Splanchnic extraction and clearance of tissue plasminogen activator (t-PA) after injection of recombinant t-PA (Actilyse) in resting healthy subjects is proportional to the arterial concentration.

The purpose of the study was to evaluate the splanchnic extraction of tissue plasminogen activator (t-PA) in normal healthy fasting subjects after the injection of recombinant t-PA (rt-PA; Actilyse). In nine healthy volunteers (five male, four female), 21-29 years of age, the concentration of t-PA was determined in plasma samples taken simultaneously from a femoral artery and a large liver vein after a bolus injection (5, 10 or 20 mg) of rt-PA. The splanchnic plasma flow rate, the plasma volume, and the splanchnic extraction fraction of t-PA were determined. After the rt-PA injection, the measured arterial concentration of t-PA decreased from 36 750 to 45 pmol/l for t-PA antigen and from 50 700 to 17 pmol/l for active t-PA. The splanchnic extraction fraction decreased from 0.95 to 0.02 for t-PA antigen and from 0.78 to 0.08 (n = 3) for active t-PA. The extraction fraction was proportional to the arterial concentration of t-PA when the arterial concentration of t-PA was above about 300 pmol/l (both t-PA antigen and active t-PA). The median splanchnic plasma flow rate was 911 ml/min (range, 651-1149 ml/min). In the individual subject, the splanchnic plasma flow rate remained constant during the experimental period. The main conclusion of the study is that the splanchnic clearance and extraction fraction of t-PA, following an injection of rt-PA in the resting fasting steady state, depends on the arterial concentration of t-PA. The higher the arterial concentration of t-PA, the higher the extraction fraction of t-PA.

Mean transit times and the sites of synthesis and catabolism of tissue plasminogen activator and plasminogen activator inhibitor type 1 in young subjects.

Using an invasive technique, we studied the mean transit time, the net quantitative turnover rate, and the sites of synthesis and catabolism of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in healthy young volunteers in the fasting, steady state. Blood was sampled simultaneously from a large hepatic vein, an artery and the inferior caval vein, while measuring the splanchnic plasma flow rate and the plasma volume. We found that the catabolism of active t-PA and t-PA antigen took place in the splanchnic circulation with net rates of 7.2 and 6.3 pmol/min, respectively. The extraction fraction and the mean transit time in the splanchnic circulation were, respectively, 0.63 and 5.6 min for active t-PA and 0.17 and 21 min for t-PA antigen. Active PAI-1 was synthesized in the splanchnic circulation at a rate of 890 IU/min and had a mean transit time of about 9.8 min. No net extraction of PAI-1 antigen took place in the splanchnic circulation. In conclusion, we demonstrated that active t-PA and t-PA antigen are catabolized and active PAI-1 produced in the splanchnic circulation in young healthy subjects during steady state. Furthermore, our data show that active t-PA was also eliminated outside the splanchnic region with a catabolism rate of about 8.4 pmol/min. No net complex formation could be demonstrated in the peripheral circulation. We therefore suggest that active t-PA is eliminated by a re-uptake in the endothelium in the peripheral vessels or in the lung circulation.

Early results of percutaneous transluminal angioplasty (PTA) of failing below-knee bypass grafts.

OBJECTIVES: An audit of treating femoro-crural bypass stenosis in the first instance by PTA. DESIGN: Prospective clinical pilot study in consecutive patients. MATERIALS: Prior to vascular bypass grafting all patients had critical ischaemia. Sixty-four PTA procedures in 50 grafts in 49 patients were carried out. Thirteen were in situ saphenous grafts, 16 were combined venous segments, 18 were combined PTFE and vein and three were PTFE only. METHODS: Conventional cross-over or antegrade PTA, eventually combined with local thrombolytic therapy. RESULTS: The nine-month assisted patency using PTA was 72%, following surgical repair in five cases after failed PTA the secondary patency was 86%. The amputation free survival rate was 88%. In 11 cases thrombosis was treated successfully with local thrombolysis. In two cases the balloon ruptured the native artery wall below the distal anastomosis with pseudoaneurysm formation. Six limbs were amputated during follow-up. The frequency of stenosis in combined grafts was significantly higher than in in situ vein grafts. CONCLUSION: Our results are comparable with surgery. About 600 hospital beds/days were saved. This shortened the time from the diagnosis of stenosis to therapy and shortened the waiting list for vascular surgery.

Comparison of efficacy in crossing femoropopliteal artery occlusions with movable core and hydrophilic guidewires.

PURPOSE: Compare the recanalization rate of femoropopliteal occlusions between movable core wire guide (MG) and hydrophilic guidewire (HG). METHODS: Conventional PTA technique was used, followed by enclosed thrombolysis. The MG was used for all patients in the first 2 years, the HG in the following 2 years. Baseline characteristics were similar for the two groups of patients. RESULTS: Recanalization of 124 femoropopliteal occlusions was attempted. Technical success was achieved with the MG in 45 of 59 procedures; 42 procedures were clinically successful. Using the HG, technical success was achieved in 35 of 65 procedures; clinical success was achieved in 35 of 65 procedures; clinical success was achieved in 29 cases (p < 0.0048). At 1-year follow-up, 32 extremities improved after treatment with MG and 22 extremities after treatment with HG (p < 0.035). CONCLUSION: The results suggest that the MG should be the first choice in recanalization of femoropopliteal occlusions.

Double-blind, controlled, multicenter study of indobufen versus placebo in patients with intermittent claudication.

The objective of the study was to evaluate the efficacy and safety of indobufen compared with placebo in the treatment of moderately severe intermittent claudication. The study consisted of a four-week single-blind, placebo-controlled run-in phase, followed by a six-month double-blind randomized treatment period. A total of 302 patients were allocated to treatment with either placebo (154 patients) or indobufen (148) 200 mg twice daily. The results of the overall intention-to-treat analysis of the study population showed statistically significant superiority of indobufen over placebo after six months for both the initial (ICD) and absolute claudication distances (ACD). The ICD before treatment with indobufen or placebo averaged 137.9 +/- 68.2 and 136.6 +/- 63.2 m (mean +/- SD), respectively. After six months' treatment with active drug or placebo, this parameter reached 227.9 +/- 174.4 and 153.1 +/- 86.8 m (mean +/- SD), respectively (p < 0.01). Similar results were obtained on ACD. The reduction of lower limb symptoms also suggested a greater clinical benefit in the indobufen-treated patients. There was no significant change in either group in the ankle/arm pressure ratio at the end of treatment. Adverse events of any type were reported by 18 patients (12.2%) in the indobufen group and by 11 patients (7.2%) in the placebo group. The mechanism whereby the drug is effective in this clinical condition could be related to both its antiplatelet and hemorheologic effects.

Prolonged binding of radiolabeled recombinant tissue-type plasminogen activator after angioplasty and enclosed thrombolysis of the femoropopliteal arteries.

The authors measured the binding of indium-111-labeled recombinant tissue-type plasminogen activator (rt-PA) within the recanalized femoropopliteal segment after percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis. In patients with long occlusions (n = 3), 91 micrograms of rt-PA was bound 1 hour after the procedure, and the half-time of the final washout curve averaged 114 hours. After PTA in patients with multiple stenoses (n = 6), 45 micrograms of rt-PA was bound, and the half-time averaged 32 hours. These values were significantly smaller than those in patients with occlusions (P < .01). In patients with a single stenosis (n = 4), 19 micrograms of rt-PA was bound, and the half-time averaged 5 hours. These values were significantly smaller than those in patients with multiple stenoses (P < .01). The progressive accumulation of rt-PA at the sites of PTA therapy is most likely related to increasing presence of fibrin with increasing lesion severity. Fibrin accumulation may be partly responsible for early failures after PTA in extensive lesions. Removal of this fibrin with enclosed thrombolysis might improve patency.

Late hemodynamic failure following percutaneous transluminal angioplasty for long and multifocal femoropopliteal stenoses.

The outcome of percutaneous transluminal angioplasty (PTA) was evaluated for treatment of 87 limbs with femoropopliteal stenoses, including 55 short stenoses (2.4 +/- 1.6 cm, mean +/- SD), seven single long stenoses (10.4 +/- 2.0 cm), and 25 multifocal stenoses (2.1 +/- 1.6 cm), where two to four separate segments were dilated. Following 98% initial technical success, 3-year patency was 68% for single short stenoses, as opposed to 20% for long and multifocal stenoses (p = 0.05, logrank test). Antiplatelet therapy with acetylsalicyclic acid was not found to influence occurrence of restenosis. The study documents the poor PTA results for long and multifocal stenoses and suggests precautions to be taken during PTA in order to minimize the area of artery wall damage.

Segmentally enclosed thrombolysis in percutaneous transluminal angioplasty for femoropopliteal occlusions: a report from a pilot study.

Segmentally enclosed thrombolysis (SET) was performed immediately following 34 percutaneous transluminal angioplasties (PTAs) for femoropopliteal occlusions. The dilated segment was sealed off with a double balloon catheter, and recombinant tissue plasminogen activator (rt-PA) 1 mg/ml and heparin 200 IU/ml were injected between the balloons. The catheter was removed after 30 min and heparin treatment was continued for 24 h. Alpha-2-antiplasmin was initially reduced by 13% and normalized 2 h after SET, indicating that only small amounts of free plasmin were liberated during thrombolysis. No clinically relevant changes in plasma fibrinogen occurred. Two puncture site hemorrhages did not coincide with the coagulopathy induced by SET. One-year patency was 80%. Early rethrombosis occurred in 9% versus 41% in our previous series on standard PTA for femoropopliteal occlusions (p less than 0.001). Therefore, SET is considered beneficial in reducing the incidence of early rethrombosis.

Femoro-popliteal artery occlusions treated by percutaneous transluminal angioplasty and enclosed thrombolysis: results in 55 patients.

Removal of fibrin from the site of a newly dilated femoro-popliteal occlusion may be an attractive way of preventing rethrombosis. A double balloon catheter with a dilating tip balloon and an occlusive balloon 10, 15 or 20 cm approximately were introduced percutaneously. Following successful dilatation of femoro-popliteal occlusions, the balloons were inflated on both sides of the lesion. The dilated segment was then isolated from the circulation. Through a sideport between the balloons 5 mg of tissue type plasminogen activator and 1000 IU of heparin were installed within the segment for 30 min. The authors report the results of 53 technically successful dilatations of femoro-popliteal occlusions followed by enclosed thrombolysis. A 100% patency at 3 months was noted in 33 patients having one to three run-off arteries, and the one year patency was 90%. In 20 patients, with no infrapopliteal run-off artery, four rethrombosis occurred within 24 h, and the one year patency was 62%. This difference is significant. (Log rank test, Chi-square = 4.73, p less than 0.05). We conclude that enclosed thrombolysis prevents early reocclusion following PTA of femoro-popliteal occlusions provided that at least one infra-popliteal artery is patent.

Ambulatory measurement of nocturnal fluctuations in subcutaneous blood flow rate in the lower leg of man during 12-h periods with the portable CdTe(Cl) detector. Methodological considerations.

Possible sources of error during long-term measurements of subcutaneous blood flow rate with the portable CdTe(Cl) detector system were ruled out in the present study. Local blood flow rates were recorded in the lower legs of normal human subjects by means of the 133Xe wash-out technique. A good correlation was found between the portable CdTe(Cl) and stationary NaI(Tl) detector systems both prior to (r = 0.88, P less than 0.0001) and after (r = 0.68, P = 0.07) day over night (12 h) measurements. Identical post-ischaemic reactive hyperaemia could be demonstrated by both detector systems 12 h after the application of the isotope depot. This indicates that blood flow rates and vascular reactivity can be measured over 12 h by the portable CdTe(Cl) detector. Identical results were obtained during the 12-h measurements performed with the portable CdTe(Cl) detector attached directly to the skin surface and with the detector elevated above the skin surface. Therefore, geometrical changes were without any influence on our measurements. We conclude that measurements of subcutaneous blood flow rates in the lower leg of human subjects can be performed under out-patients conditions by means of the 133Xe wash-out technique and portable CdTe(Cl) detectors. A skin area greater than or equal to 4 cm should be labelled by means of the atraumatic, epicutaneous labelling technique and the detector attached directly to the skin surface with a single layer of a 20-micron thick gas-tight Mylar membrane interposed between the skin surface and the detector. The investigation of the subcutaneous blood flow rate should not be initiated until at least 90 min after labelling.(ABSTRACT TRUNCATED AT 250 WORDS)

Early rethrombosis in femoropopliteal occlusions treated with percutaneous transluminal angioplasty.

One hundred and thirty-seven consecutive percutaneous transluminal angioplasties (PTA) were performed for femoropopliteal vascular disease including 58 stenoses and 79 total occlusions. Nine occlusions could not be crossed with the guidewire, but in the remaining 128 the haemodynamic and clinical success as well as vascular patency were evaluated. The results were grouped into the following subsets: the indication for PTA, the severity of the vascular lesion, the crural run-off and the length of lesion. The results were in every respect poor with total occlusions when compared with stenoses. This was explained by a high incidence (41%) of rethrombosis within hours of dilatation. Early rethrombosis was seen with all lengths of occlusion (1-27 cm) with no statistically significant difference from other subsets. This study concludes that conventional PTA in femoropopliteal occlusions should be reserved for cases of limb salvage, preferably in patients who are technically inoperable. We suggest a new technique of segmentally enclosed thrombolysis to prevent early rethrombosis after PTA in femoropopliteal occlusions.

[Intermittent claudication--social aspects in young patients not undergoing surgical treatment]. / Claudicatio intermittens--sociale aspekter hos yngre ikke-opererede patienter.

A total of 107 patients suffering from intermittent claudication (CI) was studied after a mean observation time of 5.9 years. Thirty-one (29%) had died during the observation period. A questionnaire was sent to 76 patients and 78% replied. All patients were under 50 years of age at the first consultation. No patients had been operated upon. The ratio women:men was 1:1.3. 33% received disability pensions or some other kind of pensions. Fifty-eight had limited their spare-time activities because of CI. It is concluded that a close control and reconstructive arteria surgery must still be recommended when the working ability is threatened.

Femoral artery recanalisation with percutaneous angioplasty and segmentally enclosed plasminogen activator.

To establish whether re-occlusion of the femoral artery could be prevented, in 6 consecutive patients undergoing percutaneous transluminal angioplasty (PTA) for superficial femoral artery occlusion the recanalised segment was isolated, with a 7-French double-balloon catheter. 5 mg recombined human tissue-type plasminogen activator (rt-PA) and 1000 IU heparin were then infused into the enclosed space for 30 minutes, followed by intravenous heparin for 24 hours. At 10 and 30 days all 6 patients had evidence of recanalisation and remission of symptoms. Mean ankle-arm pressure index improved by 72% at 24 hours, by 118% at 10 days, and by 103% at 30 days after the procedure. No patients had major complications. Treatment of superficial femoral artery occlusions by PTA with rt-PA and intravenous heparin seems to prevent rethrombosis.

Percutaneous transluminal angioplasty of iliac and femoral arteries in severe lower-limb ischaemia.

Percutaneous transluminal angioplasty was performed 92 times in 86 patients with severe lower-limb ischaemia (40% occlusion), giving rise to rest pain and/or gangrene. The patients were thereafter observed for periods up to 5 years. Criteria for success were appearance of normal groin pulse (iliac angioplasty) or persistent greater than or equal to 0.15 rise in arm/ankle blood pressure index (femoropopliteal angioplasty). The respective technical success rates were 82% and 64%. The complication rate was 10.9%, including 5.4% distal embolization. Patency rates were higher in iliac than in femoropopliteal lesions, in stenotic than occluded vessels, and also when the lesion was shorter than 5 cm and if there was good run-off. Limb salvage exceeded patency by 10% in the iliac procedures and by 15% in the femoropopliteal. Percutaneous transluminal angioplasty is recommended for selected cases of severe lower-limb ischaemia, and should always be considered for limb salvage. Reocclusion does not necessarily imply clinical failure. Technical failures should be included in calculated patency rates in order to document the method's limitations.

Percutaneous transluminal angioplasty of infrarenal arteries in intermittent claudication.

Percutaneous transluminal angioplasty was performed on 55 iliac and 31 femoropopliteal arteries in 71 patients with intermittent claudication (23 women, 48 men). The two-year patency rate was 80% after iliac and 41% after femoropopliteal angioplasty. In 17 femoropopliteal cases with lesions greater than or equal to 5 cm the 2-year patency rate was only 32%, but the corresponding figure for shorter lesions was 53%. Complicating haematoma appeared in 10% of the cases and the arterial state deteriorated in one patient. There was no distal embolization. Percutaneous transluminal angioplasty in intermittent claudication is indicated for all cases of occlusion or stenosis of the iliac artery and for occlusion or stenosis shorter than 5 cm of the superficial femoral or the popliteal artery.

Percutaneous transluminal angioplasty of the superficial femoral artery by retrograde catheterization via the popliteal artery.

We report the results of 50 angioplasty procedures via the popliteal artery. A 3-year follow-up including control of blood pressures at ankle and toe levels show results comparable to reports in the literature. This new approach for angioplasty of the superficial femoral artery and eventually of coexisting iliac lesions enables treatment of previously inaccessible lesions. The technique is especially suited for lesions close to the takeoff of the superficial femoral artery.

The cause of ischaemic nocturnal rest pain.

Adipose tissue blood flow in the forefoot was measured simultaneously with mean systemic arterial blood pressure over 24 hours in 8 patients (15 feet) with different degrees of arterial insufficiency. Mean systemic arterial pressure decreased by 19 +/- 9% during sleep, irrespective of symptomatology. In two limbs, with a normal peripheral circulation, blood flow decreased by 8 +/- 7%. In five limbs with arterial insufficiency, but no rest pain, blood flow decreased by 16 +/- 8% and in eight limbs with ischaemic nocturnal rest pain blood flow was reduced by 32 +/- 12% during sleep. It is concluded that nocturnal hypotension is a major factor in the production of nocturnal ischaemic rest pain.

Influence of renal function on the elimination of morphine and morphine glucuronides.

The influence of renal function, measured by 51Cr-EDTA clearance, on morphine and morphine glucuronide kinetics has been studied in 13 patients after a single i.v. injection of morphine. Unconjugated morphine and morphine glucuronides were measured by a sensitive, specific RIA after extraction from plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r = 0.94, p less than 0.001). A relatively long terminal elimination of half-life of morphine was found in all patients (mean +/- SD: 9.2 +/- 2.5 h), irrespective of glomerular function.