Treatment of acute stent thrombosis with local urokinase therapy using catheter-based,drug delivery systems: A case report

Abrupt thrombotic stent closure remains a difficult problem to treat in the cardiac catheterization laboratory. A 63-yr-old white female initially underwent successful placement of a Palmaz-Schatz biliary stent in the proximal RCA following failed coronary angioplasty. One week later, the patient represented with an acute inferior infarction and thrombotic occlusion of the stent site in spite of adequate anticoagulation. A new, local drug infusion catheter (the Dispatch? catheter) was placed at the angioplasty site and 150,000 units of urokinase were locally infused, with immediate restoration of normal distal flow and a subsequent marked decrease in angiographic thrombus. A small, residual thrombotic filling defect was further treated with a urokinase-coated hydrogel balloon (Hydro Plus?). Following local urokinase delivery with the Dispatch catheter and hydrogel balloon, there was complete resolution of angiographic thrombus with TIMI 3 flow and no evidence of distal embolization or no-reflow. Local urokinase delivery directly to the site of thrombus with catheter-based drug delivery systems may be a useful technique for rapidly lysing intracoronary clot and re-establishing coronary flow in the setting of acute stent thrombosis.     

Local urokinase delivery with the Channel balloon: Device safety,pharmacokinetics of intracoronary drug delivery,and efficacy of thrombolysis

The Channel balloon is a new local drug-delivery catheter that has the dual capability of high-pressure lesion dilation and low-pressure drug infusion. The purpose of this study was to assess the safety and efficacy of this device in the local delivery of urokinase in the porcine model. Three in vivo protocols were performed in 57 anesthetized swine to assess the safety of Channel balloon use in the coronary vasculature, the pharmacokinetics of local urokinase delivery, and the ability of the catheter to lyse intraluminal thrombus. First, safety studies were performed in 18 coronary vessels in 13 pigs to compare angiographic and histologic changes following use of the Channel balloon with conventional balloon angioplasty. Second, intramural deposition of ¹²³I-labeled urokinase was measured in 24 coronary arteries in 20 pigs to assess the efficiency and technical determinants of urokinase delivery and the time course of intramural drug retention. Finally, an in vivo thrombus model was used in 24 pigs to compare the thrombolytic capacity of local urokinase delivery with the Channel balloon in comparison with conventional urokinase infusion techniques. All balloon inflations and drug infusions with the Channel balloon were well tolerated in all animals without adverse angiographic, hemodynamic, or electrical sequelae. Comparative histologic studies with the Channel balloon demonstrated no additional vessel trauma beyond that seen with conventional balloon angioplasty. Between 0.09 and 0.35% of infused urokinase was intramurally deposited, with intracoronary persistence for at least 5 h. Drug infusion pressure did not significantly affect drug deposition, although larger amounts of urokinase were deposited with larger balloon:artery ratios and higher urokinase concentrations. In comparison to conventional systemic and guiding catheter infusions, local delivery of urokinase with the Channel balloon resulted in higher levels of clot dissolution. These studies have demonstrated safe intracoronary use of the Channel balloon in the porcine model. Local infusion of urokinase with this device results in significant intramural drug deposition that persists for at least 5 h. In comparison with conventional thrombolytic techniques, local urokinase delivery with the Channel balloon may result in enhanced intravascular thrombolysis. Cathet. Cardiovasc. Diagn. 41:254–260, 1997. © 1997 Wiley-Liss, Inc.     

Catheter-based local thrombolysis with urokinase: Comparative efficacy of intraluminal clot lysis with conventional urokinase infusion techniques in an in vivo porcine thrombus model

Local delivery of urokinase directly to the site of intraluminal clot using catheter-based technology has recently been introduced as a new technique to treat intracoronary thrombus and thrombus-containing stenoses. The purpose of this study was to compare the efficacy of urokinase therapy administered by local drug-delivery catheters with conventional urokinase-infusion techniques in dissolving intraluminal clot and intramurally depositing drug at the site of arterial injury in an in vivo porcine model. Five techniques of urokinase administration were studied in 65 pigs, including intravenous systemic bolus (1,000,000 units), guiding catheter infusion (500,000 units), local intraluminal infusion with a Roubin catheter (150,000 units), local infusion by the Dispatch catheter (150,000 units), and local delivery by the hydrogel-coated balloon (700 units). All five techniques were initially compared with respect to the quantity of intraluminal lysis of ¹²³I-fibrinogen-labeled thrombus in an in vivo thrombus model. Conventional balloon angioplasty was also assessed in this model as a nonpharmacologic, mechanical control. In addition, all five techniques were compared with respect to the quantity and efficiency of intramural urokinase deposition at coronary angioplasty sites. In the in vivo thrombolysis experiments, the quantity of artificial clot lysis measured 8.8% for systemic therapy, 20.8% for guiding catheter infusion, 25.2% for Roubin catheter infusion, 62.8% for Dispatch catheter infusion, 98.8% for hydrogel balloon delivery, and 53.6% for conventional balloon angioplasty. Both the Dispatch catheter and the hydrogel balloon resulted in more clot lysis than the systemic, guiding catheter, or Roubin catheter approaches (P < 0.05). In comparison with conventional balloon angioplasty, only the hydrogel balloon resulted in higher levels of thrombus dissolution (P < 0.05). In the intramural deposition studies, the efficiency of urokinase delivery was 0.0004% for systemic therapy, 0.004% for guiding catheter infusion, 0.004% for Roubin catheter infusion, 0.08% for Dispatch catheter infusion, and 1.8% for hydrogel balloon delivery. The Dispatch catheter resulted in higher intramural drug levels than did all other techniques (P < 0.05), whereas the efficiency of urokinase deposition was higher with the hydrogel balloon than with all other approaches (P < 0.05). In the porcine model, it is subsequently concluded that local delivery of urokinase by catheter-based techniques can result in more complete lysis of intraluminal thrombus by using similar or lower doses of drug than by using conventional urokinase infusion techniques. Mechanical deformation of thrombus, possibly to increase the surface area available for thrombolysis and to physically disrupt clot, may be an important component of the mechanism of site-specific thrombolysis, particularly with the hydrogel balloon. Local delivery techniques also deposit significant quantities of urokinase at balloon angioplasty sites, creating an intramural reservoir of drug that may result in prolonged local thrombolysis. Cathet. Cardiovasc. Diagn. 41:293–302, 1997. © 1997 Wiley-Liss, Inc.     

Angiographic outcome after intracoronary X-Sizer helical atherectomy and thrombectomy: first use in humans.

The objective of this study was to evaluate the early angiographic outcome in the first human subjects who underwent intracoronary atherectomy and thrombectomy using the X-Sizer helical cutting and aspiration system. Percutaneous coronary interventions in patients with thrombo-occlusive disease or friable degenerative saphenous vein grafts are associated with considerable periprocedural morbidity and mortality, predominantly related to microscopic distal embolization. X-Sizer catheter system is a novel atherectomy and thrombectomy device that consists of a helix cutter connected to a handheld motor drive unit and a vacuum collection chamber for aspiration of excised atheroma, thrombus, and debris. Quantitative coronary angiography was obtained in 14 patients before and after X-Sizer extraction atherectomy with adjunctive balloon angioplasty and stenting. Thirteen native coronary arteries and one saphenous vein graft were treated. Mean preprocedural reference vessel diameter was 3.06 +/- 0.66 mm. There were 71.4% AHA/ACC type B2 and C lesions. Preprocedural thrombus was present in nine patients and total occlusion in 64% of cases. Minimal luminal diameter was increased from 0.29 +/- 0.47 mm to 1.32 +/- 0.64 mm, a gain of 1.04 +/- 0.69 mm after atherectomy. Final total gain was 1.47 +/- 0.61 mm. Mean diameter stenosis was reduced from 89.3% to a final residual stenosis of 14.4%. Postatherectomy distal embolization occurred in one patient who had heavy preprocedural thrombus burden. No episodes of perforation, distal coronary spasm, abrupt closure, or slow/no-reflow occurred. The angiographic analysis of the first cohort of human subjects suggests that X-Sizer helical atherectomy is a feasible method of removing occlusive tissue or thrombus in coronary artery disease with a low angiographic complication rate. A large-scale randomized phase II clinical trial is underway to determine the ultimate safety and efficacy of this device in thrombo-occlusive native coronary arteries and saphenous vein grafts.     

Treatment of thrombotic saphenous vein bypass grafts using local urokinase infusion therapy with the Dispatch catheter

Percutaneous treatment of thrombotic stenoses or total occlusions in aged saphenous vein bypass grafts is associated with a significant incidence of complications primarily related to distal embolization. The purpose of this study was to assess the efficacy of local urokinase delivery with the Dispatch catheter prior to balloon angioplasty and/or intragraft stent placement as a new technique of vein graft revascularization. Local urokinase delivery with the Dispatch catheter was performed in 15 saphenous vein grafts (mean age = 11.7 ± 2.5 yr) in 13 patients with unstable or postinfarction angina. The target lesion was a total occlusion in 5 of the procedures and a severe vein graft stenosis in the remaining 10. In all cases, urokinase was administered directly to the site of the stenosis/occlusion via the Dispatch catheter at 0.5 cc/min and at a concentration of 30,000 units/cc. The mean urokinase infusion time for the 15 procedures was 33 ± 10 min (range = 10–60 min) and the mean urokinase dose was 495,000 ± 158,000 units (range = 150,000–900,000 units). Following Dispatch therapy, mean minimal lumen diameter increased from 0.34 ± 0.32 to 1.81 ± 0.78 mm (P < 0.01), mean TIMI flow increased from 1.9 ± 1.4 to 2.8 ± 0.8 (P < 0.06), and mean thrombus score was reduced from 2.3 ± 0.6 to 0.3 ± 0.8 (P < 0.01). Mild no reflow was noted in two cases, although no patient demonstrated angiographic evidence of gross distal embolization. One of the patients with no reflow also demonstrated a small increase in cardiac enzymes. Subsequent balloon angioplasty/stent placement was successful in 14 of the 15 procedures (93% success rate). This preliminary report suggests that pretreatment of thrombotic saphenous vein graft stenoses with local urokinase delivery via the Dispatch catheter may decrease intragraft thrombus and possibly decrease the incidence of vascular complications associated with percutaneous intervention. This technique may allow for recanalization of totally occluded vein grafts with large clot burdens by using significantly less urokinase and shorter drug administration times than conventional infusion protocols. Cathet. Cardiovasc. Diagn. 41:261–267, 1997. © 1997 Wiley-Liss, Inc.     

Reduced distal embolization with transluminal extraction atherectomy compared to balloon angioplasty for saphenous vein graft disease

Extraction atherectomy utilizes suction aspiration as an attempt to limit distal emboll during atherectomy. We sought to test the hypothesis that extraction atherectomy produces less distal embolization than balloon angioplasty when treating saphenous vein grafts. Among 163 consecutive, nonrandomized patients, 103 patients underwent transluminal extraction catheter (TEC)^® atherectomy with or without adjunctive balloon angioplasty, and 60 patients had conventional balloon angioplasty. Both groups showed comparably high procedural success rates (TEC 90.3%, angioplasty 83.3%, P = NS). TEC cases had a significantly lower incidence of angiographic distal embolization, compared with angioplasty (3.9% vs. 16.7%, P = 0.005). In cases with angiographic evidence of thrombus in the grafts, TEC maintained a significantly lower incidence of distal embolization than angioplasty (5.6% vs. 31.8%, P = 0.004). There were no statistical differences between the two groups regarding the incidence of other procedure-related complications, including death, myocardial infarction, or emergency coronary artery bypass grafting. TEC atherectomy appears to have a significantly lower incidence of distal embolization than balloon angioplasty when treating saphenous vein grafts, particularly in the presence of angiographically apparent thrombus. © 1996 Wiley-Liss, Inc.     

Site-specific intracoronary thrombolysis with urokinase-coated hydrogel balloons: Acute and follow-up studies in 95 patients

Conventional balloon angioplasty in the presence of intracoronary thrombus is associated with an elevated risk for acute myocardial infarction, emergency bypass surgery, and death. The purpose of this study was to assess the safety and efficacy of a new technique to treat thrombus-containing stenoses consisting of the local delivery of urokinase directly to the site of intraluminal clot with hydrogel-coated balloons. Ninety-five patients with angiographically apparent intracoronary thrombus were treated with urokinase-coated hydrogel balloons either prior to (n = 74) or following (n = 21) conventional balloon angioplasty. Clinical diagnoses for the study group included acute myocardial infarction in 50 patients, postinfarction angina in 23 patients, and unstable angina in 22 patients. All hydrogel balloons were initially coated with urokinase by immersing the inflated balloon in a concentrated Abbokinase solution (50,000 units/ml) for 60 s. All patients were subsequently treated with drug-coated balloons using a balloon:artery ratio of 1:1, a mean of 2.2 ± 1.2 inflations, and a mean total inflation time of 7.5 ± 4.9 min. Use of urokinase-coated balloons resulted in angiographic disappearance of intracoronary thrombus in 78 patients, improvement in 14, and no change in the remaining 3 patients. Following hydrogel balloon use for the entire 95 patients, TIMI flow increased from 1.4 ± 1.2 to 2.9 ± 0.4, minimal lumen diameter increased from 0.4 ± 0.4 to 2.0 ± 0.6 mm, and thrombus score decreased from 2.0 ± 0.9 to 0.2 ± 0.6 (all P < 0.01). Procedural and early in-hospital complications were noted in 7 of the 95 patients (7.4%) and included abrupt closure in 3 patients, distal embolization in 1 patient, no reflow in 1 patient, sidebranch occlusion in 1 patient, and late closure in 1 patient. Two of the 3 patients with abrupt closure and the single patient with late closure required intracoronary stenting to maintain vessel patency. Two of these 7 patients sustained small myocardial infarctions, although no patient required emergency bypass surgery or experienced a procedural death. Late clinical follow-up (mean = 8.3 ± 6.6 months; range = 2 wk to 29 mo) demonstrated adverse recurrent events in 29 of the 95 patients (30.5%), including death (n = 5), myocardial infarction (n = 2), and recurrence of angina (n = 22). The results of this study suggest that intracoronary thrombolysis can be safely and rapidly achieved by using limited quantities of urokinase delivered directly to the site of intraluminal clot with hydrogel balloons. Use of this technique may result in improved acute outcomes in comparison with conventional techniques currently being used to treat thrombus-containing stenoses. Cathet. Cardiovasc. Diagn. 41:246–253, 1997. © 1997 Wiley-Liss, Inc.     

A novel minimal-invasive model of chronic myocardial infarction in swine

BACKGROUND: Most animal studies on myocardial infarction (MI) have used open-chest models with direct surgical coronary artery ligation, which imply local as well as generalized side effects of major surgery. Some closed-chest models of MI have been established, mainly using catheterization techniques with coronary artery embolization, balloon occlusion, and intracoronary injection of thrombogenic agents. The aim of this study was to develop a closed-chest technique of chronic coronary artery occlusion at a selected location with subsequent thrombus formation without use of balloon inflation or thrombotic chemical agents. METHODS AND RESULTS: A coronary angiography via the carotid artery was performed using a 7 F guiding catheter in 21 pigs. After insertion of a percutaneous transluminal coronary angioplasty (PTCA) guide wire into the distal coronary artery, a vessel-size adapted flexible foreign body comprising an open-cell sponge was advanced into the coronary artery via the guide wire by a non-inflated PTCA balloon. Five min after removal of the guide wire and the balloon catheter, total coronary artery occlusion was documented by angiography. Retrograde thrombosis of the coronary artery occurred in three animals. After one week, total vessel occlusion at the previously selected location was visualized by coronary angiography in animals that had survived. Macroscopic analysis demonstrated the foreign body with subsequent thrombus formation in the coronary artery and distal MI. Post-mortem histological analysis revealed myocardial necrosis and granulocyte infiltration at the margin of the infarction, without damage to remote myocardium. CONCLUSIONS: This new easy-to-perform closed-chest technique provides reproducible chronic coronary artery occlusion at a selected location with subsequent MI. It avoids major surgery and thoracotomy and does not require balloon inflation or intracoronary injection of thrombotic or chemical agents.     

Intracoronary thrombus formation causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease

BACKGROUND. Experimental studies have demonstrated that intracoronary platelet aggregation and thrombus formation may induce marked vasoconstriction of epicardial arteries with endothelial injury. METHODS AND RESULTS. To examine the effects of intracoronary thrombus formation on coronary vasomotor tone of human epicardial arteries in vivo, we studied 15 patients who developed intracoronary thrombi adherent to the guide wire during balloon dilatation. Epicardial artery luminal area was evaluated by quantitative coronary angiography proximal and distal to the site of intracoronary thrombus formation and in a reference vessel before and after thrombus formation as well as after intracoronary injection of 0.2-0.3 mg nitroglycerin. All artery segments distal to the site of thrombus formation showed vasoconstriction with a luminal area reduction of -27.4 +/- 17.1% (p less than 0.001), whereas proximal vessel segments and reference vessels not manipulated during percutaneous transluminal coronary angioplasty did not demonstrate any significant luminal area changes during thrombus formation. Angiographic measurements after advancing the guide wire with the adherent thrombus (performed in six of the 15 patients) revealed in all patients that vasoconstriction did develop at a new site distal to the thrombus persistence of the initial vasoconstriction now residing proximal to the thrombus. Thus, there was a sequential association between thrombus formation and subsequent distal vasoconstriction. Intracoronary injection of nitroglycerin abolished the thrombus-induced vasoconstriction. No significant luminal area changes were observed in 20 patients without angiographic evidence of intracoronary thrombus formation. CONCLUSIONS. Intracoronary thrombus formation during percutaneous transluminal coronary angioplasty causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease. Although caution must be advised in the extrapolation of this phenomenon, which was observed in a manipulated artery during coronary angioplasty, the vasoconstrictor response to intracoronary thrombus formation in vivo may play an important role in the dynamic mechanisms of acute coronary heart disease syndromes.     

Local delivery of heparin to balloon angioplasty sites with a new angiotherapy catheter: Pharmacokinetics and effect on platelet deposition in the porcine model

The purpose of this study was to assess the efficacy of local heparin delivery to balloon angioplasty sites in an in vivo porcine model by using a newly designed angiotherapy catheter that allows for prolonged drug infusion while maintaining distal arterial perfusion. Protocols were designed to assess the safety of intracoronary drug delivery, the effect of infusion time and drug concentration on intramural heparin deposition, the distribution of heparin within the arterial wall, the histologic effects of local heparin delivery, the wash-out of intramurally deposited heparin, and the effect of heparin delivery on early platelet deposition following balloon injury in peripheral and coronary vessels. Local intracoronary delivery of heparin was well tolerated in all animals. Between 0.04 and 0.08% of infused heparin was intramurally deposited at the time of drug delivery, with longer infusion durations and higher concentrations of heparin resulting in greater intramural deposition. Autoradiography demonstrated homogenous distribution of heparin throughout the intima, media, and adventitia, with localization in the nuclei, cytoplasm, and extracellular space. Histologic analysis demonstrated no additional vessel trauma from local drug delivery beyond that seen with conventional angioplasty. Wash-out studies demonstrated a biexponential disappearance of intramurally deposited drug, with rapid release of heparin over the first 60 min and persistence of small amounts of drug for at least 7 d. Locally delivered heparin significantly attenuated the deposition of platelets in peripheral vessels, although a similar decrease in platelet deposition in the coronary arteries was not statistically significant. Local delivery of heparin directly to coronary angioplasty sites is possible with the use of a new angiotherapy catheter. Wash-out of heparin from the arterial wall is initially rapid, although drug is detectable for up to 1 wk following delivery. In porcine peripheral arteries, use of this technique significantly decreases early platelet deposition following balloon injury. Cathet. Cardiovasc. Diagn. 41:275–286, 1997. © 1997 Wiley-Liss, Inc.     

Recanalization of totally occluded saphenous vein grafts using local urokinase delivery with the dispatchTM catheter

Current techniques for the percutaneous revascularization of totally occluded vein grafts are limited by a low initial success rate, a significant incidence of distal embolization, and a high rate of early graft reclosure. This case report describes two patients in whom graft recanalization was attempted with the combined use of balloon angioplasty/intra-graft stent placement and local urokinase delivery using a new angiotherapy catheter. Successful recanalization was achieved in both patients without major complications, in spite of a large thrombus burden as demonstrated by angiography. © 1995 Wiley-Liss, Inc.     

Rapid thrombus dissolution by continuous infusion of urokinase through an intracoronary perfusion wire prior to and following PTCA: Results in native coronaries and patent saphenous vein grafts

Even with aspirin and heparin therapy, thrombus present prior to or forming after percutaneous transluminal coronary angioplasty (PTCA) results in significant complications. We report on 33 patients who were treated with continuous infusion of Urokinase through an intracoronary perfusion wire for 24 hr because of visible intracoronary thrombus. Seventeen native vessels (9 pre-PTCA and 8 post-PTCA) and sixteen saphenous vein grafts (12 pre-PTCA and 4 post-PTCA) were treated. All vessels were patent at the time of perfusion wire placement. Complete thrombus resolution, successful PTCA and sustained patency was seen in 31 of 33 patients. One native vessel treated post PTCA (originally occluded) re-occluded. One saphenous vein graft treated prior to PTCA showed improvement in thrombus but distal embolization with balloon inflation occurred. No significant complications related to the intracoronary infusion technique were observed. In conclusion, rapid lysis of intra-coronary thrombus can be accomplish safely using this technique and can result in improved PTCA outcome.     

A pilot study with a new, rapid-exchange, thrombus-aspirating device in patients with thrombus-containing lesions: the Diver C.E. study.

BACKGROUND: In patients with acute coronary syndromes (ACS), distal embolization of thrombotic material is more likely to play a key role in the pathogenesis of myocardial no-reflow during percutaneous coronary intervention (PCI). Thus, interventional techniques able to reduce thrombus burden at the culprit vessel might improve final myocardial reperfusion. OBJECTIVE: To evaluate a new rapid-exchange thrombus-aspirating catheter, the Diver C.E., in patients with thrombotic coronary lesions undergoing PCI. METHODS: Fifty patients with acute myocardial infarction (n = 44) or with non-ST-elevation ACS and angiographic evidence of coronary thrombus (n = 6) undergoing urgent PCI were prospectively enrolled. The Diver C.E. was used to aspirate coronary thrombus from the culprit lesion after placement of the guidewire. Adjunctive balloon inflations and stent implantation were used to achieve good angiographic result. Angiographic coronary flow (by means of TIMI score and corrected TIMI frame count, cTFC), thrombus score (TS), and myocardial perfusion (by means of postintervention myocardial blush grade, MBG) were assessed in all patients. RESULTS: The device could be successfully employed in 96% of the cases (48/50) and yielded significant (P < 0.0001) acute reduction in thrombus burden (TS: predevice 3.5 +/- 0.8, postdevice 2.5 +/- 0.9) and improvement in coronary flow (TIMI grade: predevice 1.0 +/- 0.9, postdevice 2.0 +/- 0.9; CTFC predevice 71 +/- 31, postdevice 39 +/- 26). Final TIMI grade 0-1 was observed in one patient only (2%). A significant (P = 0.02) correlation was found between preintervention TS and efficacy of thrombus aspiration. A more pronounced acute reduction of thrombus burden after thrombus aspiration (TS reduction > or = 2) was associated with a better postintervention angiographic myocardial perfusion (MBG 2.3 +/- 0.9 vs 1.7 +/- 0.8; P = 0.05). CONCLUSIONS: This new, easy-to-use, device is able to reduce thrombus burden and to improve coronary flow in patients with thrombus-containing lesions. The improvement in myocardial perfusion associated to greater thrombus removal highlights the importance of thrombus aspiration in the management of thrombus-burdened coronary lesions.     

PCI结合冠脉内溶栓治疗右冠状动脉急性闭塞13例

目的：总结右冠状动脉（RCA）内注射大剂量尿激酶结合球囊扩张挤压的方法处理13例RCA急性血栓性闭塞的临床资料，评价其效果和安全性。方法：回顾性分析18例急性下壁心肌梗死病人的临床资料，在RCA近、中段急性闭塞部位急诊植入18枚普通支架后，闭塞的血管完全开通。但是，其中13例病人出现血栓栓塞支架以远的RCA主干，单纯球囊低压扩张挤压（4～6atm）等机械方法不能粉碎血栓，开通血管，遂通过导管向RCA注射50万U尿激酶（20min），再用球囊扩张挤压血栓；如果血栓不能被溶解粉碎，再注射尿激酶50万U，重复球囊扩张挤压。结果：6例接受冠脉内注射尿激酶50万U，其他7例接受尿激酶100万U，RCA血流恢复TIMI3级，远端RCA主干未见栓塞征象。13例病人住院期间无出血等并发症，随访2～20（10±8）个月未见发作心脏事件。结论：尤其是在没有Angiojet流体溶血栓吸引术或血管远端保护装置情况下，冠脉内注射大剂量尿激酶结合球囊扩张挤压血栓，不失为一种解决急性血栓性病变的简便易行而安全的补救方法。     

Distal administration of very high doses of intracoronary adenosine for the treatment of resistant no-reflow

No-reflow is a serious condition, and is associated with substantial morbidity and mortality after percutaneous coronary intervention. The most feared complication of no-reflow is a case of no-reflow that is resistant to multiple drug therapy. This condition usually occurs in patients with distal coronary disease or high thrombus burden. In the present case, a patient with resistant no-reflow that could be reversed by distal intracoronary administration of very high doses of adenosine (1 mg) is described. Administration of very high doses of adenosine via a balloon catheter was safe and did not cause any changes in the heart rate or blood pressure. The present case is the first to be reported in the literature.     

Salvage atherectomy: Using retrieved tissue to determine the etiology of acute closure

Directional coronary atherectomy was successfully performed in the mid-left anterior descending artery at the site of failed balloon angioplasty. We presumed that intracoronary thrombus had resulted in acute vessel closure following balloon angioplasty, due to the angiographic appearance of the lesion and the clinical situation. However, examination of the extracted specimen from the atherectomy device revealed predominantly atheromatous tissue with minimal thrombus. © 1996 Wiley-Liss, Inc.     

The intracoronary administration of urokinase following direct PTCA for acute myocardial infarction reduces early restenosis.

Early restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) without antecedent thrombolytic therapy in patients with acute myocardial infarction (AMI) was assessed by performing in-hospital cardiac catheterization in 62 (88%) of 70 consecutive patients. Specific attention was focused on the effectiveness of the intracoronary administration of urokinase in cases with angiographic residual thrombus after successful direct PTCA. The following two treatment regimens were used: PTCA alone (43 patients) and PTCA followed by the intracoronary infusion of urokinase (27 patients). The rate of early restenosis was higher after successful direct PTCA alone (28%) than after direct PTCA followed by intracoronary urokinase (5%). Bleeding complications were no different between the two groups. These findings suggest that intracoronary urokinase can be effective in reducing early restenosis in patients with angiographic residual thrombus after successful direct PTCA. Therefore early restenosis may be related to residual intracoronary thrombus.     

Intracoronary urokinase as an adjunct to percutaneous transluminal coronary angioplasty in patients with complex coronary narrowings or angioplasty-induced complications.

The effectiveness of intracoronary urokinase infusion as an adjunct to percutaneous transluminal coronary angioplasty (PTCA) was studied in 50 patients who underwent angioplasty for complex coronary narrowings or had thromboembolic complications during PTCA (29 [58%] men, 3 [6%] stable and 37 [74%] unstable angina, and 16 [32%] prior coronary bypass surgery). The primary indications for intracoronary urokinase infusion were intracoronary thrombus in 27 patients (54%), distal coronary embolization in 9 (18%), and abrupt reclosure in 14 (28%). Urokinase was infused in a mean (+/- standard deviation) dosage of 399,000 +/- 194,000 IU (range 150,000 to 1,000,000) at an average rate of 5,000 to 20,000 IU/min. Angiographic success was achieved in 43 patients (86%). Complications included the need for urgent bypass surgery in 3 patients, Q-wave myocardial infarction in 2, and non-Q-wave myocardial infarction in 12 (8 of whom had peak creatine kinase less than twice the upper normal limit). The incidence of myocardial infarction was significantly higher in patients with vein grafts (69%) than in those with PTCA of native vessels (14%). Two patients died (1 massive gastrointestinal necrosis 24 hours after angioplasty, and 1 after urgent bypass surgery). Mean (+/- standard deviation) fibrinogen levels were 355 +/- 73 mg/dl before urokinase infusion, and 361 +/- 70, twelve hours afterward. Three patients had local bleeding, but no transfusions were needed. It is concluded that intracoronary urokinase is a safe and effective adjunct to PTCA in patients with associated thrombi and may improve the success rate in angioplasty complicated by thrombus formation.     

Preliminary experiences using X-sizer catheter for mechanical thrombectomy of thrombus-containing lesions during acute coronary syndromes.

Thrombus-containing lesions are frequently observed in patients with acute coronary syndromes. These lesions are prone to increased procedural risks, including distal embolization and abrupt closure of the vessel. This preliminary report evaluates if thrombus removal using a new X-Sizer catheter could reduce thrombotic burden and optimize angioplasty results. Thrombectomy was attempted with the X-Sizer catheter in 11 patients (age, 59 +/- 10 years) undergoing coronary angioplasty with angiographic evidence of intracoronary thrombus. The device uses a helix cutter contained in a 4.5 or 5.5 Fr catheter tip connected to a closed vacuum aspiration system. Procedural outcomes using detailed angiographic analysis and clinical data were obtained from all treated patients. Seven patients (64%) had acute or recent myocardial infarction and four patients (36%) presented with unstable angina. The culprit lesion was located in right coronary, left anterior, vein graft, and circumflex-marginal in five, three, two, and one patient, respectively. The mean proximal reference diameter was 3.37 +/- 0.39 mm and % diameter stenosis was 90% +/- 15% prior to thrombectomy and decreased to 72% +/- 16% afterward and was 9% +/- 10% at the end of the procedure. The TIMI flow increased from 0.8 +/- 1.0 to 2.1 +/- 0.9 following thrombectomy and the final TIMI grade was 2.9 +/- 0.3. Stents were used in 9 of 11 patients. Procedural success was achieved in 10 of 11 patients (91%). No evidence of stent thrombosis was noted among treated patients in hospital and at 30-day follow-up. In this preliminary series of patients with angiographic evidence of thrombus, the use of X-Sizer thrombectomy seems to be feasible and relatively safe, permitting thrombus removal and improved intracoronary flow.     

New multifunctional percutaneous transluminal coronary angioplasty catheter device capable of balloon inflation, local drug delivery and coronary perfusion

A new percutaneous transluminal coronary angioplasty catheter with multiple functions of balloon inflation, local drug delivery and coronary perfusion has been devised. The device consists of an inflatable lumen, a drug delivery lumen, and a perfusion (or guide wire) lumen. A drug can be infused from the port located distal to the inflated balloon during continuous blood perfusion via the perfusion lumen. Fluorescence-labeled heparin and peroxidase administered using the device permeated into denuded vessel tissues during ongoing perfusion and remained there for over 24 hr. This prototype device indicates the potential therapeutic implications of the concepts of the device.