RESUMEN
Propafenone and lidocaine have a rate dependent negative dromotropic effect on intraventricular conduction. We investigated the use dependent actions of propafenone and lidocaine on intraventricular conduction in isolated guinea pig hearts perfused by the method of Langendorff. Of primary interest was how the number of stimuli of the conditioning train (S1) might influence the ventricular effective refractory period (VERP) when refractoriness is assessed at a high pacing rate. Propafenone (0.3 microM) and lidocaine (50 microM) caused a comparable prolongation of the intraventricular conduction time during sinus rhythm. During ventricular pacing in the presence of propafenone an abrupt decrease of the pacing cycle length (220 to 120 ms) resulted in an initial peak of rate dependent prolongation of the QRS interval that subsequently decreased to a stable steady-state level. Lidocaine also induced a rate dependent increase of the intraventricular conduction time up to a steady-state level. The time constant, characterizing the changes of the intraventricular conduction time after shortening the ventricular pacing cycle length from 220 to 120 ms was significantly (P < 0.01) longer in the presence of propafenone (tau = 31 +/- 4 beats; mean +/- SEM; n = 11) than for lidocaine (tau = 3 +/- 1; n = 10). Both drugs caused the greatest increase of the VERP when the number of conditioning stimuli (S1, interstimulus interval = 120 ms) was in the range of their respective time constant. However, when the number of conditioning stimuli was further increased, VERP progressively diminished. These effects may be explained by a shortening of the action potential during high rates that results in a decreased binding of propafenone to Na+ channels and by the direct shortening of repolarization period by lidocaine (Class IB drug).
Asunto(s)
Antiarrítmicos/farmacología , Estimulación Cardíaca Artificial/métodos , Sistema de Conducción Cardíaco/efectos de los fármacos , Lidocaína/farmacología , Propafenona/farmacología , Periodo Refractario Electrofisiológico/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Antiarrítmicos/administración & dosificación , Nodo Atrioventricular/efectos de los fármacos , Fascículo Atrioventricular/efectos de los fármacos , Estimulación Eléctrica , Electrocardiografía/efectos de los fármacos , Femenino , Cobayas , Sistema de Conducción Cardíaco/fisiología , Frecuencia Cardíaca , Ventrículos Cardíacos/inervación , Lidocaína/administración & dosificación , Masculino , Conducción Nerviosa/efectos de los fármacos , Propafenona/administración & dosificación , Análisis de Regresión , Canales de Sodio/efectos de los fármacos , Factores de TiempoRESUMEN
The calcium channel blocking agents, verapamil and diltiazem, and the digitalis compound, digoxin, caused drug specific rate-dependent changes of the atrioventricular conduction time (AVCT). The purpose of this study was to investigate this rate adaptation of the AVCT in isolated guinea pig hearts perfused by the method of Langendorff to get an insight in drug-specific binding kinetic to the respective channel. In the presence of 10 nM verapamil, 30 nM diltiazem, or 0.6 nM digoxin, the atrioventricular conduction time was prolonged to a comparable degree during sinus rhythm. The drug-specific time constant, characterizing the rate-dependent adaptation of the AVCT, in the presence of a substance was comparable if evaluated after abruptly changing the heart rate from the pacing cycle length of 240 ms to 180 ms (tau-on) or from 180 to 240 ms (tau-off). The adaptation of the AVCT in the presence of verapamil (tau-on = 178 +/- 45 beats, tau-off = 125 +/- 33 beats, mean +/- SEM) was more pronounced than in the presence of digoxin (tau-on = 144 +/- 24 beats, tau-off = 98 +/- 15 beats) or diltiazem (tau-on = 70 +/- 11 beats, tau-off = 98 +/- 15 beats). In conclusion, the differences in the rate adaptation of the AVCT may be explained by the drug-specific association and dissociation kinetic to the calcium channel, slow in the case of verapamil, and fast in the case of dilitiazem, whereas this phenomenon in the presence of digoxin may be explained by its direct effects on passive membrane properties.
Asunto(s)
Nodo Atrioventricular/efectos de los fármacos , Nodo Atrioventricular/fisiología , Bloqueadores de los Canales de Calcio/farmacología , Digoxina/farmacología , Diltiazem/farmacología , Verapamilo/farmacología , Adaptación Fisiológica , Animales , Bloqueadores de los Canales de Calcio/farmacocinética , Digoxina/farmacocinética , Diltiazem/farmacocinética , Femenino , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Nodo Sinoatrial/efectos de los fármacos , Nodo Sinoatrial/fisiología , Factores de Tiempo , Verapamilo/farmacocinéticaRESUMEN
In isolated spontaneously beating guinea pig hearts, the effects of AWD 23-111 (N-(dicyclohexylcarbamoylmethyl)-N-(3-diethylamino-propyl)-4-nit robenzamid -hydrochloride), a new synthetic class III antiarrhythmic agent with sodium antagonistic properties, were investigated on cardiac electrophysiological parameters, that is, conduction and refractoriness. Concentration-dependent prolongation of the atrioventricular, intraventricular, and His bundle conduction times and of sinus node cycle length were present. At 0.3 microM the repolarization period was prolonged significantly. No reverse use-dependent effect on the repolarization period was observed. During rapid pacing (pacing cycle length = 120 ms for the ventricle and 180 ms for the atrium) the rate-dependent intraventricular (QRS) or atrioventricular conduction time (AVCT) prolongation follows an exponential function of the beat number and is characterized by a drug-specific time constant. The time constant for the intraventricular conduction time prolongation in the presence of 0.1 microM AWD 23-111 was very long at 150 +/- 29 beats (mean +/- SEM; n = 6), indicating a slow binding kinetic to the sodium channel. At 0.1 microM AWD 23-111, a significant increase in the ventricular effective refractory period was reached when the interstimulus interval (S1-S1) was 120 ms and the number of conditioning stimuli (S1) was higher than the time constant. The time constant for the rate-dependent AVCT prolongation in the presence of 0.3 microM AWD 23-111 was 34 +/- 6 beats (n = 6). The effective refractory period of the atrioventricular conduction significantly increased with the number of conditioning stimuli (S1), until the number was comparable with the time constant. In conclusion, AWD 23-111 exerts a wide variety of actions on the cardiac conduction system. Its combined effects on the potassium and sodium channels seem to be responsible for the marked rate-dependent effect on ventricular refractoriness and for the lack of a reverse use-dependency on JT prolongation.
Asunto(s)
Antiarrítmicos/farmacología , Benzamidas/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Electrocardiografía , Femenino , Cobayas , Inyecciones Intraperitoneales , MasculinoRESUMEN
To compare the direct effects of verapamil and diltiazem on the ventricular rate during atrial flutter, we developed an atrial flutter model in guinea pig isolated hearts. Atrial flutter was simulated by rapid atrial pacing (cycle length = 50 ms). At this atrial pacing cycle length, the shape of the frequency of distribution of the ventricular cycle lengths was comparable to that during spontaneous atrial flutter. Verapamil (0.01, 0.03 microM) and diltiazem (0.03, 0.09 microM) caused a comparable prolongation of the atrioventricular conduction time and atrioventricular refractoriness. Also, the anterograde Wenckebach cycle length was increased to a comparable degree by both substances. The mean ventricular cycle length during atrial flutter was comparable prolonged by both substances. The prolongation of the maximal ventricular cycle length was significantly more pronounced in the presence of verapamil. The time dependence of drug-induced alterations in atrioventricular conduction time during abrupt changes of heart rate is significantly more pronounced in the presence of verapamil compared to diltiazem. In conclusion, the more pronounced effect of verapamil on the maximal ventricular cycle length compared to the action of diltiazem may be explained by the slow binding kinetic of this drug to the Ca2+ channel resulting in a longlasting blockade of the Ca2+ channel.
Asunto(s)
Aleteo Atrial/fisiopatología , Bloqueadores de los Canales de Calcio/farmacología , Diltiazem/farmacología , Corazón/fisiología , Función Ventricular/efectos de los fármacos , Verapamilo/farmacología , Animales , Modelos Animales de Enfermedad , Electrocardiografía , Femenino , Cobayas , Corazón/efectos de los fármacos , Técnicas In Vitro , Masculino , Músculo Liso/efectos de los fármacosRESUMEN
The aim of the present study was to characterize the time dependence of the depressant effects of ajmaline and propafenone on the Ca(2+)-channel-dependent tissue of the atrioventricular node in isolated guinea pig hearts perfused by the method of Langendorff. Ajmaline at a concentration of 0.03 microM and propafenone at a concentration of 0.3 microM caused a significant and comparable prolongation of the His bundle and atrioventricular conduction time (AVCT). When the pacing cycle length was abruptly shortened from 240 to 180 ms, the mean time constant (tau on) of the rate-dependent AVCT prolongation was comparable for ajmaline and propafenone. In contrast, if the pacing cycle length was abruptly increased from 180 to 240 ms the mean time constant (tau off) for ajmaline was significantly higher than for propafenone. The rate-dependent increase of the atrioventricular effective refractory period was significantly more pronounced in the presence of ajmaline than of propafenone. Ajmaline and propafenone affect the Ca(2+)-channel-dependent tissue of the myocardium. The more pronounced rate-dependent effect of ajmaline on the atrioventricular effective refractory period may be explained by a slower dissociation kinetic from the channel.
Asunto(s)
Ajmalina/farmacología , Antiarrítmicos/farmacología , Nodo Atrioventricular/efectos de los fármacos , Propafenona/farmacología , Animales , Nodo Atrioventricular/fisiología , Electrocardiografía , Femenino , Cobayas , Corazón/fisiología , Sistema de Conducción Cardíaco/efectos de los fármacos , Masculino , PerfusiónRESUMEN
On the AV node the negative dromotropic action of verapamil, amiodarone, digoxin, and diltiazem is known to be rate dependent. The effective refractory period of the AV node (AV-ERP) at a short cycle length is related to the AV conduction at that cycle length. We investigated how the number of stimuli during the conditioning train (S1) (during measurement of refractoriness at a high pacing rate [cycle length = 180 ms]) might influence the AV-ERP in isolated guinea pig hearts in a Langendorff preparation. Verapamil (10 nM), amiodarone (10 microM), digoxin (0.6 nM), and diltiazem (30 nM) caused a comparable prolongation of the AV conduction time (AVCT). All four drugs caused a significant prolongation of the AV-ERP when evaluated by a standard stimulation protocol with a conditioning train of 10 stimuli (10 S1) at a pacing cycle length of 180 ms followed by the test stimulus (S2). When the number of stimuli during the conditioning train (S1) was increased (> 10), until the prolongation of AVCT reached steady state, the AV-ERP in the presence of verapamil (132 +/- 4 vs 141 +/- 3 ms; P < 0.05, mean +/- S.E.M.) and diltiazem (143 +/- 3 vs 151 +/- 3 ms; P < 0.05) was prolonged significantly further. These results indicate that the effect of drugs on AV-ERP should be measured with a modified stimulation protocol, whereby the number of conditioning stimuli is comparable to the time constant characterizing the prolongation of AVCT at fast pacing rates.
Asunto(s)
Amiodarona/farmacología , Antiarrítmicos/farmacología , Nodo Atrioventricular/efectos de los fármacos , Digoxina/farmacología , Diltiazem/farmacología , Electrocardiografía/efectos de los fármacos , Verapamilo/farmacología , Animales , Estimulación Cardíaca Artificial , Femenino , Análisis de Fourier , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Procesamiento de Señales Asistido por ComputadorRESUMEN
A now 92-year-old patient presented in 1990 with a massive 6 x 4 x 4 cm aneurysm of the left internal carotid artery which completely occluded the left oro- and nasopharynx. The main complaint of dysphagia was not only a consequence of the narrowed pharynx but was also due to a palsy of the glosso-pharyngeal nerve and caused one to two episodes of aspiration pneumonia per year. The patient could not be operated on because the aneurysm extended to the base of the skull. Remarkably the patient never experienced a cerebral ischemic event and during a follow-up of five years the aneurysm did not increase in size and partial thrombosis of the aneurysm was never detected. Thus conservative management seems feasible, when partial thrombosis of the aneurysm can be ruled by CT-examination.
Asunto(s)
Aneurisma/complicaciones , Enfermedades de las Arterias Carótidas/complicaciones , Neumonía por Aspiración/etiología , Anciano , Anciano de 80 o más Años , Obstrucción de las Vías Aéreas/diagnóstico por imagen , Obstrucción de las Vías Aéreas/etiología , Aneurisma/diagnóstico por imagen , Angiografía , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Externa , Humanos , Masculino , Neumonía por Aspiración/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Detajmium (4--3'-diethylamino-2'-hydroxypropyl--ajmalin) is an Na(+)-channel-blocking drug with an extremely long recovery from use-dependent sodium channel block. The aim of the present study was to investigate the rate-dependent effects of detajmium on the intraventricular conduction of isolated, spontaneously beating, guinea pig hearts in comparison with the effects of propafenone. Detajmium (0.3 microM) and propafenone (0.3 microM) caused comparable prolongations of the intraventricular conduction time during sinus rhythm. The time to steady state of the rate-dependent QRS prolongation during rapid ventricular pacing follows an exponential function of the beat number after an abrupt change of frequency and is characterized by a drug-specific time constant. This time constant was significantly longer for detajmium (tau = 265 +/- 165 beats; mean +/- SEM; n = 6) than for propafenone (tau = 31 +/- 4 beats; n = 11; p < 0.01). In the presence of propafenone, QRS duration peaked initially before decreasing to a steady state. Detajmium, in contrast, progressively broadened the QRS complex. Both substances caused the greatest increase in the ventricular effective refractory period (V-ERP) when the number of conditioning stimuli (interstimulus interval, 120 ms) was in the range of the time constant. However, when the number of conditioning stimuli was further increased, the V-ERP for propafenone diminished progressively. In conclusion, propafenone displayed, in comparison with detajmium, only a transient rate-dependent effect on intraventricular conduction and V-ERP.
Asunto(s)
Ajmalina/análogos & derivados , Antiarrítmicos/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Propafenona/farmacología , Ajmalina/farmacología , Animales , Femenino , Cobayas , Ventrículos Cardíacos/efectos de los fármacos , MasculinoRESUMEN
Semotiadil, a new Ca2+ antagonist with a high vasoselectivity, in high concentrations depresses AV nodal conduction in a frequency-dependent manner. The aim of the present study was to investigate the effects of semotiadil on intact cardiac conduction and the pacemaker system in comparison with diltiazem, amlodipine and nifedipine. The effects were studied in isolated guinea pig hearts perfused by the method of Langendorff. Both semotiadil and diltiazem decreased markedly the sinus rate in a concentration-dependent manner whereas this was not the case in the presence of amlodipine and nifedipine. Semotiadil (10 microM) markedly prolonged sinus node recovery time and in the presence of diltiazem (10 microM) in 5 out of 7 experiments an intermittent sinus node arrest occurred. Atrioventricular conduction and the effective refractory period of the AV node were most affected by diltiazem and semotiadil. The Ca2+ channel blocking compound semotiadil showed the most pronounced rate-dependent effects on the AV node. In the presence of diltiazem the QT interval became even shorter than in untreated hearts. In contrast, semotiadil did not act on the QT interval. In conclusion, as semotiadil exerts a clear rate-dependent effect on AV nodal conduction with a long time constant, it mimics the electrophysiological behavior of a substance of the verapamil type.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Tiazoles/farmacología , Amlodipino/farmacología , Animales , Depresión Química , Diltiazem/farmacología , Electrocardiografía/efectos de los fármacos , Femenino , Cobayas , Técnicas In Vitro , Masculino , Nifedipino/farmacologíaRESUMEN
To slow ventricular rate during supraventricular tachycardia, a drug must have a strong rate-dependent depressant effect on atrioventricular (AV) conduction. We investigated the frequency-dependent effects of verapamil, amiodarone, digoxin, and diltiazem on AV conduction time (AVCT) in isolated guinea pig heart perfused by Langendorff method. Verapamil (0.01 microM), amiodarone (10 microM), digoxin (0.6 nM), and diltiazem (0.03 microM) caused comparable prolongation of AVCT and also a comparable reduction in sinus rate. To evaluate the time dependence of drug-induced alterations in AVCT, we abruptly increased the atrial pacing rate and shortened the pacing cycle length (CL) from 240 to 180 ms. The resulting time constant was longest in the presence of verapamil (tau = 194 +/- 45 beats, mean +/- SEM) and the shortest during perfusion with diltiazem (tau = 89 +/- 9 beats). The magnitude of AVCT prolongation after abrupt increase in pacing rate was significantly greater for digoxin as compared with all other drugs tested. The calculated beat-to-beat increase in AVCT evaluated by dividing the magnitude of AVCT prolongation by the time constant tau was greatest with diltiazem, which may explain the high efficacy of diltiazem in controlling ventricular rate during atrial fibrillation.
Asunto(s)
Amiodarona/farmacología , Nodo Atrioventricular/efectos de los fármacos , Digoxina/farmacología , Diltiazem/farmacología , Verapamilo/farmacología , Animales , Estimulación Cardíaca Artificial , Simulación por Computador , Estimulación Eléctrica , Electrocardiografía , Femenino , Cobayas , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , MasculinoRESUMEN
ATP is an effective treatment of supraventricular tachycardia when the atrioventricular (AV) node is part of the reentrant circuit. However, the lower a pace-maker in the pacemaker hierarchy, the more sensitive it is to adenosine. Therefore, we investigated the effects of ATP on ventricular automaticity in in vivo and in vitro conditions. Wide and narrow QRS complex tachycardia in 46 patients was treated with 6, 12, and 18 mg ATP as sequential intravenous (i.v.) bolus. ATP terminated tachycardias in 67%. Bolus infusion ATP caused < or = 6.4-s asystole that was self-limited. Perfusion of isolated spontaneously beating guinea pig heart with 100 microM ATP completely suppressed ventricular automaticity. After ATP-infusion was discontinued, the first ventricular beat was evident after 3.1 +/- 0.9 s and sinus node activity recovered with a time constant of 3.0 +/- 1.1 s. Because sinus node and ventricular automaticity recovered within seconds after ATP infusion was discontinued in vitro, recovery in vivo is also likely to be determined by the short half-life (+1/2) of ATP.
Asunto(s)
Adenosina Trifosfato/uso terapéutico , Antiarrítmicos/uso terapéutico , Ventrículos Cardíacos/efectos de los fármacos , Taquicardia Supraventricular/tratamiento farmacológico , Adenosina Trifosfato/administración & dosificación , Adenosina Trifosfato/farmacología , Antagonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/uso terapéutico , Ajmalina/farmacología , Ajmalina/uso terapéutico , Animales , Antiarrítmicos/farmacología , Austria , Estimulación Cardíaca Artificial , Interacciones Farmacológicas , Servicios Médicos de Urgencia , Femenino , Cobayas , Humanos , Inyecciones Intravenosas , Masculino , Propafenona/farmacología , Propafenona/uso terapéutico , Estudios Prospectivos , Quinidina/farmacología , Quinidina/uso terapéutico , Función Ventricular/efectos de los fármacos , Verapamilo/farmacología , Verapamilo/uso terapéuticoRESUMEN
The aim of this study was to provide estimates of sensitivity and specificity of clinical history, pulses, and ankle/brachial index (ABI) in the follow-up of atherosclerotic occlusions of the superficial femoral artery treated by peripheral transluminal angioplasty (PTA). A total of 116 patients were followed prospectively for 1 year after angioplasty with follow-up visits immediately after angioplasty, and at 3, 6, and 12 months. All patients underwent digital subtraction angiography after 1 year of if they reported a deterioration of their symptoms. Reobstruction was defined as reocclusion or as restenosis exceeding 70%. Patency rates were calculated separately by clinical and ankle/brachial criteria; sensitivity and specificity were derived using angiography as standard. The presence or absence of pulses distal to the treated vessel segment had a sensitivity of 78% and a specificity of 66% for a reocclusion or significant restenosis; subjective complaints evaluated by history had a sensitivity of 83% and a specificity of 51%. The sensitivity of the ABI was 72% and 66%, with a specificity of 82% and 100% for cutoff values of 0.10 and 0.15, respectively. One year after PTA the angiographic patency rate was 39% +/- 5%; the patency rate based on ABI criteria 34% +/- 5%. A deterioration in the ABI by 0.15 indicated with reasonable certainty a reocclusion or significant restenosis whereas the sensitivity of the ABI was poor in detecting significant restenosis after PTA of occlusions of the superficial femoral artery. When only clinical criteria were used, the true patency rate was significantly overestimated as more than half of all reobstructions remained asymptomatic.
Asunto(s)
Angioplastia de Balón , Tobillo/irrigación sanguínea , Brazo/irrigación sanguínea , Arteriopatías Oclusivas/terapia , Determinación de la Presión Sanguínea , Arteria Femoral , Angiografía de Substracción Digital , Tobillo/diagnóstico por imagen , Brazo/diagnóstico por imagen , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/diagnóstico por imagen , Estudios de Evaluación como Asunto , Arteria Femoral/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Arteria Poplítea/diagnóstico por imagen , Valor Predictivo de las Pruebas , Estudios Prospectivos , Pulso Arterial , Recurrencia , Flujo Sanguíneo Regional , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
Na+ channel blockers terminate tachyarrhythmias primarily by rate-dependent effects. The purpose of this study was to investigate the use-dependent effects of propafenone in isolated guinea pig and rabbit hearts perfused by the method of Langendorff. In the presence of propafenone (0.3 microM) during ventricular pacing, an abrupt decrease of the pacing cycle length (220 ms to 120 ms) slowed the intraventricular conduction with a transient peak QRS prolongation of 33.8 +/- 2.0% after 5.7 +/- 0.5 s (P < 0.01) which subsequently decreased to a steady state of 14.0 +/- 2.5% after 38.0 +/- 5.5 s (mean +/- S.E.M.; n = 10; P < 0.01). The ventricular effective refractory period was significantly prolonged if evaluated by a train of 10 basic stimuli (S1) (interstimulus interval: 120 ms) followed by a premature stimulus (S2). However, when the train of basic stimuli was increased the effective refractory period diminished progressively. An initial increase in total activation time vanished with continued rapid ventricular stimulation. These effects may be explained by a shortening of the action potential during high rates resulting in a decreased binding of propafenone to Na+ channels.
Asunto(s)
Electrocardiografía/efectos de los fármacos , Propafenona/farmacología , Bloqueadores de los Canales de Sodio , Taquicardia Ventricular/fisiopatología , Potenciales de Acción/efectos de los fármacos , Animales , Femenino , Cobayas , Sistema de Conducción Cardíaco/efectos de los fármacos , Técnicas In Vitro , Masculino , ConejosRESUMEN
The maintenance of adequate local tissue perfusion is the result of control mechanisms which reside at the level of microscopic blood vessels: The constriction and relaxation of the vessels whose vascular walls are endowed with smooth muscle. This phenomenon of vasomotion guarantees homeostatic conditions in peripheral tissues. Superior disorders of homeostasis are primarily compensated by activating the vasomotion. The increase of vasomotion results in prostration of the vasomotoric activity and ends in the local biological disaster finally. Therefore an essential therapeutic strategy to avoid or remove peripheral arterial reduced or lacking perfusion is the reactivation of vasomotion. In this pilot study the effect of conservative therapeutic strategies to the vasomotion was investigated with dynamic capillaroscopy in normal perfused areas of the finger nailfold. A significant influence of buflomedil and alprostadil to the capillary blood cell velocity was found. Vasomotion was susceptible to hydroxyethylstarch and alprostadil but was influenced significantly only by buflomedil. Nevertheless we cannot conclude that the applicated substances will have a favourable effect in ischemic areas too, where maximum dilatation still exists.
Asunto(s)
Alprostadil/uso terapéutico , Arteriopatías Oclusivas/tratamiento farmacológico , Hemodilución , Uñas/irrigación sanguínea , Pirrolidinas/uso terapéutico , Resistencia Vascular/efectos de los fármacos , Vasodilatadores/uso terapéutico , Arteriopatías Oclusivas/fisiopatología , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/fisiología , Capilares/efectos de los fármacos , Capilares/fisiopatología , Terapia Combinada , Femenino , Humanos , Isquemia/tratamiento farmacológico , Isquemia/fisiopatología , Pierna/irrigación sanguínea , Masculino , Resistencia Vascular/fisiologíaRESUMEN
OBJECTIVE: To evaluate nonsurgical alternatives in reopening chronically occluded aortic bifurcation. DESIGN: Uncontrolled randomized study. SETTING: University-affiliated referral center for vascular diseases. PATIENTS: Twenty-five of 39 consecutive patients with chronic aortoiliac disease including a totally occluded aortic bifurcation were found to be acceptable candidates for an aortobifemoral prosthetic graft. INTERVENTION: Patients were randomly assigned to receive either streptokinase or urokinase or recombinant tissue-type plasminogen activator (rt-PA). In cases of successful thrombolysis and residual obstructions, subsequent balloon angioplasty was attempted. Prosthetic bypass grafting was done if thrombolytic treatment and balloon angioplasty failed. RESULTS: Complete lysis was achieved in 5 of 25 patients (20%). In 10 (40%) patients, lysis showed residual obstructions, which were reopened mechanically in 8 patients; 2 patients had extra-anatomical bypass grafts. Ten patients (40%) without thrombolysis had surgical aortobifemoral bypass grafts. Overall, recanalization and clinical improvement were achieved in 13 of 25 patients (52%) by thrombolytic therapy and subsequent balloon angioplasty. The recanalization rate did not differ among the different thrombolytic drugs. However, rt-PA therapy resulted in reopening after 4 days of treatment; streptokinase, after 6 days; and urokinase, after 9 days (P < 0.005). No major complications or deaths occurred. CONCLUSION: Thrombolytic treatment followed by balloon angioplasty may help avoid the need for aorto-bifemoral prosthetic bypass grafting in more than 50% of patients with chronic aortoiliac disease.
Asunto(s)
Angioplastia de Balón , Enfermedades de la Aorta/terapia , Arteriopatías Oclusivas/terapia , Terapia Trombolítica , Adulto , Aorta Abdominal , Enfermedades de la Aorta/tratamiento farmacológico , Arteriopatías Oclusivas/tratamiento farmacológico , Distribución de Chi-Cuadrado , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Distribución Aleatoria , Proteínas Recombinantes/uso terapéutico , Estreptoquinasa/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéuticoRESUMEN
Adenosine and verapamil are effective in the treatment of supraventricular arrhythmias. Also, both substances can provoke sinus node arrest or a third-degree atrioventricular (AV) block with a ventricular escape rhythm. The aim of this study was to compare the effects of adenosine and verapamil on sinus rate and on the rate of the ventricular escape rhythm while a third-degree AV block was induced by both drugs. Experiments were performed on isolated spontaneously beating guinea pig hearts perfused by the method of Langendorff. A third-degree AV block was induced by adenosine at a concentration of 30 microns and by verapamil at a concentration of 1 micron. Adenosine (30 microns) reduced sinus rate only moderately whereas it nearly halved the rate of the ventricular escape rhythm compared with that produced by cutting the AV node. In contrast, verapamil left the rate of the ventricular escape rhythm unchanged but nearly halved the spontaneous sinus rate compared with control conditions. In conclusion, adenosine and verapamil given at dosages with comparable effect on the AV node have markedly different effects on different pacemakers in the same heart. In the treatment of supraventricular arrhythmias, adenosine probably should be used with great caution since it can cause a very slow ventricular escape rhythm.
Asunto(s)
Adenosina/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Verapamilo/farmacología , Adenosina/efectos adversos , Animales , Femenino , Cobayas , Bloqueo Cardíaco/inducido químicamente , Bloqueo Cardíaco/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Técnicas In Vitro , Masculino , Nodo Sinoatrial/efectos de los fármacos , Nodo Sinoatrial/fisiopatología , Verapamilo/efectos adversosRESUMEN
Frequency-dependent depressant effects of a drug on slow channels in the atrioventricular (AV) node are important in its efficacy against supraventricular tachycardias. Verapamil terminates reentrant supraventricular arrhythmias by depressing conduction through the AV node. Similar effects have been described for adenosine. We compared the use-dependent effects of both drugs on AV nodal conduction in isolated guinea pig hearts perfused by the method of Langendorff. Adenosine 3 microM and verapamil 0.01 microM caused a comparable prolongation of AV conduction time (AVCT) and reduction in sinus rate (SR). The time dependence of drug-induced changes in AV conduction was characterized after the atrial pacing rate was changed abruptly. The basic cycle length was shortened abruptly from 240 to 180 ms. The resulting time constant for adenosine (tau = 467 +/- 187 beats, mean +/- SD) was significantly (p < 0.05) longer than that for verapamil (tau = 264 +/- 121 beats). At a pacing cycle length of 180 ms, the rate-dependent conduction slowing tended to be more pronounced in the presence of adenosine than of verapamil. Adenosine had more pronounced frequency-dependent effects on AV conduction than did the calcium channel blocker verapamil. This may explain the higher clinical efficacy of adenosine in supraventricular tachycardias in which the AV node forms a part of the reentrant circuit.
Asunto(s)
Adenosina/farmacología , Nodo Atrioventricular/efectos de los fármacos , Sistema de Conducción Cardíaco/efectos de los fármacos , Verapamilo/farmacología , Animales , Electrocardiografía/efectos de los fármacos , Femenino , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Técnicas In Vitro , MasculinoRESUMEN
One-hundred and fifty patients with thrombotic and 60 patients with embolic occlusions of the superficial femoral and/or popliteal artery underwent a simplified IAT (intra-arterial thrombolysis) procedure. Ten mg rt-PA combined with 3000 IU Heparin were infused over 6 h, thereafter the extent of thrombolysis was checked fluoroscopically and the above mentioned treatment course repeated up to four times if necessary. The IAT regimen employed did not involve mechanical recanalization attempts; if complete thrombolysis revealed an underlying stenosis, a PTA (percutaneous transluminal angioplasty) was subsequently performed. IAT resulted in complete recanalization of 88 thrombotic occlusions (59%; 95% confidence interval: 50.8%-66.8%) and of 53 embolic occlusions (88%; 95% confidence interval: 77.1%-94.8% P < 0.001). In a further 33 (22%) thrombotic and four (7%) embolic occlusions IAT reduced the length of the occluded segment. At discharge, 102 (67%) patients with thrombotic and 55 (92%) patients with embolic occlusions were clinically improved. Overall, untoward effects occurred in 60 patients (29%): 47 (22%) were minor. Four patients (2%) suffered a systemic haemorrhage (three gastrointestinal, one macrohaematuria). The cumulative potency rate was significantly higher in patients with embolic occlusions throughout follow-up (82% vs 49% for thrombotic occlusions at 2 years, P < 0.001). Although all amputations were carried out in patients with thrombotic occlusions, follow-up mortality did not differ significantly between patients with embolic and thrombotic occlusions.
Asunto(s)
Arteriopatías Oclusivas/tratamiento farmacológico , Arteria Femoral , Arteria Poplítea , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/mortalidad , Protocolos Clínicos , Quimioterapia Combinada , Embolia/tratamiento farmacológico , Embolia/mortalidad , Femenino , Estudios de Seguimiento , Heparina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/tratamiento farmacológico , Enfermedades Vasculares Periféricas/mortalidad , Terapia Trombolítica/efectos adversos , Trombosis/tratamiento farmacológico , Trombosis/mortalidad , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/farmacología , Resultado del Tratamiento , Grado de Desobstrucción Vascular/efectos de los fármacosRESUMEN
Negative chronotropic and dromotropic effects of adenosine seem to be responsible for its antiarrhythmic action on supraventricular tachyarrhythmias. To further characterize the effects of adenosine on supraventricular arrhythmias heart rate, conduction, refractoriness, the time to steady-state of AV-nodal conduction slowing and of sinus rate reduction were evaluated. Changes of heart rate, conduction intervals and effective refractory periods were determined by the use of a high-resolution ECG recording technique in isolated guinea pig hearts perfused by the method of Langendorff. Adenosine in concentrations of 3 and 10 microM reduced sinus rate and prolonged AV-nodal conduction significantly, while intraventricular and His bundle conduction were not altered. The maximal effect of adenosine on the sinus node and AV nodal conduction occurred after 636 +/- 109 and 111 +/- 35 (mean +/- SE) beats, respectively. During programmed stimulation at a cycle length of 250 ms, adenosine reduced atrial ERP in a dose-dependent manner. At cycle lengths of 170 and 200 ms, adenosine increased the atrial ERP at 3 microM, and then progressively shortened the ERP at higher doses. At all adenosine concentrations used, the usual rate-dependent adaption in ERP was suppressed. These observations explain the efficacy of adenosine against supraventricular tachyarrhythmias where the AV-node forms a part of a reentrant circuit. Adenosine shortened the atrial ERP, but at high pacing rates also led to a relative prolongation of the atrial ERP as the rate-dependent adaption was suppressed. These opposite effects of adenosine may explain earlier contradictory findings of its action on atrial arrhythmias.
Asunto(s)
Adenosina/farmacología , Corazón/efectos de los fármacos , Animales , Estimulación Cardíaca Artificial , Estimulación Eléctrica/métodos , Electrofisiología , Femenino , Cobayas , Corazón/fisiología , Sistema de Conducción Cardíaco/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Programas Informáticos , Factores de TiempoRESUMEN
Early clinical studies of coronary and peripheral laser angioplasty showed that arterial occlusions could be recanalised by continuous-wave lasers delivered with contact probes and by pulsed lasers applied with multifibre catheters. However, whether laser-assisted angioplasty improves success rates in reopening occlusions and in long-term patency rates is unclear. We have compared the primary recanalisation and long-term patency rates after laser-assisted and conventional percutaneous transluminal angioplasty (PTA) of femoropopliteal artery occlusions in 116 consecutive symptomatic patients (excimer laser 37, Nd:YAG laser 40, PTA 39). Primary recanalisation was achieved in 81 patients (70%). The primary recanalisation rate achieved with the excimer laser was significantly lower than that with the Nd:YAG laser (49% vs 78%, p < 0.01) or with PTA (82%, p < 0.003). The overall angiographic recanalisation rate (primary and secondary recanalisation) after laser and PTA was 89%. After 3 months, clinical improvement was recorded in 76% of patients. Clinical long-term results were available in 94 (91%), and angiographic long-term results in 77 (75%), of 103 successfully recanalised patients. Life-table analysis of the long-term results revealed no significant difference of the restenosis rate between the three treatment groups. The 12-month patency rate was 60% as assessed clinically and 39% as judged by angiography. Primary and secondary recanalisation rates and long-term patency rates were significantly correlated with length of the occlusion. Our results suggest that PTA of femoropopliteal artery occlusions is only indicated if the occlusion is short (< 8 cm) and that laser-assisted angioplasty should only be used after failure of conventional PTA.