Has stenting killed local drug delivery?
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
D C Cumberland
Publications and source records attributed to D C Cumberland.
Intravascular stents: a new technique for tissue processing for histology, immunohistochemistry, and transmission electron microscopy.
BACKGROUND: Study of the vascular response to stent implantation has been hampered by difficulties in sectioning metal and tissue without distortion of the tissue stent interface. The metal is often removed before histochemical processing, causing a loss of arterial architecture. Histological and immunohistochemical sections should be 5 microns with an intact tissue stent interface. OBJECTIVES: To identify the most suitable cutting and grinding equipment, embedding resin, and slides for producing thin sections of stented arteries with the stent wires in situ for histological, immunohistochemical, and transmission electron microscopic (TEM) analyses. METHODS: 20 balloon stainless steel stents were implanted in the coronary arteries of 10 pigs. Twenty eight days later the stented arterial segments were excised, formalin fixed, embedded in five different resins (Epon 812, LR white, T9100, T8100, and JB4), and sectioned with two different high speed saws and a grinder for histological, immunohistochemical, and TEM analyses. Five stented human arteries were obtained at necropsy and processed using the best of the reported methods. RESULTS: The Isomet precision saw and grinder/polisher unit reliably produced 5 microns sections with most embedding resins; minimum section thickness with the horizontal saw was 400 microns. Resin T8100, a glycol methacrylate, enabled satisfactory sectioning, grinding, and histological (toluidine blue, haematoxylin and eosin, and trichromatic and polychromatic stains) and immunohistochemical analyses (alpha smooth muscle actin, von Willebrand factor, vimentin, proliferating cell nuclear antigen, and CD68 (mac 387)). T9100 and T8100 embedded stented sections were suitable for ultrastructural examination with TEM. Stented human arterial sections showed preserved arterial architecture with the struts in situ. CONCLUSION: This study identified the optimal methods for embedding, sawing, grinding, and slide mounting of stented arteries to achieve 5 microns sections with an intact tissue metal interface, excellent surface qualities, histological and immunohistochemical staining properties, and suitability for TEM examination. The technique is applicable to experimental and clinical specimens.
Animals↗
Is a US analysis of cost-effectiveness in interventional cardiology relevant to a centrally funded health care system?
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Angioplasty, Balloon, Coronary↗
The effect of oligonucleotides to c-myb on vascular smooth muscle cell proliferation and neointima formation after porcine coronary angioplasty.
Proto-oncogenes, including c-myb, are expressed early after vascular injury. The application of antisense oligodeoxynucleotides (AS-ODNs) against these genes inhibits cell proliferation and neointima formation in small animals and in peripheral arteries. The aim of this study was to investigate the specificity of action of AS-ODN-c-myb in vitro and to assess its effect, when delivered locally, on neointima formation after percutaneous transluminal coronary angioplasty (PTCA) in porcine coronary arteries. AS-ODN-c-myb inhibited the proliferation of vascular smooth muscle cells (VSMCs) in vitro in a dose-dependent manner. There was a corresponding reduction in steady state levels of c-myb mRNA and protein. Expression of another early gene, c-fos, was unaffected. S1 nuclease analysis demonstrated intact full-length AS-ODN-c-myb retrieved from VSMCs in culture after 12 hours. A range of ODNs, related and unrelated to c-myb, with and without a GGGG sequence, inhibited VSMC proliferation. Phosphorothioated AS-ODN-c-myb was 30 times less potent than unphosphorothioated AS-ODN-c-myb. PTCA induced porcine coronary artery neointima formation. c-myb mRNA was maximally induced 18 hours after injury. Unmodified AS-ODN-c-myb, sense-ODN-c-myb, saline, or nothing was delivered immediately after balloon dilatation via a double-skinned porous balloon (Transport, SciMed). Fluorescence-labeled AS-ODN-c-myb was deposited throughout the vessel wall. Mean maximum intima/media cross-sectional area 4 weeks after PTCA was reduced with AS-ODN-c-myb by 79% compared with saline (P < .05), 82% compared with sense-ODN-c-myb, and 63% compared with nothing (P < .10). Conclusions are as follows: (1) c-myb is expressed in VSMCs after vascular injury. (2) AS-ODN-c-myb is retained intact in VSMCs, reducing their proliferation in vitro in dose-dependent fashion, with reduction in c-myb mRNA and protein, whereas sense-ODN-c-myb is not. (3) A range of ODNs can reduce VSMC proliferation by a non-sequence-specific mechanism. (4) Phosphorothioate protection of antisense molecules may reduce their efficacy. (5) Local delivery of unmodified AS-ODN-c-myb via the Transport catheter reduces neointima formation after porcine PTCA. (6) Local delivery of fluid may exacerbate neointimal thickening.
Angioplasty, Balloon↗
Dyslipoproteinemias in atherosclerosis, thrombosis and restenosis after coronary angioplasty.
Lipids play a vital role in normal metabolic function in mammals. However, dyslipoproteinemias have been implicated in the pathophysiologic process of atherogenesis, thrombogenesis and restenosis after interventional procedures. Lipoproteins provide important chemical linkages among these three complex phenomena. Lipoproteins participate in atherogenesis and play a major role in plaque fissuring, the pathophysiologic common denominator of acute ischemic syndromes. Thrombogenesis is majoraly affected by the action of lipids on platelets, coagulation and fibrinolysis. LDL tend to destabilize platelet membrane activity, macrophages, endothelial and smooth muscle cell function; HDL tend to reverse these abnormalities. The metabolism of arachidonic acid, a metabolite of the essential polyunsaturated lipoprotein, linoleic acid, is integral to platelet and endothelial cell membrane formation, via the cyclooxygenase-prostanoid pathway. Arachidonic acid also is metabolized by the lipoxygenase-leukotreine pathway in neutrophils and monocytes. The relationship of dyslipoproteinemias (increased LDL and Lp(a); decreased HDL) to restenosis after angioplasty has been reported, though there is not universal agreement about causality. Lipid lowering regimens and other pharmacotherapy have had favorable effect slowing the rate of atherogenesis, decreasing the frequency of cardiac events (perhaps by "stabilizing" vulnerable plaques) and causing regression in some atheromata. The salutary effect of lipid-lowering agents upon the incidence of restenosis after angioplasty is problematic. Some investigators have found a statistically significant correlation, while others have not; but studies have not been standardized. In conclusion, the study of lipid metabolism across a wide range of physiochemical activities and the interaction of these phenomena describe complex, genetically determined linkages which instruct (and often humble) investigators in their study of lipids in health and disease.
Angioplasty↗
High intensity, low frequency catheter-delivered ultrasound dissolution of occlusive coronary artery thrombi: an in vitro and in vivo study.
OBJECTIVES: This study assessed the efficacy of a new high intensity, low frequency therapeutic coronary ultrasound catheter for thrombus dissolution in vitro and in vivo in canine coronary arteries. BACKGROUND: Therapeutic ultrasound has been shown to dissolve thrombi in vitro and in peripheral arteries in vivo. There have been no previous studies on in vivo coronary thrombus dissolution by ultrasound. METHODS: In vitro, we exposed 1- to 4-h old human blood clots for 3 min to pulsed-wave ultrasound. Clot dissolution under various conditions was evaluated. In vivo occlusive coronary thrombi were induced in 18 dogs. RESULTS: In vitro irrigation alone (10 ml/min of normal saline solution) and ultrasound alone each contributed to a reduction of clot weight by 47.1 +/- 11.4 mg and 84.6 +/- 25.6 mg, respectively, after 3 min (p < 0.001). Ultrasound plus irrigation resulted in a reduction of clot weight by 216.5 +/- 31.5 mg after 3 min (p < 0.001). The magnitude of clot dissolution was considerably amplified when ultrasound energy was combined with irrigation, probably because of cavitational effects. In vivo, in three dogs mechanical passage of the unactivated probe failed to recanalize the artery, and the arteries remained thrombotically occluded. After passage of the activated ultrasound probe, angiography revealed widely patent coronary arteries in 13 of 15 dogs and partial recanalization with filling defects indicative of residual thrombus in 2 of 15 dogs. Three of 15 coronary arteries were histologically free of residual thrombi. Mural thrombi extending to < or = 10% of the vessel circumference were seen in 10 of 15 dogs. Residual thrombi > or = 50% of the vessel circumference were found in two cases. There was no histologic evidence of ultrasound-mediated vessel damage. CONCLUSIONS: Catheter-delivered therapeutic ultrasound effectively dissolves clots in vitro and in canine coronary arteries in vivo. Thus, therapeutic catheter-delivered ultrasound has the potential to serve as an adjunct or alternative treatment for thrombus-mediated coronary ischemic syndromes or myocardial infarction.
Animals↗
Percutaneous aspiration thromboembolectomy to manage the embolic complications of angioplasty and as an adjunct to thrombolysis.
Percutaneous aspiration thromboembolectomy (PAT) can be used to treat the embolic complications of angioplasty. The same technique is of value during thrombolysis to remove large pieces of thrombus. We report on our experience with PAT in 21 patients. Fourteen of these patients had embolization complicating peripheral angioplasty and in one case embolus complicated directional atherectomy. PAT was successful in 87% of these patients (13/15). In six patients undergoing thrombolysis of acute peripheral occlusions, all had successful PAT to shorten their treatment episode immediately prior to angioplasty of any underlying stenosis. PAT can be performed with a simple, inexpensive catheter under fluoroscopic control and therefore offers significant advantages over a surgical embolectomy using the Fogarty balloon catheter. PAT is a useful treatment option for the vascular radiologist.
Aged↗
Triple vessel revascularization: coronary angioplasty versus coronary artery bypass surgery: initial results and five-year follow-up. Comparative costs and loss of working days and wages.
OBJECTIVES: The purpose of this study was to compare early and late outcomes in patients undergoing PTCA or CABG for triple vessel disease. BACKGROUND: Although early results of PTCA/CABG randomized trials have recently become available, at present little data exists on long-term medical and socioeconomic effects of these treatment modalities in patients with triple vessel revascularization. METHODS: During 1986-87, 76 patients undergoing triple vessel PTCA and 85 patients having triple vessel CABG were selected from a consecutive series of patients having multivessel revascularization. Initial results and 5 year outcome, hospital stay and charges and out-of-work time were assessed from prospectively collected data. RESULTS: Clinical and morphological factors were similar in the PTCA and CABG groups. Hospital success and complications were also similar, except for higher mortality in the CABG cohort (0 vs. 3.5%). Five year follow-up showed no differences in survival, nonfatal infarction and angina-free status; however, there was a difference in need for repeat revascularization (PTCA 55.4% vs. CABG 6.3%, p less than 0.001). Repeat PTCA accounted for 49% of the revascularization in the PTCA cohort. Crossovers were similar (PTCA[CABG 6.8%; CABG[PTCA 6.3%, pNS). Predictors of late death in the entire population were female gender (p less than 0.0001), diabetes (p<0.05) and depressed LVEF (p less than 0.05). The choice of revascularization procedure (PTCA vs. CABG) was not an independent predictor of late death or MI. Analysis of initial hospital charges showed a 2:1 advantage in favor of PTCA but this advantage was lost in late followup due to the need for repeat revascularization in the PTCA group. However, the PTCA cohort lost fewer working days than CABG patients (3017 vs 5874 days) and therefore, lost less wages ($7,022 vs. $14,685). CONCLUSIONS: The study shows that for selected triple vessel disease patients, PTCA and CABG results are comparable after 5 years, though repeat revascularization (mainly due to restenosis) was necessary in the PTCA group to maintain these favorable results. After 5 years, hospital charges are similar in the 2 groups, though out-of-work time and lost wages were 2:1 in favor of PTCA.
Absenteeism↗
Clinical trial of percutaneous peripheral ultrasound angioplasty.
OBJECTIVES: The purpose of this study was to present follow-up data as well as short-term results on a larger clinical series of patients undergoing ultrasound angioplasty. BACKGROUND: Previous pilot studies have demonstrated the feasibility of peripheral arterial ultrasound angioplasty. METHODS: We performed percutaneous ultrasound angioplasty on 50 arterial lesions in 45 patients. Our ultrasound ablation system had a frequency of 19.5 kHz. A fixed-wire probe with 2- or 3-mm ball tips and a 3-mm over-the-wire probe were used to treat 40 femoral, 7 popliteal and 3 tibioperoneal lesions. Seventeen (34%) of the lesions were calcific. Thirty (86%) of 35 occluded segments, 0.5 to 28 cm long (mean 6.2 +/- 5.7), were recanalized. RESULTS: In the 45 patent arteries, the stenosis decreased from 94 +/- 10% to 55 +/- 23% after ultrasound angioplasty and to 12 +/- 8% after balloon angioplasty. Mechanical arterial dissections (n = 4) and perforations (n = 4) without clinical consequence occurred only with the fixed non-over-the-wire probes. No evidence of embolism or vasospasm was detected; in fact, vasodilation occurred. There were no clinical manifestations of acute reocclusion. At 24 h, ankle-brachial indexes increased by 0.23 +/- 0.21 (range -0.27 to 0.72). Six- to 12-month clinical and ankle-brachial index follow-up data for 35 patients treated with ultrasound and adjunctive balloon angioplasty were indicative of restenosis in 7 patients (20%). CONCLUSIONS: Our findings indicate that percutaneous peripheral ultrasound angioplasty 1) is useful for recanalization of fibrous, calcific and thrombotic arterial occlusions; 2) reduces arterial stenoses; and 3) has clinical and ankle-brachial index data indicative of a restenosis rate of 20% at 6 to 12 months in a small cohort of patients. A larger randomized series of patients will need to be studied to assess the impact of ultrasound ablation on restenosis.
Adult↗
Issues in evaluating new devices: lasers.
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Angioplasty, Laser↗
Intravascular ultrasound imaging combined with coronary angioplasty.
A novel catheter combining ultrasound imaging and coronary balloon angioplasty was used in the treatment of 69 coronary-artery lesions in 51 patients. The ultrasound transducer enables real-time cross-sectional imaging and qualitative and quantitative assessment of the vessel wall before and after angioplasty. The combination catheter successfully dilated 67 lesions. There was a characteristic three-layered appearance, representing intima, media, and adventitia, in 60 cases. Intravascular imaging provided information on the vessel wall unobtainable by standard contrast angiography in 28 cases and influenced our management in 6 cases.
Adult↗
Percutaneous transluminal angioplasty in transplant renal arterial stenoses: a long-term follow-up.
Transplant renal artery stenosis is a potentially treatable cause of post-transplant hypertension. Transluminal angioplasty under radiological control facilitates treatment, and in this study the results of 15 consecutive patients treated in one department have been analysed to assess the safety and success of the technique, blood pressure control and transplant function. Technical success was achieved in 14 patients (93%), with zero mortality and only 1 major complication requiring surgical intervention. Blood pressure control was significantly improved by angioplasty, mean blood pressure (diastolic + 1/3 pulse pressure) being lower 4-6 weeks later (P less than 0.05) and a mean of 34 months later (P less than 0.01), and transplant renal function was unaffected. In the treatment of transplant renal artery stenosis percutaneous transluminal angioplasty is effective, safe and often of lasting benefit.
Adolescent↗
CASSPERT--an expert system to guide choice and strategy in coronary angioplasty.
Coronary angioplasty is a technique widely used in the treatment of coronary artery disease. The success of coronary angioplasty depends on patient selection, the use of an appropriate technique, and to a large extent a carefully considered choice of angioplasty equipment. The authors have developed an expert system which can assist in this decision making process. CASSPERT was developed using the expert system shell 'Leonardo' running on a standard Personal Computer. The user interacts with CASSPERT to build up a detailed profile of clinical, investigational and angiographic features of the patient. This information, together with technical data stored within Leonardo's own object orientated database, is used to infer a suitable choice of equipment. To make the expert system useful in clinical practise, it was interfaced within a functional, readily accessible, data acquisition and storage environment which could be used within the day to day running of the department.
Angioplasty, Balloon, Coronary↗
Clinical demonstration that catheter-delivered ultrasound energy reverses arterial vasoconstriction.
OBJECTIVES: This study was designed to describe the clinical effects of ultrasound energy on guide-wire-induced arterial vasoconstriction. BACKGROUND: We have previously shown that ultrasound energy (20 kHz) delivered by a wire probe produces dose-dependent, endothelium-independent smooth muscle relaxation capable of reversing both receptor-mediated and voltage-dependent vasoconstriction in vitro. METHODS: A high intensity, low frequency ultrasound catheter system was used to recanalize total occlusions in the superficial femoral arteries of two patients. After recanalization, the proximal residual stenoses were each less than 15%. However, distal arterial vasospasm was found angiographically in a popliteal artery of one patient and in an anterior tibial artery of another. Subsequently, the ultrasound catheter probe was advanced to the sites of arterial vasospasm (diffuse in one, focal in one). RESULTS: After 30 and 90 s, respectively, of exposure to ultrasound energy with a frequency of 19.5 kHz, peak tip amplitude of 111 microns and power output at the transducer of 25 W, the vasospasm resolved in each arterial segment. CONCLUSIONS: Our findings are the first reported clinical cases documenting that catheter-delivered low frequency, high intensity ultrasound induces arterial vasodilation at the site of vasoconstriction. These biologic effects appear to be relatively unique for an angioplasty device and may have potential clinical importance.
Aged↗
Lesion morphology and coronary angioplasty: current experience and analysis.
From July 1, 1990 to February 28, 1991, 533 consecutive patients with 764 target vessels and 1,000 lesions underwent coronary angioplasty. Procedural success was achieved in 92.3%, untoward (major cardiac) events occurred in 3% (0.8% myocardial infarction, 1.3% emergency coronary bypass grafting and 0.9% both; there were no deaths). An unsuccessful uncomplicated outcome occurred in 4.7%. Lesion analysis using a modified American College of Cardiology/American Heart Association classification system showed that 8% were type A, 47.5% were type B and 44.5% were type C (36% of type B and 11% of type C were occlusions). Angioplasty success was achieved in 99% of type A, 92% of type B and 90% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.01). Untoward events occurred in 1.2% of type A, 1.9% of type B and 2% of type C lesions (p = NS). An unsuccessful uncomplicated outcome occurred in 0% of type A, 6% of type B and 7% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.05). Among the unsuccessful uncomplicated outcome group, occlusion occurred in 49%: 38% of type B and 59% of type C lesions. With B1 and B2 subtypes, success was obtained in 95% and 89.5% and untoward events occurred in 1.5% and 2.3% and an unsuccessful uncomplicated outcome in 3.7% and 8%, respectively. C1 and C2 subtyping showed success in 91% and 86%, untoward events in 1.3% and 6% and an unsuccessful uncomplicated outcome in 7.5% and 8.5%, respectively. Among the 764 vessels, success was obtained in 89.5% and untoward events occurred in 2.5% and an unsuccessful uncomplicated outcome in 8%. Assessment of lesion-vessel combinations showed a less favorable outcome with type C lesions and combinations of A-B, B-C and multiple (more than three lesions) type B and C vessels. Statistical analysis of morphologic factors associated with angioplasty success included absence of (old) occlusion (p less than 0.0001) and unprotected bifurcation lesion (p less than 0.001), decreasing lesion length (p less than 0.003) and no thrombus (p less than 0.03). The only significant factor associated with untoward events was the presence of thrombus (p less than 0.003). Predictors of an unsuccessful uncomplicated outcome included old occlusion (p less than 0.0001) and increasing lesion length (greater than 20 mm) (p less than 0.001), unprotected bifurcation lesion (p less than 0.05) and thrombus (p less than 0.03).
Angioplasty, Balloon, Coronary↗
Percutaneous transluminal angioplasty of the subclavian and axillary arteries: initial results and long term follow-up.
The early and long term outcomes of 25 subclavian and axillary angioplasties in a series of 19 patients treated at one centre over a period of 10 years were assessed. The eventual outcome was long lasting improvement in most cases. Two of 25 PTAs were technical failures as defined as > 30% residual stenosis. Twenty-three of 25 PTAs were technical successes: 17 of these were first procedures, one was a repeat after an initial failure, two were repeats for restenosis and three were for separate new lesions. Clinically, 13 of the 19 patients were asymptomatic at long term follow-up. Four had only occasional, mild symptoms (in one of those they were due to shoulder arthropathy). Two patients had technically successful dilatations but developed problems with arterial occlusion distally which in one patient required amputation of that limb.
Adult↗
Treatment of intestinal angina by percutaneous transluminal angioplasty of a superior mesenteric artery occlusion.
A 47-year-old woman with intestinal angina due to multiple visceral artery occlusions was treated surgically but suffered early thrombosis of an aorta-to-superior mesenteric artery (SMA) bypass graft and the return of her symptoms. Percutaneous transluminal angioplasty (PTA) of the occluded native origin of the SMA was successful. Three months later she is well and gaining weight. Several series of patients treated by PTA of superior mesenteric artery stenoses have been published, but to our knowledge this is the first report of the successful application of the technique to a complete SMA occlusion.
Abdominal Pain↗