Wavelet analysis of skin perfusion to assess the effects of FREMS therapy before and after occlusive reactive hyperemia.

Laser Doppler Fluxmetry is used to evaluate the hemodynamics of skin microcirculation. Laser Doppler signals contain oscillations due to fluctuations of microvascular perfusion. By performing spectral analysis, six frequency intervals from 0.005 to 2 Hz have been identified and assigned to distinct cardiovascular structures: heart, respiration, vascular myocites, sympathetic terminations and endothelial cells (dependent and independent on nitric oxide). Transcutaneous electrical pulses are currently applied to treat several diseases, i.e. neuropathies and chronic painful leg ulcers. Recently, FREMS (Frequency Rhythmic Electrical Modulation System) has been applied to vasculopathic patients, too. In this study Laser Doppler signals of skin microcirculation were measured in five patients with intermittent claudication, before and after the FREMS therapy. Changes in vascular activities were assessed by wavelet transform analysis. Preliminary results demonstrate that FREMS induces alterations in vascular activities.

Amputation rate and mortality in elderly patients with critical limb ischemia not suitable for revascularization.

In spite of recent progress in revascularization and anesthesiology procedures, in vascular centers today there are still patients with Critical Limb Ischemia (CLI) who are not considered suitable for revascularization. Most of these patients are elderly, with high co-morbidity factors, poor run off arterial limb vessels, and often with a salvageable limb. They are absent or neglected in the literature, and generally go untreated. We report details of 24- month amputations and mortality rates in 90 patients with CLI who were not considered suitable for revascularization, treated from 2005 to 2008 in a dedicated unit of our department. Patients with endstage general conditions or needing immediate primary amputation were excluded from our study. All patients received multidisciplinary assessment. Their median age was 78.4 years; 28 patients (31.1%) had rest pain only, and 62 (68.8%) had ischemic skin foot-leg wounds or gangrene <2 cm. Sixteen patients (37.7%) were assessed as not suitable for revascularization because of poor functional status, and 76 (64.4%) because of inadequate outflow limb vessels. Drugs to manage pain were administered to all patients (100%), prostanoid infusions were given to 80 (88%), anti-platelet drugs to 87 (96%), low molecular weight heparin or oral anticoagulants to 13 (14%), spinal cord stimulation to 3 (3%), hyperbaric oxygen treatment to 16 (17%) and wound treatment to 62 (68.8%). Toe or other foot-sparing amputations had a rate of 13%. After 24 months, the major amputation rate was 9.3% and the mortality rate 23.2%. Our observations show that, in spite of progress in revascularization procedures, there are still patients with CLI who are not considered suitable for revascularization and who could benefit from non-surgical treatment if a tailored approach is used.

Sulodexide in the treatment of chronic venous disease.

Chronic venous disease encompasses a range of venous disorders, including those involving the lower limbs resulting from venous hypertension. The spectrum of chronic venous disease signs and symptoms shows variable severity, ranging from mild (aching, pain, and varicose veins) to severe (venous ulcers). The pathophysiology of chronic venous disease is characterized by venous hypertension, which triggers endothelial dysfunction and inflammation leading to microcirculatory and tissue damage, and eventually to varicose veins and venous ulcers. Sulodexide is an orally active mixture of glycosaminoglycan (GAG) polysaccharides with established antithrombotic and profibrinolytic activity. The agent is used in the treatment of a number of vascular disorders with increased risk of thrombosis, including intermittent claudication, peripheral arterial occlusive disease and post-myocardial infarction. Sulodexide differs from heparin because it is orally bioavailable and has a longer half-life and a smaller effect on systemic clotting and bleeding. An increasing body of preclinical evidence shows that sulodexide also exerts anti-inflammatory, endothelial-protective, and pleiotropic effects, supporting its potential efficacy in the treatment of chronic venous disease. Clinical studies of sulodexide have shown that the agent is associated with significant improvements in the clinical signs and symptoms of venous ulcers, and is therefore a recommended therapy in combination with local wound care and bandages for patients with persistent venous leg ulcers. Preliminary evidence supports the use of sulodexide in the prevention of recurrent deep venous thrombosis. Sulodexide was generally safe and well tolerated in clinical trials, without hemorrhagic complications. Sulodexide therefore appears to be a favorable option for the treatment of all stages of chronic venous disease and for the prevention of disease progression.

Videocapillaroscopy study of post traumatic lower limb loss of tissue treated with and without acellular dermal substitute.

A 46 years old male with a post traumatic loss of tissue localized on the anterior surface of the right thigh and knee due to a road accident, was treated with different surgical reconstructive techniques. Combined use of autologous skin graft and acellular dermal substitute Integra® allowed the satisfactory recovery of the patient who was discharged after 82 days from the trauma. To analyse the characteristics and the quality of the healing tissues we performed a videocapillaroscopy study to assess the microcirculatory pattern of the autologous skin grafted on the dermal substitute in comparison with the autologous skin grafted on granulation tissue. The videocapillaroscopy was performed in the zone skin grafted directly on granulation tissue, Zone 1 (Z1); on the region of the lesion in the knee, treated with dermal substitute and autologous skin graft, Zone 2 (Z2), and on the undamaged controlateral knee skin. Zone 3 (Z3). The results showed that the capillary density was similar between Z2 and Z3, while in Z1, the zone skin grafted on the granulation tissue without Integra® the capillary density was significatively reduced. These preliminary observations within the clinical data may be an useful contribute to better understand the tissue healing process.

Benign outcome of objectively proven spontaneous recanalization of internal carotid artery occlusion.

OBJECTIVE: Spontaneous recanalization of intracranial internal carotid artery (ICA) occlusion is frequent in embolic strokes. Spontaneous recanalization of the extracranial portion of the ICA occlusion of atherosclerotic or embolic origin is only anecdotally reported, and data are lacking about its incidence, natural history, and outcome in long-term follow-up. METHODS: Consecutive patients with ICA occlusion were prospectively identified and followed-up to detect the incidence of a spontaneous recanalization. Patients with objectively confirmed recanalization were prospectively followed-up to observe their natural history and the onset of new cerebrovascular events. ICA occlusion and spontaneous recanalization were diagnosed by means of color-coded Doppler ultrasound imaging or selective contrast angiography, or both. All patients were evaluated and treated for atherosclerotic risk factors. RESULTS: Spontaneous recanalization occurred in 16 of 696 patients (2.3%; 95% confidence interval, 1.3%-3.7%) with ICA occlusion after a mean interval of 38 months from the diagnosis of occlusion. Spontaneous recanalization was detected with color-coded Doppler ultrasound imaging and with selective contrast angiography, with a complete agreement of diagnostic findings. Two patients presented with symptomatic spontaneous recanalization. All patients with spontaneous recanalization were asymptomatic after a mean follow-up of 66.2 months. CONCLUSIONS: Spontaneous recanalization of previously occluded extracranial ICAs is more frequent than anticipated. Once it occurs, spontaneous recanalization seems to have a benign long-term course.

Low-molecular-weight heparin versus compression stockings for thromboprophylaxis after knee arthroscopy: a randomized trial.

BACKGROUND: Knee arthroscopy, the most common orthopedic operation worldwide, carries a definite risk for deep venous thrombosis; however, postsurgical thromboprophylaxis is not routinely recommended. OBJECTIVE: To evaluate whether low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy. DESIGN: Assessor-blind, randomized, controlled trial. SETTING: The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee surgery, random assignment, and bleeding event survey), and the Unit of Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation, follow-up, data management, and analysis), Italy. PATIENTS: 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006. INTERVENTION: Patients were randomly assigned to wear full-length graduated compression stocking for 7 days (660 patients) or to receive a once-daily subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657 patients) or 14 days (444 patients). The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis. MEASUREMENTS: Combined incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end point) and combined incidence of major and clinically relevant bleeding events (primary safety end point). All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated. All patients with normal findings were followed for 3 months, and none was lost to follow-up. RESULTS: The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4 of 444 patients) in the prematurely stopped 14-day LMWH group. The cumulative incidence of major or clinically relevant bleeding events was 0.3% (2 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, -0.6 percentage point [CI, -1.5 to 0.2 percentage points]), and 0.5% (2 of 444 patients) in the 14-day LMWH group. LIMITATIONS: The study was not double-blind or double-dummy. Almost half of the events making up the composite outcome measure were distal deep venous thromboses. Stockings were used instead of placebo because of local prophylaxis policies. CONCLUSION: In patients undergoing knee arthroscopy, prophylactic LMWH for 1 week reduced a composite end point of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality more than did graduated compression stockings.

Levo-propionyl-carnitine improves the effectiveness of supervised physical training on the absolute claudication distance in patients with intermittent claudication.

The mechanisms by which supervised physical training improves walking ability in patients with intermittent claudication (IC) are microcirculatory, rheological, and metabolic. The main mechanism of levo-propionylcarnitine (LPC) is metabolic; it increases the walking ability in claudicants, providing an additional energy to the ischemic muscle by an anaplerotic activity. Therefore, the current study was carried out to ascertain whether the combined treatment has a synergistic effect. The results confirm the effectiveness of supervised physical training in patients with IC, and we recommend the use of LPC during the exercise training program, at least in patients with severe claudication. Finally, underlining the similar mechanisms of physical training and LPC treatment, the study suggests that a cycle of LPC infusions could be advised in patients with severe claudication who cannot be included, for various reasons, in an exercise rehabilitation program.

The ILAILL study: iloprost as adjuvant to surgery for acute ischemia of lower limbs: a randomized, placebo-controlled, double-blind study by the italian society for vascular and endovascular surgery.

SUMMARY BACKGROUND DATA: High rate of complications has been reported following revascularization for acute limb ischemia (ALI). No adjuvant pharmacologic treatment, apart from anticoagulation and standard perioperative care, has been shown clinically effective. OBJECTIVE: Aim of this study was to evaluate the effects of the prostacyclin analog iloprost as adjuvant to surgery for ALI. METHODS: A total of 300 patients were randomly assigned to receive perioperative iloprost (intra-arterial, intraoperative bolus of 3000 ng, plus intravenous infusion of 0.5-2.0 ng/kg/min for 6 hours/day for 4-7 days following surgery), or placebo. The primary endpoint was the combined incidence of death and amputation at 3-month follow-up. Secondary endpoints were the incidence of each single major complication, total event rate, symptomatology, and tolerability. RESULTS: The combined incidence of death and amputation was 19.9% in the placebo and 14.1% in the iloprost group (relative risk, 1.56; 95% confidence interval, 0.89-2.75, P = 0.12, Cox regression analysis). A statistically significant lower mortality (4.7%) was reported in patients receiving iloprost, compared with controls (10.6%; relative risk, 2.61; 95% confidence interval, 1.07-6.37, P = 0.03). The overall incidence of fatal plus major cardiovascular events was 33.1% and 22.8% in placebo and iloprost groups, respectively (relative risk, 1.61; 95% confidence interval, 1.04-2.49, P = 0.03). No serious adverse reactions occurred after iloprost administration, nor differences in the incidence of bleeding or hypotension between treatment groups. CONCLUSIONS: Although at lower levels than previously reported, our results confirm the severity of ALI. Iloprost as adjuvant to surgery significantly reduced mortality and overall major event rate. Further data are needed to support this finding, and to face a still open medical issue.

Ultrasound evaluation of carotid artery in primary hyperparathyroidism.

Patients with primary hyperparathyroidism (PHPT) have an increased cardiovascular morbidity and mortality. Elevated serum calcium and/or PTH may directly contribute to vascular tissue damage, but the role of classic factors for atherosclerosis has not fully been evaluated in this disease. The aim of our study was to dissect the potential effect of hypercalcemia and/or high PTH from that of major cardiovascular risk factors (i.e. diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking habit) on the carotid artery structure of patients with PHPT. Twenty-six consecutive patients with PHPT [subdivided into two groups according to the absence (n = 10) or the presence (n = 16) of one or more risk factors] and 15 normocalcemic healthy subjects as controls were studied. At ultrasonography, a significant increase (P < 0.001) of carotid mean and maximum intima-media thickness, as well as a significant reduction of lumen diameter (P < 0.05) were found in the PHPT group with risk factors, compared with the other two groups. This suggests that hypercalcemia and/or PTH elevation per se are not determinant of carotid atherosclerosis in PHPT, and that increased cardiovascular mortality and morbility in this disease is attributable to the combined presence of classic cardiovascular risk factors.

High versus low doses of unfractionated heparin for the treatment of superficial thrombophlebitis of the leg. A prospective, controlled, randomized study.

BACKGROUND AND OBJECTIVES: The optimal treatment of superficial thrombophlebitis of the leg is undefined. The main study objective was to assess the efficacy and safety of unmonitored high doses as compared to low doses of unfractionated heparin (UFH) for prevention of venous thromboembolic complications in patients with superficial thrombophlebitis of the thigh. DESIGN AND METHODS: Sixty consecutive patients with acute thrombophlebitis of the great saphenous vein, as assessed by ultrasonography, were randomized to subcutaneous injection twice daily of UFH in high unmonitored doses (12,500 IU for one week followed by 10,000 IU) or prophylactic doses (5,000 IU) for four weeks. The rate of asymptomatic involvement of the deep venous system and/or symptomatic thromboembolic events during a six-month follow-up period was assessed and compared between the two study groups. RESULTS: Six of the 30 patients (20.0 %; 95% CI, 7.7 to 38.6) randomized to low-dose UFH developed symptomatic or asymptomatic events as compared to 1 of the 30 patients (3.3%; 95% CI, 0.07 to 17.2) who received high-dose UFH (p=0.05 by one-sided Fisher's exact test). No patient experienced major bleeding complications in either group. INTERPRETATION AND CONCLUSIONS: The results of this study suggest that in patients with acute thrombophlebitis of the thigh unmonitored high doses of UFH are more effective than prophylactic doses of UFH for prevention of venous thromboembolic complications and do not enhance the risk of bleeding complications.

L-propionyl-carnitine protects tissues from ischaemic injury in an 'in vivo' human ischaemia-reperfusion model.

OBJECTIVE: To assess the acute effects of L-propionyl-carnitine (LPC) on vaso-motion, tissue perfusion and tissue acidosis during an ischaemia-reperfusion test in patients with intermittent claudication. DESIGN: Open pharmacodynamic study. STUDY PARTICIPANTS: Sixteen male patients with intermittent claudication (mean absolute claudication distance 193.19 ± 51.51m). INTERVENTIONS: Intravenous infusion of LPC 600mg. MAIN OUTCOME MEASURES AND RESULTS: Laser-Doppler perfusion units and power spectrum, transcutaneous oxygen pressure (TcPO(2)) and transcutaneous carbon dioxide pressure (TcPCO(2)) were measured at baseline, during ischaemia (which was induced by means of an inflated pneumatic cuff wrapped around the calf) and during reperfusion, before and after LPC infusion. Perfusion units and TcPO(2) did not change significantly after LPC infusion compared with pretreatment values. Conversely, mean laser-Doppler power spectrum, which was 0.20 units at rest and 1.13 during reperfusion before treatment, increased significantly to 0.89 and 2.24, respectively, after LPC infusion (p = 0.01 and p = 0.00074, respectively, vs pretreatment values). LPC had no significant effects on resting TcPCO(2), but induced a significant decrease in TcPCO(2) measured at hypoxia point (96.9mm Hg before treatmentvs 90.2mm Hg after treatment; p = 0.001) and during reperfusion (115.9vs 103.5mm Hg, respectively; p = 0.0006). CONCLUSIONS: These results show that LPC protects tissues from ischaemic injury by improving arteriolar function and reducing acidosis, without affecting arterial inflow. This may explain the beneficial effects of LPC in patients with intermittent claudication and suggests a potential use of this drug in other stages of peripheral arterial disease and in patients undergoing surgery.