Matrix metalloproteinases and peripheral arterial disease.

It has been postulated that atherosclerosis should be considered as a chronic inflammatory process and peripheral arterial disease (PAD) is a manifestation of such an atherosclerotic vascular disease. Matrix metalloproteinases (MMPs) are significant circulating biomarkers which play a pivotal role in the initiation, progression and clinical manifestations of PAD. This review summarizes the current body of evidence with regard to the association between MMPs and PAD.

The proinflammatory mediator's production from ischemic brain during carotid endarterectomy.

AIM: The aim of the study was to determine the quantity of produced mediators of inflammation (cytokines and eicosanoids), during carotid endarterectomy (CEA), which are factors of ischemic damage of the brain. METHODS: Two groups (A and B) of 15 patients each, with internal carotid backpressure >30 mmHg were operated in our institution. We did not use a shunt in Group A during CEA and group B was operated upon with a shunt. Plasma concentrations of Interleukin-1b (IL-1b), Thromboxane B2 (TXB2), Prostaglandin E2 (PGE2) and tumor necrosis factor-a (TNFa) were measured by enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: We measured gradual increase of levels of IL-1b and TXB2 during cross-clamping and during reperfusion in group A (P<0.05). The levels of TNFa increased only during reperfusion (P<0.05). The concentration of IL-1b and TNFa remained almost stable in group B, whereas the concentration of TXB2 reduced but not significantly (P>0.05). The levels of PGE2 remained stable in both groups. CONCLUSION: We should consider the increase of proinflammatory mediators during carotid cross-clamping when no shunt is used. The critical concentration of these mediators that threaten the brain's vitality is not yet detected. However, the clinical significance of this is unclear, since there were no perioperative strokes.

Semapimod a new pretreatment modality of acute intestinal ischemia-reperfusion syndrome: experimental study in rabbits.

AIM: Semapimod is an experimental drug that strongly inhibits macrophages and stimulates the cholinergic anti-inflammatory pathway. The aim of this study was to evaluate the effect of semapimod on experimentally-induced acute intestinal ischemia-reperfusion syndrome in rabbits. METHODS: The experimental protocol included 16 adult male White New Zealand rabbits divided into two equal groups, A and B. Animals were subjected to 150 min of intestinal ischemia, followed by 30 min of reperfusion. At 30, 90 and 150 min after the onset of ischemia the animals in group A received i.v. placebo (2 mg/kg; Cytokine PharmaSciences Inc, PA, USA) and those of group B received i.v. semapimod (2 mg/kg; Cytokine PharmaSciences Inc, PA, USA). Blood samples were taken for plasma measurements of tumor necrosis factor-a (TNF-a), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) at 0, 60, 120 and 180 min after the onset of ischemia. At the same time points, wedge intestinal biopsies were taken for histopathological evaluation of mucosal injury. All data were analyzed by the non-parametric Mann-Whitney test as appropriate. The power effect of Semapimod was evaluated by mixed between-within Anova statistical analysis. RESULTS: Measurements of TNF-a and IL-1ß levels showed significant differences between groups A and B at 120 min (P=0.004 and P=0.003 respectively) and at 180 min (P=0.001 and p<0.005 respectively). IL-6 values were lower in animals of group B but the differences were not significant. Intestinal mucosal injuries were significantly milder in animals of group B at 120 and 180 min CONCLUSION: Semapimod minimized intestinal mucosa injury and reduced the systemic inflammatory response during acute intestinal ischemia-reperfusion. Further studies are required to investigate the possible value of semapimod as a new pretreatment modality in acute vascular abdomen.

Endovascular treatment of profunda femoris artery obstructive disease: nonsense or useful tool in selected cases?

BACKGROUND: To evaluate the therapeutic value of endovascular techniques for the treatment of profunda femoris artery obstructive disease (PFAOD) in critical limb ischaemia (CLI) patients, with technically demanding open profunda repair. DESIGN: Retrospective study of prospectively collected data of 15 consecutive CLI patients with technically demanding surgical treatment of PFAOD, that were treated by endovascular means in two European Centers of Vascular Surgery. MATERIALS: All patients had critical limb ischaemia with a history of at least two previous vascular reconstructions in the ipsilateral groin and severe co-morbid conditions. All patients had good common femoral artery flow, long occlusion of the superficial femoral and popliteal arteries and impairment of crural arteries. METHODS: Twelve patients underwent balloon angioplasty alone and, in the other three cases, an additional stent placement was necessary, due to flow-limiting dissection. The follow-up (mean 29.2+/-10 months) included a surveillance protocol with the best medical treatment and duplex scanning at 1, 3, 6, 12 months and yearly thereafter. RESULTS: The endovascular approach was technically successful in all cases and the procedure-related morbidity and mortality rates were 0% for the entire follow-up period. The 3-year primary and secondary patency rates of the treated segment were 80% and 86.7%, respectively. The limb salvage rate was 93.3%. CONCLUSIONS: The outcome of our series underscores the therapeutic value of balloon angioplasty in cases of severe PFAOD, as bailout treatment in critical limb ischaemia patients with technically demanding open profunda repair. This procedure can be repeated easily if significant restenosis occurs and provides a useful tool in selected cases.

Hemodynamic follow-up of iliofemoral venous thrombosis.

AIM: The aim of this pilot study was to assess the venous hemodynamic changes after deep venous thrombosis (DVT) using air-plethysmography (APG) and to study the rate and magnitude of these changes in relation to those associated with the post-trombotic syndrome. METHODS: Twenty limbs of 19 patients with acute iliofemoral thrombosis have been followed up with APG and Duplex scanning for 24 months. Patients were treated with anticoagulation and elastic stockings. The air-plethysmographic measurements of venous outflow and functional venous volume were measured on admission. These measurements, as well as venous reflux and calf muscle pump ejecting capacity, have been performer after one week, one month and 3, 6, 12, 18 and 24 months. The results were compared with similar measurements of 10 normal limbs and 10 post-thrombotic limbs with chronic venous ulcers. Duplex scanning was performed on admission, in six and 24 months. RESULTS: Plethysmographic parameters showed a dramatic improvement in the first month, fast improvement after three months and slower improvement thereafter, with the exception of the development of marked venous reflux in five of the 20 limbs studied, in the first three months. Popliteal reflux was diagnosed in these limbs. Elastic compression protected the patent veins from overdistention and incompetence and contributed to the relatively good calf muscle pump function during the first year after DVT. By the end of the study no patient had post-thrombotic changes, but four patients needed elastic stockings in order to avoid edema. CONCLUSIONS: The most important hemodynamic alterations occurred during the first three months after DVT. This is the crucial period during which conservative treatment needs to be improved. Further work is required in this field to study the effect of various newly emerging methods. The air-plethysmographic measurements described may become surrogate endpoints for testing different therapies.

S-shaped ilio-mesenteric bypass in a young high risk patient.

Symptomatic chronic mesenteric ischemia is a rare condition. Several surgical and endovascular techniques have been described, but treatment is individualized according to the conditions of each patient. We report a successful superior mesenteric artery revascularization by using an S-shaped retrograde polytetrafluoroethylene ilio-mesenteric bypass graft in a young overweight patient with a history of two abdominal vascular operations and several comorbidities.

Percutaneous endovascular management of a splenic artery aneurysm.

Splenic artery aneurysms are extremely rare lesions. Elective repair of these aneurysms is justified only if the aneurysm's size is greater than 2 cm and the predicted peri-operative mortality is below 0.5%. Percutaneous techniques minimise the peri-operative morbidity and mortality rates and offer a safe and effective treatment option. We report a coil-embolisation of a 5.1 cm splenic artery aneurysm and a short review of the literature concerning the endovascular treatment options.

Hyperhomocysteinemia and hypercoagulable state in carotid plaque evolution. Novel risk factors or coincidental risk predictors?

AIM: The majority of patients with carotid occlusive disease (COD) have one or more of the conventional risk factors of atherosclerosis. In addition, hyperhomocysteinemia (HHCY) and hypercoagulable state (HCGS) are increasingly recognized as potentially ''novel'' risk factors. The aim of this study was to determine the role of these factors in carotid plaque evolution and clinical manifestation of COD. METHODS: Between September 2003 and 2005, 153 patients were admitted in our Department with clinical and duplex ultrasound evidence of severe (>70%) COD as operative candidates and 33 patients with evidence of moderate (50-69%) stenosis included in the protocol of conservative treatment and lifelong observation. Conventional risk factors of atherosclerotic disease and plasma levels of homocysteine (HCY), fibrinogen (FBG), protein C (PC), protein S, antithrombin III and activated protein C resistance were recorded in all patients. The degree of carotid stenosis was measured in a carotid angiogram following North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria for all operative candidates. Angiographic workup revealed 147 carotid stenoses >70% and 16 internal carotid occlusions in 82 symptomatic and 52 asymptomatic patients, while in 19 patients the carotid stenosis was moderate (50-69%) and these patients included in the conservative treatment group. The study of the ''novel'' and conventional risk factors was performed with univariate and multivariate statistical analysis as well as with correlational analysis of HCY and the other risk factors between patients with severe or moderate COD and between symptomatic and asymptomatic patients with carotid stenosis >70%. RESULTS: Our data showed that HHCY was a strong independent risk factor of symptomatic carotid disease >70%. In addition, the coexistence of high FBG levels and thrombophilia factor deficiency with HHCY was significantly related with the clinical manifestation of COD. CONCLUSION: HHCY and HCGS are often detected among patients with severe and symptomatic carotid stenosis. The early diagnosis and treatment of these deficiencies might be helpful for the management of COD, but their role in future clinical practice is yet to be determined.

Celiac artery aneurysm associated with atherosclerotic common hepatic artery stenosis.

Celiac artery aneurysms are rare vascular lesions and represent 4% of all splanchnic aneurysms. Media degeneration and atherosclerosis are the most common underlying etiologic factors. The risk of rupture and the associated mortality rate are 13% and 40% respectively. In contrast, elective repair carries a low mortality rate of 5%. Most of celiac artery aneurysms are asymptomatic and in the past nearly 80% of the cases were diagnosed when ruptured. Recently, there is an increased recognition of all splanchnic aneurysm types, probably because of better diagnostic techniques. We report a case of celiac artery aneurysm with severe atherosclerotic stenosis of the common hepatic artery. We performed, through a midline supraumbilical laparotomy, extended partial aneurysmectomy and common hepatic artery ostium endarterectomy. For the closure we used Dacron patch. The uncomplicated postoperative patient's course, with no evidence of liver dysfunction and excellent patency of the common hepatic artery, suggests that this technique offered good results and minimized the perioperative risk.

Prolongation of the intestinal viability using oxygenated perfluorocarbon in an experimental model of acute intestinal ischemia.

OBJECTIVES: Liquid perfluorocarbons (PFCs) are well known for their capability to carry respiratory gases. The aim of this study was to evaluate the effectiveness of oxygenated F-Decalin on the intestinal viability, in an experimental model of acute intestinal ischemia. MATERIAL AND METHODS: Thirty-six rabbits were subjected to 8h intestinal ischemia by ligation of the superior mesenteric artery (subgroups 1), the mesenteric vein (subgroups 2) or both vessels (subgroups 3). The animals were divided into three groups: (a) Control (ischemia alone), (b) PFC-O2 (ischemia plus infusion of oxygenated F-Decalin) and (c) PFC (ischemia plus infusion of not-oxygenated F-Decalin). Intestinal biopsies from four different sites and blood samples for serum enzymes measurements were taken at 2, 4, 6 and 8 h. All tissue sections were examined blindly under light microscope. Sections from the specimens were taken at 4 and 8 h, and examined blindly under the electron microscope. Statistical analysis was performed by non-parametric Kruskal Wallis test. RESULTS: Using light microscope, the observed intestinal damages to the sections from Control and PFC groups were severe at 4 h and destructive after 8 h. On the contrary, minimal injuries were observed in the biopsies from PFC-O2 group at 4 and even after 8 h of ischemia. These findings were confirmed by the electron microscope study and correlated to the serum enzymes measurements. CONCLUSIONS: These results suggest that intestinal viability could be prolonged after acute ischemia using oxygenated perfluorocarbons and this could be a promising pretreatment modality for a variety of mesenteric ischemic forms.

Mycotic aneurysm of the infrarenal aorta.

The mycotic aneurysms of the infrarenal aorta (MAIA) are extremely rare and the associated morbidity and mortality is very high. The classification of infected aneurysms considers four types: a) true mycotic aneurysms, b) secondary mycotic aneurysms due to bacterial arteritis, c) infected preexisting abdominal aortic aneurysms and d) post-traumatic infected false aneurysms. The prognosis of true MAIA's is better than the other forms of infected aneurysms. The standard treatment includes the resection of the aneurysm and infectious surrounding tissues and the restoration of the flow using ex situ (axillobifemoral) bypass or in situ replacement with autologous vein or a rifampicinebonded graft. We present a case of mycotic aneurysm of the infrarenal aorta and a brief discussion of the alternative treatments from the relevant literature.

Incidence of abdominal wall hernias in patients undergoing aortic surgery for aneurysm or occlusive disease.

BACKGROUND: The aim of this study was to compare the incidence of abdominal and incisional hernias in patients with abdominal aortic aneurysm (AAA) versus patients with aortoiliac occlusive disease (AOD). PATIENTS AND METHODS: The study included retrospectively 121 patients, who underwent elective aortic surgery due to AAA (n = 63) or AOD (n = 58) in the period between January 1998 and January 2000. The patients were examined for the presence of abdominal hernias upon admission, as well as for the development of incisional hernias on follow-up. RESULTS: The incidence of inguinal hernias was significantly higher in the group AAA (21/6-33.3%) compared to the group with AOD (6/58-10.3%) (p < 0.01). The incidence of other abdominal wall hernias (umbilical, epigastric or miscellaneous hernias) was also significant higher in AAA group. Furthermore, the incidence of inguinal hernias was significantly higher in the subgroup of patients with an aneurysm diameter more than 6 cm (41.5% vs 18.2%, p < 0.05). The mean follow-up of the patients was 1.7 +/- 0.3 years. 7 cases of incisional hernia were noted in the AAA group (11.1%) and only 2 cases in the AOD group (3.4%) (p < 0.05). The size of the aneurysm had no influence on the incidence of incisional hernias in the AAA group. CONCLUSION: We conclude that there seems to be an increased incidence of abdominal wall hernias as well as postoperative incisional hernias in patients undergoing aortic surgery for aneurysm disease compared with aortoiliac occlusive disease.

Alterations in carbon dioxide release during abdominal aortic clamping for aneurysmal or occlusive repair.

BACKGROUND: Application and removal of an infrarenal aortic clamp is associated with changes in oxygen consumption, especially when collateral perfusion is limited. Carbon dioxide production during abdominal aortic clamping is expected also to change. The aim of this study was to evaluate the alterations of CO2 release during abdominal aortic surgery. DESIGN: prospective study. SETTING: University Hospital, Greece. PATIENTS: 17 patients undergoing abdominal aortic aneurismal (AAA) repair and 8 patients undergoing repair of aortoiliac occlusive disease. INTERVENTION: intraoperative record or calculation of PaCO2, PetCO2, PECO2, VD, VDalv, and VCO2. Patients with aneurysms were randomly divided to have constant ventilation (group AA) or modified ventilation to preserve normocapnia (group AB) during clamping. Ventilation was kept constant in the occlusive patients group (group OD). RESULTS: Patients with AAA showed a significant decrease of VCO2 during clamping and an elevation after unclamping in both groups (AA and AB), with no difference of statistical importance between them. During clamping, PetCO2/ PaCO2 ratio was decreased and VDalv was increased especially in group AA, while unclamping produced the opposite effect. Occlusive patients showed insignificant alterations. CONCLUSIONS: Our results suggest that, the calculated alveolar dead space is only an indicator of the true V/Q in patients with AAA, because it is strongly dependent on the CO2 load to the lungs, which is markedly altered in the same period. The modification of ventilation during clamping based only on PetCO2 and not on arterial sampling, could possibly lead to hypercarbia in these patients.

Continuous contralateral jugular acid-base and blood gas monitoring during carotid endarterectomy.

BACKGROUND: The aim of this study is to evaluate the intravascular multiparameter sensor Paratrend 7 (P7) for continuous acid-base and blood gas monitoring after retrograde jugular catheterization during carotid endarterectomy. PATIENTS AND METHODS: We studied 11 patients with history of smoking (72.7%), coronary artery disease (72.7%), hypertension (100%), diabetes mellitus (55.5%) and TIA's and/or nondisabling stroke (90.9%). The contralateral internal jugular vein was punctured retrogradely and the calibrated P7 sensor was introduced. The sensor was removed after surgery. The P7 provides continuous graphical display of pH, pCO2, and pO2, while temperature, oxygen saturation, HCO3 concentration and base excess are displayed numerically. RESULTS: Mean duration of carotid cross-clamping was 17.0 +/- 6.2 min. Mean stump pressure was 50.2 +/- 12.9 mmHg. Intraluminal shunting was not used in any operation. All sensors were easily inserted. During clamping, pH became persistently more acidic (7.31 to 7.28; p < 0.05), pCO2 was elevated (44.7 to 49.8 mmHg; p < 0.05) while, in the majority of the patients, there was a non significant decrease in pjvO2/SjvO2. Declamping was followed by a short period of decrease of pH and elevation of pCO2 reminiscent of wash out phenomena. PjvO2 was significantly elevated (53.8 +/- 5.2 to 59.0 +/- 5.8 mmHg; p < 0.001) after the restoration of flow. In one case, P7 was diagnostic for unsuccessful endarterectomy. CONCLUSIONS: P7 is useful during carotid endarterectomy providing continuous and "on-line" information on brain metabolism. It is a simple and powerful technique, which should be further investigated.