the native valve but not the experimental valve transplantations VFT normalized. These data suggest that insertion of a single competent superficial femoral vein valve into an incompetent lower limb venous system corrects venous pressure measurements initially but soon provides only a partially competent system. The experimental valve, although competent, is less responsive than a native valve.

To develop a large-animal model of chronic venous valve incompetence, 13 greyhound dogs underwent unilateral hindlimb venous valve lysis with a valve cutter apparatus pulled retrograde through the iliac, femoral, and lateral saphenous veins. Bilateral venous pressures in the lateral saphenous vein were recorded before valve lysis, immediately after valve lysis, and at intervals from 1 to 14 weeks after valve lysis, with the dogs in the supine position and elevated 80 degrees semierect, as well as after stimulated hindlimb muscle contraction to empty the hindlimb veins. Passive venous filling time with elevation and 90% venous refilling time after muscle contraction were calculated. From immediately after through 14 weeks after valve lysis, a shortened venous filling time and 90% venous refilling time as well as an elevated poststimulation venous pressure were noted. This valve lysis method successfully produced a hemodynamically verified model of venous valvular insufficiency.

A short-term canine model of lower extremity venous hypertension was created to study the hemodynamics of crossfemoral venous bypass grafts (CFB). Specifically, the hemodynamic effects of bypass conduit diameter and adjunctive arteriovenous fistulas (AVFs) were investigated. Unilateral hind limb venous hypertension was produced by iliofemoral venous ligation in six groups of five greyhounds each. Group I had venous ligation alone. CFBs were constructed in the remaining five groups: group II, 3 mm bypass conduit alone; group III, 3 mm bypass plus sequential AVF; group IV, 3 mm bypass plus caudad AVF; group V, 3 mm bypass plus cephalad AVF; group VI, 6 mm bypass conduit alone. Venous hypertension was significantly reduced by CFB (group II, p less than 0.025; group VI, p less than 0.001); increasing the diameter of the bypass conduit from 3 to 6 mm produced significantly greater graft flow (p less than 0.05), while completely relieving venous hypertension. Addition of adjunctive AVFs significantly augmented graft flow (p less than 0.001) but tended to aggravate ipsilateral venous hypertension (group III, p less than 0.01; group IV increase, NSS; group V, p less than 0.001). During the 4 hours of pressure monitoring, venous hypertension diminished significantly (p less than 0.05) with the sequential AVF but not with the other AVF. We conclude that (1) AVFs may be required for adequate graft flow if a small-diameter (3 mm) bypass conduit is used to relieve venous hypertension; (2) adjunctive AVFs aggravate venous hypertension; (3) sequential AVFs seem to be the most hemodynamically efficacious; (4) AVFs may not be necessary if a large, isodiametric (6 mm) conduit is used.