RESUMEN
BACKGROUND: Glycoprotein II b/IIIa antagonists (GPII b/IIIa-A) lower the periprocedural rate of ischemic events during high risk percutaneous coronary interventions. Their clinical impact on carotid artery stenting (CAS) remains to be determined. METHODS: We analyzed data from the Carotid Artery Stent (CAS) Registry. RESULTS: From 01/ 2000 to 06/2005 1322 CAS interventions were registered. In 94 (7.1%) procedures a GPII b/IIIa-A was used: abciximab in 8 cases (8.6%), tirofiban in 53 cases (57%) and eptifibatide in 32 cases (34.4%). The use of a GPII b/IIIa-A during CAS decreased significantly over time: from 17.6% in 2000 to 3% in 2005, p for trend <0.0001. The mean use of a GPII b/IIIa-A at the hospitals was 5.2%. More than 50% of the hospitals never used a GPII b/IIIa-A. There were no significant differences in baseline characteristics and concomitant diseases in CAS patients treated with GPII b/IIIa-A compared to those without GPII b/IIIa-A. A bilateral intervention was performed more often in patients treated with GPII b/IIIa-A (2.1 vs 0.2%, p = 0.04), a thrombus was more often visible (27 vs 12.4%, p <0.001) and an ulcer more frequently diagnosed (50 vs 37.5%, p = 0.03). There was no significant difference in the combined death or stroke rate between the two groups (5.3 vs 3.0%, p = 0.22, OR = 1.81, 95% CI: 0.69-4.72), which was confirmed by logistic regression analysis after adjusting for possible confounders (OR = 1.67, 95% CI: 0.62-4.46, p = 0.31). CONCLUSIONS: Our data neither demonstrate a significant benefit nor a significant risk with the use of GPIIb/IIIa-A during CAS. However, only an adequately sized randomized controlled clinical trial could establish the real value of GPII b/IIIa-A during CAS. Until then, considering the potential increase in cerebral hemorrhage, we should not use GPII b/ IIIa-A routinely during CAS.
Asunto(s)
Estenosis Carotídea/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Stents , Abciximab , Anciano , Anticuerpos Monoclonales/uso terapéutico , Eptifibatida , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Péptidos/uso terapéutico , Sistema de Registros , Tirofibán , Tirosina/análogos & derivados , Tirosina/uso terapéuticoRESUMEN
BACKGROUND: Carotid artery stenting (CAS) for symptomatic and asymptomatic carotid stenosis seems to be on the doorstep of more widespread use. However, its feasibility and safety in clinical practice at a broad spectrum of hospitals needs to be determined. METHODS: We analyzed data of the prospective multi-centre Carotid Artery Stenting (CAS) Registry of the German Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK). RESULTS: From 7/1996 to 5/2004 1888 patients from 28 hospitals were included in the CAS Registry. The median hospital stay from CAS until hospital discharge was 3 days (quartiles: 2-6 days). Median patients age was 70 years (quartiles: 64-76 years) with 72.1% males. CAS for symptomatic stenosis was performed in 55% of cases. Patients treated with CAS suffered from coronary artery disease in 66.5%, had arterial hypertension in 91.7%, hyperlipidemia in 86.3% and 34.2% were diabetics. The intended CAS procedure was completed in 98.1% of cases. A stent was implanted in 97.3% of completed cases. The median intervention time was 43 min (quartiles: 30-60 min). During the hospital stay death rate was 0.3% (5/1888) and the rate of ipsilateral stroke 3.2% (58/1840). A contralateral ischemic event occurred in 1.4% (26/ 1840) of patients. The combined rate of all death or strokes was 3.8% (70/1841). Between 1996 and 2004 there was a steady increase in the use of protection devices during CAS (0% in 1996 and 97.9% in 2004; p for trend <0.0001). There was also an increase in the proportion of patients treated for asymptomatic stenoses (p for trend <0.0001). We observed a decrease of the combined endpoint of death or stroke from 6.3% in 1996 to 1.9% in 2004 (p for trend=0.021). CONCLUSION: The multi-centre ALKK CAS Registry data confirm the feasibility and shot-term safety of CAS even in daily clinical practice. There was a rapid penetration of the use of embolic protection devices, an increase in treatment of asymptomatic carotid stenoses and a decrease in acute complication rates from 1996 to 2004.
Asunto(s)
Estenosis Carotídea/terapia , Sistema de Registros/estadística & datos numéricos , Sociedades Médicas , Stents/tendencias , Anciano , Estenosis Carotídea/mortalidad , Causas de Muerte/tendencias , Comorbilidad , Diseño de Equipo , Estudios de Factibilidad , Femenino , Alemania , Mortalidad Hospitalaria/tendencias , Humanos , Embolia Intracraneal/mortalidad , Embolia Intracraneal/prevención & control , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
Partial malposition of a PFO closure device occurred, probably due to a right atrial ligamentous structure. Despite absence of residual shunt and uneventful postprocedural course, elective surgical removal was performed. Indications, procedural and anatomical aspects are discussed.
Asunto(s)
Implantación de Prótesis Vascular , Remoción de Dispositivos , Ecocardiografía Transesofágica , Defectos del Tabique Interatrial/cirugía , Complicaciones Posoperatorias/cirugía , Falla de Prótesis , Adulto , Cateterismo Cardíaco , Defectos del Tabique Interatrial/diagnóstico por imagen , Humanos , Ligamentos/diagnóstico por imagen , Ligamentos/cirugía , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Diseño de Prótesis , ReoperaciónRESUMEN
The increasing limitation of resources has stimulated the discussion of the reuse of medical devices labelled for "single use" by the manufacturer. The prerequisites for employment of reprocessing measures are patient safety and cost saving potential. Although reprocessing of single use medical devices has been general practice by many institutions, health care providers and authorities have remained insecure as to hygienic and functional risks, liability and legal aspects. Changes in legislation (German Medical Device Act), guidelines of the Robert Koch Institute (and position of the FDA) and the high quality guaranteed by innovative reprocessing technology have now created the basis for expanded but controlled use of reprocessing techniques for medical devices as a contribution to cost containment. A significant cost saving potential is calculated for the cost-intensive field of interventional cardiology.
Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Cateterismo Cardíaco/instrumentación , Equipos Desechables/economía , Equipo Reutilizado/legislación & jurisprudencia , Garantía de la Calidad de Atención de Salud/legislación & jurisprudencia , Esterilización/legislación & jurisprudencia , Angioplastia Coronaria con Balón/economía , Cateterismo Cardíaco/economía , Control de Costos/legislación & jurisprudencia , Equipos Desechables/normas , Equipo Reutilizado/economía , Alemania , Humanos , Programas Nacionales de Salud/economía , Programas Nacionales de Salud/legislación & jurisprudencia , Garantía de la Calidad de Atención de Salud/economía , Garantía de la Calidad de Atención de Salud/normas , Esterilización/economía , Esterilización/normasRESUMEN
Despite the use of lytics, aggressive antiplatelet agents, stents and thrombectomy devices, intracoronary thrombus remains a challenge for interventional catheter-based techniques, mainly due to insufficient reduction of thrombus and risk of distal embolization. This study assesses the clinical safety and efficacy of the X-SIZER catheter (EndiCOR Medical, Inc., San Clemente, California), a novel device designed to remove soft atherothrombotic tissue from native coronary arteries, saphenous vein grafts and restenotic stents. The X-SIZER was used during catheter-based intervention as the initial device in patients with angiographically suspected thrombus at the target. Inclusion criteria were target lesion stenosis of > or = 70% diameter stenosis (DS) or > or = 50% DS with Thrombolysis in Myocardial Infarction (TIMI) flow reduction and a reference diameter of 3 mm. Analyses were performed for reduction of stenosis, improvement of TIMI flow grade by X-SIZER alone (X-SIZER outcome) and after final adjunct procedure (final outcome), angiographic complications (dissection, embolization, perforation), adverse clinical events during hospitalization, and device-related technical failures. Eighty-five patients (age range, 31-82 years old; 69 male) were studied. Forty-four patients with unstable angina and 31 with acute myocardial infarction (MI) were treated, including 18 saphenous vein grafts and 17 re-occluded stents. In 71/85 patients (84%), the X-SIZER reached the target lesion and was successfully activated. Technical failures were associated with tortuous anatomy or vessel caliber < 3 mm. In 60/71 patients (85%), X-SIZER success was achieved by either improving TIMI flow by at least one grade or reducing DS by at least 20% (DS pre-X-SIZER = 88 +/- 19%; DS post-X-SIZER = 60 +/- 29%) without a major adverse clinical event (i.e., death, Q-wave MI, three-fold elevation of creatine kinase, or total occlusion or perforation requiring emergency bypass surgery or emergency stenting). Creatinine kinase rise greater than 3 times baseline occurred in 2 patients without preexisting acute MI. Thrombus dislodgement occurred in 3 patients and vessel perforation without clinical sequelae occurred in 1 patient. No other major procedural complications were noted. Adjunct interventions (balloon and stent) were employed in all except two X-SIZER stand-alone cases for a final DS of 11 +/- 18%. The X-SIZER Catheter System is simple to use, safe and effective for patients with relatively large, non-tortuous target vessels. Improved catheter characteristics may expand its use to more complex anatomy.
Asunto(s)
Cateterismo Cardíaco/instrumentación , Cateterismo , Trombosis Coronaria/cirugía , Trombectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Trombosis Coronaria/diagnóstico por imagen , Creatina Quinasa/sangre , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Dedicated catheter and stent systems for use in the carotid circulation have only been developed recently. Almost exclusively, self-expandable metallic stents are being used. Longitudinal flexibility, contourability of the luminal configuration, sufficient radial resistive force, narrow meshwork for sealing of the diseased vessel wall, low profile of the constraint stent, and compatibility of the devices with routine angioplasty techniques are the premier requirements. Most of the current experience is based on the longitudinal wire mesh design (Carotid Wallstent). The narrow meshwork has excellent sealing capacity but the inherent (yet manageable) problem of foreshortening with expansion needs attention. The segmented ring designs of the more recent Nitinol stents permit more precise positioning and contouring of the luminal surface, yet their capacity to seal a complex or thrombotic lesion and their clinical safety needs further evaluation. As more distinct features of dedicated carotid stents are being developed and as their differential importance gets recognized, a more meaningful and individual stent selection for the carotid anatomy may further improve clinical outcome.
Asunto(s)
Arterias Carótidas/cirugía , Estenosis Carotídea/cirugía , Stents , HumanosRESUMEN
The increase in minimum lumen diameter achieved by coronary stent placement can be further enhanced by reducing the immediate recoil that occurs after stent deployment. The effect of various stent designs-flexible coils, slotted tubes, and a locking stent-on minimization of postdilation stent recoil was evaluated using an in vitro model of circumferential compression. The stents were expanded to 7 atm (3.82 +/- 0.02 mm); as pressure was reduced, lumen diameter and cross-sectional area (CSA) were determined by on-line intravascular ultrasound imaging (30 MHz) positioned inside the dilating balloon (n = 10-15 inflation-deflation cycles). Stent recoil was assessed by calculation of percent change in CSA from 7 atm to negative balloon pressure: -33.1 +/- 5.6% (GR-II) and -22.4 +/- 3.8% (Wiktor) in the coil stents; -20.0 +/- 4.2% (JJIS coronary), -8.4 +/- 2.6% (JJIS biliary), and -6.9 +/- 1.5% (Multilink) in the slotted tube stents; and -1.9 +/- 3.2% in the Navius ZR1 locking stent (P < 0.05 vs. Multilink, P < 0.0001 vs. others). A range of resistances to recoil is demonstrated by this model, with coil stent designs undergoing greater elastic recoil than slotted tube stent designs. The locking stent design demonstrated the greatest radial strength and the most reduction in elastic recoil.
Asunto(s)
Cateterismo , Stents , Ultrasonografía Intervencional , Angioplastia Coronaria con Balón , Artefactos , Elasticidad , Estudios de Evaluación como Asunto , Humanos , Diseño de PrótesisRESUMEN
Although the use of coronary stents has virtually abolished the threat of periprocedural obstructive dissection, subacute and acute intracoronary thrombosis and late restenosis remain a major problem with catheter-guided transluminal coronary interventions, despite significant technical advances over the last 10 years. Acute stent thrombosis emerged as a new problem with the introduction of metallic coronary prostheses (stents), which unfortunately represent an ideal stimulus for platelet deposition. Recently, dramatic progress has been achieved by focusing on the inhibition of thrombin and platelets, before and during interventional procedures. This has stimulated the search for powerful and well-tolerated antithrombotic agents-platelet inhibitors and antithrombins-so that long-term (oral) administration may become possible, if necessary. The current roles of unfractionated and low-molecular-weight heparins (LMWHs), direct thrombin inhibitors (such as hirulog and hirudin), antiplatelet agents (such as aspirin, clopidogrel, and ticlopidine) and the potential of the glycoprotein IIb/IIa receptor blockers are reviewed and put into perspective with respect to their acute and long-term clinical value.
Asunto(s)
Cardiología/métodos , Trombosis Coronaria/prevención & control , Fibrinolíticos/uso terapéutico , Angioplastia Coronaria con Balón/efectos adversos , Enfermedad Coronaria/terapia , Trombosis Coronaria/etiología , Humanos , Stents/efectos adversos , Terapia Trombolítica , Resultado del TratamientoRESUMEN
Although several randomized trials have been performed to compare the outcomes of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass surgery (CABG) in patients with multivessel disease, there is little data available on angiographic follow-up results. The present substudy of the German angioplasty versus bypass surgery investigation (GABI Trial) compares the angiographic revascularization status in these two cases 6 months after treatment. Follow-up angiograms were available in 102 CABG patients and 117 PTCA patients. Although the protocol excluded patients with total occlusion, on follow-up 6 months after treatment we found total occlusion of 94 native arteries (36.9%) in the CABG group and of six arteries (2.5%) in the PTCA group (P < 0.001). The rate of occluded native vessels did not correlate significantly with the severity of the lesion before bypass surgery. In the CABG group 31 bypass grafts (12.2%) were found to be occluded at the 6 month follow-up examination (29/225 vein grafts [12.9%]; 2/30 mammary artery grafts [6.7%]). The main pathway, defined as the nutrient vessel (native vessel or bypass graft) providing the least resistance to blood flow, was narrowed by a lesion with a diameter stenosis of 70-100% for 36 target lesions (14.1%) in the CABG group and 39 target lesions (16.2%) in the PTCA group (P, ns). However, the prevalence of moderately severe lesions with a 50-69% diameter reduction of the main pathway was significantly greater in the PTCA group (44 lesions, 18.3%) than in the CABG group (19 lesions, 7.5%, P < 0.01). Thus, 6 months after randomized allocation to PTCA or CABG, we found comparable rates of high-grade lesions in the main pathways of both treatment groups. Whereas moderately severe lesions of the main pathway were predominantly seen in the PTCA group, there was marked disease progression to total occlusion in the native circulation after bypass grafting.
Asunto(s)
Angioplastia Coronaria con Balón , Puente de Arteria Coronaria , Enfermedad Coronaria/terapia , Anciano , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/patología , Vasos Coronarios/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: The standard treatment for patients with symptomatic multivessel coronary artery disease is coronary-artery bypass grafting (CABG). Percutaneous transluminal coronary angioplasty (PTCA) is widely used as an alternative approach to revascularization, but a systematic comparison of the two procedures is needed. We compared the outcomes in patients one year after complete revascularization with CABG or PTCA. METHODS: A total of 8981 patients with multivessel coronary disease were screened at eight clinical sites, and 359 patients were randomly assigned to undergo CABG (177 patients) or PTCA (182 patients). Enrollment required that complete revascularization of at least two major vessels supplying different myocardial regions be deemed clinically necessary and technically feasible. RESULTS: Among the patients in the CABG group, an average of 2.2 +/- 0.6 vessels were grafted, and among those in the PTCA group, 1.9 +/- 0.5 vessels were dilated. After CABG, hospitalization was longer (median, 19, as compared with 5 days for PTCA), and Q-wave myocardial infarction in relation to the procedure was more frequent (8.1 percent, as compared with 2.3 percent after PTCA; P = 0.022), whereas in-hospital mortality did not differ significantly between the two groups (2.5 percent in the CABG group and 1.1 percent in the PTCA group). At discharge 93 percent of the patients in the CABG group were free of angina, as compared with 82 percent of those in the PTCA group (P = 0.005). During the first year of follow-up, further interventions were necessary in 44 percent of the patients in the PTCA group (repeated PTCA in 23 percent, CABG in 18 percent, and both in 3 percent) but in only 6 percent of the patients in the CABG group (repeated CABG in 1 percent and PTCA in 5 percent; P < 0.001). Seventy-four percent of the patients in the CABG group and 71 percent of those in the PTCA group were free of angina one year after treatment. Exercise capacity improved similarly in both groups. However, 22 percent of the CABG group, as compared with only 12 percent of the PTCA group, did not require antianginal medication (P = 0.041). CONCLUSIONS: In selected patients with multivessel coronary disease, PTCA and CABG as initial treatments resulted in equivalent improvement in angina after one year. However, in order to achieve similar clinical outcomes, the patients treated with PTCA were more likely to require further interventions and antianginal drugs, whereas the patients treated with CABG were more likely to sustain an acute myocardial infarction at the time of the procedure.
Asunto(s)
Angioplastia Coronaria con Balón , Puente de Arteria Coronaria , Enfermedad Coronaria/terapia , Anciano , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/cirugía , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Experimental results from human cell culture studies have shown that smooth muscle cells derived from human atherosclerotic plaques react more sensitively to photoactivated dihematoporphyrin-ester and -ether (DHE) than smooth muscle cells from human nonatherosclerotic arteries. A therapeutic concept of photodynamic therapy of vascular stenosis appears, therefore, to be promising. The prerequisite for an intravascular application is a relatively harmless application of the photosensitizing agent to the luminal lining of endothelial cells. METHODS: The effect of DHE with and without photoactivation was examined on endothelial cell cultures from human saphenous veins. The cellular uptake of DHE in relation to the serum content of the culture medium was evaluated, as well as its effect on proliferative activity, cell size, cell volume, and cellular viability. RESULTS: Intracellular uptake of DHE decreased significantly when higher serum concentrations were present in the culture medium. Incubation of cells with the photosensitizer for 9 days in the dark without light activation resulted in a significant decrease of endothelial cell proliferation only at concentrations higher than 2.5 micrograms/mL (= 2.5 mg/kg body weight for systemic application in vivo). Additional photoactivation caused no reduction of cell viability at DHE concentrations of 1 microgram/mL, but at 2.5 micrograms/mL and 5 micrograms/mL, a reduction of viable cells within 24 hours was observed in relation to the energy densities used for irradiation. CONCLUSIONS: Because smooth muscle cells from atherosclerotic plaques are, however, much more sensitive to photodynamic treatment, the concept of a photodynamic therapy of vascular stenosis may provide a good tool in the reduction of restenosis rates after recanalization of severely stenosed or even occluded arteries.
Asunto(s)
Arteriosclerosis/patología , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Fotorradiación con Hematoporfirina , Células Cultivadas , Éter de Dihematoporfirina/farmacocinética , Humanos , Vena SafenaRESUMEN
A new video-enhanced fluorescence imaging technique has been used for the first time for in vitro differentiation of human atherosclerotic plaques vs normal arterial wall. Laser-induced superficial tissue fluorescence of specimens from human aorta was documented after alternating excitation with violet (405 nm +/- 5 nm) and blue (470 nm +/- 10 nm) krypton-ion laser light. Subsequent digital subtraction of the corresponding fluorescence images allowed to differentiate areas of atherosclerosis from normal intima. Fluorescence intensity was correlated with the morphological aspect of samples and histology of the plaque. Dihematoporphyrin-ether/ester (DHE) incubation enhanced fluorescence contrast of plaques in comparison to normal artery vessel wall. Depending on the concentration of the incubation solution (10, 20, and 40 micrograms DHE/ml NaCl solution), fluorescence increased. Fluorescence intensity was highest in fatty plaque areas, while calcific lesions showed no substantial DHE uptake.
Asunto(s)
Angioplastia por Láser/instrumentación , Arteriosclerosis/cirugía , Hematoporfirinas , Procesamiento de Imagen Asistido por Computador/instrumentación , Aorta/patología , Arteriosclerosis/patología , Éter de Dihematoporfirina , Humanos , Técnica de Sustracción/instrumentaciónRESUMEN
It is little known that photosensitizing porphyrins can be used not only for the localization and photodynamic therapy of tumors, but that they also accumulate in atherosclerotic plaques. This observation might be of interest for the detection and therapy of vascular stenoses. The present study examines whether dihematoporphyrin-ester and -ether, at clinically relevant concentrations, selectively influence cultured smooth muscle cells from human atherosclerotic plaques (primary stenoses and secondary stenoses) in comparison to smooth muscle cells obtained from non-atherosclerotic arteries. The results demonstrate that the drug accumulated to a greater extent in plaque-derived cells than in smooth muscle cells from normal arteries. Even without photoactivation, dihematoporphyrin-ester and -ether significantly decreased the proliferative activity of cells from atherosclerotic plaques. Light exposure of porphyrin-labeled cells resulted in a more pronounced sensitivity of plaque cells when compared with smooth muscle cells from non-atherosclerotic arterial wall. A comparison of the proliferative activity of cells before and after photodynamic reaction demonstrated that this activity was unaltered in surviving smooth muscle cells from non-atherosclerotic arteries, whereas surviving plaque-derived cells exhibited a significantly decreased or even non-proliferative activity. From the in vitro studies, a porphyrin concentration of 1-5 micrograms/ml (= 1-5 mg/kg body weight in vivo after systemic application) seems to be the most suitable dosage. In addition, morphological alterations of the cells caused by photodynamic reaction were documented.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Arteriosclerosis/patología , Enfermedad de la Arteria Coronaria/patología , Fotorradiación con Hematoporfirina , Músculo Liso Vascular/efectos de los fármacos , Adulto , División Celular/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/ultraestructura , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/patología , Éter de Dihematoporfirina , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Femenino , Hematoporfirinas/farmacocinética , Humanos , Masculino , Microscopía Electrónica de Rastreo , Músculo Liso Vascular/patologíaRESUMEN
The effect of dihematoporphyrin-ester or -ether (DHE), a photosensitizing porphyrin with different amounts of aggregates, on the growth of cultured smooth muscle cells obtained from nonatherosclerotic arteries and from atheromatous plaques (primary stenosing and restenosing lesions) was examined without photoactivation of the drug. Clinically relevant DHE concentrations ranging from 0.1 to 25 micrograms/ml were used. In all proliferation studies with cells of second and third passage (approximately 10 cumulative population doublings in vitro), the growth rates decreased in a dose-dependent manner. Smooth muscle cells from atherosclerotic lesions were significantly more sensitive than smooth muscle cells from normal arteries. Cells derived from restenosing lesions retained their increased sensitivity even after eight passages in culture (approximately 20 cumulative population doublings). Cell size measurements showed that the decreased proliferative activity mainly occurred in smooth muscle cell subpopulations consisting of small cells. A cytotoxic effect of DHE was observed at concentrations above 5 micrograms/ml, causing cytoplasmic protrusions, vacuoles, and even complete cell lysis. At a DHE concentration of 5 micrograms/ml, the number of viable cells was 73% +/- 14% (means +/- SD) for smooth muscle cells from nonatherosclerotic arterial media and only 38% +/- 11% (means +/- SD) for smooth muscle cells from atherosclerotic plaques. In all experiments, no significant difference in response to DHE treatment was observed between cells from primary stenosing and restenosing lesions, suggesting a specific mechanism for plaque-derived cells causing an increased sensitivity in comparison to smooth muscle cells from nonatherosclerotic arteries. The pronounced sensitivity of plaque cells against DHE treatment suggests that this drug--even without photoactivation--is potentially valuable in vivo as a therapeutic approach to vascular stenoses.
Asunto(s)
Arteriosclerosis/fisiopatología , Hematoporfirinas/farmacología , Músculo Liso Vascular/citología , Arterias Carótidas , División Celular , Supervivencia Celular , Células Cultivadas , Éter de Dihematoporfirina , Arteria Femoral , Humanos , Desarrollo de Músculos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/crecimiento & desarrolloRESUMEN
Cultured smooth muscle cells from human nonatherosclerotic arteries and from primary stenosing lesions were labeled with dihematoporphyrinester and ether, a photosensitizing probe used mainly for the detection and photodynamic therapy of tumors. After labeling for 24 h, cells were irradiated with ultraviolet light (wavelength 365 nm, energy densities ranging from 30 to 1,200 mJ/cm2). Twenty-four hours after photoradiation, 80% of smooth muscle cells from nonatherosclerotic arteries and only 20% of smooth muscle cells from atherosclerotic plaques were viable and still adherent. Moreover, dynamic cell and cytoskeletal alterations in response to irradiation are described. The differential sensitivity of smooth muscle cells from nonatherosclerotic arteries and from atherosclerotic plaques provides evidence that a photodynamic treatment might be a valuable therapeutic approach to vascular stenosis.
Asunto(s)
Arteriosclerosis/tratamiento farmacológico , Fotorradiación con Hematoporfirina , Músculo Liso Vascular/efectos de los fármacos , Fotoquimioterapia , Arteriosclerosis/patología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Células Cultivadas , Constricción Patológica/patología , Humanos , Músculo Liso Vascular/patología , Músculo Liso Vascular/efectos de la radiación , Valores de ReferenciaRESUMEN
In 29 consecutive patients (pts) coronary wedge pressure (CWP) was determined as an indicator of coronary collateral function during coronary angioplasty. Collaterals to the target vessel were angiographically detectable in 21 pts. CPW, aortic pressure (AOP), pulmonary wedge pressure (PCP), intervals to appearance of angina pectoris, surface and intracoronary ECG-changes were registered during two (n = 10) or three (n = 19) consecutive balloon dilatations. A total of 21 pts received 0.8-1.0 mg nifedipine intravenously before a second or third dilatation was performed; a control group (n = 8) received placebo. Hemodynamic parameters were reproducible for all dilatations without nifedipine. After administration of nifedipine significant changes occurred: decreases of CPW (from 34 to 29 mm Hg), AOP (from 121 to 110 mmHg), and PCP (from 12.4 to 9.4 mm Hg), and increase of ischemic tolerance time (angina pectoris) (from 35 to 56 s) (p less than 0.01). Changes in CWP and AOP showed a statistical tendency to correlate (p = 10). Thus, intravenous administration of nifedipine can improve ischemic tolerance during coronary angioplasty. Simultaneous measurement of coronary wedge pressure could not prove enhancement of collateral function as being responsible for these antiischemic effects.
Asunto(s)
Angioplastia Coronaria con Balón/métodos , Circulación Colateral/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Enfermedad Coronaria/terapia , Nifedipino/administración & dosificación , Adulto , Anciano , Angina Inestable/terapia , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Terapia Combinada , Electrocardiografía/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Estudios Prospectivos , Método Simple CiegoRESUMEN
A modified concept using a movable fiber with radial light dispersion was developed for combining mechanical balloon dilatation and intraluminal circumferential Nd-Yag laser irradiation of the arterial wall. The aims of the study were the technical feasibility and the acute and chronic vascular tissue effects of laser-assisted balloon dilatation. The carotid arteries (n = 9 dogs) and femoral arteries (n = 5 dogs) of dogs were mechanically dilated and simultaneously circumferentially irradiated through the balloon by 1,064 nm Nd-Yag laser (20-25 W). Temperature at the adventitial surface was kept constant at 50 degrees C, 60 degrees C, 70 degrees C, or 80 degrees C for either 8 or 15 seconds by a computerized feedback system for temperature control. Angiographic and histological results were available acutely, subacutely (2 days), and at 3 months. Angiographically, stable and smooth enlargement of the lumen was demonstrated acutely. At 3 months, occlusions, probably thrombotic in origin, had occurred in 5 of the carotid arteries and none of the femoral arteries. Histologically, laser-induced coagulation of the arterial wall with loss of cellular elements was demonstrated. Collagen and elastic fibers remained relatively intact. In two carotid arteries intimal proliferation was observed at the treated site. Thus, this technique appears to be technically feasible, yet further study is needed to assess its potential to reduce or repair acute vascular complications (dissections) and to reduce restenoses after percutaneous transluminal coronary angioplasty (PTCA). However, the clinical value of this technique appears to be limited in view of the thromboses and reactive proliferations observed in this preliminary study.
Asunto(s)
Angioplastia de Balón/métodos , Terapia por Láser/métodos , Procedimientos Quirúrgicos Vasculares , Angioplastia de Balón/instrumentación , Animales , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Arterias Carótidas/cirugía , Perros , Arteria Femoral/patología , Arteria Femoral/cirugía , Terapia por Láser/instrumentación , Radiografía , TemperaturaRESUMEN
Techniques of percutaneous transluminal application of laser energy for vessel recanalization have been used clinically since 1983. The commonly used Nd:YAG and argon lasers achieve ablation of atherosclerotic plaques by thermal action (vaporization). In order to reduce undesirable thermal damage in the neighborhood of the target tissue and to avoid vessel perforation, optimal irradiation parameters, modified (atraumatic) fiber tips (hot tips, sapphires), and steerable catheter systems needed to be implemented. Favorable results from peripheral application have encouraged use in the coronary circulation. More recently, coagulative tissue effects of circumferential irradiation of the vessel wall during balloon dilatation have been used for stabilization of acute and late results after mechanical balloon angioplasty. Enhancement of the differential light absorption of atherosclerotic plaque by use of biological dyes may further improve selective intravascular laser application. Intraoperative ECG-guided laser coagulation of arrhythmogenic areas of myocardium is a method for treatment of malignant arrhythmias. Transluminal non-operative application of myocardial laser photocoagulation has now been tested experimentally and shown to be safe and effective. There was no arrhythmogenicity or thermal damage of coronary arteries associated with this method. Innovative techniques such as nanosecond pulsed excimer lasers (athermal action) and development of "intelligent" lasers--which are equipped with spectroscopy-guided feedback systems for plaque recognition--have opened new perspectives and will further improve safety and efficacy of clinical laser application. However, according to current experience, the thermally acting Nd:YAG laser is an effective and versatile mode of laser therapy for selected cardiovascular indications.