Pulse-spray thrombolysis with reteplase: optimization and comparison with tPA in a rabbit model.

PURPOSE: To critically evaluate and optimize methodology for pulse-spray thrombolysis with reteplase in a rabbit inferior vena cava (IVC) thrombosis model and to compare results with optimized parameters for the use of tissue plasminogen activator (tPA). MATERIALS AND METHODS: Occlusive IVC thrombus was produced in 102 rabbits and treated 2 days later for 1 hour with pulse-spray thrombolysis using reteplase. Methodologic variables included pulse frequency, concentration and amount of reteplase, infusion versus pulse therapy, and admixture of heparin. After the rabbits were killed, residual thrombus was weighed and percent lysis was estimated on the basis of previous control values. Results were compared with those achieved with tPA in 18 additional rabbits and also with previous tPA results. RESULTS: As in earlier tPA studies, pulse-spray methods were far more effective than constant infusion. Pulses at 30-second intervals produced better results than pulses at 2-minute intervals. At the optimal concentration of 0.02 U/mL (molarity 90 x 10(-8) ), reteplase produced 79% lysis. At two-fold higher or lower concentrations, lysis was reduced by approximately 25%, and at eight-fold higher or six-fold lower concentrations, lysis was reduced by approximately 50%. Optimal concentration of tPA was 0.02 mg/mL, yielding 78% lysis. Admixture of reteplase with heparin suggested improvement, but differences were statistically insignificant. CONCLUSION: When used with pulse-spray methodology, reteplase demonstrated a steep bell-shaped response-concentration curve similar in pitch and amplitude to that of tPA. The optimal molar concentration of reteplase was approximately three times that of tPA. However, at their respective optimal concentrations, reteplase and tPA were equally effective.

Plasminogen-enriched pulse-spray thrombolysis with tPA: further developments.

PURPOSE: To further improve methods for pulsed plasminogen-enriched thrombolysis and to compare results with the best obtainable with use of tissue plasminogen activator (tPA) alone. MATERIALS AND METHODS: Parameters of plasminogen-enriched pulse-spray thrombolysis were manipulated in groups of rabbits with inferior vena cava thrombosis, and weights of 1-hour residual thrombus were compared. Variables evaluated were (i) tPA pulse frequency, (ii) amount of plasminogen used for enrichment, (iii) tPA concentration and amount, (iv) pulsed versus infused tPA, and (v) admixture versus separation of plasminogen and tPA. RESULTS: With use of 3 mg of tPA and approximately 0.9 mg plasminogen enrichment, efficacy varied directly with pulse frequency over a pulse range of every 15 minutes to every 30 seconds. With use of 30-second pulses of tPA at a concentration 0.125 mg/mL, efficacy also correlated directly with increasing plasminogen enrichment up to, but not beyond, approximately 1.8 mg per 1.24 g of clot. Optimized methodology yielded 89% lysis in 1 hour, as compared to 74% lysis previously reported with use of optimized low-concentration (0.01 mg/ mL) tPA alone. Plasminogen enrichment in conjunction with low concentrations of tPA, admixture of tPA and plasminogen, and fractionation of the plasminogen enrichment all proved to be nonproductive or counterproductive. CONCLUSION: Optimized in vivo postthrombotic plasminogen enrichment significantly accelerated thrombolysis of experimental clots compared to use of optimized tPA alone.

Augmented experimental pulse-spray thrombolysis with tissue plasminogen activator, enabling dose reduction by one or more orders of magnitude.

PURPOSE: To critically evaluate and optimize methodologic details of pulse-spray thrombolysis with tissue plasminogen activator (tPA) in a subacute rabbit inferior vena cava thrombosis model. MATERIALS AND METHODS: Occlusive inferior vena cava thrombi were produced in 104 rabbits and 2 days later were treated for 1 hour with pulse-spray thrombolysis using tPA. Methodologic variables included pulse frequency, concentration and amount of tPA, infusion versus pulse therapy, and admixture of heparin. After the rabbits were killed, residual thrombus was weighed. RESULTS: The authors' earlier standard regimen (3 mg of tPA in 6 mL of heparinized saline, 0.2-mL hand pulses, frequency 1 pulse per 2 minutes) produced 60% mean lysis. Optimization involved increasing the pulse frequency to two per minute and decreasing tPA concentration by 98% to 0.01 mg/mL, modifications that produced 22% more thrombolysis, despite 92% reduction in amount of tPA to 0.25 mg. CONCLUSION: Consistent with the in vitro work of other investigators, a roughly bell-shaped dose-response curve was elicited in vivo for pulse-spray with tPA. By diluting tPA to an optimal level, and increasing pulse frequency to two per minute, thrombolysis was markedly augmented. These results suggest that the conventional dose of tPA used for clinical pulse-spray thrombolysis can be reduced by one to two orders of magnitude, possibly markedly reducing procedural risk.

Percutaneous introducibility of the expandable vascular sheath system and injury potential of balloon-assisted thrombectomy: preliminary In vivo results.

PURPOSE: To test the percutaneous introducibility of the expandable vascular sheath (EVS) system and the safety of percutaneous balloon-assisted thrombectomy. METHODS: The EVS was inserted directly (n = 9) or through a 9.5 Fr regular vascular introducer sheath (n = 9) into the femoral arteries and veins and carotid arteries in four dogs (18-21 kg). Balloon-assisted thrombectomies were simulated in iliac arteries. Histologic examinations were done at sites of funnel deployment immediately (n = 4) and 25 days (n = 8) after the intervention. RESULTS: The EVS was successfully introduced into six of nine vessels by a direct percutaneous approach. Balloon-assisted thrombectomy using the EVS device caused localized intimal denudation, disruption of the internal elastic lamina, and mild hemorrhages into the media; one arterial dissection at the site of funnel deployment was seen. All indirect insertions and funnel deployments were successful. Twenty-five days after the experiments, intimal hyperplasia was noted in all cases. CONCLUSION: Percutaneous balloon-assisted thrombectomy may cause mild vascular injuries. Direct percutaneous introduction of the EVS device cannot be recommended yet.

Augmented pulse-spray thrombolysis with tPA by early pulsed intrathrombic plasminogen enrichment.

PURPOSE: This study was designed to evaluate the efficacy of plasminogen enrichment of subacute thrombus in further accelerating pulse-spray pharmacomechanical thrombolysis (PSPMT) with urokinase (UK) or tissue plasminogen activator (tPA) in a rabbit model. MATERIALS AND METHODS: With use of a subacute rabbit inferior vena cava (IVC) thrombosis model, 78 rabbits were divided into eight groups according to the agents used for thrombolysis: (i) controls (IVC thrombosis, no lysis performed), (ii) pulse-spray thrombolysis with saline only, (iii) PSPMT with UK, (iv) PSPMT with UK, plus interim pulse-spray plasminogen enrichment after 14 minutes, (v) pulse-spray plasminogen enrichment, followed at 10 minutes by PSPMT with UK, (vi) PSPMT with tPA, (vii) PSPMT with tPA, plus interim plasminogen enrichment, and (viii) pulse-spray plasminogen enrichment, followed at 10 minutes by PSPMT with tPA. RESULTS: Intrathrombic pulsed injection of glu-plasminogen after 14 minutes of tPA PSPMT demonstrated significant augmentation of lysis (approximately 31% decrease in residual thrombus) compared with tPA alone (P = .006). Lysis was not augmented significantly when plasminogen was sprayed into thrombus before tPA, or before or after UK. CONCLUSION: Plasminogen enrichment of thrombus after onset of PSPMT with tPA significantly accelerated thrombolysis in a subacute in vivo rabbit model. A clinical trial of this method may be warranted.

Percutaneous balloon-assisted thrombectomy: preliminary in vivo results with an expandable vascular sheath system.

PURPOSE: To test an expandable vascular sheath system for percutaneous transcatheter balloon-assisted thrombectomy in vivo. MATERIALS AND METHODS: A 9-F expandable vascular sheath system was used. The system consisted of a sheath with a deployable funnel configuration and a 3-F balloon catheter used coaxially. Thrombus was created in the inferior vena cava of 24 rabbits. Thrombus with a mean weight +/- 1 standard deviation of 1,028 mg +/- 67 was removed percutaneously with the expandable sheath system at 2 days (n = 16) and 7 days (n = 8) after formation; 7-day patency was examined after removal of 2-day-old thrombus (n = 8). Histologic examination was performed in the inferior vena cava. RESULTS: In all cases of 2-day-old occlusion, complete patency of the inferior vena cava was achieved. In cases of 7-day-old occlusion, patency could be completely restored in four (50%) cases; in two (25%) cases each, there was partial removal or no thrombus could be extracted. Histologic findings were comparable with those observed after balloon embolectomy. CONCLUSION: Percutaneous transcatheter balloon-assisted embolectomy is feasible with the expandable vascular sheath system.

Accuracy of contrast-enhanced magnetic resonance angiography in chronic thromboembolic disease.

RATIONALE AND OBJECTIVES: We evaluated the accuracy of contrast-enhanced magnetic resonance (MR) angiography in demonstrating the findings of chronic pulmonary thromboembolism (CPTE) compared with conventional pulmonary angiography. METHODS: We examined 18 patients with CPTE proved by conventional pulmonary angiography and 16 healthy control patients. T1-weighted and single-breathhold, two-dimensional multiplanar spoiled gradient-recalled pulmonary images were obtained after injection of gadopentetate dimeglumine. Images were interpreted independently by two radiologists. RESULTS: All patients with CPTE were identified on MR angiography images by both readers. Sensitivity and specificity for MR angiography in diagnosing abnormal segments were 76% and 95% for reader 1 and 68% and 93% for reader 2, respectively. Sensitivity and specificity for MR angiography in depicting abnormal lobes were 83% and 96% for reader 1 and 82% and 93% for reader 2, respectively. Interobserver agreement was high; kappas for abnormal segments and abnormal lobes were .72 and .84, respectively. The T1-weighted spin-echo images demonstrated a mosaic signal intensity pattern in all patients with CPTE. CONCLUSION: Contrast-enhanced MR angiography accurately depicts abnormal segments and lobes in occlusive vascular disease and clearly distinguishes between patients with CPTE and those with healthy lungs.

Hand ischemia in patients with hemodialysis access grafts: angiographic diagnosis and treatment.

PURPOSE: To determine the cause of symptoms and efficacy of transcatheter therapy in a series of patients with dialysis grafts and hand pain referred for arteriography. MATERIALS AND METHODS: Thirteen patients with 14 hemodialysis grafts underwent arteriography for possible hand ischemia. The sites of proximal graft anastomosis were the distal radial artery (n = 6) and the mid- to distal brachial artery (n = 6). Transcatheter therapy was performed via the graft or by antegrade brachical puncture. RESULTS: The cause of symptoms was ischemia from obstructive arterial disease in seven cases (three with superimposed steal), graft steal alone in three, ischemic monomelic neuropathy in two, and carpal tunnel syndrome in two. Five arterial stenoses were treated with angioplasty, with improvement or resolution of symptoms in four patients. CONCLUSION: In this group, symptoms were usually the result of inflow or outflow arterial disease, alone or in combination with graft steal. Transcatheter therapy (angioplasty or embolization) is effective in selected cases.

Pulse-spray pharmacomechanical thrombolysis of thrombosed hemodialysis access grafts: long-term experience and comparison of original and current techniques.

OBJECTIVE: Pulse-spray pharmacomechanical thrombolysis is an evolving method for the treatment of vascular occlusions in which a highly concentrated fibrinolytic agent is injected as a high-pressure spray directly into thrombus. The purpose of this retrospective study was to analyze our long-term experience with this technique for the treatment of clotted hemodialysis grafts and to compare the efficacy and safety of the original and current methods. SUBJECTS AND METHODS: Over 6 years, 284 cases of dialysis graft thrombosis were considered suitable for treatment with pulse-spray thrombolysis. The original technique involved the injection of highly concentrated urokinase directly into a clot through two crisscross catheters with multiple side holes. The current technique includes early fragmentation of residual clot with a balloon catheter, intrathrombic injection of heparin, mechanical treatment of a lysis-resistant clot at the arterial anastomosis, and routine administration of aspirin. After thrombolysis, underlying obstructions were treated with balloon angioplasty, atherectomy, or stents. The technical success, immediate clinical success, and frequency of complications for the entire population were analyzed. In addition, the results for 36 cases treated with the original technique were compared with the results for 37 recent cases treated with the current technique. RESULTS: Of 284 cases considered suitable for treatment, thrombolysis was not done in eight cases because the venous anastomosis could not be crossed. Thrombolysis was discontinued in two cases because of extravasation of contrast material. The technical success for all grafts considered for treatment was 96%; 92% of treated grafts remained patent for at least 24 hr. Major complications occurred in 1% of cases, and minor complications occurred in 9% of cases. The clinical efficacies of the original and current techniques were 86% and 92%, respectively. The mean thrombolytic agent infusion time was reduced from 44 +/- 20 min to 23 +/- 13 min (p < .001). The overall procedure time for the recently treated subgroup was 67 +/- 26 min. There was no significant difference in the frequencies of major and minor complications between the treatment subgroups. CONCLUSION: Pulse-spray pharmacomechanical thrombolysis is a reliable, rapid, and safe method for recanalization of occluded dialysis grafts. The current technique has been proven as safe and effective as the original technique but offers the advantage of a significant reduction in the time required for the infusion of thrombolytic agent.

Experimental investigation of hypercoagulant conditions associated with angiography.

PURPOSE: To evaluate changes in blood coagulability after high-velocity intravascular fluid injections under conditions relevant to angiography. MATERIALS AND METHODS: In 101 rabbits, fluids were injected at 1,000 psi (6,890 kPa) via a multiple-side-hole catheter in the abdominal aorta, while blood was simultaneously aspirated via a second downstream catheter. The fluids injected included saline, contrast media, blood, tissue plasminogen activator, and heparin. The aspirate was evaluated for clotting time with an activated clotting time (ACT) device, for elevated levels of plasma hemoglobin to confirm capture of at least part of the injection bolus in the sample, and sometimes for hematocrit or fibrin degradation products (FDP). RESULTS: A single high-pressure injection of 2 mL of saline briefly accelerated the ACT of a blood-saline bolus (mean, 38% +/- 4). The mean volume of the hypercoagulable bolus was 15 mL. Systemic FDP levels became elevated within a few minutes after initial injection, suggesting activation of the fibrinolytic system by intravascular clot formation. Subsequent injections produced less hypercoagulability, probably reflecting the anticoagulant effects of FDP. Pressure-injected contrast agents had anticoagulant effects. The ACT was accelerated by up to 80% after injection of blood that had remained within the catheter for 3-10 minutes. Glove powder or gauze lint from wiping the guide wire markedly accelerated intracatheter clotting. Hypercoagulability after injection of clotting blood was partially prevented by injections with contrast agent and was completely inhibited by low-dose systemic heparinization. CONCLUSION: A hypercoagulable bolus may occur after angiographically relevant high-pressure fluid injections. The major contributing factors appear to be high jet velocities and injection of small amounts of clotting blood. Heparinization provides a simple and effective means of prevention.

Postangiographic femoral artery pseudoaneurysms: further experience with US-guided compression repair.

PURPOSE: To assess the efficacy of ultrasound-guided compression repair (UGCR) in postcatheterization femoral artery pseudoaneurysms. MATERIALS AND METHODS: One hundred thirty-three patients with pseudoaneurysms were considered for UGCR. Patients underwent compression with duplex and color Doppler ultrasound. Immediate and long-term successes were evaluated. RESULTS: Seven patients were not candidates for UGCR. UGCR was technically possible in 117 of the 126 patients who were candidates. UGCR was successful in 109 patients. The failure rate was significantly higher in patients who were receiving anticoagulant medication (P < .001). Pseudoaneurysm size, age, and structure (simple vs multiloculated) had no bearing on success or failure. The time required for successful compression was not related to treatment with anticoagulants but was related to pseudoaneurysm structure. Complications included one case of a distal embolus and two episodes of hypotension. CONCLUSION: UGCR is a simple and expedient method for the treatment of postcatheterization femoral artery pseudoaneurysms.

Use of a direct thrombin inhibitor (argatroban) during pulse-spray thrombolysis in experimental thrombosis.

PURPOSE: To evaluate the effectiveness of intravenous and intrathrombic injection of the thrombin inhibitor argatroban during pulse-spray pharmacomechanical thrombolysis (PSPMT) in experimental venous thrombosis. MATERIALS AND METHODS: Clots were produced in the inferior vena cava in 52 rabbits by placement of steel coils and balloon injury to the vessel wall. Two days later, clots were treated with PSPMT. Several treatment methods were used: intrathrombic saline, intrathrombic tissue plasminogen activator (t-PA), intrathrombic t-PA with intrathrombic and intravenous heparin, intrathrombic t-PA with intravenous argatroban, and intrathrombic t-PA with intrathrombic and intravenous argatroban at two different doses. After treatment, the rabbits were killed and residual clot was weighed. Pretreatment clot weight was estimated and clot lysis was assessed. RESULTS: PSPMT with t-PA and adjunctive intrathrombic heparin resulted in greater lysis than PSPMT with only t-PA (percentage of residual clot, 59% +/- 14 vs 81% +/- 28; P = .02). Addition of intravenous argatroban did not increase lysis, but adjunctive intrathrombic argatroban significantly increased lysis at low doses (37% +/- 16; P = .02) and high doses (34% +/- 6; P = .006) compared with t-PA and intrathrombic heparin. CONCLUSION: In a rabbit model of venous thrombosis, the use of intrathrombic argatroban during PSPMT with t-PA significantly improved clot lysis.

Is thrombolysis of occluded popliteal and tibial bypass grafts worthwhile?

PURPOSE: We analyzed the short- and long-term results for patients undergoing thrombolysis of occluded infrainguinal bypass grafts at our institution over a 62-month period. METHODS: Thirty-one patients with 40 episodes of graft thrombosis in 33 grafts managed by thrombolysis were retrospectively reviewed. The effects of graft age, material, and anatomy, symptoms, treatment, anticoagulation, and occlusion duration were evaluated for impact on patency after thrombolysis. Dose and duration of therapy with use of the technique of pulse-spray thrombolysis was assessed. RESULTS: Thrombolysis successfully reestablished patency in 92% of grafts treated. Mean lysis time and urokinase dose were 118 minutes and 607,000 units, respectively. Responsible lesions were identified and treated by angioplasty or surgery in 35 of 37 cases. The patency rate after thrombolysis was 28% at 30 months, and the secondary patency rate was 46% at 18 months. Duration of occlusion, symptoms, treatment, graft anatomy, and prior graft revision did not impact on patency. Mean secondary patency was 21.5 months in grafts in place over 1 year and 7.0 months in grafts in place for less than 1 year. Mean secondary patency was 23.8 months in polytetrafluoroethylene grafts and 8.4 months in vein grafts. The limb salvage rate was 84% at 30 months, and the patient survival rate was 84% at 42 months. CONCLUSIONS: Pulse-spray thrombolysis is effective in rapidly recanalizing thrombosed infrainguinal grafts. Grafts failing in the first year after placement should generally be replaced, reserving thrombolysis and revision for grafts greater than 1 year old. Vein grafts tolerate thrombosis less well than synthetic conduits and have decreased long-term patency.

Overdilation of the Wallstent to optimize portal decompression during transjugular intrahepatic portosystemic shunt placement.

PURPOSE: To optimize shunt size with overdilation of the Wallstent during creation of a transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: A TIPS was created in 25 patients with variceal bleeding (n = 22) or intractable ascites (n = 3). All shunts were created with one or more Wallstents that were dilated with an 8- or 10-mm balloon. In 11 patients with inadequate portal decompression or persistent filling of varices, shunts were overdilated with a 12-mm balloon. RESULTS: Mean portosystemic pressure gradient fell from 18.0 mm Hg +/- 6.4 (standard deviation) to 6.8 mm Hg +/- 2.8 after shunt placement. In 11 patients in which shunts were overdilated, the mean gradient fell from 12.7 mm Hg +/- 5.6 after 10-mm dilation to 6.9 mm Hg +/- 2.8 (P = .01) after 12-mm dilation. In six, variceal filling occurred after 10-mm dilation but diminished or ceased after overdilation. Stent disruption did not occur. New or worsened encephalopathy occurred in four of 14 patients with 10-mm and six of 11 patients with 12-mm shunt dilation and responded to medical therapy in all but two. CONCLUSION: Overdilation of the Wallstent during TIPS placement is effective and safe in patients with inadequate portal decompression after 10-mm shunt dilation.

Transcatheter manipulation of asymmetrically opened titanium Greenfield filters.

PURPOSE: The problem of asymmetric opening of the modified hook titanium Greenfield inferior vena cava filter necessitating transcatheter manipulation was evaluated in a retrospective study. PATIENTS AND METHODS: Titanium Greenfield filters were placed in 166 patients over a 36-month period. The radiographic reports of all patients were reviewed to identify cases in which the filter failed to open symmetrically after deployment and catheter or wire manipulation of the filter was performed. The reports and angiograms from these patients were reviewed with respect to the circumstances surrounding filter placement and methods to achieve more symmetric opening. RESULTS: Transcatheter manipulation of asymmetrically opened filters was performed in 15 of 166 cases (9%). In 12 of these patients, acceptable and uneventful opening of the filter was achieved with a guide wire, pigtail catheter, or occlusion balloon catheter. In one case manipulation only partly improved orientation of the limbs, while in another case successful manipulation was complicated by distal migration. In the final case, the asymmetric filter covered only part of the lumen of the vena cava despite manipulations and a second filter was placed for optimal caval interruption. No specific cause for incomplete expansion was identified in any case. CONCLUSION: Marked asymmetry in opening of the modified hook titanium Greenfield filter that warrants manipulation occurs infrequently, but recognition and proper management may be important to ensure optimal caval interruption.