RESUMO
We present a combined experimental and theoretical investigation of the dynamics and angular dependence of dissociative electron attachment to methane. We show that a triply degenerate (T2) Feshbach resonance is responsible for the broad 10 eV dissociation peak in methane. This resonance alone is shown to correlate asymptotically to the various dissociation channels observed experimentally. The molecular-frame entrance amplitude for electron attachment is calculated for each component of the threefold degenerate resonance. By investigating the topology of the anion potential energy surfaces, we deduce the main pathways to two- and three-body breakup channels involving both bond scission and bond formation. The computed fragment angular distributions reproduce the main trends of the experimental measurements.
Assuntos
Metano/química , Ânions/química , Elétrons , Modelos QuímicosRESUMO
Momentum imaging experiments on dissociative electron attachment (DEA) to a water molecule are combined with ab initio theoretical calculations of the angular dependence of the quantum mechanical amplitude for electron attachment to provide a detailed picture of the molecular dynamics of dissociation attachment via the two lowest energy Feshbach resonances. The combination of momentum imaging experiments and theory can reveal dissociation dynamics for which the axial recoil approximation breaks down and thus provides a powerful reaction microscope for DEA to polyatomics.
RESUMO
The aims of this study were twofold: (1) to determine the prevalence and clinical features of hepatitis delta virus (HDV) infection among subjects positive for hepatitis B surface antigen (HBsAg) living in the Miyako Islands, Okinawa Prefecture, Japan, and (2) to clarify the relationship between HDV-RNA level and severity of HDV-related liver disease. One hundred and ninety-nine HBsAg-positive subjects (123 asymptomatic carriers [ASCs], 3 patients with acute hepatitis [AH], 50 patients with chronic hepatitis [CH], 15 patients with liver cirrhosis [LC], and 8 patients with hepatocellular carcinoma [HCC], were tested for antibody to HDV (anti-HDV) by radioimmunoassay. Anti-HDV-positive individuals were examined to determine semi-quantified HDV-RNA level by polymerase chain reaction (PCR). The overall prevalence of anti-HDV among the 199 subjects was 21.1%. The positivity rate tended to increase with age or the severity of the underlying liver disease: anti-HDV-positive rates were 10.6% (13/123) in ASCs, 32.0% (16/50) in patients with CH, 40.0% (6/15) in patients with LC, and 87.5% (7/8) in patients with HCC. None of the patients with AH were positive for anti-HDV. There was no correlation between semi-quantified serum HDV-RNA levels and the severity of chronic liver disease in patients positive for anti-HDV. The present study showed the local spread of HDV infection in the Miyako Islands, Okinawa, Japan. Although the anti-HDV positivity rate tended to increase with the severity of the underlying liver disease, the severity of HDV-related liver disease did not correlate with the semi-quantified serum HDV-RNA level.
Assuntos
Hepatite D/diagnóstico , Hepatite D/epidemiologia , Vírus Delta da Hepatite/isolamento & purificação , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Prevalência , RNA Viral/análise , Fatores de Risco , População Rural , Testes Sorológicos/métodos , Distribuição por SexoRESUMO
Electrophysiological effects of bisaramil, a novel antiarrhythmic agent, were examined using the conventional microelectrode technique applied to cardiac multicellular preparations from guinea-pigs, rabbits and dogs and the whole-cell patch-clamp technique applied to guinea-pig ventricular myocytes. Bisaramil at 10(-6) M or higher concentrations produced a dose-dependent decrease in the maximum rate of rise (Vmax) of action potentials of guinea-pig papillary muscles without changes in resting membrane potentials. In the presence of bisaramil, trains of stimuli at rates greater than 0.1 Hz led to the use-dependent block of Vmax, which was enhanced at higher frequencies. At a concentration of 3 x 10(-6) M, the degree of use-dependent block was about 35% at 3.3 Hz, of which degree was comparable to those of 10(-4) M disopyramide and lidocaine. The development of Vmax block by bisaramil was expressed by a single exponential function in the same manner as flecainide, whereas the time courses of the block development by disopyramide and lidocaine were described by two exponentials. Recovery time constants from Vmax block were 44.1 +/- 3.4 s and 20.3 +/- 2.3 s for bisaramil and flecainide, respectively. Bisaramil at 10(-6) and 3 x 10(6) M did not change the action potential duration of guinea-pig papillary muscles and rabbit atrial muscles with a significant reduction of Vmax. No change in action potential duration can be explained by depression of both the Ca2+ and the delayed outward K+ currents by bisaramil. On the other hand, 10(-6) M bisaramil shortened action potential duration of canine Purkinje fibers at 50% and 90% of repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Antiarrítmicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes , Compostos Bicíclicos com Pontes/farmacologia , Coração/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Função Atrial , Clorobenzenos , Cães , Eletrofisiologia , Cobaias , Coração/fisiologia , Átrios do Coração/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Técnicas In Vitro , Cinética , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Miocárdio/citologia , Músculos Papilares/efeitos dos fármacos , Músculos Papilares/fisiologia , Ramos Subendocárdicos/efeitos dos fármacos , Ramos Subendocárdicos/fisiologia , Coelhos , Nó Sinoatrial/efeitos dos fármacos , Nó Sinoatrial/fisiologia , Função VentricularRESUMO
We describe an experimental approach to image the three-dimensional (3D) momentum distribution of the negative ions arising from dissociative electron attachment (DEA). The experimental apparatus employs a low energy pulsed electron gun, an effusive gas source and a 4π solid-angle ion momentum imaging spectrometer consisting of a pulsed ion extraction field, an electrostatic lens, and a time- and position-sensitive detector. The time-of-flight and impact position of each negative ion are measured event by event in order to image the full 3D ion momentum sphere. The system performance is tested by measuring the anion momentum distributions from two DEA resonances, namely H(-) from H(2)O(-) ((2)B(1)) and O(-) from O(2)(-) ((2)Π(u)). The results are compared with existing experimental and theoretical data.
RESUMO
We have used cold target recoil ion momentum spectroscopy to study the continuum correlation between the photoelectron of core-photoionized neon and the subsequent Auger electron. We observe a strong angular correlation between the two electrons. Classical trajectory Monte Carlo calculations agree quite well with the photoelectron energy distribution that is shifted due to the potential change associated with Auger decay. However, a striking discrepancy results in the distribution of the relative angle between Auger and photoelectron. The classical model predicts a shift in photoelectron flux away from the Auger emission direction, and the data strikingly reveal that the flux is lost rather than diverted, indicating that the two-step interpretation of photoionization followed by Auger emission is insufficient to fully describe the core-photoionization process.
RESUMO
We investigate single-photon double ionization of H(2) by 130 to 240 eV circularly polarized photons. We find a double slitlike interference pattern in the sum momentum of both electrons in the molecular frame which survives integration over all other degrees of freedom. The difference momentum and the individual electron momentum distributions do not show such a robust interference pattern. We show that this interference results from a non-Heitler-London fraction of the H(2) ground state where both electrons are at the same atomic center.
RESUMO
The wave nature of particles is rarely observed, in part because of their very short de Broglie wavelengths in most situations. However, even with wavelengths close to the size of their surroundings, the particles couple to their environment (for example, by gravity, Coulomb interaction, or thermal radiation). These couplings shift the wave phases, often in an uncontrolled way, and the resulting decoherence, or loss of phase integrity, is thought to be a main cause of the transition from quantum to classical behavior. How much interaction is needed to induce this transition? Here we show that a photoelectron and two protons form a minimum particle/slit system and that a single additional electron constitutes a minimum environment. Interference fringes observed in the angular distribution of a single electron are lost through its Coulomb interaction with a second electron, though the correlated momenta of the entangled electron pair continue to exhibit quantum interference.
RESUMO
The function of the atrial preferential conduction routes was examined by the microelectrode technique under normal and abnormal conditions in excised rabbit hearts. The sinus impulse during normal conditions traveled faster along the left and the right branch of the crista terminalis (anterior and posterior preferential routes, respectively) in the atrium toward the A-V node. Cutting of either route caused a delay of the impulse arrival in the zone beyond the lesion. The internodal conduction time was delayed 12 msec upon cutting of the posterior route, but there was no conduction delay after cutting the anterior route. This indicates that the posterior path is the dominant conduction route under normal conditions. When both routes were cut, the internodal conduction time was delayed 33 msec from the control value. During abnormal conditions, an ectopic pacemaker was found to occur mainly in the regions of two routes, as well as in the coronary sinus region. The cutting of either route, combined with the application of acetylcholine or high external K+, resulted in easier provocation of re-entrant arrhythmias in response to premature-stimuli than before the cutting.
Assuntos
Arritmias Cardíacas/fisiopatologia , Eletrocardiografia , Átrios do Coração/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Animais , Estimulação Cardíaca Artificial , Frequência Cardíaca , Coelhos , Nó Sinoatrial/fisiopatologia , Taquicardia/fisiopatologiaRESUMO
Effects of a new antiarrhythmic agent, E-4031, on reentrant types of tachycardias in rabbit right atrial preparations were studied using the microelectrode technique. E-4031 at concentrations of 0.1 and 1.0 microM prolonged the refractory period (RP) of the atrium and atrioventricular node (AVN) without affecting the intraatrial conduction time. In 13 of 17 preparations, premature stimulation repeatedly induced tachycardias lasting more than 10 beats. Twelve of 13 preparations exhibited a smooth AV conduction curve and showed activation patterns compatible with intraatrial reentry (IAR) during tachycardias, whereas the remaining preparation started tachycardia with a jump on the AV conduction curve, indicating dual AVN reentrant tachycardia (AVNRT). Application of 0.1 and 1.0 microM E-4031 completely prevented the initiation of both types of tachycardias by producing intraatrial conduction block due to prolonged effective refractory period (ERP) of the atrium. The results indicated that E-4031 exhibiting pure class III antiarrhythmic properties is effective for prevention of reentrant type of supraventricular tachycardias (SVTs).
Assuntos
Antiarrítmicos/farmacologia , Coração/efeitos dos fármacos , Piperidinas/farmacologia , Piridinas/farmacologia , Animais , Nó Atrioventricular/efeitos dos fármacos , Estimulação Elétrica , Coração/fisiologia , Átrios do Coração/efeitos dos fármacos , Técnicas In Vitro , Reperfusão Miocárdica , Coelhos , Período Refratário Eletrofisiológico/efeitos dos fármacos , Taquicardia/induzido quimicamente , Taquicardia/fisiopatologiaRESUMO
We studied conduction properties and histological findings at branching sites of the pectinate muscle (PM) from the crista terminalis (CT) in the dog right atrium. Propagation was faster in the longitudinal direction along CT than along PM. When the rate of stimulation was increased, conduction blocks to PM occurred at a longer cycle length than those to CT in 10 of 19 cases without differences in the refractory period. There were two block sites, one at the lateral edge within CT and the other at the branching site of PM from CT. The former was dominant with normal solution and the latter with high K+ solution. Histological studies showed no apparent differences between the two groups. CT consisted of a number of unit bundles in a longitudinal direction. The unit bundles continuing from the edge of CT proceeded into PM. Their orientation in PM, however, became irregular and tangled. Between the branches of PM, conduction block occurred unpredictably without regard to direction. These observations indicated the importance of the arrangement and orientation of the unit bundles in the appearance of the preferential conduction and block.
Assuntos
Sistema de Condução Cardíaco/fisiologia , Inibição Neural , Animais , Cães , Eletrofisiologia , Coração/anatomia & histologia , Átrios do Coração , Músculos/anatomia & histologia , Músculos/fisiologia , Vias Neurais/fisiologiaRESUMO
The isolated rabbit sinus node was partly divided into two parts by a cut in the middle portion. Microelectrode recording near the bridge connecting the two parts revealed an interference between action potentials from the two parts. Comparison of microelectrode recordings from the two parts taken near the bridge suggested that an induced peculiar rhythm change in one part was probably induced by the electrotonic effects of the action potentials of the other part. To prove this, a subthreshold depolarizing square-wave pulse was applied extracellularly to the isolated uncut sinus node. When the pulse was applied in the early portion of slow diastolic depolarization, diastole was prolonged, and when it was applied in the later portion, diastole was shortened. These findings can explain the observed peculiar thythm and suggest that in the mammalian sinus node, pacemaker cells accelerate or decelerate mutually by the electrotonic effects of their action potentials, depending on the phase of application of the effects. In particular, for some time the faster pacemaker cells could be influenced by dragging effects from the neighboring slower pacemaker cells and the slower pacemaker cells by pulling effects from the neighboring faster pacemaker cells.
Assuntos
Nó Sinoatrial/citologia , Potenciais de Ação , Animais , Diástole , Estimulação Elétrica , Métodos , Microeletrodos , Oscilometria , Coelhos , Nó Sinoatrial/fisiologiaRESUMO
We examined the effects of Mg2+ on aconitine-induced polymorphic ventricular tachycardias (PVT) in excised rabbit hearts under Langendorff perfusion and in Purkinje-muscle preparations. Local electrograms using bipolar electrodes and transmembrane potentials with the microelectrode technique were recorded from Langendorff hearts and Purkinje-muscle preparations, respectively. In Langendorff preparations, intracoronary application of 0.1 microM aconitine induced PVT 28.8 +/- 3.4 min after development of regular monomorphic ventricular tachycardias (MVT) in all 18 preparations. Application of 5 and 10 mM Mg2+ restored aconitine-induced PVT to sinus rhythm after 26.8 +/- 3.4 min (n = 9), but < 3 mM Mg2+ was not effective in restoring of sinus rhythm. Increased Mg2+ concentrations < or = 5 mM in the coronary perfusate prevented development of PVT by aconitine. Intracoronary application of 10 microM tetrodotoxin (TTX) also restored aconitine-induced PVT to sinus rhythm after 3.2 +/- 0.8 min (n = 4). Although applications of 50 microM lidocaine, 10 microM flecainide, or 1 microM verapamil could change PVT to MVT, they were not effective in restoring sinus rhythm. In Purkinje-muscle preparations, spontaneous action potentials (AP) from slow diastolic depolarization appeared after aconitine at the maximum diastolic potential of -75.0 +/- 3.7 mV in Purkinje fibers and were conducted to ventricular muscles (n = 5). Spontaneous activity gradually increased in rate and then developed triggered activity arising from early after depolarization (EAD). EAD induced by aconitine always appeared first in Purkinje fibers and later in muscle fibers. Once triggered activities started from EAD, rate, rhythm and amplitudes of APs became fast and variable.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Aconitina/toxicidade , Coração/efeitos dos fármacos , Magnésio/uso terapêutico , Ramos Subendocárdicos/efeitos dos fármacos , Taquicardia Ventricular/tratamento farmacológico , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Eletrofisiologia , Coração/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Técnicas In Vitro , Magnésio/administração & dosagem , Magnésio/farmacologia , Microeletrodos , Ramos Subendocárdicos/metabolismo , Coelhos , Taquicardia Ventricular/induzido quimicamente , Tetrodotoxina/farmacologia , Tetrodotoxina/uso terapêuticoRESUMO
We examined the underlying mechanism for rate-dependent effects of sematilide on action potential duration (APD) in guinea pig ventricular myocytes. Sematilide at 10 microM or higher concentrations caused prolongation of the APD without changing other electrical parameters at a stimulation rate of 0.2 Hz. Although 30 microM sematilide significantly prolonged APD by 20 to 40% at 0.2 Hz, the drug-induced prolongation became non-significant at 2.5 Hz, exhibiting a reverse use-dependent effect. Sematilide depressed the delayed outward K+ current (IK) without affecting the inward rectifier K+ current and the L-type Ca++ current. Suppression of IK by sematilide was more prominent on the tail current elicited by short pulses than on those elicited by long pulses, suggesting that its main action was on the rapidly activating component of IK. Sematilide was shown to have an affinity to the rested state of the IK channel, because the inhibition was increased with prolongation of diastolic intervals at -80 mV. Rapid-rate depolarizations induced a transient outward current that was abolished by 5 mM caffeine. This caffeine-sensitive transient outward current could contribute to the shortening of the APD at rapid pulsation, but sematilide had no effects on this current. Therefore, we conclude that sematilide principally blocked the rapidly activating component of IK with affinity for the rested state of the IK channel and did not block the slowly activating component. Also the drug did not affect the caffeine-sensitive transient outward current during rapid-rate depolarizations. All of these factors may contribute to reverse use-dependent effects on action potential prolongation by sematilide.
Assuntos
Antiarrítmicos/farmacologia , Coração/efeitos dos fármacos , Procainamida/análogos & derivados , Potenciais de Ação/efeitos dos fármacos , Animais , Cobaias , Coração/fisiologia , Técnicas In Vitro , Canais de Potássio/efeitos dos fármacos , Procainamida/farmacologia , Fatores de TempoRESUMO
The role of the ATP-sensitive K+ channel (IK,ATP) in the development of A-V block during hypoxic interventions was studied using Langendorff perfused rabbit hearts, multicellular rabbit A-V nodal preparations and single guinea-pig ventricular myocytes. With the Langendorff perfused hearts, hypoxic perfusion (PO2 not equal to 40 mmHg) for 30 min caused slowing of the sinus rate and prolongation of the A-H interval without the appearance of blocked beats. Substrate-free hypoxic perfusion induced second or third degree A-V block in 8/10 hearts and substrate-free hypoxic perfusion plus 2-deoxyglucose (5 mM) produced third degree A-V block in 6/6 preparations. Addition of 50 mM glucose in the perfusate restored A-V conduction during hypoxic intervention. Application of glibenclamide, a specific blocker of IK,ATP, prevented the development of second or third degree A-V block during substrate-free hypoxia (n = 6), whereas pinacidil, an opener of IK,ATP, caused development of third degree A-V block during hypoxia (n = 9). Application of theophylline (100 microM) or 8-phenyl-theophylline (10 microM) did not prevent the development of advanced degrees of A-V block during hypoxic interventions. In multicellular A-V nodal preparations, 10 microM glibenclamide prevented the shortening of action potential duration and block development without marked effects on the maximum upstroke velocity of action potentials during hypoxic intervention. In isolated ventricular myocytes studied by the patchclamp method, the substrate-free hypoxia plus 2-deoxyglucose induced the openings of IK,ATP in 9/25 preparations with cell-attached patches, while 2/20 patches exhibited sporadic channel openings in the normoxic condition during comparable observation period. These results suggest that openings of the ATP-sensitive K+ channels play a role in the development and aggravation of advanced A-V block during hypoxic interventions.
Assuntos
Trifosfato de Adenosina/farmacologia , Nó Atrioventricular/fisiologia , Bloqueio Cardíaco/fisiopatologia , Coração/fisiologia , Canais de Potássio/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Nó Atrioventricular/efeitos dos fármacos , Nó Atrioventricular/fisiopatologia , Desoxiglucose/farmacologia , Feminino , Glucose/farmacologia , Glibureto/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Hipóxia , Técnicas In Vitro , Cinética , Masculino , Perfusão , Canais de Potássio/efeitos dos fármacos , Coelhos , Teofilina/análogos & derivados , Teofilina/farmacologia , Fatores de TempoRESUMO
The effects of antiarrhythmic agents, including Classes I and IV and 3-10 mM Mg2+ on aconitine-induced arrhythmias were examined using a conventional microelectrode and patch clamp method in Langendorff-perfused rabbit hearts and isolated guinea-pig ventricular myocytes. Intracoronary application of 0.1 microM aconitine induced polymorphic ventricular tachycardia (PVT) which continued for more than 60 minutes. Application of aconitine to ventricular myocytes caused a prolonged action potential duration (APD) and the appearance of early afterdepolarization (EAD) together with the occurrence of an inward hump of the I-V curve around -60 to -40 mV and increased outward current at positive voltages. Application of 10 microM TTX and 5 mM or higher Mg2+ restored aconitine-induced PVT to sinus rhythm in Langendorff-perfused preparations and also shortened the prolonged APD, demonstrating the abolishment of EAD by aconitine in ventricular myocytes. However, antiarrhythmic agents did not exert such effects. In conclusion, the antiarrhythmic actions of Mg2+ and TTX in aconitine-induced arrhythmia are to abolish EAD and shorten the prolonged APD by suppression of the inward Na+ current around -60 to -40 mV.
Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Magnésio/farmacologia , Aconitina , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Cobaias , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Miocárdio/citologia , Técnicas de Patch-Clamp , Coelhos , Taquicardia Ventricular/induzido quimicamente , Taquicardia Ventricular/fisiopatologia , Tetrodotoxina/farmacologiaRESUMO
INTRODUCTION: In the development of atrial flutter due to reentry, the crista terminalis is supposed to pose a conduction barrier, but the role of its longitudinal conduction in determining the propagation pattern of the reentrant impulse is not known. In rabbit right atrial preparations, we induced reentrant atrial tachycardias and examined the effects of transverse section of the crista terminalis on the development and conduction patterns of arrhythmias. METHODS AND RESULTS: Right atrial preparations from 12 albino rabbits were placed endocardial surface down in a chamber with an array of 48 bipolar electrodes to draw activation maps. A single premature stimulus was delivered to induce tachycardias at the free wall. In the control, five instances of tachycardia per preparation were induced and another five were induced after cutting the crista terminalis. In the control, the mean duration of tachycardia was 127.1+/-25.2 seconds. The tachycardia was counterclockwise in 39 of 60 instances, clockwise in 12, and undetermined in 4 defined as "atypical." After transverse section of the crista terminalis, the duration was prolonged to 372.6+/-30.4 seconds, but the conduction patterns were not changed. In the free wall, counterclockwise reentry had a broader wavefront and faster conduction than clockwise reentry. CONCLUSION: Longitudinal conduction block at the crista terminalis contributed to maintenance of reentrant atrial tachycardias, but had no influence on their propagation patterns. Clockwise and counterclockwise rotation of impulses in reentrant tachycardias had different paths and velocities of the wavefront in the free wall of the right atrium.
Assuntos
Flutter Atrial/etiologia , Sistema de Condução Cardíaco/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/complicações , Animais , Anisotropia , Flutter Atrial/fisiopatologia , Mapeamento Potencial de Superfície Corporal , Estimulação Cardíaca Artificial , Modelos Animais de Doenças , Frequência Cardíaca/fisiologia , Técnicas In Vitro , Coelhos , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologiaRESUMO
Electrophysiological effects of clentiazem, a new 1,5-benzothiazepine type Ca(2+) antagonist, were examined in comparison with those of diltiazem in excised rabbit heart preparations. In Langendorff-perfused hearts electrically driven at basic cycle lengths of 400-500 ms, clentiazem (10(-8)-10(-6)M) and diltiazem (10(-8)-10(-6)M) caused a concentration-dependent prolongation of the atrio-His bundle conduction time (A-H interval) without affecting the His bundle-ventricular conduction time (H-V interval). The effects of clentiazem were equivalent to those of diltiazem. In isolated rabbit atrioventricular (A-V) node preparations electrically driven at 400- to 500-ms intervals, clentiazem and diltiazem at >10(-6)M concentrations produced concentration-dependent decreases in action potential amplitude (APA), maximum rate of depolarization (V max), and shortened action potential duration at 20 and 50% repolarization (APD(20) and APD(50)), whereas APD(90) was little affected. Application of 10(-6)M clentiazem prolonged effective refractory period (ERP) of the A-V node by approximately 7% of the control, an effect similar to that of diltiazem. In spontaneously beating sinoatrial (S-A) node preparations, clentiazem l0(-6)M or the higher concentration significantly decreased APA, V(max), and slope of slow diastolic depolarization, while reducing the maximum diastolic potential. The inhibitory effects of clentiazem showed strong suppression of APA and V(max) by 31.1 and 47.2% of the control, respectively, whereas both clentiazem (10(-7)-10(-5)M) and diltiazem (10(-7)-10(-5)M) had no effects on parameters of ventricular APs. These results suggest that dentiazem, like diltiazem, has a preferential inhibitory action on cardiac slow Ca(2+) channels.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Diltiazem/análogos & derivados , Sistema de Condução Cardíaco/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Diltiazem/farmacologia , Sistema de Condução Cardíaco/fisiologia , Técnicas In Vitro , CoelhosRESUMO
The electrophysiological and antiarrhythmic effects of pirmenol HCl were examined using the microelectrode technique applied to multicellular preparations and the suction-pipette whole-cell clamp method applied to ventricular myocytes from rabbit and guinea pig hearts. Pirmenol at 5 microM and higher doses suppressed the sinus node automaticity by depressing the slow diastolic depolarization without changing the maximum diastolic potential. Pirmenol at 1 microM and higher doses depressed the maximum upstroke velocity (Vmax) of action potentials and prolonged the action potential duration at 90% repolarization in atrial muscles and Purkinje fibers without affecting resting membrane potentials. Pirmenol at 5 microM depressed the early part of the plateau and lengthened the final repolarization of the action potentials in ventricular myocytes, of which effects were attributed to the depression of the calcium current and the delayed outward K+ current. Triggered tachyarrhythmias arising from delayed afterdepolarizations in papillary muscles and ventricular myocytes were markedly inhibited by 1-5 microM pirmenol. The drug changed the amplitude and appearance of the transient inward current in ventricular myocytes. These results suggest that pirmenol has electrophysiologic properties that could provide an antiarrhythmic action on various types of arrhythmias.