Venous valve reconstruction in patients with secondary chronic venous insufficiency.

OBJECTIVES: To evaluate the durability of venous valve reconstruction (VVR) and its benefits in terms of symptom improvement, ulcer healing and symptom/ulcer recurrence among patients with secondary chronic venous insufficiency (SCVI) in whom superficial venous surgery and compression treatment had failed. METHODS: During a ten year period (1993-2004) 1800 patients with chronic venous insufficiency (CVI) were evaluated by colour duplex ultrasound (CDU) and ambulatory venous pressure measurement (AVP). Approximately two thirds of patients had SCVI. Initial treatment consisted of compression therapy for a 6 month period. In addition, superficial vein and perforator surgery was performed in those presenting with reflux in these venous systems. 121 patients who did not improve with this treatment were investigated by ascending venography, descending video venography, air plethysmography and measurement of post-ischaemic venous pressure gradient. Thirty two cases having venous reflux without obstruction were selected for VVR. RESULTS: The ulcer healing rate within three months was 68% (13/19 patients). VVR resulted in valvular competence and a clinical success rate of 47% and 40% after 3 and 7 years respectively. In 8/13 (54%) of patients with a healed leg ulcer, a median post-operative AVP reduction of 33 mm Hg (range 20-38) was recorded. The durability of clinical success was numerically longer in patients with haemodynamic improvement (n=10) median 24 months (12-108), when compared with that in those without haemodynamic improvement (n=22) median 18 months (6-108). Popliteal vein reconstruction was part of the VVR procedure in all patients with haemodynamic improvement (post-op. AVP reduction >or=20 mm Hg). VVR at the popliteal level alone or combined with inguinal reconstruction seemed to be the one significant factor associated with haemodynamic improvement (P=0.014, Chi squared). CONCLUSION: VVR may lead to ulcer healing, but when performed at the popliteal level, haemodynamic improvement can be obtained along with a longer recurrence-free period (durability). VVR should be considered in the treatment of patients with SCVI who do not respond to superficial venous surgery and compression treatment.

Treatment with autologous bone marrow mononuclear cells in patients with critical lower limb ischaemia. A pilot study.

BACKGROUND AND AIMS: Treatment with autologous, bone marrow mononuclear stem cells has shown effects in patients with chronic limb ischaemia in one randomized clinical study. The aim of the study was to test the potential effect of stem cell treatment in a strict defined group of patients with stable critical limb ischaemia (CLI). DESIGN: A prospective, combined-centre pilot study. MATERIAL: Eight patients with CLI of the lower extremities, and without any other treatment options. METHODS: Bone marrow cells were harvested from the patient's iliac crest and, after separation, injected into the calf muscles of the affected leg. Outcome was evaluated by digital subtraction angiography (DSA), visual analogue scale (VAS) and several non-invasive circulatory physiological tests. RESULTS: There were no complications from the procedures. Two patients were amputated two months after cell injection. Five patients reported pain relief after four months. Five patients could be evaluated at eight months. According to VAS and physiological tests, they were all either stable or showed improvement. CONCLUSION: This method seems to be a safe option for treating patients with CLI. Inclusion of patients took a long time, mainly because many patients with CLI are offered endovascular treatment in our institution. While symptomatic improvement was found in individual patients, larger trials are required to investigate efficacy. This will probably require multi-centre participation.

The role of blood perfusion and tissue oxygenation in the postischemic transcutaneous pO2 response.

The transcutaneous pO2 (TCpO2) response following release of tourniquet cuff occlusion is expressed as oxygen reappearance time (ORT) and oxygen recovery index (ORI). In the present study the effects of blood perfusion and tissue oxygenation on ORT and ORI in healthy control subjects and two patient groups with peripheral arterial insufficiency were assessed. In control subjects, ORT reflects diffusion time for O2 molecules from capillaries to the TCpO2 sensor. In patients with claudication, ORT was prolonged probably because of delayed postischemic reperfusion and reduced tissue oxygenation. In patients with critical ischemia, prolonged ORT seems to be attributed more to reduced tissue oxygenation than to delayed postischemic reperfusion. ORI in control subjects and patients with claudication apparently depends more on capillary pO2 than on magnitude and duration of the postischemic reperfusion. In patients with critical ischemia, ORI is more related to decreased O2 delivery subsequent to reduced or absent reactive hyperemia response. In addition, increased O2 extraction ("O2 steal") and extensive countercurrent O2 exchange during low flow states may reduce ORT and ORI in severely ischemic skin.

Alterations in capillary permeability in the lower limb of patients with chronic critical limb ischaemia and oedema.

BACKGROUND: Oedema formation in lower limbs of patients with chronic critical limb ischaemia (CLI) is a common clinical feature. The rate of fluid filtration through the capillary wall depends on the capillary permeability, i.e. capillary filtration coefficient (CFC). In order to elucidate the pathogenesis of this ischaemic oedema, CFC was measured in the limbs with CLI and oedema and was compared with CFC measurements both in the contralateral sides and in the lower limbs of a control group. PATIENTS AND METHODS: Eleven women and 4 men, with a mean age of 75 +/- 8.8 years, with unilateral CLI and leg and foot oedema were included. Leg and foot volume was measured with water displacement volumetry (WDV). CFC was measured in both limbs by strain-gauge plethysmography using a double-stranded mercury in silicone strain gauge around the middle portion of the foot. As a control group, 8 patients, 5 women and 3 men, with a mean age of 77 +/- 7.6 years with a proximal femur fracture were included and the CFC in this group was measured in the foot of the non-fractured limb. RESULTS: Mean CFC in the limbs with CLI and oedema was 0.0036 +/- 0.001 ml/min.100 ml.mmHg, significantly greater than both the contralateral limbs (0.0019 +/- 0.0003 ml/min.100 ml.mmHg, p < 0.01) and mean CFC in the control limbs (0.0017 +/- 0.0002 ml/min.100 ml.mmHg, p < 0.003). There was a mean volume difference of 13 +/- 9% between limbs with CLI and contralateral sides measured by WDV. There was no significant correlation between total leg-foot volume and CFC (p > 0.05). CONCLUSION: CFC in the ischaemic limb was twice as great as both the contralateral side and the limbs of the control group. It is therefore concluded that an increased CFC is probably one of the important factors in the development of this ischaemic oedema.

The distribution of oedema in the lower limb of patients with chronic critical limb ischaemia: a study with computed tomography.

BACKGROUND: A substantial number of patients with chronic critical limb ischaemia (CLI) have considerable oedema at the distal leg and foot of non deep venous thrombosis origin. The primary aim of the present study was to quantify the distribution of oedema in the different tissues of the leg and foot by applying computed tomography and planimetry. The interstitial fluid hydrostatic pressure (Pif) in the subcutaneous tissue was measured to evaluate the effect of oedema on local tissue pressure. PATIENTS AND METHODS: Six men and 12 women with unilateral CLI and peripheral pitting oedema were included. Cross sectional areas (CSA) of subcutaneous tissue, muscle and bone were measured by computer tomography combined with planimetry to assess the distribution of oedema within the soft tissues. Pif was measured by "wick-in-needle" technique. RESULTS: The median total CSA of soft tissue, subcutaneous and muscle tissues at the foot level were respectively 17%, 34% and 9% greater in the limbs with CLI compared to the contralateral limb (p < 0.001). At ankle level these differences were 13%, 30% and 4%, respectively (p < 0.001). At the level of the calf these differences were not significant. Mean Pif in the limbs with CLI was 0.3 mmHg, significantly higher than in limbs without CLI (-1.8 mmHg), (p < 0.003). CONCLUSION: The study verified oedema of considerable magnitude at the ankle and foot. The great part of the oedema was located within the subcutaneous tissue, which was associated with a relatively moderate, but significant increase in Pif confirming the high compliance of the subcutaneous tissue. The combination of the excessive fluid and increased Pif in the interstitial tissue might aggravate the microcirculation. The aetiology of oedema formation is probably multifactorial.

The concentration of protein-compounds in interstitial tissue of patients with chronic critical limb ischaemia and oedema.

BACKGROUND: Many of chronic critical limb ischaemia (CLI) patients have distal leg and foot oedema. Previous electronmicroscopic studies have shown that chronic severe ischaemia may cause hypoxic damage of the capillary endothelium, including morphological changes i.e. multiplicated/thickened basal lamina, and formation of interendothelial gaps. To assess the functional consequences of these morphologic derangements, where proteins can leak through, we investigated the composition of the interstitial fluid in oedematous ischaemic limbs. PATIENTS AND METHODS: Nine female and 3 male patients with a mean age of 79 +/- 7.9 years were included. All had unilateral CLI and peripheral pitting oedema. Leg and foot volume was measured with water displacement volumetry. Blister suction technique was used to collect subcutaneous interstitial fluid. The concentration of albumin, transferrin, immunoglobulin G and alpha 2-macroglobulin in plasma and blister fluid was measured by immunoturbidimetry. Nine patients, 8 women and 1 man with a mean age of 83 +/- 5.5 years with a proximal femur fracture served as an age-matched control group. RESULTS: The mean concentration of albumin in blister fluid was significantly lower in the patients, whereas the mean concentration of alpha 2-macroglobulin in blister fluid did not differ between patients and controls. Mean ratio between concentrations in blister and serum of albumin, transferrin and immunoglobulin G in the limbs with CLI and oedema were significantly lower than respective values in the control group. However, there was no significant difference in the ratio of alpha 2-macroglobulin between these groups. CONCLUSION: A higher transcapillary concentration gradient for proteins in CLI limbs signifies an increase in the net osmotic pressure gradient across the capillary wall, which may be a potential oedema limiting factor.

Beneficial effects of 1-year optimal medical treatment with and without additional PTA on inflammatory markers of atherosclerosis in patients with PAD. Results from the Oslo Balloon Angioplasty versus Conservative Treatment (OBACT) study.

The influence of optimal medical treatment (OMT) with or without additional percutaneous transluminal angioplasty (PTA) on vascular inflammation in peripheral arterial occlusive disease (PAD) patients was investigated. Patients with intermittent claudication (IC) and angiographically verified PAD were randomized to OMT (n = 28) or OMT + PTA (n = 28) and followed for 12 months. Ankle-brachial index (ABI), treadmill walking distances (WD), visual analogue scale (VAS), and blood sampling for the determination of selected soluble biomarkers were undertaken at baseline and after 3 and 12 months. After both 3 and 12 months, ABI, WD and VAS were highly significantly improved in favour of OMT + PTA (p < 0.05 for all). Significant improvements were recorded in both groups in serum lipids (p < 0.01 for all), except for triglycerides, and in the inflammatory markers P-selectin, interleukin-6, interleukin-10, monocyte chemoattractant protein-1 and fibrinogen (p < 0.05 for all). There were, however, no differences in the changes from baseline between the groups in any variable. Intervention with OMT alone or in combination with PTA did not differ with regard to the effects on serum lipids and markers of inflammation in our population of PAD patients. The combined treatment was, however, better for the treadmill walking distance.

The Oslo balloon angioplasty versus conservative treatment study (OBACT)--the 2-years results of a single centre, prospective, randomised study in patients with intermittent claudication.

OBJECTIVES: To compare the effect of optimal medical treatment only (OMT) with OMT combined with percutaneous transluminal angioplasty (OMT+PTA) in patients with intermittent claudication (IC). DESIGN: A single centre prospective, randomised study. Quality of life (QoL) was the primary outcome measure. Secondary measures were ankle-brachial-index (ABI), treadmill walking distances and mortality. METHODS: From a total of 434 patients considered for inclusion into the trial, only 56 patients with disabling IC fulfilled the inclusion criteria. The patients were randomised into treatment groups consisting of 28 patients each and followed for 2 years. ABI and treadmill walking distances were measured in addition to the visual analogue scale (VAS) for pain evaluation, and QoL assessment using the Short Form (SF-36 and Claudication Scale (CLAU-S). RESULTS: The demographic data in the 2 groups were almost identical. After 2 years of follow-up the ABI, the treadmill walking distances and the VAS were significant improved in the group treated with OMT+PTA, compared to the group treated with OMT only (p<0.01 for all). Furthermore, some variables from the QoL assessment also showed a significant improvement in favour of the OMT+PTA group (p<0.05 for all). CONCLUSION: The advantage of conducting a single centre study and adhering to very strict inclusion criteria was illustrated by the homogenous demographic data of the two groups. This partly outweighed the disadvantage of having included a relatively small number of patients. Early intervention with PTA in addition to OMT seems to have a generally more positive effect compared to OMT only, on haemodynamic, functional as well as QoL aspects during the first 2 years in patients with IC.

External venous valve plasty (EVVP) in patients with primary chronic venous insufficiency (PCVI).

OBJECTIVES: To evaluate the patency of EVVP and its effect in symptom relief, ulcer healing and ulcer-free period in patients with PCVI. METHODS: Between 1993 and 2004, 1800 patients with CVI were evaluated and seventeen with PCVI were selected for EVVP. They were all investigated with ambulatory venous pressure measurement (AVP), colour duplex ultrasound (CDU), ascending venography and descending video venography. The CEAP classification was used to group the patients. Six patients were C4, four C5 and seven C6. All had deep reflux and high levels of AVP. RESULTS: All procedures were technically successful. The ulcer healing rate was 4/7 (57%) within 3 months. All C4 patients experienced symptom improvement postoperatively and had a median recurrence free period of 72 (range 60-122) months. The C5 group had an median ulcer free period of 61 months (12-72) and the C6 of median 48 (12-72) months. Single valve plasties (4) reached a median competence period of 48 months (12-72), 12 multiple valve plasties at the same level show a median 78 months (63-122) and 10 multilevel repairs median 54 months (12-96). Multiple valve plasties at the same level (multi-station plasties) performed on the C4 group seemed to yield the longest durability with a median of 103 months (84-122). CONCLUSION: EVVP with an ulcer healing rate of 57% and satisfactory symptom improvement seems to be an alternative of surgical treatment for selected patients with PCVI. The durability of this technique seems to be related to clinical severity and the multiplicity of repairs.

The effect of inactivity on reactive hyperaemia in the human calf: a study with strain gauge plethysmography.

In order to study the influence of muscular inactivity on reactive hyperaemia, postischaemic blood flow was measued with strain gauge plethysmography in the calf of twenty-nine patients, who had been treated with a plaster cast for a trauma of the lower limb. The contralateral leg served as a comparison. In all but two patients postischaemic maximal flow was lower in the immobilized calf. A negative correlation existed between maximal flow and the duration of immobilization. In the course of 6 weeks after removal of the cast, the difference in maximal flow between both sides became insignificant. Venous volume and venous emptying were not different in the two limbs. The effect of inactivity on reactive hyperaemic response may be explained by an effect of inactivity on the arterioles, muscle atrophy, a decrease in capillarization and in oxidative capacity of the muscle fibres. It is concluded that inactivity and atrophy of the lower limb musculature in patients with peripheral arterial disease may be a contributing factor to the low reactive hyperaemic response in the calf of such patients.

The influence of age on reactive hyperaemia in the human calf: a study with strain gauge plethysmography.

Postischaemic reactive hyperaemia in the calf was investigated by strain gauge plethysmography in four groups of ten subjects. The mean age of the different groups was 6, 13, 24 and 57 years respectively. Basal calf flow, repayment and recovery time in the 6-year-old children were greater than in the other groups, which may be related to a higher metabolic rate in young children. Maximal flow in the four groups was not significantly different, which indicates that the arteriolar response to circulatory arrest is not altered by increasing age. The cause of delay in maximal flow in the group of 6-year-olds is not clearly understood. Basal and postischaemic lowest peripheral resistance increased with age, which is probably caused by changes of the arterioles due to ageing and possibly inactivity. The fall in peripheral resistance induced by 3 min of ischaemia was positively correlated with mean blood pressure. This may be due to a greater net reduction in blood pressure during ischaemia, which brobably elicits a stronger myogenic response of the vessel wall. It is concluded that in clinical use of the reactive hyperaemia test in the calf, the influence of age is of minor importance, whereas postischaemic peripheral resistance is a more accurate measure of vasocilation for comparison of subjects with different blood pressure.

Reactive hyperaemia in the calf of trained and untrained subjects: a study with strain gauge plethysmography.

Postischaemic reactive hyperaemia in the calf was investigated by strain gauge plethysmography in three pairs of trained and untrained groups of different ages. Maximal flow and repayment in the trained adults were greater than in corresponding untrained groups. This may be due to training effect on the arterioles and a relatively great muscle volume and vascular bed in athletes. The 58-year-old trained men revealed a postischaemic hyperaemic response of approximately the same magnitude as the 25-year-old athletes. Training in old age may result in less degeneration of vascular smooth muscle as well as striated muscle and may induced a relatively great cardiac stroke volume, factors which probably influence reactive hyperaemia in the calf. Hyperaemia in 13-year-old children of different conditions of training was approximwtely the same. It is concluded that the influence of training state on postischaemic calf flow may be considered when reactive hyperaemia is used as a test of the peripheral circulation.

How critical is chronic critical leg ischaemia?

"Critical" according to the Oxford dictionary means: a "turning point" where an acute change for better or worse may be anticipated. Thus, the meaning of the word "critical" complies with its use in relation to ischaemia. We don't really know, prospectively, what will happen to the critically ischaemic limb, whether it will improve or worsen. The answer to the question "How critical is critical leg ischaemia (CLI)?" must be: "We don't know!" The addition of ankle systolic pressure as an objective haemodynamic measurement has not made the definition of the Second European Consensus Group significantly better than the original Fontaine classification, grade III and IV. For clinical practice the Fontaine classification will be sufficient. For scientific purposes macro- and microcirculatory assessments and information about the patient's risk profile should be added.

Arterio-intestinal fistula as a complication following insertion of an aorto-iliac bifurcation graft. A case report.

A patient who had been treated with insertion of an aorto-iliac bifurcation dacron prosthesis for atherosclerosis 6 years previously, developed a fistulous communication between a false aneurysm at the distal anastomosis to the left iliac artery and an ileal loop. Intestinal haemorrhage and signs of infection were the main symptoms. Successful surgical treatment consisted of suturing the intestinal defect, removal of the left limb of the graft and vascular reconstruction by means of a subcutaneous femorofemoral vein bypass.

The risk of deep-vein thrombosis after operations on a bloodless lower limb. A venographic study.

In 17% of 40 patients undergoing operation in a bloodless field on the lower limb, thrombosis was diagnosed phlebographically. Phlebography was performed between the second and eighth postoperative day. The incidence of thrombosis in this series was relatively low, considering other reports on postoperative thrombosis and the theoretical dangers of thrombosis involved in the use of a tourniquet. Factors which could explain the relatively low frequency of postoperative thrombosis are discussed.

The role of the veno-arteriolar reflex (VAR) in the pathogenesis of peripheral oedema in patients with chronic critical limb ischaemia (CLI).

BACKGROUND AND AIMS: Relatively many patients with chronic critical limb ischaemia (CLI) have oedema in the afflicted limb. Previous studies in these patients indicate derangement in the Starling forces governing transcapillary fluid balance. An impaired veno-arteriolar reflex (VAR) may cause an increase in capillary pressure and hence increased filtration pressure resulting in oedema. The aim of the present study was to investigate VAR in patients with CLI to come to a better understanding of the pathogenesis of ischaemic oedema. MATERIAL AND METHODS: Sixteen patients (mean age of 78+/-9.4 years) with unilateral CLI and oedema were included. There were two control groups of similar age, one consisted of 8 patients with unilateral CLI but without oedema and the other of 9 healthy subjects. Laser Doppler fluxmeters were used to evaluate the foot skin microcirculation, with the limbs in supine as well as in the dependent position, simultaneously in 4 different areas: the pulp of the first toe (Sitel), at the level of the second metatarsal body (Site 2), at the anterolateral part of ankle (Site 3) and the pulp of the first toe of the contralateral limb (Site 4) as reference. Laser Doppler flux (LDF) values (expressed in perfusion unit, PU) were recorded with the foot dependent (PUd), in the horizontal position (PUh), and the orthostatic response (OR) was calculated at all measuring sites as PUd/PUh. RESULTS: In none of the measured sites there was a significant difference in OR between the limbs with CLI and oedema and the limbs with CLI but without oedema. The median OR of CLI limbs at site 1 [2.5 (0.61-8.96)] was greater than at sites 2 [0.99 (0.46-2.38), p < 0.01] and 3 [0.95 (0.68-10.31), p < 0.04] respectively, while the differences in OR between site 2 and 3 were not significant. The median OR in the limbs of healthy controls at sites 1, 2 and 3 were 0.58 (0.37-1.43), 0.54 (0.28-1.33) and 0.51 (0.34-0.91), respectively. There were no significant differences in OR between sites 1, 2 and 3 of the control group. The OR of CLI at site 1, 2 and 3 were significantly greater than the corresponding sites in the healthy subjects (p < 0.001, p < 0.008, p < 0.001). CONCLUSIONS: The VAR is disturbed in limbs with CLI, both in the ones with and without oedema. There were regional differences in the OR in these ischaemic feet but there were no differences in OR between those with and without oedema. Thus, disturbances in VAR may play a role in the development of ischaemic oedema, but is probably not the only causative factor.

Vascular and stromal features in the skin of the lower limb in patients with chronic critical limb ischaemia (CLI) and oedema.

OBJECTIVE: peripheral oedema is often observed in limbs affected by chronic critical limb ischaemia (CLI) and is mainly subcutaneous in distribution. Previous work has shown that capillary filtration coefficient (CFC) in limbs with CLI and oedema was twice as great as that in the contralateral limb. These changes might be due to morphological changes. Transmission electron microscopy (TEM) was used to examine the morphological features of the capillary walls and surrounding stromal tissues in the skin of these limbs. MATERIAL AND METHODS: eight patients with unilateral CLI and peripheral pitting oedema (four men, four women, a mean age of 81+/-6.9 years) was studied. Skin biopsies were taken from the pulp of the first toe, interdigital space between the first and second digits and dorsal part of forefoot just prior to amputation. RESULTS: stromal oedema and dilated capillaries were most prominent in the distal part of the foot. Some of the capillaries were filled with blood cells and some were empty. The endothelium of the dilated vessels was elongated and distended. In some patients a number of capillaries were collapsed with degenerate endothelial cells. <<<>>>, i.e. large openings, were found between the elongated oedematous endothelial cells. The basal lamina was thickened in all patients. Stromal haemorrhage and degeneration were seen in approximately 50% of patients. CONCLUSION: CLI causes ultrastructural changes in the capillary endothelium and surrounding stroma. The presence of large gaps between endothelial cells as well as an increased capillary pressure may enhance transcapillary transudation, and are most likely the causative factors in the formation of the ischaemic oedema. The stromal haemorrhage as well as degeneration probably signifies a terminal stage of CLI.

Patterns of skin flowmotion in the lower limbs of patients with chronic critical limb ischaemia (CLI) and oedema.

OBJECTIVE: To study flowmotion (FM) in lower limbs with critical limb ischaemia (CLI) and oedema and to elucidate FM patterns when skin viability is threatened. MATERIAL AND METHODS: Fourteen patients with unilateral CLI and oedema and two control groups were included - one consisting of 10 healthy participants and the other nine patients with unilateral CLI without oedema. Laser Doppler was used to evaluate the foot skin microcirculation simultaneously at four different areas, with the limbs in supine and dependent position. FM was expressed using fast Fourier transformation (FFT) as low frequency (LF) and high frequency (HF) waves and their respective FFT-powers. RESULTS: All patients with CLI, both with and without oedema, showed HF waves in both diseased and contralateral limbs. These were absent in healthy controls. There were no regional differences in frequency in the critically ischaemic feet (with and without oedema) and between ischaemic and their contralateral feet. Changing the position of ischaemic limbs from supine to dependency had no significant effect on the frequency, while a significant increase of the median FFT-powers of LF and HF waves at the pulp of the first toe was observed. This manoeuvre resulted in decrease of the median FFT-powers of LF in healthy controls. CONCLUSIONS: HF waves are associated with CLI. Ischaemia also appears to influence the FFT-power of each frequency domain. Ischaemic oedema does not seem to affect the pattern of FM in the foot of patients with CLI.

Pre- and postischemic transcutaneous oxygen tension measurements and the determination of amputation level in ischemic limbs.

The value of transcutaneous pO2 (TCpO2) measurements in determining amputation levels was studied in patients with atherosclerotic lower limb ischemia. A postischemic TCpO2 response did not predict healing of the amputation stump better than measurements at rest. No minimal resting or postischemic TCpO2 was found below which healing could not occur. However high TCpO2 values probably are indicative of a good healing potential. In patients with poor skin viability, assessed clinically, the method may be of value; in some cases TCpO2 values compatible with healing may be found. Attention should be paid to the TCpO2 sensor as its characteristics may influence the measurements in patients with critical ischemia causing underestimation of tissue pO2.