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OBJECTIVES: To find variables associated with outcome following thrombolytic treatment for acute lower limb ischemia. DESIGN: Re-analysis of a prospective multicentre study. MATERIAL AND METHODS: One hundred and twenty-one patients with acute lower limb ischemia previously included in a randomised study comparing high- with low-dose thrombolysis were re-analysed ignoring the mode of lytic treatment. All possibly predictive variables were subjected to multivariate analyses to find associations with outcome. RESULTS: Previous successful thrombolysis, ankle-brachial index over 0.33, absence of motor dysfunction, presence of cardiac arrhythmia, and lysis of a vascular graft were all associated with successful thrombolysis (p=0.003). Previous thrombolysis, age less than 70 years, and ankle-brachial index over 0.33 were all perfect predictors of absence of life-threatening complications or death. Successful lysis, age<70, and lysis of a native artery as opposed to a vascular graft were all associated with clinical success (preserved patency, limb, and life) after one year (p=0.002). CONCLUSIONS: Previous thrombolysis, age under 70 years, and non-severe ischemia predict successful thrombolysis free from severe complications. Successful thrombolysis is strongly predictive of amputation-free survival with vascular patency for at least one year. Occluded grafts could often be reopened, but long-term outcome is better after thrombolysis of native arteries.

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OBJECTIVES: To test if initial high-dose, pulse-spray thrombolysis improves the early and late outcome of lower limb ischaemia as compared with low-dose infusion alone. DESIGN: Prospective randomised multicentre study. MATERIAL AND METHODS: Patients with acute and sub-acute (<30 days) lower limb ischaemia were randomised following angiography. Group 1 (n=58) received pulse-spray infusion of recombinant plasminogen activator (rt-PA, 15 mg/h) for 2h followed by low-dose infusion if needed. Group 2 (n=63) were only treated with low-dose infusion (0.5mg/h) of rt-PA for 48 h. Underlying lesions were corrected if required. RESULTS: The study was stopped prematurely. Complications were equally frequent in both groups. More than 75% lysis was accomplished in 78 versus 67% of the patients (p=0.21). Primary endpoints (re-occlusion, incomplete lysis, life-threatening complication, amputation, or death) were reached in 24 versus 32% of the patients (p=0.35). Neither vascular patency nor clinical parameters differed during the first year, but re-interventions tended to be more frequent (p=0.040 at 1 month; p=0.090 at 1 year) and of a greater magnitude (p=0.028) in group 2. CONCLUSIONS: There was no obvious advantage with initial high-dose thrombolysis, which may be a type-2 error. A reduction of major re-interventions was recorded.

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OBJECTIVES: To study if venous thrombectomy prevents late post-thrombotic sequelae, venous obstruction reflux, and improves venous physiology following an acute iliofemoral venous thrombosis. DESIGN: Prospective randomised controlled study. MATERIAL: Thirty patients returned for follow-up 10 years after an acute iliofemoral venous thrombosis initially treated with conventional anticoagulation treatment (medical group, n = 17) or with thrombectomy combined with a temporary arteriovenous fistula and anticoagulation (surgical group, n = 13). Clinical assessment, radionuclide angiography, duplex ultrasound and venous physiology tests were performed. RESULTS: Leg swelling was recorded in 12 (71%) and leg ulcers in three (18%) of the medical patients and in, respectively, six (46%) and one (8%) of the surgical patients. The surgical patients had less severe sequelae (class 0-2). Radionuclide angiography demonstrated that the iliac vein was more commonly occluded following medical (59%) than following surgical (17%) treatment (p < 0.05). Duplex examination demonstrated slightly (n.s.) more reflux in the femoral and popliteal veins in the medical group. Venous physiology (occlusion plethysmography, foot volumetry, and foot vein pressures) did not show any significant differences, although the medical group tended to have a more severe pathology. CONCLUSION: Venous thrombectomy improves venous patency and possibly reduces venous reflux and post-thrombotic sequelae as compared to anticoagulation treatment.

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AIM: To investigate a series of patients with secondary aortoenteric fistulas and compare it with a previous series (1985-93 vs. 1973-84). DESIGN: Retrospective study of medical records. SETTING: Sixteen vascular surgical centers in Sweden. PATIENTS: Twenty-seven patients were identified making an overall incidence of 0.5% of all aortoiliac operations. Among aneurysm patients the incidence was significantly lower than in the previous series. One patient record could not be identified. Fourteen primary operations were for aortic aneurysm, 12 for occlusive disease and one was an aortorenal vein bypass. RESULTS: Symptoms of the fistula occurred after a median interval of 90 months which is significantly later than the previous series (32 months; p<0.05). The commonest presentation was bleeding followed by septis. The median diagnostic delay was 10.5 days, which was significantly shorter than in the previous series. Most fistulas involved the duodenum (88%). One patient died before surgery. The postoperative mortality was 28%, significantly lower than in the previous series (58%) (p<0.05). At the end of follow up (median 43 months) significantly more patients were alive than in the previous series (42% vs 18%) (p<0.05). CONCLUSION: Over a 21 year period there seems to have been a decrease in the frequency of secondary aortoenteric fistulas after aneurysm surgery, a longer interval before they occur, a shorter diagnostic delay, and a better survival.

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OBJECTIVE: To study the effect of polymorphonuclear leucocytes (PMNLs) on reperfusion injury in rabbit skeletal muscle and to evaluate the role of oxygen-derived free radicals in PMNL-mediated reperfusion injury. EXPERIMENTAL DESIGN: An isolated rabbit limb perfusion model. Amputated hindlimbs were subjected to 4 hours of ischaemia followed by 2 hours of reperfusion with oxygenated Krebs' buffer. SETTING: Department of experimental surgery. ANIMALS: 14 rabbits. INTERVENTIONS: In group I (n = 8), one limb from each animal was reperfused with PMNL-supplemented buffer while the other limb was reperfused with cell-free buffer (control). In group II (n = 6), SOD and catalase were added to the limb reperfused with PMNL-supplemented buffer while the other limb was reperfused with cell-free buffer without SOD and catalase (control). MEASURES: PMNL accumulation as myeloperoxidase (MPO) activity, muscle necrosis as uptake of [Tc99]methylenediphosphonate (MDP), and oedema as increase in muscle water content (MWC). Electron microscopy was performed for histological demonstration of reperfusion injury. RESULTS: Addition of PMNLs increased MPO activity (p < 0.05) and MDP uptake (p < 0.05) but did not affect MWC. SOD and catalase treatment of limbs perfused with PMNLs prevented the increase in MPO activity (p < 0.05) and reduced MDP uptake (p < 0.05) and MWC (p < 0.05). PMNLs aggravated histological changes seen after reperfusion. CONCLUSIONS: Reperfusion injury in skeletal muscle is, at least partially, mediated by PMNLs. Free radical scavengers reduce PMNL-dependent injury and prevent PMNL accumulation suggesting that oxygen-derived free radicals are mediators of PMNL-dependent injury and/or engaged in the interaction between PMNLs and the microvascular endothelium.

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Mannitol has previously been shown to reduce skeletal muscle reperfusion injury and postischaemic compartment pressure. The present study was designed to evaluate whether these effects result from hyperosmolarity or free radical scavenging. A rabbit hindlimb perfusion model was used to compare the effects of mannitol (n = 6), glucose (n = 6)--an isomer of mannitol without scavenging effect--and fasciotomy (n = 6) on oedema, compartment pressure, energy charge, and muscle injury after 4 hours of ischaemia and 2 hours of reperfusion. One limb from each animal received treatment, while the other limb served as an untreated control. Mannitol and glucose reduced (p < 0.05) muscle water content and decreased (p < 0.01) the compartment pressure. Fasciotomy had no effect on muscle water content but normalised compartment pressure. The increase in energy charge following reperfusion was improved (p < 0.05) and uptake of [Tc99]methylenediphosphonate--an indicator of muscle injury--was reduced (p < 0.05) by mannitol only. In conclusion, mannitol reduces postischaemic oedema mainly by its hyperosmolar property whereas restitution of energy production and reduction of muscle necrosis seem to be an effect of free radical scavenging. The compartment pressure is reduced by hyperosmolarity and free radical scavenging.

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OBJECTIVE: To evaluate the role of oxygen-derived free radicals in reperfusion injury of skeletal muscle in rabbits. DESIGN: Open experimental study. SETTING: Department of experimental surgery. MATERIAL: 32 rabbits. INTERVENTIONS: Four groups according to pretreatment: group I: superoxide dismutase-superoxide scavenger; group II: catalase-hydrogen peroxide scavenger; group III: superoxide dismutase and catalase; group IV: mannitol-hydroxyl scavenger. Amputated hindlimbs were subjected to 4 hours of ischaemia followed by 2 hours of reperfusion. One limb was treated while the other served as a control. MAIN OUTCOME MEASURES: Muscle water content, energy charge, and muscle injury (uptake of 99mTc-methylenediphosphonate). RESULTS: Muscle water content was reduced in group III (p < 0.05) and IV (p < 0.05). Energy charge was improved in group IV (p < 0.05). Muscle injury was reduced in groups II (p < 0.05), III (p < 0.05), and IV (p < 0.01), but most in group IV (p < 0.01). CONCLUSION: Oxygen-derived free radicals seem to be mediators in reperfusion injury of skeletal muscle. The hydroxyl radical seems to be the most important of the xanthine oxidase-derived free radicals.

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OBJECTIVE: To clarify the effects of ischaemia and reperfusion on membrane potential of skeletal muscle in rabbits, and to study its correlation with the energy charge and the lactate content. DESIGN: Open experimental study. MATERIAL: 20 isolated rabbits' hindlimbs. INTERVENTIONS: The femoral arteries were cannulated and the limbs amputated at the level of the hip joint. Blood was removed by thorough perfusion with Ringer's solution. Below knee fasciotomies were done, and the whole limbs were immersed in Ringer's solution during periods of ischaemia. Reperfusion was with a modified Krebs' buffer with Dextran T70 saturated with oxygen. OUTCOME MEASURES: Measurements of membrane potential; ATP, ADP, and AMP concentrations; and lactate concentrations in muscles after 1 (n = 8), 2 (n = 4), 4 (n = 4), or 6 (n = 4) hour periods of ischaemia followed by a 2 hour period of reperfusion compared with those in 4 limbs that were made ischaemic for 8 hours and not reperfused. RESULTS: During the first hour of ischaemia the membrane potential decreased from -90 mV to -63 mV and the energy charge remained unchanged at 0.9. After 8 hours of ischaemia the membrane potential had decreased to -20 mV, the energy charge was 0.2, and the lactate content had increased by a factor of 12. During reperfusion the membrane potential was restored only in limbs that had been subjected to 1 hour of ischaemia, whereas energy charge was also restored in those subjected to 2 and 4 hours of ischaemia. The lactate content decreased during reperfusion in all limbs. CONCLUSION: Assessment of membrane potential is more sensitive than that of energy charge as an indicator of recovery of skeletal muscle after a period of ischaemia followed by reperfusion.

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Cardiac monitoring and the selective use of initial non-operative management is reported to reduce the high mortality rate in patients with acute lower limb ischaemia. Early estimation, prior to selection of initial therapy, of the risk for intraoperative or postoperative cardiac death following thrombo-embolectomy is therefore important. The aim of this prospective multi-centre study was to develop a simple and clinically useful index for assessment of the risk of post-operative cardiac death. Patients judged to need thrombo-embolectomy for acute lower limb ischaemia were evaluated on admission for routine clinical, cardiac and limb ischaemia parameters that could be related to cardiac function and these parameters compared to postoperative cardiac outcome. Sixteen per cent of the 117 patients died from intraoperative or postoperative cardiac complications. Analysis revealed five admission parameters that significantly and independently predicted a high risk for cardiac death: mean arterial blood pressure below 90 mmHg, clinical sign(s) of cardiac decompensation, ischaemia affecting the thigh, haemoglobin concentration exceeding 140 gl-1, and a history of a myocardial infarction in the previous 4 weeks. Definition of risk points for each risk factor allowed a simple classification of each patient into one of three significantly different cardiac risk classes with cardiac death rates of 6 +/- 3%, 27 +/- 8% and 75 +/- 16%, respectively. More than two thirds of the patients belonged to the low risk group. The described risk index provides a tool for preoperative assessment of the cardiac death risk associated with early thrombo-embolectomy in patients with acute lower limb ischaemia.

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Reperfusion of ischaemic skeletal muscle may lead to increased vascular permeability, oedema and ultimately muscle necrosis. Oxygen-derived free radicals have been suggested as aetiological factors in reperfusion injury. Amputated rabbit hindlimbs were subjected to 4 h of ischaemia followed by 2 h or reperfusion with Krebs' buffer. One limb from each animal was reperfused with oxygen-saturated buffer (reoxygenated limb) while the other limb was reperfused with nitrogen-saturated buffer (non-reoxygenated limb). Six animals received allopurinol orally 2 days prior to the experiment and ten animals received no treatment. The energy charge dropped from 0.90 to 0.54 during ischaemia and increased to 0.82 after reperfusion with oxygenated perfusate. Oedema was determined by limb weight and water content in muscle biopsies and muscle injury was assessed by uptake of [Tc99]methylenediphosphonate ([Tc99]MDP). The results were expressed in ratios, between the reoxygenated and nonreoxygenated limb. Without allopurinol treatment, the increase in water content and limb weight in reoxygenated limbs exceeded (p less than 0.05) non-reoxygenated limbs (ratios = 1.73 and 1.89, respectively). Allopurinol treatment significantly reduced (p less than 0.05 and p less than 0.02, respectively) the increase in water content and limb weight (ratios = 0.54 and 1.01, respectively). Without treatment, [Tc99]MDP-uptake was greater (p less than 0.05) in reoxygenated limbs than in non-reoxygenated limbs (ratio = 1.60). Allopurinol treatment significantly reduced (p less than 0.002) [Tc99]MDP-uptake in reoxygenated limbs (ratio = 0.80). These results demonstrate that additional injury to ischaemic skeletal muscle occurs during reperfusion with oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

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Forty-one patients with acute iliofemoral venous thrombosis were randomised to conventional anticoagulation or acute thrombectomy combined with a temporary arterio-venous fistula (AVF) and anti-coagulation. Follow-up after 5 years in 22 medical and 19 surgical patients revealed slightly more asymptomatic patients (37 vs. 18%) and less frequent severe post-thrombotic sequelae (16 vs. 27%) in the surgical group (N.S.). The iliac vein was more frequently (P less than 0.05) normal following thrombectomy (71 vs. 30%) as demonstrated by radionuclide angiography, but occlusion plethysmography showed an outflow capacity (61 vs. 45 ml/min/100 ml) that was not significantly better. There was no obvious difference in muscle pump function (EVrel) and reflux (Q/EVrel) assessed by foot volumetry. Still, the ambulatory venous pressure was significantly (P less than 0.05) lower in the surgical group. There was a tendency towards better results following thrombectomy in patients with fresh thrombosis and a successful initial procedure. Although the numbers of observations in many cases were too small to provide statistical evidence of benefit with venous thrombectomy + AVF, this procedure seems to improve the long-term outcome following acute iliofemoral venous thrombosis. Since the difference in outcome is not very striking, anticoagulation treatment is still an acceptable alternative.

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To determine the chronological changes of venous physiology following major thromboses, 20 patients were repeatedly examined for over 5 years after an acute ilio-femoral thrombosis which was treated with conventional anticoagulation. Radionuclide angiography showed that 70% of the patients had obstructive lesions of the iliac vein with only minor changes occurring from 6 months to 5 years. In spite of this, the plethysmographic maximum venous outflow increased from 31 to 45 ml/min/100 ml (P less than 0.001). The foot volumetric reflux did not change with time and about half of the patients had abnormal values. Venous reflux assessed by the refill time of foot vein pressure, deteriorated with time (P less than 0.05), and at 5 years all but one patient had a refill time less than 20 s. The muscle pump function, examined by foot volumetry, was abnormally low in about half of the patients throughout the study. The ambulatory foot vein pressure was constantly pathological (greater than 60 mmHg) in half of the patients and only two of 18 patients had normal values (less than 45 mmHg) at 5 years. Five patients with thromboses involving only the proximal veins had better physiological results than 15 patients with thromboses that extended to the peripheral veins. Three patients who developed venous claudication had iliac vein obstruction and an impaired venous outflow and three patients who developed venous ulcers had venous reflux and severe venous hypertension. Although venous outflow continuously improves following ilio-femoral thromboses, valvular competence and muscle pump function are constantly pathological, creating severe venous hypertension with a risk of post-thrombotic sequelae.

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Experimental atherosclerosis was induced in a rabbit model by intimal damage of the infrarenal aorta followed by two months cholesterol feeding. The influence of four different antiplatelet drug regimens on acute platelet and fibrin deposition after transluminal angioplasty of the atherosclerotic abdominal aorta was then evaluated. The study group consisted of 32 New Zealand rabbits: 7 controls, 7 treated with prostacyclin (10 mg/kg/min i.v.), 5 treated with low-dose acetylsalicylic acid (2 mg/kg i.v.), 7 treated with acetyl-salicylic acid (5 mg/kg i.v.) and dipyridamole (2 mg/kg i.v.), and 6 treated with low molecular dextran (5 ml/kg). By 2 hours after angioplasty, there was a significant increase of the deposition of platelets (P less than 0.001) as well as fibrin (P less than 0.01) when comparing dilated to non-dilated segments in the control animals. There was no significant difference in the amount of platelets and fibrin deposition among the control and drug treated groups. Thus, in this animal model there appears to be no immediate benefit in using antiplatelet drugs during transluminal angioplasty. Although, this study did not address the potential long-term effects of antiplatelet drug therapy, future evaluation of the clinical benefits of these drugs in conjunction with transluminal angioplasty seems warranted.

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Radionuclide angiography (RNA), was compared to contrast phlebography (CP) for evaluation of iliofemoral venous patency. Twenty-three patients that six months earlier had been treated for iliofemoral venous thrombosis were investigated. The reproducibility of RNA was good as the interindividual and intraindividual variation was 80-85% and 90-95% respectively. The sensitivity of RNA was 91% in the iliac and 65% in the femoral segment. The specificity was 78% in the iliac and 74% in the femoral segment. The advantages as compared to CP are: easy performance, easy to repeat, no adverse reactions and visualization of the whole venous system. The disadvantages are: e.g. difficulties in interpretation in bilateral disease or abnormal anatomy. RNA is recommended as a screening method for suspected iliac venous obstruction and for follow-up of venous patency after iliofemoral venous thrombosis.

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In this follow-up of 1,112 patients operated on for abdominal aortic aneurysm (AAA) it was noted that cerebrovascular accidents (CVAs) caused significant (8.2%) late mortality. Seventy-one patients developed non-fatal or fatal CVAs at 5.9 +/- 2.9 (mean +/- SD) years after the initial aneurysm repair. The incidence of CVA was 4.2% and 9.5% within five and ten years, respectively. In patients with preoperative evidence of both hypertension and heart disease, the incidence of CVA within five years was 9.1% compared to an incidence less than 4% in patients with either or neither of these risk factors (p less than 0.01). Multivariate analysis of individual risk factors revealed that only age (p less than 0.001), hypertension (p less than 0.001), angina pectoris (p less than 0.02) and other heart disease (p less than 0.001) were independently associated with a reduced survival free of CVA. Thus, cerebrovascular accidents are responsible for significant late morbidity after AAA repair. Patients at high age or with evidence of hypertension and heart disease carry a greater risk for this complication.

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