RESUMEN
In this paper the structures of 4-aminophenol(H2O)1+ and 3-aminophenol(H2O)1+ clusters are investigated in molecular beam experiments by different IR/UV-double resonance techniques as well as the mass analyzed threshold ionization spectroscopy yielding both inter- and intramolecular vibrations of the ionic and neutral species. Possible structures are extensively calculated at the level of density functional theory (DFT) or at the ab initio level of theory. From the experimental and theoretical investigations it can be concluded that in the case of 4-aminophenol(H2O)1 one O-H...O hydrogen-bonded structure exists in the neutral cluster but two structures containing either an O-H...O or a N-H...O hydrogen-bonded arrangement are observed in the spectra of the ionic species. This observation is a result of an intramolecular rearrangement reaction within the ion which can only take place if high excess energies are used. A reaction path via the CH bonds is calculated and explains the experimental observations. In the case of 3-aminophenol(H2O)1+ only one O-H...O bound structure is observed both in the neutral and ionic species. Ab initio and DFT calculations show that due to geometrical and energetical reasons a rearrangement cannot be observed in the 3-aminophenol(H2O)1+ cluster ion.
RESUMEN
AIMS: Efficacy of pace-termination of atrial arrhythmias (ATP) may depend on atrial cycle length and regularity. Whether device programming of ATP therapies can improve ATP efficacy and alter atrial tachyarrhythmia burden is unknown. METHODS AND RESULTS: ATP efficacy was evaluated in 61 patients (39 males; 66 +/- 10 years) with a standard indication for pacing, 95% with a history of AT/AF. Each patient was implanted with a novel DDDRP pacemaker capable of delivering ATP therapy. ATP efficacy and AT/AF frequency and burden were compared within each patient during a period of nominal ATP programming (NP) followed by a period of aggressive incremental programming (IP). Adjusted ATP-termination efficacy was higher during IP than during NP (54.8% vs 37.9%, P < 0.05). No differences in AT/AF frequency (3.3 +/- 5.9 vs 3.2 +/- 6.9 day(-1)) or burden (18 +/- 28% vs 18 +/- 29%) were observed comparing NP with IP. The majority of episodes during both the NP (81%) and IP (77%) periods terminated within 10 min. Episodes lasting 24 h or more accounted for only 0.4% of the episodes in both groups. but accounted for 38% of the average burden during NP and 51% during IP. CONCLUSIONS: Device programming of ATP therapies can influence the number of treated episodes and the efficacy of ATP therapies although arrhythmic frequency and burden may not change. Total atrial arrhythmia burden is disproportionately influenced by long (>24 h) episodes.
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Fibrilación Atrial/terapia , Aleteo Atrial/terapia , Marcapaso Artificial , Taquicardia/terapia , Anciano , Estimulación Cardíaca Artificial/métodos , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de TiempoRESUMEN
UNLABELLED: Automatic atrial anti-tachy pacing (aATP) is a novel approach to treat paroxysmal/persistent atrial tachyarrhythmias in pacemaker patients. To evaluate the efficacy of aATP in terminating spontaneous atrial flutter/tachycardia episodes (AT), a dual-chamber stimulator with extensive diagnostic capabilities and programmable aATP therapies (AT500(TM), Medtronic Inc.) was implanted in 30 patients with conventional pacing indications. During a mean follow-up time of 5.5 (1-12) months, aATP was delivered for 10494 AT. According to automatic device analysis, 8289 AT were treated with success (success-rate 79.0%). On 468 AT stored with the corresponding atrial EGM, an additional manual analysis was performed. The success-rate based on automatic analysis of these AT episodes (73.1%) was comparable to that found for all treated AT (79.0%), but manual EGM analysis revealed that only 209 of the 468 treated AT episodes (44.7%) were actually terminated by aATP. The aATP success-rate in the slower (cycle length 360-270 ms) AT detection zone was significantly higher (73.8%, 62/84 eps) than in the overlapping, faster (cycle length 270-220 ms) AT zone (38.3%, 147/384 eps, P<0.01). CONCLUSIONS: According to manual analysis, 1. aATP was safe and had a success-rate of 44.7%, 2. aATP success-rate was higher for AT in the slower than in the faster detection zone and 3. automatic analysis overestimated the efficacy of aATP.
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Estimulación Cardíaca Artificial , Atrios Cardíacos/cirugía , Taquicardia Atrial Ectópica/terapia , Adulto , Anciano , Anciano de 80 o más Años , Técnicas Electrofisiológicas Cardíacas/instrumentación , Seguridad de Equipos/instrumentación , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Marcapaso Artificial , Sensibilidad y Especificidad , Taquicardia Atrial Ectópica/diagnóstico , Resultado del TratamientoRESUMEN
INTRODUCTION: Patients with bradycardia requiring permanent pacing frequently suffer from additional atrial tachyarrhythmias (ATs). This study evaluated the safety and efficacy of atrial antitachycardia pacing (ATP) and the performance of pacing for AT prevention implemented into a new pacemaker. METHODS AND RESULTS: In patients with conventional indications for permanent pacing, an investigational DDDRP pacemaker (Medtronic AT500, model 7253) was implanted. The primary study objectives were to determine the safety of overall device functioning and its efficacy in terminating spontaneous AT. A secondary endpoint was to determine the reliability of AT detection. Pacemaker memory functions were used to analyze the impact of dedicated pacing algorithms on AT prevention. In 33 European and Canadian centers, 325 patients were enrolled (mean follow-up 2.3+/-1.3 months). Complication-free survival at 3 months was 88%. In 2,145 episodes stored with atrial electrograms, AT detection was confirmed in 97%. The algorithm for continuous overdrive pacing increased the percentage of atrial pacing to 97%. After ATP activation, 16,683 of 52,468 AT episodes were treated (120 patients). Of these, 8,903 episodes (53%) were terminated successfully by ATP. No proarrhythmic effect of preventive pacing or atrial ATP was observed. Preventive pacing algorithms increased the median percentage of atrial pacing from 62% to 97%. However, the number of AT/AF (atrial fibrillation) episodes (4.1 vs 4.1 per patient per day) and the time in AT/AF (13.7% vs 12.8%) was not significantly different before and after activation of preventive pacing. CONCLUSION: DDDRP pacing with a new system for AT therapy was safe and associated with successful pace-termination of AT in 53% of episodes. Preventive pacing and atrial ATP algorithms represent two new functions that can be implemented safely into pacemaker systems for nonpharmacologic treatment of ATs in patients requiring pacemaker therapy.
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Estimulación Cardíaca Artificial , Taquicardia Atrial Ectópica/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Fibrilación Atrial/terapia , Canadá/epidemiología , Desfibriladores Implantables , Electrocardiografía Ambulatoria , Seguridad de Equipos , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Atrios Cardíacos/cirugía , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Marcapaso Artificial , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de Supervivencia , Taquicardia Atrial Ectópica/complicaciones , Taquicardia Atrial Ectópica/mortalidad , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Coartación Aórtica/etiología , Claudicación Intermitente/etiología , Complicaciones Posoperatorias/etiología , Mallas Quirúrgicas , Adulto , Cateterismo/métodos , Constricción Patológica , Embolia/etiología , Embolia/terapia , Humanos , Claudicación Intermitente/patología , Masculino , Tereftalatos Polietilenos/uso terapéutico , Arteria Poplítea , Complicaciones Posoperatorias/cirugía , Recurrencia , Reoperación , Factores de TiempoRESUMEN
BACKGROUND: Because of limited long-term success, aortic balloon valvuloplasty is considered to be a palliative procedure, including patients at excessive risk for standard therapy-aortic valve replacement-that is, those in cardiogenic shock. HYPOTHESIS: The study was undertaken to evaluate the outcome of balloon valvuloplasty for critical aortic stenosis complicated by cardiogenic shock. METHODS: Over a 10-year-period, we followed 14 patients (age 74+/-11 years, range 50-91) presenting in cardiogenic shock and critical aortic stenosis, who underwent valvuloplasty, together with 19 patients with critical aortic stenosis requiring urgent major noncardiac surgery. RESULTS: In patients in shock, calculated aortic valve area could be increased successfully by at least 0.3 cm2, from 0.38+/-0.09 to 0.81+/-0.12 cm2, with an insignificant increase in cardiac index from 1.89+/-0.33 to 2.01+/-0.41 l/min * m2. In-hospital mortality was 71% (10 patients). Two patients underwent valve replacement within 16 days and survived after 1 year, as did two patients refusing surgery. By multivariate logistic regression analysis, only an interval between onset of shock symptoms and valvuloplasty of > 48 h was significantly associated with fatal outcome (p < 0.01). In those patients requiring noncardiac surgery, this was possible after valvuloplasty in 95% who survived 1 year after hospital discharge. One patient in this group died of pulmonary embolism the day after the procedure. CONCLUSION: These data support the concept of causal treatment in patients with cardiogenic shock, as well as in the setting of cardiogenic shock and critical aortic stenosis, at the earliest possible convenience.
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Estenosis de la Válvula Aórtica/terapia , Cateterismo , Choque Cardiogénico/terapia , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/complicaciones , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Choque Cardiogénico/complicacionesRESUMEN
HISTORY AND ADMISSION FINDINGS: A 21-year-old woman with known endocardial fibroelastosis diagnosed when aged 3 months was admitted because of progressive dyspnoea. The physical examination revealed symptoms of heart failure, with pulmonary rales, mild hepatomegaly, and tachyarrhythmia. INVESTIGATIONS: The electrocardiogram showed atrial fibrillation, complete right bundle branch block and right ventricular hypertrophy. Echocardiography indicated hypertrophy and dilatation of the right ventricle (61 mm) with tricuspid regurgitation and hypoplasia of the left ventricle. Heart catheterization confirmed pulmonary hypertension (60/46 mmHg) as well as dilatation and hypokinesia of the right ventricle. Right ventricular biopsy showed severe myocardial hypertrophy resulting from secondary pulmonary hypertension, while no evidence of myocarditis or idiopathic dilated cardiomyopathy was found. TREATMENT AND COURSE: Symptoms of heart failure improved under medical treatment with digitalis, angiotensin-converting enzyme inhibitor and diuretics. CONCLUSION: Primary endocardial fibroelastosis of the contracted type must be included in the differential diagnosis of heart failure occurring in young adults.
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Fibroelastosis Endocárdica/complicaciones , Fibroelastosis Endocárdica/diagnóstico , Insuficiencia Cardíaca/etiología , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Fibrilación Atrial/complicaciones , Cateterismo Cardíaco , Diagnóstico Diferencial , Digitalis/uso terapéutico , Diuréticos/uso terapéutico , Disnea , Ecocardiografía , Electrocardiografía , Fibroelastosis Endocárdica/fisiopatología , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Fitoterapia , Plantas Medicinales , Plantas TóxicasRESUMEN
HISTORY AND CLINICAL FINDINGS: A 29-year-old female was admitted with the diagnosis of multiple deep vein thrombosis of the upper limbs and neck and pneumonia secondary to pulmonary embolism on the right side. Medical history revealed that in vitro fertilization with hormone stimulation had been carried out 5 weeks before. For ten days the patient had noticed a growing, painful swelling on the right side of her neck accompanied by difficulties in swallowing. Since this time she had experienced episodes of shortness of breath without chest pain. Clinical findings showed a soft and slightly painful swelling of the right side of the neck without dyspnoea or cyanosis at rest. Breath sounds were decreased over the right lower lung on auscultation. INVESTIGATIONS: Magnetic resonance imaging (MRI) confirmed complete obstruction of the subclavian and brachiocephalic vein on the right side and clots in the superior vena cava, left subclavian vein, bilateral internal jugular veins and the right axillar vein. Chest x-ray showed pleural effusion on the right side. TREATMENT AND COURSE: As the seven-week pregnancy was found not to be viable anymore, fibinolysis with streptokinase was started under protection of a temporary cava filter. During the following hours the patient developed serious bleeding as a complication of this therapy and fibrinolysis had to be discontinued after 16 hours. In subsequent examinations the obstruction of the left internal jugular vein was unchanged but collaterals around the obstruction were noticed. The other veins affected were open, some with reduced flow. Several risk factors were found in the history of the patient such as smoking, immobilization, a positive family history, protein S deficiency and APC resistance. After 3 weeks of hospital therapy the patient was discharged under oral anticoagulation with coumarin. CONCLUSION: In vitro fertilization with hormonal stimulation may cause serious complications in patients with unknown coagulation disorders or with an ovarian hyperstimulation syndrome. Risk factors for thromboembolism need to be ruled out carefully before starting the procedure.
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Fertilización In Vitro/efectos adversos , Vena Cava Superior , Trombosis de la Vena/etiología , Aborto Espontáneo , Adulto , Anticoagulantes/uso terapéutico , Cumarinas/uso terapéutico , Estradiol/efectos adversos , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Hidroxiprogesteronas/efectos adversos , Imagen por Resonancia Magnética , Embarazo , Estreptoquinasa/efectos adversos , Estreptoquinasa/uso terapéutico , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/tratamiento farmacológicoRESUMEN
We report the case of a 69 year old patient, who underwent transvenous implantable cardioverter defibrillator (ICD) device change (Medtronic GEM VR 7227 Cx Active Can) because the ICD reached its replacement indicators. Preoperative chest X-ray and intraoperative defibrillation threshold tests and high voltage impedance did not show lead fracture of the five year old lead (Transvene 6936-65). At the second postoperative day the alarm of the newly implanted ICD device was activated because of high impedance in the painless lead impedance measurement (PLI) and the lead was replaced. The explanted lead showed a fracture detectable only by PLI.
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Desfibriladores Implantables , Anciano , Impedancia Eléctrica , Electrocardiografía , Electrodos , Falla de Equipo , Humanos , MasculinoRESUMEN
Inappropriate therapy by ICDs due to SVTs is an important problem. A third generation ICD with a new detection criterion ("EGM width criterion") for differentiation of SVTs and VTs by measuring the width of the intracardiac EGM was studied in 47 patients. A wide EGM was defined as the longest measured EGM plus 4-12 ms (programmed as EGM width threshold). EGM width detection function was programmed to the "Passive" mode so that no therapy was withheld. During a follow-up of 29.9 +/- 8.3 (12-45) months, 489 spontaneous episodes were analyzed. SVTs occurred in ten patients with 305 episodes; 301 were correctly classified by use of the new detection criterion. In four patients four episodes were incorrectly detected as wide QRS tachycardias. Thus specificity for SVT was 98.7% (on a per episode basis) and 60% on a per patient basis. Of 184 VTs in 23 patients, 118 episodes were correctly classified (19 patients), however, in 4 patients 66 VTs were falsely detected as SVTs, 62 (94%) of which occurred in 1 patient with complete left BBB and continuously increasing QRS width in 12-lead surface ECGs. Overall sensitivity (on a per episode basis) for VT detection was 64.1% and 96.7% in patients with stable width of the QRS complex in a 12-lead surface ECG. These data show that this criterion is not superior to data on rate dependent detection criteria and furthermore not applicable in patients with complete BBB.
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Desfibriladores Implantables/normas , Electrocardiografía/métodos , Técnicas Electrofisiológicas Cardíacas/métodos , Taquicardia Supraventricular/diagnóstico , Taquicardia Ventricular/diagnóstico , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Taquicardia Supraventricular/terapia , Taquicardia Ventricular/terapia , Tiempo , Resultado del TratamientoRESUMEN
The discrimination of supraventricular versus ventricular tachycardias by an implantable cardioverter-defibrillator (ICD) is still a remaining clinical problem. The false positive detection of supraventricular as ventricular tachycardias causes inadequate electrical therapies of the ICD. To improve the increase of specificity criterias like "Onset" or "Stability" are offered. If these criterias during tachycardia are not fulfilled, the "sustained rate duration" (SRD) is offered as a security criterion. The SRD reasons the delivery of the therapy during tachycardia after a programmable time. Aim of the study was to evaluate, if SRD in patients with known arrhythmia absoluta (AA) in atrial fibrillation and programmed "Onset"/"Stability" increases the sensitivity without loss of specificity in the treatment of hemodynamically tolerated ventricular tachycardias and which programming should be chosen. Our patient collective included 274 patients (pts) with new implanted ICD of the third generation. In 39 (14%) pts AA was known in the medical history. From these 39 (100%) pts, 18 (46%) pts had known tachyarrhythmic episodes (group I) in the area of the ventricular tachycardia-zone > or = 160 beats per minute, whereas in 21 (54%) pts a tachyarrhythmia absoluta (TAA) was unknown (group II). During follow-up of 12 +/- 8 (2-26) months, 151 tachycardias occurred and could be classified as supraventricular tachycardias by stored electrograms. In 9/18 pts of group I, a TAA occurred during follow-up. The initial programmed SRD during first TAA was 62 +/- 39 (35-90) s and was prolonged to 135 +/- 64 (90-180) s. After this prolongation, no inadequate therapy was delivered. In group II, 19/21 (90%) were inadequately treated during TAA. The initial SRD-programming was 45 +/- 28 (0-90) s and was prolonged to 201 +/- 150 (60-480) s during follow-up. After prolongation of the SRD, no more inadequate therapies due to AA were delivered. In pts with new implanted ICD and known TAA, which is hemodynamically tolerated, the SRD should be programmed beside all other available detection parameters for improving the increase of specificity at least 135 s to avoid inadequate therapies of the ICD. In pts with unknown TAA, SRD should be prolonged to 135 s at least the second tachyarrhythmic episode, which is hemodynamically well tolerated.
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Fibrilación Atrial/terapia , Desfibriladores Implantables , Electrocardiografía/instrumentación , Frecuencia Cardíaca/fisiología , Programas Informáticos , Adolescente , Adulto , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/etiología , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador/instrumentaciónRESUMEN
HISTORY AND CLINICAL FINDINGS: 24-hour ECG monitoring in a 64-year-old man revealed self-limited (< 30 s) ventricular tachycardias (VT) of > 200/min. He had triple-vessel coronary artery disease with both anterior and posterior wall infarctions treated by three aortocoronary venous grafts. Physical examination was unremarkable except for a well healed thoracotomy scar. INVESTIGATIONS: Programmed ventricular stimulation induced prolonged monomorphic VT of 320 beats/min, despite aminodarone treatment. Left-heart catheterization demonstrated the three patent aortocoronary grafts and a left-ventricular ejection fraction of only 20%. TREATMENT AND COURSE: Because of the inducible and prolonged VT, despite antiarrhythmic treatment with amiodarone, a cardioverter-defibrillator was implanted (ICD). During threshold measurements of the pacemaker integrated into the ICD the pacemaker impulse was noted to produce a right bundle branch block pattern, the ICD lead having erroneously been placed in the left ventricle via a patent foramen ovale. The lead was left in place, because the ICD was functioning well and lead removal with the possible need of a thoracotomy carried a high risk. CONCLUSION: Extreme caution is needed to avoid malpositioning an implantable cardioverter-defibrillator. If the lead tip is unwittingly fixed in the left ventricle but functions well it should be left in place under prophylactic anticoagulation, because of the potentially high risk of its operative removal.
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Desfibriladores Implantables/efectos adversos , Defectos del Tabique Interatrial/complicaciones , Taquicardia Ventricular/terapia , Amiodarona/uso terapéutico , Cateterismo Cardíaco , Puente de Arteria Coronaria , Ecocardiografía , Electrocardiografía , Frecuencia Cardíaca , Defectos del Tabique Interatrial/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Taquicardia Ventricular/diagnóstico por imagenRESUMEN
BACKGROUND: The renin-angiotensin system is mainly involved in several cardiovascular diseases and in the pathophysiology of heart failure. It exists as a circulating and a local system which can be differently regulated. Interventions in this system by angiotensin-converting enzyme (ACE) antagonists or angiotensin-receptor antagonists slow the progression of heart failure and result in prolongation of life expectancy and improvement of hemodynamics. MECHANISMS OF ACTION: The main underlying mechanisms are: 1. Heart failure results in activation of the renin-angiotensin system as a compensatory mechanism with elevation of circulating angiotensin II, norepinephrine and vasopressin. Antagonists of this compensatory mechanisms acutely result in improvement of the hemodynamic situation. 2. Elevated circulating and local renin-angiotensin systems cause chronic structural myocardial and vascular effects. Angiotensin-converting enzyme antagonists and angiotensin-receptor blockers modulate and partly antagonize these structural changes such as myocardial hypertrophy, myocardial fibrosis and vascular proliferative responses. Gene and receptor regulation of the system are currently not fully understood and are subject of intensive research. 3. The renin-angiotensin system is closely related to the bradykinin system and thus indirectly to nitric oxide and endothelial function. Bradykinin has multiple other effects on the hemostatic system as a well as on the myocardium and vascular system. CONCLUSION: These complex interactions require further evaluation. Research with specific bradykinin antagonists will give new insights into this system.
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Enfermedades Cardiovasculares/fisiopatología , Sistema Renina-Angiotensina/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Humanos , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
The necessity of routine invasive implantable cardioverter-defibrillator (ICD) testing before hospital discharge was analyzed in 268 patients. In 98% of the patients, invasive ICD testing was not necessary if a preimplant electrophysiologic test was performed; most of the observed problems can be solved by noninvasive control.
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Desfibriladores Implantables , Taquicardia Ventricular/prevención & control , Fibrilación Ventricular/prevención & control , Cateterismo Cardíaco/estadística & datos numéricos , Estimulación Cardíaca Artificial/estadística & datos numéricos , Electrofisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Two strategies to achieve optimal expansion of Wiktor stents in coronary arteries, oversizing at normal balloon pressures (group 1) and high-pressure dilatation (group 2), were compared. We randomly assigned 20 symptomatic patients with de novo coronary artery stenoses of <15 mm length to one of the two treatment groups. Intracoronary ultrasound catheter pull-backs after stent implantation showed incomplete stent attachment with one or two struts protruding into the vessel lumen in 3 of 10 patients in group 1 but in no patient after high-pressure dilatation in group 2 (p<0.01). Recross and high-pressure dilatation of the 3 stents in group 1 achieved complete attachment of all stents. Minimal luminal diameter was comparable between the groups (2.61 +/- 0.34 mm in group 1 after stent delivery, and 2.68 +/- 0.45 mm in group 2 after high-pressure dilatation). Minimal luminal area (expressed as a percentage of the reference cross-sectional area) was slightly but insignificantly greater in the high-pressure group (91.1% +/- 25.6% vs 85.5% +/- 15.1%). We conclude that implantation of Wiktor stents at normal inflation pressures does not reliably result in complete attachment of all struts to the vessel wall.
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Vasos Coronarios/diagnóstico por imagen , Stents , Anciano , Análisis de Varianza , Angioplastia Coronaria con Balón/economía , Angioplastia Coronaria con Balón/instrumentación , Angioplastia Coronaria con Balón/métodos , Angioplastia Coronaria con Balón/estadística & datos numéricos , Angiografía Coronaria/economía , Angiografía Coronaria/instrumentación , Angiografía Coronaria/métodos , Angiografía Coronaria/estadística & datos numéricos , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/economía , Enfermedad Coronaria/terapia , Dilatación , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Stents/economía , Stents/estadística & datos numéricos , Ultrasonografía Intervencional/economía , Ultrasonografía Intervencional/instrumentación , Ultrasonografía Intervencional/métodos , Ultrasonografía Intervencional/estadística & datos numéricosRESUMEN
OBJECTIVES: Platelets aggregating at the site of angioplasty, shown to be a potent proliferative stimulus for cultured smooth muscle cells (SMC), could contribute to proliferation after angioplasty. METHODS: SMC were cultivated from human aorta and restenosed coronary lesions as well as from minipig aorta and from normal and post angioplasty coronary artery segments (n = 6 per source). 3H-thymidine incorporation was used as a measure of proliferation. RESULTS: 3H-thymidine incorporation varied greatly after passage 7 in all cell lines, but was significantly higher in SMC from human coronary restenosed lesions compared to those from human aorta and minipig coronary post angioplasty segments in passage 2 (44 +/- 6.4 x 10(3) cpm/5000 SMC vs 20 +/- 3.9 and 12.1 +/- 2.1). However, all SMC exhibited a dramatic increase of 3H-incorporation after passage 7. Growth factors stimulated 3H-thymidine incorporation either dose dependently (PDGF-BB and bFGF) or only very modestly (PDGF-AA, EGF, IGF-1). The most potent stimulation was seen with PDGF-BB, 50 ng/ml, and was 17 +/- 6% (human restenosed) and 16 +/- 8% (minipig post angioplasty) of the values observed after stimulation with 10% fetal calf serum. The most effective combination of growth factors, PDGF-BB (50 ng/ml) + bFGF(20 ng/ml) + IGF-1 (50 ng/ml), produced a 3H-thymidine incorporation of 44 +/- 10% (human restenosed) and 42 +/- 11% (minipig post angioplasty) of FCS values. Stimulation by isolated platelets was dose dependent and significantly higher: 75 +/- 19% and 70 +/- 15% of FCS values for those SMC. CONCLUSIONS: 1) SMC from all sources studied exhibit significant changes of proliferation with increasing passages, excluding the comparability of data obtained with cells in different passages. 2) Data obtained with SMC from any source might not apply for SMC from human coronary restenosed lesions. 3) Currently tested growth factors do not fully account for the proliferative effect of platelets on cultured SMC.
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Angioplastia de Balón , Plaquetas/fisiología , Enfermedad Coronaria/terapia , Sustancias de Crecimiento/farmacología , Músculo Liso Vascular/fisiología , Adulto , Anciano , Animales , Aorta/citología , Aorta/efectos de los fármacos , División Celular , Células Cultivadas , Enfermedad Coronaria/patología , Vasos Coronarios/citología , Vasos Coronarios/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Persona de Mediana Edad , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Porcinos , Porcinos EnanosRESUMEN
Proliferation of medial smooth muscle cells (SMC) plays a major role in restenosis after coronary angioplasty and can be inhibited by heparin. Platelets stimulate SMC proliferation, and their aggregation after angioplasty can be reduced by the direct thrombin inhibitor hirudin. In a porcine coronary stent-angioplasty model (16 animals, 4 per group), we studied the effect of 3- and 14-day treatment with a novel long-lasting polyethyleneglycol-conjugated (PEG-hirudin, LU 57291), at a dose of 1 mg/kg intravenously (i.v.) and then subcutaneously once daily as compared with chronic low-molecular-weight heparin (LMWH) clivarine at a dose of 150 IU/kg as an intravenous bolus, followed by 10 IU/kg/h i.v. for 24 h, followed by 75 IU/kg twice daily, as compared with acute unfractionated heparin (100 IU/kg) as a control. Sixteen animals were randomly assigned to the four treatment groups. Four weeks after angioplasty, hearts were perfusion-fixed and six slices per angioplasty segment were analyzed for neointimal thickness and neointimal area (% of total vessel cross-sectional area). Maximal neointimal thickness was 1.10 +/- 0.2 mm in the control group (mean +/- SD, n = 9 arteries) and was significantly lower in both PEG-hirudin (0.62 +/- 0.22 and 0.86 +/- 0.18 mm, 11 and 10 arteries) and in clivarine-treated animals (0.75 +/- 0.33 mm, 11 arteries, p < 0.01). Similarly, neointimal area was smaller in PEG-hirudin groups (20 +/- 12 and 21 +/- 12%) and in the clivarine group (24.8 +/- 13.2%) as compared with the control group (41 +/- 17%, p < 0.02). We conclude that PEG-hirudin and clivarine reduce neointimal proliferation in a coronary stent-angioplasty model. Prolonged PEG-hirudin has no better effect than therapy limited to 3 days.
Asunto(s)
Angioplastia Coronaria con Balón , Anticoagulantes/farmacología , Antitrombinas/farmacología , Vasos Coronarios/efectos de los fármacos , Heparina de Bajo-Peso-Molecular/farmacología , Hirudinas/análogos & derivados , Músculo Liso Vascular/efectos de los fármacos , Animales , División Celular/efectos de los fármacos , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Heparina/administración & dosificación , Heparina/farmacología , Heparina de Bajo-Peso-Molecular/administración & dosificación , Hirudinas/farmacología , Músculo Liso Vascular/patología , Porcinos , Porcinos EnanosRESUMEN
Calponin, a basic smooth-muscle protein capable of binding to F-actin, tropomyosin and calmodulin in vitro, was tested for its expression and subcellular localization in resting and stimulated human platelets. Using immunoblotting techniques calponin was revealed as a single protein band with a molecular weight of 34 kDa. Although calponin has been shown to be proteolytically degraded by calpain, in the presence of the calpain inhibitor E-64 and EGTA a significant hydrolysis of calponin could not be detected. Upon stimulation with 10 microM arachidonic acid calponin became increasingly incorporated into Triton X-100 insoluble cytoskeletal fractions reaching a plateau after 15 s. The accumulation of calponin in the cytoskeletons of stimulated platelets paralleled the polymerization of actin into newly formed microfilaments. Immunofluorescence microscopy revealed a submembranous co-localization of calponin and actin in aggregated platelets. Since isolated calponin is phosphorylated by protein kinase C and Ca2+/calmodulin-dependent protein kinase II thereby losing its inhibitory effect on the actomyosin MgATPase activity, we examined whether changes in cell shape due to platelet stimulation are accompanied by a phosphorylation of calponin. By performing immunoblotting analysis on either resting or stimulated platelets phosphorylation of calponin on tyrosine, serine or threonine residues could not be demonstrated. In line, [32P]radiolabeling experiments were unable to detect phosphate incorporation into calponin. These observations support the hypothesis that calponin plays a physiological role in regulating contraction and secretion of human platelets even in the absence of its phosphorylation.
Asunto(s)
Ácido Araquidónico/farmacología , Proteínas de Unión al Calcio/sangre , Proteínas del Citoesqueleto/sangre , Proteínas Musculares/sangre , Activación Plaquetaria/efectos de los fármacos , Actinas/sangre , Actinas/ultraestructura , Humanos , Proteínas de Microfilamentos , Microscopía Fluorescente , Fosforilación , Fosfotirosina/sangre , Unión Proteica , Serina/química , Estimulación Química , Treonina/química , CalponinasRESUMEN
OBJECTIVES: We tested the hypothesis that reduced acute platelet deposition after angioplasty results in reduced late neointimal proliferation. BACKGROUND: Platelet-mediated mechanisms contribute to smooth muscle cell proliferation and migration. METHODS: Indium-111-labeled platelets were injected 16 h before coronary stent angioplasty in 10 Göttinger minipigs: group 1 (n = 5) = heparin (100-U/kg bolus) before angioplasty; group 2 (n = 5) = recombinant hirudin (CGP 39393, 1.0-mg/kg body weight bolus intravenously), followed by subcutaneous doses of 6 to 10 mg/kg every 8 h. Furthermore, stent angioplasty was performed in coronary arteries of 16 minipigs: group 3 (n = 5, nine stents) = 100 U/kg heparin only; group 4 (n = 5, 10 stents) = 1-mg/kg bolus hirudin before and 45 min after angioplasty; group 5 (n = 6, 11 stents) = hirudin (1-mg/kg intravenous bolus) before and 45 min after angioplasty, followed by 6 to 10 mg/kg subcutaneously every 8 h. RESULTS: In segments with deep arterial injury, the number of platelets/angioplasty segment in group 2 after 72 h (mean 21, range 9.7 to 39.7 x 10(6)) was significantly less than that in group 1 (mean 375, range 72 to 787 x 10(6)). Morphometric analysis after 4 weeks showed no difference between groups in degree of vessel wall injury. Mean (+/- SD) neointimal thickness was 0.70 +/- 0.06 mm in group 3 and was significantly reduced in both group 4 (0.46 +/- 0.11 mm) and group 5 (0.48 +/- 0.21 mm). CONCLUSIONS: The direct thrombin inhibitor hirudin significantly reduces platelet deposition up to 72 h after coronary stent angioplasty. A hirudin bolus alone as well as continued subcutaneous administration for 14 days substantially reduced neointimal proliferation compared with heparin 4 weeks after coronary stent angioplasty in minipigs.