Automatic Rhythms Research Articles

Reduced Ca2+ transport across sarcolemma but enhanced spontaneous activity in cardiomyocytes isolated from left atrium-pulmonary veins tissue of myopathic hamster

BackgroundSeveral lines of evidence point to a particularly important role of the left atrium (LA) in initiating and maintaining atrial fibrillation (AF). This role may be related to the location of pulmonary veins (PVs) in the LA. The aim of the present study was to investigate the action potential (AP) and ionic currents in LA-PV cardiomyocytes isolated from Bio14.6 myopathic Syrian hamsters (36-57 week-old) versus age-matched F1B healthy control hamsters.Methods and ResultsWhole-cell patch-clamp techniques were used to record AP in current-clamp mode and ionic currents in voltage-clamp mode. The results obtained show that in both healthy and myopathic LA-PV tissue spontaneously discharging cardiomyocytes can be found, but they are more numerous in myopathic (9/29) than in healthy hamsters (4/42, p < 0.05 by χ2 analysis). Myopathic myocytes have shorter AP duration (APD) with smaller ICa,L and INCX than the healthy control. The currents ITO, IK, IK1 and ICa,T are not significantly different in myopathic versus healthy cells.ConclusionsOur results indicate that in myopathic Syrian hamsters LA-PV cardiomyocytes are more prone to automatic rhythms. Also, they show altered electrophysiologic properties, which may be due to abnormal Ca2+ channels and may account for contractile dysfunction.

On the mechanisms of arrhythmias in the myocardium of mXinα-deficient murine left atrial-pulmonary veins

We have previously shown that left atrial-pulmonary vein tissue (LA-PV) can generate reentrant arrhythmias (atrial fibrillation, AF) in wild-type (mXinα+/+) but not in mXinα-null (mXinα−/−) mice. With the present experiments, we investigated the arrhythmogenic activity and the underlying mechanisms in mXinα+/+ vs. mXinα−/− LA-PV. Electrical activity and conduction velocity (CV) were recorded in LA-PV by means of a MED64 system. CV was significantly faster in mXinα+/+ than in mXinα−/− LA-PV and it was increased by 1 μM isoproterenol (ISO). AF could be induced by fast pacing in the mXinα+/+ but not in mXinα−/− LA-PV where automatic rhythms could occur. ISO increased the incidence of AF in Xinα+/+ whereas it increased that of automatic rhythms in mXinα−/− LA-PV. In LA-PV with the right atrium attached (RA-LA-PV), automatic rhythms occurred in all preparations. In mXinα+/+ RA-LA-PV simultaneously treated with ISO, strophanthidin and atropine, the incidence of the automatic rhythm was about the same, but AF increased significantly. In contrast, in mXinα−/− RA-LA-PV under the same condition, the automatic rhythm was markedly enhanced, but still no AF occurred. Conventional microelectrode techniques showed a longer APD 90 and a less negative maximum diastolic potential (MDP) in mXinα−/− than mXinα+/+ LA-PV tissues. Whole-cell current clamp experiments also showed a less negative MDP in mXinα−/− vs. mXinα+/+ LA-PV cardiomyocytes. The fact that AF could be induced by fast pacing under several conditions in mXinα+/+ but not in mXinα−/− LA-PV preparations appears to be due to a slower CV, a prolonged APD 90, a less negative MDP and possibly larger areas of conduction block in mXinα−/− myocardial cells. In contrast, the non-impairment of automatic and triggered rhythms in mXinα−/− preparations may be due to the fact that the mechanisms underlying these rhythms do not involve cell-to-cell conduction.

Spontaneous automaticity arising from a successfully ablated Mahaim fiber

The authors describe a 22-year-old woman with regular and irregular arrhythmias exhibiting left bundle branch block (LBBB) morphology at various heart rates. An atriofascicular fiber was diagnosed as the underlying mechanism for the antidromic reciprocating tachycardia. In addition, spontaneous automaticity of the Mahaim fiber was present during electrophysiologic study. The accessory pathway was ablated successfully, targeting a Mahaim potential at the supero-anterior tricuspid valve annulus. Relatively slow automatic rhythms with identical LBBB morphology were recorded immediately after ablation, as well as during long-term follow-up in a more sporadic and subclinical form. Abnormal automaticity arising from the distal portions of the remnant pathway was considered to be the origin of the slow ventricular rhythms in this peculiar case.

Atrial entrainment differentiates ventricular tachycardia from antidromic atrioventricular reentrant tachycardia

challenge. Case: A 60 year old man who presented with an acute myocardial infarction and nonsustained VT, underwent coronary artery bypass grafting. Post-operatively, he had recurrent episodes of polymorphic and unimorphic VT. A VPB of identical morphology triggered each episode. He was brought to the lab and VPBs were provoked identical to the clinical VPB. The VPBs were mapped to the inferior basal septum in the region of the posterior fascicle. A Purkinje like potential (PLP) preceded the QRS by 65ms and radiofrequency ablation (RFA) delivered at that site created transient abolition of VPBs. The subsequent QRS axis changed to a pattern consistent with a posterior hemi block. The VPBs recurred with a second morphology with same coupling interval. Early activation of the second VPBs was mapped to the anterior fascicular system. However, further RFA failed to eliminate the arrhythmia at this site. A more detailed activation mapping was performed of the entire posterior basal septal and free wall region, confirming earliest activation of the second VPB to the inferior basal septum with a PLP preceding the QRS by 85ms. A single targeted RFA to the region eliminated the second VPBs. This area was in close proximity to the apparent “successful” site of RFA for the first morphology VPBs. This was believed to represent a single focus VPB with exit block after the initial RFA and preferential Purkinje activation creating inferior QRS axis despite inferior origin. Conclusions: The case highlights the possible impact of altering PN activation on QRS morphology associated with Purkinje fiber firing. Local exit block may completely shift the activation with presumed spread of specialized conduction over the PN from more distant sites. This information is critical for optimum mapping and localization of presumed automatic or triggered rhythms from the PN.

Dissociated Activity and Pulmonary Vein Fibrillation Following Functional Disconnection:

The present study sought to investigate the electrophysiological properties of isolated pulmonary veins following successful radiofrequency (RF) catheter ablation in patients with paroxysmal atrial fibrillation (PAF). Overall, 71 pulmonary veins in 37 consecutive patients (age: 56 +/- 9 years) with recurrent PAF were targeted for RF ablation at the ostial region in order to achieve a complete functional block. Following disconnection, the incidence of dissociated pulmonary vein (PV) activity and its response to orciprenalin were studied. RF ablation abolished conduction in 67 (94%) of 71 potentially arrhythmogenic PVs after a mean of 10.7 +/- 6.4 RF applications for each PV. After ablation, spontaneous dissociated automatic activity (9 to 52 beats/min, median 27) was found in 6 out of 67 isolated PVs (left superior: n = 1, left inferior: n = 1, right superior: n = 2, common left PV: n = 2). Slight acceleration (13 to 68 beats/min, median 29) of dissociated PV activity was observed during infusion of orciprenalin. Following isolation, initiation of sustained or nonsustained local fibrillation was recorded in only two cases of the common left sided PV with preceding automatic activity. In one patient PV fibrillation occurred during orciprenalin infusion following a repetitive response to a dissociated automatic rhythm with increasing duration as well as destabilization. In the other patient, PV fibrillation occurred immediately after the occurrence of PV automaticity. Slow dissociated automatic rhythms are detectable within 9% of disconnected PVs. The unique anatomic substrate of common left PVs seem to favor the occurrence of local fibrillation following isolation. The initiation pattern of fibrillation within the isolated PV has pathophysiological implications and underlines the contribution of multiple factors to the onset and sustenance of PAF.

The effects of halothane on abnormal automaticity in canine cardiac Purkinje fibers.

Abnormal automaticity is the spontaneous beating of cardiac cells with abnormally depolarized resting membrane potentials. The effects of halothane on cardiac arrhythmias caused by abnormal automaticity are controversial, with either antiarrhythmic effects or enhancement of abnormal automaticity reported by different authors. The goal of the present investigation was to clarify the effects of halothane on abnormal automaticity induced by superfusing excised canine Purkinje fibers (PF) with barium chloride. Intracellular microelectrodes recorded action potentials from fibers superfused with buffer solution in a tissue bath. Barium chloride 0.25 mM reduced maximal diastolic potential from -82.1 +/- 5.6 mV to -67.4 +/- 9.4 mV (mean +/- SD, P < 0.05). Fibers developed abnormal automatic rhythms at a rate of 47.1 +/- 5.9 bpm. Halothane, 0.5%-4%, was added to the superfusate. Halothane reduced the rate of firing in a dose-dependent manner, so that abnormal automaticity was abolished by 4% halothane and reduced by lesser concentrations. Serendipitously, during barium superfusion, two additional fibers developed early afterdepolarizations, a cause of triggered arrhythmias in patients with long Q-T syndrome. Halothane abolished early afterdepolarizations in each. In this model of barium toxicity in excised canine PF, halothane antagonized both abnormal automaticity and early afterdepolarizations. Life-threatening cardiac arrhythmias may occur during anesthesia. An arrhythmia called abnormal automaticity occurs after heart attacks and can be mimicked by adding barium to small segments of heart tissue. Halothane abolished abnormal automaticity in these tissues, which suggests that it or similar agents may benefit patients prone to developing such abnormal rhythms during surgery.

The Effects of Halothane on Abnormal Automaticity in Canine Cardiac Purkinje Fibers

Abnormal automaticity is the spontaneous beating of cardiac cells with abnormally depolarized resting membrane potentials.The effects of halothane on cardiac arrhythmias caused by abnormal automaticity are controversial, with either antiarrhythmic effects or enhancement of abnormal automaticity reported by different authors. The goal of the present investigation was to clarify the effects of halothane on abnormal automaticity induced by superfusing excised canine Purkinje fibers (PF) with barium chloride. Intracellular microelectrodes recorded action potentials from fibers superfused with buffer solution in a tissue bath. Barium chloride 0.25 mM reduced maximal diastolic potential from -82.1 +/- 5.6 mV to -67.4 +/- 9.4 mV (mean +/- SD, P < 0.05). Fibers developed abnormal automatic rhythms at a rate of 47.1 +/- 5.9 bpm. Halothane, 0.5%-4%, was added to the superfusate. Halothane reduced the rate of firing in a dose-dependent manner, so that abnormal automaticity was abolished by 4% halothane and reduced by lesser concentrations. Serendipitously, during barium superfusion, two additional fibers developed early afterdepolarizations, a cause of triggered arrhythmias in patients with long Q-T syndrome. Halothane abolished early afterdepolarizations in each. In this model of barium toxicity in excised canine PF, halothane antagonized both abnormal automaticity and early afterdepolarizations. Implications: Life-threatening cardiac arrhythmias may occur during anesthesia. An arrhythmia called abnormal automaticity occurs after heart attacks and can be mimicked by adding barium to small segments of heart tissue. Halothane abolished abnormal automaticity in these tissues, which suggests that it or similar agents may benefit patients prone to developing such abnormal rhythms during surgery. (Anesth Analg 1998;86:488-92)

ELECTROPHYSIOLOGIC EVALUATION OF SUPRAVENTRICULAR TACHYCARDIA

The evolution of intracardiac recording and programmed stimulation has allowed a better definition of the mechanisms and types of a variety of supraventricular tachyarrhythmias . This article describes the evaluation of supraventricular tachycardias resulting from atrioventricular (AV) nodal reentry, circus movement tachycardia using a concealed accessory pathway , and atrial tachycardia. The appropriate interpretation of intracardiac recordings and programmed stimulation to assess the mechanism of arrhythmia is based on understanding of the characteristic responses of known mechanisms of arrhythmias to programmed stimulation as well as response to drugs. 8 , 19 The mechanisms of all paroxysmal tachycardias are due to either abnormalities of impulse formation or abnormalities of conduction leading to reentry. Enhanced impulse formation may be due to abnormal automaticity or triggered activity as a result of either delayed afterdepolarizations or early afterdepolarizations. In the atrium and in particular for supraventricular arrhythmias , early afterdepolarizations probably do not play a role. The characteristics of automatic rhythms are that they can neither be initiated nor terminated in a reproducible way by programmed stimulation. Although annihilation of an automatic focus may be possible in experimental models, it is not predictable and has not yet been described in humans. The most common response of automatic rhythms to overdrive pacing is overdrive suppression or, in mildly depolarized tissue, no effect or, rarely, acceleration. Triggered rhythms caused by delayed afterdepolarizations are characterized by their ability to be initiated by programmed stimulation; however, such tachycardias are more readily induced by overdrive pacing rather than timed extrastimuli and do not require conduction delay or block for initiation. A direct relationship between the coupling interval or paced cycle length initiating rhythm and the interval to the onset of the rhythm and early cycle lengths of the rhythm as well as overdrive acceleration in response to rapid pacing are typical of arrhythmias related to delayed afterdepolarizations. Reentrant arrhythmias are most well understood and constitute the vast majority of clinical arrhythmias. The requirements for reentry include the presence of at least functional or anatomically distinct potential pathways that are linked proximally and distally to form a closed circuit of conduction, unidirectional block in one of these pathways, and slow conduction over the unblocked pathway allowing the previous blocked pathway time to recover. Reentrant arrhythmias can be reproducibly initiated and terminated by timed extrastimuli (usually in association with conduction delay or block) or rapid pacing. Frequently the conduction delay can be seen as an inverse relationship between the coupling interval of the initiating extrastimulus and the interval to the onset of the first complex of the tachycardia. In addition, during reentrant arrhythmias, continuous resetting of the tachycardia with fusion (i.e., entrainment) is diagnostic of reentry because fusion represents the presence of wavefronts, orthodromic and antidromic , occurring at the same time. This cannot happen in a focal tachycardia. Thus, the electrophysiologic evaluation of supraventricular tachycardia should include analysis of (1) mode of initiation of tachycardia, (2) atrial activation sequence during the tachycardia, (3) effect of atrial or ventricular stimulation during the tachycardia, (4) requirement of the atrium or ventricles to initiate and sustain the tachycardia, (5) influence of bundle-branch block on conduction and cycle length of the tachycardia, and (6) effect of drugs or physiologic perturbation of the autonomic nervous system on the tachycardia. 8 , 19

Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts

The aim of the study was to assess the occurrence of triggered activity and automaticity in ventricular trabeculae from failing human hearts and normal and failing rabbit hearts during exposure to a normal and altered extracellular environment. Ventricular trabeculae were harvested from failing human hearts (from patients undergoing cardiac transplantation) and from normal and failing rabbit hearts (combined volume and pressure overload). Trabeculae were superfused with normal Tyrode solution followed by a modified Tyrode solution, which mimicked the extracellular milieu in patients with severe heart failure. Modified Tyrode solution contained low potassium (3.0 mM), low magnesium (0.4 mM), and noradrenaline (1 microM). During superfusion with normal Tyrode solution, early afterdepolarisations, delayed afterdepolarisations, and automaticity were not observed in trabeculae from failing hearts. In the modified Tyrode solution, early afterdepolarisations could be induced in 26% of control rabbit and 30% of failing rabbit trabeculae, but never in human trabeculae. During superfusion with the modified solution delayed afterdepolarisations or triggered activity could be induced in 50% of the human failing trabeculae, in 43% of the failing rabbit trabeculae, and in 9% of the normal rabbit trabeculae (p < 0.01); automaticity was observed in 44% of the human trabeculae, and in 7% of the failing rabbit trabeculae, but in none of the control rabbit trabeculae. In failing rabbit myocardium action potential duration was prolonged at cycle lengths > or = 350 ms, but not at shorter cycle lengths. Delayed afterdepolarisations and automaticity, but not early afterdepolarisations, occur more frequently in myocardium from failing hearts, but only during superfusion with a modified Tyrode solution. This emphasises that the extracellular environment is important with respect to arrhythmogenesis in heart failure, apart from the fixed cellular defect due to heart failure per se. Prolongation of the action potential in failing hearts does not occur at physiological and higher heart rates and therefore cannot be regarded as a protective factor in the prevention of reentrant arrhythmias. The rate of triggered and automatic rhythms was slow. Therefore these mechanisms cannot be responsible for clinical ventricular tachycardias or fibrillation, but may serve as triggers for reentrant arrhythmias.

Cardiac Electrophysiologic Effects of 9-Deoxydoxorubicin

Electrophysiology of 9-Deoxydoxorubicin.Introduction: The purpose of this investigation was to use standard microelectrode techniques to study the actions of the anthracycline antibiotic, 9-deoxydoxorubicin (9-DOD), on cellular electrophysiologic properties of canine Purkinje fibers and on ouabain-induced ventricular tachycardia (VT) in intact dogs. Methods and Results: 9-DOD, 1-5 μM, suppressed delayed afterdepolarizations and prolonged repolarization and the effective refractory period in Purkinje fibers. It had no effect on maximum diastolic potential, Vmax of phase 0, or action potential overshoot through a 10 μM concentration. Although 9-DOD did augment early afterdepolarizations (EAD) induced by cesium, it did not induce EAD. In six of eight intact dogs with ouabain-induced VT, 9-DOD, 0.32-1.28 mg/m2 IV, brought conversion to sinus or junctional rhythm. In its cellular and intact animal antiarrhythmic actions, 9-DOD is about 50 times more potent than the parent compound, doxorubicin. Like doxorubicin, it is highly selective for delayed afterdepolarization-induced rhythms, suppressing these at concentrations lower than those required to reduce the rate of automatic rhythms. Moreover, it has a greater Class III action than doxorubicin and prolongs the duration of normal and calcium-induced (slow response) action potentials. Hence, this subtle variation on the doxorubicin molecule adds greatly to the antiarrhythmic action of the drug. Conclusions: Although useful as an investigative tool, clinical development of 9-DOD as an antiarrhythmic is not possible because the antitumor activity of the parent compound, which results in lipid peroxidation and cardiotoxicity, persists.

Abnormal automatic rhythms in ischemic Purkinje fibers are modulated by a specific alpha 1-adrenergic receptor subtype.

Recent advances in adrenergic pharmacology have made possible the identification of alpha 1-adrenergic receptor subtypes using the specific blockers chloroethylclonidine and WB 4101. In the present study, we used these two blockers to determine the mechanisms responsible for automatic rhythms occurring during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Experiments were done in the presence of propranolol to minimize beta-adrenergic contributions to the rhythms studied. In the control situation, all fibers showed membrane potentials greater than -90 mV and normal automatic rhythms. During simulated ischemia, membrane potential depolarized to the -60 mV range. Abnormal automaticity was seen in 20% of fibers not treated with phenylephrine and in 50% of those superfused with 1 x 10(-7) M phenylephrine. The incidence of abnormal automaticity was reduced to 0% by WB 4101 (which blocks phosphoinositide metabolic effects of alpha 1-adrenergic stimulation in the heart) and was increased to 90% by chloroethylclonidine (which blocks Na-K pump-stimulating effects of alpha-agonists). Moreover, the ischemic fibers were significantly more hyperpolarized during superfusion with WB 4101 than with chloroethylclonidine. Triggered activity induced by delayed or early after depolarizations was not seen in any experiment. Automatic arrhythmias induced by alpha 1-adrenergic stimulation during simulated ischemia may be attributed to a specific alpha 1-adrenergic receptor subtype that is blocked by WB 4101. These results have important implications with respect to the induction of arrhythmias in the setting of ischemia and the means for their prevention or treatment.

Electropharmacological effects of sandostatin in human atrial fibers

We studied the actions of sandostatin (0.1–1000 nM), an analogue of somatostatin, on human atrial tissues obtained from hearts of 20 patients undergoing corrective cardiac surgery. In 3 preparations showing fast response action potential in normal [K] 0 Tyrode solution, sandostatin induced little effect, even at the highest concentration (1 μM). In 10 preparations showing a slow rate of phase-0 depolarization when atrial fibers were depolarized (maximum diastolic potential near −40 mV) in high [K] 0 (27 mM), sandostatin at concentrations as low as 1 nM decreased significantly the velocity of the upstroke, and the amplitude of slow response of the action potential as well as the force of contraction. In 6 experiments on spontaneously active atrial fibers (maximum diastolic potential = −53.8 ± 2.7 mV), sandostatin increased the spontaneous cycle length in a fashion dependent upon concentration. The decrease in spontaneous rate of firing was associated with an inhibition of the late diastolic slope, a change also induced by somatostatin. A longer period of washout, however, (30 min or longer) was required for complete recovery from the depressant effects. Sandostatin (0.1–100 nM) also depressed triggered activity induced by cardiotonic agents. The present findings indicate that sandostatin induces a prolonged action in human atrial cells. Sandostatin may depress abnormal automatic rhythms through an inhibition of transmembrane influx of calcium.

Depressant effect of adenosine in isolated human and canine atrial fibres

STUDY OBJECTIVE0--he aim was to explore the cellular mechanisms responsible for the depressant effects of adenosine in human atrial tissues. Conventional microelectrode technique was used to record transmembrane action potential of human atrial tissues obtained at cardiac surgery. Effects of adenosine (0.1-100 microM) on action potential characteristics and contractile force of human atrial fibres in the absence and presence of an adenosine receptor antagonist (DPSPX) were evaluated. Results were then compared with those obtained from the canine atrial tissues. Atrial tissues obtained from hearts of 25 patients undergoing corrective cardiac surgery were used. Seven mongrel dogs were anaesthetised and strands of atrial muscle were removed and used for comparison. In human atrial fibres showing fast response action potential (mean dV/dtmax around 100 V.s-1) in normal [K]o (4 mM) Tyrode solution, adenosine (1 nM-10 microM) did not induce consistent effects on the action potential characteristics. When the fibres were depolarised in high [K]o (27 mM) or in atrial fibres showing slow response action potential (dV/dtmax less than 50 V.s-1), however, 10 microM adenosine reduced the upstroke velocity and the amplitude of action potential significantly and markedly depressed the contractile force. In atrial fibres spontaneously active in normal Tyrode solution (maximum diastolic potential around -50 mV), adenosine inhibited rate of spontaneous discharge in a concentration dependent manner. Delayed afterdepolarisation and aftercontraction induced by adrenaline or/and high [Ca]o were also suppressed. The depressant effects of adenosine were blocked after pretreatment with 50 microM DPSPX, a specific antagonist for adenosine receptor. These findings show that adenosine may abolish abnormal automatic rhythms and triggered activity in human atria.

Developmental Electrophysiologic Effects of Propafenone and 5-Hydroxypropafenone on the Canine Cardiac Purkinje Fiber

Standard microelectrode techniques were used to investigate the in vitro developmental electrophysiologic effects of propafenone and 5-hydroxypropafenone on the adult and neonatal canine Purkinje fiber. The tonic and frequency-dependent depressant effects of these compounds on Vmax and amplitude were similar in both age groups. However, the ability of these compounds to shorten repolarization parameters was more pronounced in the adult. The extent of reduction of abnormal automaticity produced by propafenone was greater in the neonate compared to the adult, and 5-hydroxypropafenone significantly reduced automaticity only in the neonate. The sensitivity of neonatal abnormal automaticity to the effects of these compounds may prove to be important if the use of these agents is to be expanded into the realm of therapy for pediatric automatic rhythms.

Alpha-adrenergic receptor stimulation during simulated ischemia and reperfusion in canine cardiac Purkinje fibers.

We studied the effects of alpha-adrenergic receptor stimulation and calcium on automaticity of isolated canine Purkinje fibers during simulated ischemia and reperfusion. Ischemia included acidosis (pH 6.7), hypoxia (PO2 = 10-25 mm Hg), hyperkalemia (10 mM K+), and either normal or elevated [Ca2+]o (2.7 or 10.8 mM). Control automatic rate and maximum diastolic potential were 18 +/- 2 beats/min and -94 +/- 1 mV, respectively. Simulated ischemia led to depolarization (to -60 +/- 1 mV), cessation of normal automaticity, and in 21% of fibers, bursts of an abnormal automatic rhythm. Phenylephrine, 5 X 10(-8) M, increased the incidence of the automatic rhythm during ischemia to 44%; this effect was blocked by prazosin but not by propranolol. During reperfusion after simulated ischemia at 2.7 mM [Ca2+]o, automatic rhythm and maximum diastolic potential returned toward control values; after simulated ischemia at 10.8 mM [Ca2+]o, automatic rates were greater than those seen after normal Ca2+ ischemia and were associated with sustained membrane depolarization. Phenylephrine (5 X 10(-8) M) at 2.7 mM [Ca2+]o rapidly restored membrane potential during reperfusion, an effect that was blocked by prazosin. At 10.8 mM [Ca2+]o, phenylephrine also restored membrane potential during reperfusion and blunted the increase in reperfusion rate induced by high [Ca2+]o alone. These effects were blocked by propranolol but not by prazosin. Our results show that the effects of phenylephrine on automatic rhythms during simulated ischemia are blocked by alpha-adrenergic receptor antagonists and that rhythms occurring during reperfusion have alpha- and beta-adrenergic receptor components.

The effects of single premature stimuli on automatic and triggered rhythms in isolated canine Purkinje fibers.

We studied the effects of single premature stimuli on automatic and triggered rhythms occurring in preparations of isolated canine Purkinje fibers. Preparations were made from false tendons, the subendocardial right bundle branch, and infarct zone Purkinje fibers 24 hr after occlusion of the left anterior descending coronary artery, and were studied by standard microelectrode techniques. Single premature impulses almost always produced reset of automatic rhythms, whether the pacemaker had a low (less than -60 mV), intermediate (-61 to -70 mV), or high (greater than -70 mV) maximum diastolic potential. In contrast, single premature impulses imposed on triggered rhythms sometimes were found to alter these rhythms; often, early premature impulses (i.e., during phase 3) resulted in either a shortened first return cycle or a short period of arrest of the rhythm. The results of this study indicate that it may be possible to design simple electrophysiologic tests using single premature stimuli to determine whether an arrhythmia is being caused by an automatic focus or by triggered activity.

Effects of diltiazem on triggered activity in canine 1 day old infarction.

Triggered activity arising from a delayed after-depolarisation occurs in canine subendocardial Purkinje fibres 1 day following infarction. Standard microelectrode techniques were used to study small preparations (less than 50 mm2) in vitro. Diltiazem, 1 mg X litre-1, reversibly suppressed triggered activity by reducing maximum diastolic potential, action potential amplitude and the rate of depolarisation of the delayed after-depolarisation. Complete quiescence or exit block resulted. The effects of diltiazem were antagonised by elevating extracellular Ca ion concentration. These results suggest that automatic ectopic rhythms 1 day following myocardial infarction, that are the result of triggered activity, are dependent on transmembrane Ca ion movement which diltiazem can directly antagonise.

Dissimilar length-tension relations of canine ventricular muscle and false tendon: Electrophysiologic alterations accompanying deformation

Length-passive tension (strain-stress) relations were determined in right ventricular trabeculae and right and left ventricular false tendons removed from dog hearts. Preparations were isolated in tissue bath (1 Hz; 36°C) and resting length was progressively increased. False tendons are more compliant than ventricular muscle, requiring a greater increase in length to reach a specified resting tension. The difference in compliance was significant ( P < 0.05) at extensions of 40% or more. Right ventricular false tendons are slightly more compliant than left ventricular false tendons; the differences become significant ( P < 0.05) at an extension of 40%. The apex of the length-active force relation occurred at greater extensions in false tendon. Scanning electron microscopy demonstrates that extensions of 40 to 50% orient contractile elements uniformly parallel in ventricular muscle while in false tendon undulations remain at these extensions. Stretch caused alterations in resting and action potentials (during stimulation at 1 Hz) of seven false tendons studied with microelectrodes (three of the false tendons demonstrated automatic rhythms) and four of six ventricular muscles. The strains at which the electrical changes occurred were similar in muscle and false tendon (∼65%).

Automaticity and automatic rhythms

The nature of the automatic process in cardiac pacemakers is discussed with special reference to the mechanism of diastolic depolarization in cardiac Purkinje fibers as investigated by the use of the voltage clamp technique. The major factors controlling cardiac automaticity—the sympathetic nerves, the vagi and overdrive suppression —are analyzed. Under different conditions, both sympathetic and vagus nerve stimulation can lead to a slowing or acceleration of cardiac pacemakers. The mechanism by which the sympathetic nerves can slow and the vagus nerve accelerate the pacemaker rate is reported. The inhibition exerted by the sinus node on idioventricular pacemakers through overdrive suppression is described: Overdrive suppression is a form of inhibition that operates when a pacemaker is driven at a rate faster than its own. The mechanism of overdrive suppression is indicated by a frequency-dependent electrogenic sodium extrusion. Automatic rhythms are classified according to different mechanisms of production; they can result from an exaggeration of the normal automatic process or from mechanisms absent under normal conditions. Examples of different arrhythmias are given, and it is noted that some types of tachycardias can occur while automaticity is depressed.

AUTOMATIC RHYTHMS PRODUCED BY ECTOPIC VENTRICULAR CONTRACTIONS.

Facilitation of A-V nodal and automatic ventricular rhythms by ectopic ventricular contractions was described. In one case only A-V nodal beats were induced, but in the other three, the self-sustained rhythms presented themselves as intermittent parasystole, nodal tachycardia, and automatic ventricular beats. The elicited automatic rhythms were never seen after im-pulses traveling in an orthograde fashion. The term facilitation was employed here in reference to disturbances in impulse formation, contrasting with its previous use in connection chiefly to impulse conduction.The examples presented represent another instance in which an automatic rhythm was precipitated by a coupled (true) extrasystole, thereby emphasizing the relationship between both types of ectopic beats.