Ectopic Events Research Articles

Homologous recombination‐mediated knock‐in targeting of the MET1a gene for a maintenance DNA methyltransferase reproducibly reveals dosage‐dependent spatiotemporal gene expression in rice

Although homologous recombination-promoted knock-in targeting to monitor the expression of a gene by fusing a reporter gene with its promoter is routine practice in mice, gene targeting to modify endogenous genes in flowering plants remains in its infancy. In the knock-in targeting, the junction sequence between a reporter gene and an endogenous target promoter can be designed properly, and transgenic plants carrying an identical and desired knock-in allele can be repeatedly obtained. By employing a reproducible gene-targeting procedure with positive-negative selection in rice, we were able to obtain fertile transgenic knock-in plants with the promoterless GUS reporter gene encoding beta-glucuronidase fused with the endogenous promoter of MET1a, one of two rice MET1 genes encoding a maintenance DNA methyltransferase. All of the primary (T(0)) transgenic knock-in plants obtained were found to carry only one copy of GUS, with the anticipated structure in the heterozygous condition, and no ectopic events associated with gene targeting could be detected. We showed the reproducible, dosage-dependent and spatiotemporal expression of GUS in the selfed progenies of independently isolated knock-in targeted plants. The results in knock-in targeted plants contrast sharply with the results in transgenic plants with the MET1a promoter-fused GUS reporter gene integrated randomly in the genome: clear interindividual variation of GUS expression was observed among independently obtained plants bearing the randomly integrated transgenes. As our homologous recombination-mediated gene-targeting strategy with positive-negative selection is, in principle, applicable to modify any endogenous gene, knock-in targeting would facilitate basic and applied plant research.

Laplace Periodogram for Time Series Analysis

A new type of periodogram, called the Laplace periodogram, is derived by replacing least squares with least absolute deviations in the harmonic regression procedure that produces the ordinary periodogram of a time series. An asymptotic analysis reveals a connection between the Laplace periodogram and the zero-crossing spectrum. This relationship provides a theoretical justification for use of the Laplace periodogram as a nonparametric tool for analyzing the serial dependence of time series data. Superiority of the Laplace periodogram in handling heavy-tailed noise and nonlinear distortion is demonstrated by simulations. A real-data example shows its great effectiveness in analyzing heart rate variability in the presence of ectopic events and artifacts.

Gene Targeting by Homologous Recombination as a Biotechnological Tool for Rice Functional Genomics

The modification of an endogenous gene into a designed sequence by homologous recombination, termed gene targeting (GT), has broad implications for basic and applied research. Rice (Oryza sativa), with a sequenced genome of 389 Mb, is one of the most important crops and a model plant for cereals, and the single-copy gene Waxy on chromosome 6 has been modified with a frequency of 1% per surviving callus by GT using a strong positive-negative selection. Because the strategy is independent of gene-specific selection or screening, it is in principle applicable to any gene. However, a gene in the multigene family or a gene carrying repetitive sequences may preclude efficient homologous recombination-promoted GT due to the occurrence of ectopic recombination. Here, we describe an improved GT procedure whereby we obtained nine independent transformed calli having the alcohol dehydrogenase2 (Adh2) gene modified with a frequency of approximately 2% per surviving callus and subsequently isolated eight fertile transgenic plants without the concomitant occurrence of undesirable ectopic events, even though the rice genome carries four Adh genes, including a newly characterized Adh3 gene, and a copy of highly repetitive retroelements is present adjacent to the Adh2 gene. The results indicate that GT using a strong positive-negative selection can be widely applicable to functional genomics in rice and presumably in other higher plants.

Clinical correlates of non-linear indices of heart rate variability in chronic heart failure patients

We assessed the clinical correlates of a comprehensive set of non-linear heart rate variability (HRV) indices computed from 24-h Holter recordings for 200 stable chronic heart failure (CHF) patients [median age (lower quartile, upper quartile) 54 (47, 58) years, LVEF 23% (19%, 28%)]. A total of 19 non-linear indices belonging to six major families, namely symbolic dynamics, entropy, empirical mode decomposition, fractality-multifractality, unpredictability and Poincaré plots, were considered. Most indices showed a significant association with ejection fraction and with the severity of symptoms, while only two (one each from the fractality and Poincaré plot families) showed an association with aetiology. Only one symbolic dynamics variable was associated with the presence of non-sustained ventricular tachycardia and two symbolic dynamics variables were associated with the rate of ventricular ectopic events. Our results demonstrate the existence of selective links between non-linear indexes of HRV and the clinical status and functional impairment of CHF patients. This indicates that further studies should be designed to investigate the physiopathological mechanisms involved in such links.

Anesthesia for Percutaneous Transcatheter Closure of Perimembranous Ventricular Septal Defect

To review the anesthetic management for percutaneous transcatheter closure of perimembranous ventricular septal defect (VSD) with an Amplatzer asymmetric occluder device and to highlight the hemodynamic effects and potential complications associated with its delivery. Retrospective review of prospectively collected data. University-affiliated teaching hospital. Nine consecutive children undergoing elective percutaneous transcatheter closure of perimembranous VSD. General anesthesia with sevoflurane for cardiac catheterization and percutaneous transcatheter device placement. Ten anesthetics were delivered in 9 children ages 23 to 65 months with perimembranous VSD for attempted placement of an Amplatzer asymmetric device. The device was successfully placed in 7 patients. In 1 patient the device embolized to the right femoral artery, and was retrieved with a bioptome. Fluoroscopy time (59.8 +/- 17.24 min) was prolonged compared to that in other studies of placement of this device. All patients had episodes of arrhythmia and hemodynamic disturbance. Arrhythmias ranged from atrial or ventricular ectopic events to various degrees of atrioventricular block. Complete heart block occurred during the procedure in 1 patient and after the procedure in another patient. Hypotensive episodes occurred in 7 patients, and were attributed to arrhythmias in 5 patients and hypovolemia in 2 patients. Two patients were given blood transfusions after the procedure because they had signs of hypovolemia and a greater than 10% decrease in hemoglobin levels. Anesthesia for perimembranous VSD occluder placement is associated with hemodynamic instability, arrhythmias, prolonged procedure times, and inevitable and sometimes substantial blood loss.

Disruption of p53 by the Viral oncoprotein HPV16-E6 does not Deregulate Chromosomal Homologous Recombination in a Transcriptional Interference-Free Assay System

In addition to its well established role in the maintenance of genome integrity by regulating transcription of genes involved in cell cycle arrest and programmed cell death, the tumour suppressor p53 has also been shown to inhibit spontaneous chromosomal homologous recombination (HR) between adjacent transcription units, raising the possibility that p53 may prevent chromosomal rearrangements by suppressing HR between repetitive DNA elements (ectopic HR). Consistent with its role in the maintenance of genome integrity is that p53 does not suppress HR between homologous chromosomes (allelic HR) or identical sister chromatids, raising the question of how p53 discriminates between ectopic and allelic HR events. Here, we report that disruption of human p53 by the viral oncoprotein HPV16-E6 does not result in increased rates of chromosomal HR between adjacent DNA repeats in a transcriptional interference-free assay system in which a HR reporter gene can escape transcription repression. These results argue against a direct role for p53 in the regulation of HR mechanisms, imply that HR assay systems may be important determinants of the outcome, and suggest that p53 may suppress ectopic HR through its known ability to repress transcription and alter chromatin structure.

A tale of two integrations, transgene and T-DNA: gene targeting by homologous recombination in rice.

The first successful and reproducible gene targeting by homologous recombination, without the concomitant occurrence of ectopic events, has been reported. This will be a powerful approach for the characterization of gene function in rice, an important crop and a model for other cereal species. Models have been proposed to explain gene replacement by homologous recombination, including a possible model for Agrobacterium-mediated gene targeting using a strong positive-negative selection.

Cardiovascular Safety of Salmeterol in COPD

Patients with COPD have an increased risk of cardiovascular disease. Despite the clinical benefits of long-acting beta-agonist agents in the treatment of COPD, patients may be at an increased risk of cardiovascular toxicity, including tachyarrhythmia due to beta-adrenergic stimulation. To evaluate the cardiovascular safety of salmeterol in COPD patients by conducting a pooled analysis of cardiovascular safety data. Randomized, double-blind, parallel group, multiple-dose studies, which included salmeterol, 50 micro g bid, and placebo arms. Seven of a total of 17 studies met the predefined inclusion requirements and were pooled. A total of 1,443 patients received placebo, while 1,410 patients received salmeterol, 50 micro g bid. The median duration of treatment was 24 weeks (range, 12 to 52 weeks). Treatment with salmeterol, 50 micro g bid, showed no increased risk of cardiovascular adverse events (AEs) compared with placebo (relative risk, 1.03; 95% confidence interval, 0.8 to 1.3; p = 0.838). Both groups had a similar incidence of cardiovascular events (8%), including cardiovascular deaths. The incidence of cardiovascular AEs increased with age, concurrent cardiovascular conditions, and treatment with antiarrhythmic/bradycardic agents, although increases were comparable in both treatment groups. There were no episodes of sustained ventricular tachycardia, and no clinically significant differences were observed in 24-h heart rate, ventricular and supraventricular ectopic events, qualitative ECGs, QT intervals, or vital signs between the salmeterol, 50 micro g bid, group and the placebo group. Similar findings were observed when patients were stratified for age of > 65 years or the known presence of cardiovascular disease. Treatment with salmeterol, 50 micro g bid, does not increase the risk of cardiovascular AEs in this population of COPD patients compared with placebo.

Long-term Cardiovascular Safety of Salmeterol Powder Pharmacotherapy in Adolescent and Adult Patients With Chronic Persistent Asthma: A Randomized Clinical Trial

This study investigates the long-term cardiovascular safety of salmeterol powder vs placebo in adolescent and adult patients with mild persistent asthma. Multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Eighteen US clinical centers. Three hundred fifty-two patients (> or = 12 years) with mild persistent asthma (duration > or = 6 months) requiring pharmacotherapy; with FEV1 of 70 to 90% of predicted and without abnormal ECG/continuous ambulatory ECG (Holter). Randomized to twice-daily salmeterol powder (50 microg) or placebo via breath-actuated device for 52 weeks. Backup albuterol was available to control asthma symptoms. Cardiovascular safety was regularly assessed by 12-lead ECG with a 15-s lead II rhythm strip, 24-h continuous ambulatory ECG (Holter) monitoring, serial vital sign measurements, and review of adverse cardiovascular events. No deaths occurred during the study. No clinically significant between-group differences were observed in pulse rate, ECG QTc interval, median number of ventricular or supraventricular ectopic events, incidence of ventricular ectopic couplets and runs, or incidence of > 100 ventricular or supraventricular ectopic events in 24 h. No clinically significant between-group differences were observed in arterial BP or incidence of adverse cardiovascular events. Salmeterol was well tolerated throughout the 52-week study period, with a cardiovascular safety profile similar to that of placebo. Long-term, twice-daily pharmacotherapy with salmeterol powder is safe and is not associated with unfavorable clinically significant changes in cardiac function or increases in cardiovascular adverse effects.

GABA-dependent generation of ectopic action potentials in the rat hippocampus.

Intracellular recordings from CA3 pyramidal cells of rat hippocampus in a slice preparation revealed the occurrence of interictal epileptiform discharges and synchronous GABA-mediated potentials during application of 4-aminopyridine (4AP, 50 micrometer). The synchronous GABA-mediated potential consisted of a sequence of early hyperpolarization, long-lasting depolarization (LLD), and late hyperpolarization. Action potentials of variable amplitude occurred at the peak of the early hyperpolarization and during the LLD rising phase (48 of 64 cells); they were not prevented by membrane hyperpolarization and displayed inflections that were reminiscent of the initial segment-somatodendritic (IS-SD) fractionation. Interictal discharges were blocked by excitatory amino acid receptor antagonists, while both GABA-mediated potentials and action potentials of variable amplitude continued to occur (n = 10). The latter events were still recorded in the presence of the GABAB receptor antagonist CGP-35348 (0.5-1 mm, n = 4), but were abolished by the GABAA receptor antagonist bicuculline methiodide (BMI, 10 micrometer, n = 5). Localized application of BMI (20 micrometer, n = 6) or tetrodotoxin (TTX, 5 micrometer, n = 3) to the CA1 stratum radiatum blocked the variable amplitude action potentials; these effects were not seen when BMI (n = 4) or TTX (n = 4) were applied to the CA3 stratum radiatum, although both procedures made LLDs disappear. Our findings indicate that action potentials of variable amplitude recorded from CA3 pyramidal cells in the 4AP model are generated at or near the terminal region of the Schaffer collaterals and that they represent TTX-sensitive ectopic events. These action potentials are generated at this site by a BMI-sensitive (and thus GABAA-mediated) mechanism. We propose that the ectopic action potentials reflect an increased excitability of axon terminals that is presumably caused by [K+]o elevations associated with the 4AP-induced synchronous GABA-mediated potential.

Intensive Care Unit ECG Monitoring

Perhaps the most useful means of monitoring the critically ill patient is the electrocardiogram (ECG). A 12lead ECG is useful to rule out cardiac complications in the acutely injured patient, the postoperative patient, and the septic patient [1]. Limb lead II or chest lead V may be continuously monitored for evidence of progressive cardiac disease and complicating dysrhythmias [1]. This section summarizes the usefulness and indications of the ECG in monitoring of the high-risk, critically ill patient and possibilities for future clinical use. Interpretation of the ECG waveform provides the basis for diagnosis and therapy of numerous conditions associated with disorders of the myocardium in the intensive care unit (ICU) [1]. Continuous ECG monitoring is essential for the adult patient with acute myocardial infarction because dysrhythmias are the most common life-threatening complication [1]. Continuous ECG monitoring of the postoperative general surgical patient is not as useful because the incidence of lifethreatening dysrhythmias is lower [1,2]. However, in adults and children with decreased myocardial function, hypovolemia, or hypoxemia, the ECG may show PVCs, PACs, ST segments changes, altered T-waves, and bradycardia [1]. These abnormalities may be produced by inadequate oxygen delivery to the myocardium and therefore serve to alarm the physician of potentially signi~cant pathophysiologic disturbances. One of the main uses for the ECG is the determination of heart rate or pulse. Most ICUs measure heart rate as a calculated time-averaged signal from the bedside ECG monitor. Heart rate is a very nonspeci~c cardiorespiratory variable. However, tachycardia may signal signi~cant and abrupt cardiovascular compromise such as hypovolemia, hypoperfusion, or diminished myocardial contractility in the critically ill patient [3]. The degree of tachycardia is roughly proportional to the severity of the cardiovascular impairment. Tachycardia is also present in association with infection, anxiety, stress, fever, exercise, pain, and anxiety. Bradycardia may occur with inferior myocardial infarction, arteriosclerotic heart disease, or severe systemic hypoxemia [3]. Heart rate may also be used during invasive hemodynamic monitoring with thermodilution pulmonary arterial catheters to calculate stroke volume and other hemodynamic variables. The ECG may be used directly or as an adjunctive test in the diagnosis of numerous diseases and conditions affecting the critically ill patient. Myocardial ischemia may occur in the critically ill patient with shock, even in the absence of primary coronary artery disease [1]. Myocardial ischemia ultimately results in T-wave inversion. Myocardial injury due to ischemia may cause elevation of the ST segment if the ischemia is transmural or ST segment depression if the ischemia is nontransmural and predominantly subendocardial [1]. Progressive ischemia results in myocardial infarction which is often manifested in the ECG by Qwave deepening and distortion, loss of R-wave voltage, and/or an increased R-wave amplitude [1]. However, ECG abnormalities characterizing myocardial ischemia and infarction are nonspeci~c. Serial ECGs should be followed to speci~cally diagnose and localize myocardial ischemia and infarction [1]. Table 1 lists characteristic changes in the ECG associated with other disease states commonly seen in critically ill patients. ECG changes observed in drug overdose or poisoning, and electrolyte and metabolic disturbances are shown in Tables 2 and 3. Abnormal cardiac rhythms may occur during critical illness at any time and are the most common mechanism of death in adults [1]. Automated arrhythmia detection algorithms are commercially available and in use in many ICUs. These algorithms ~lter the incoming ECG signal, detect and classify the QRS complex, identify ectopic events and ventricular rhythms, and generate alarms. For ventricular ectopic beats, the system has a reported sensitivity of up to 90% with a false positive rate of #1%. However, the algorithms may result in false positive alarms if the Tor P-waves are $50% of the R-wave amplitude, and are not useful for detection of aberrantly conducted beats, atrial ~brillation and _utter, and intermittent bundle branch block. In summary, the clinical utility and cost effectiveness of these and other automated forms of ECG monitoring in the ICU, such as automated ST segment monitoring [5] and signal-averaged electrocardiography (detailed in subsequent sections), have yet to be determined. The ECG waveform itself may be an important source of clinical information that has only recently

Elimination of ectopic events in heart period duration series without loss of information

Elimination of ectopic events in heart period duration series without loss of information

The incidence of atrial arrhythmias during inferior wall myocardial infarction with and without right ventricular involvement

The atrial arrhythmia profile during inferior wall acute myocardial infarction (AMI) has not been systematically examined with respect to right ventricular (RV) involvement. To this end, 62 consecutive patients with first inferior wall AMI and no other conditions known to increase susceptibility for rhythm disturbances were studied by 24-hour Holter monitoring during the first and tenth day of infarction. Based on radionuclear ventriculography performed on day 2 of infarction, patients were allocated to two groups: group A—36 patients (58%) with right ventricular ejection fraction (RVEF) <40% (mean ± SD, 31 ± 6%) and group B—26 patients (42%) with normal (>40%) RVEF (mean ± SD, 47 ± 5%). There were no significant differences between the two groups with respect to age, sex, or left ventricular (LV) function. In the group as a whole, ectopic activity in the different categories of atrial arrhythmias was significantly higher during the first day than on the tenth day of infarction. Comparing the two groups, 33 patients (92%) in group A had a mean hourly frequency of one or more atrial premature contractions (APCs) during the first day of infarction compared with 18 patients (69%) in group B ( p < 0.001). Atrial and supraventricular tachycardia were recorded more frequently in group A patients (16 of 36 [44%] versus 8 of 26 [31%]) as well as atrial fibrillation (AF) (7 of 36 [19%] versus 1 of 26 [4%]). Quantitative analysis showed a similar trend for a higher rate of ectopic events in group A patients. Ectopic activity was neither influenced by LVEF nor by age or sex. Using stepwise regression analysis, RVEF was independently related to the prevalence of AF and APCs. The data presented indicate that patients with inferior wall MI accompanied by RV dysfunction are more prone to develop atrial rhythm disturbances than patients with preserved RV function. Atrial infarction or ischemia, atrial distension, and a raised right atrial pressure may account for this trend.

Outcome of laparoscopic versus traditional surgery for ectopic pregnancies

To compare pregnancy rates after three surgical procedures for ectopic pregnancy (EP) over a 9-year period for normal and infertility patients. In a retrospective analysis, we examined crude pregnancy rates and life-table analysis of cumulative pregnancy rates. A proportional hazard regression model was used to examine relative risk of type of surgery and fertility rates. One hundred twenty-six cases of EPs were reviewed at the Cleveland Clinic Foundation, a tertiary institution. Comparisons of rates of viable term deliveries were calculated between three types of surgery and were stratified according to the status of infertility. Confidence intervals for relative risk of surgery and fertility status on future pregnancy were calculated. No difference in pregnancy rates was observed after the three procedures (P = 0.08). Normals had a significantly higher (4 times higher) pregnancy rate than infertility patients, independent of surgical procedure. Successful pregnancy after EP is related to history of infertility rather than type of surgery to treat ectopic event. More randomized study is needed to examine laparoscopic salpingostomy, especially in patients with other infertility problems.

Evaluation of antiarrhythmic drug effects with simultaneous analysis of single ventricular premature contractions, couplets and salvos

To improve the clinical value of ambulatory Holter electrocardiographic (ECG) monitoring as a tool of antiarrhythmic therapy control, a new statistical model was developed. In a patient group at increased risk of sudden cardiac death, the spontaneous variability of ventricular arrhythmias was assessed, with simultaneous consideration of single ventricular premature complexes, couplets and salvos. The study included 100 patients who suffered from coronary heart disease or idiopathic dilated cardiomyopathy and for whom greater than 30 ventricular premature complexes/h and couplets had been demonstrated on the last Holter ECG before the study. Between 3 and 12 Holter recordings were made for each patient in a drug-free state; the mean follow-up period was 260 days (maximum 1,403). The mean hourly values of the ectopic events (EE) were assessed separately for ventricular premature complexes, couplets and salvos. The spontaneous variability (SV) was calculated for single ventricular premature complexes, couplets and salvos as SV = log (EEday 2 + 0.01/EEday 1 + 0.01) and linked in one, two and three dimensions. Compared with the consideration of only one type of arrhythmia (one-dimensional model), the simultaneous use of two or three types of arrhythmia (two- or three-dimensional model) resulted in considerably lower reduction and aggravation rates as sufficient proof of drug effects. With control intervals up to 1 week, the one-dimensional model yielded reduction rates for ventricular premature complexes, couplets and salvos of -63%, -90% and -95%, respectively. In contrast, with the three-dimensional model, the rates were -28%, -72% and -88%. The corresponding aggravation values were +370, +1,114% and +2,189% versus +38%, +256% and +747%.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic ambulatory monitoring with a real-time analysis system

The analysis of records collected during long-term ambulatory electrocardiographic monitoring has traditionally involved the review of massive data, either manually or with the aid of interactive scanning computers. Many factors complicate this analysis, including the use of analog tape for storage of electrocardiographic waveforms, the need to analyze 100,000 waveforms from an average 24-hour study, and the need to deal with an interface that compresses 24 hours of data into as little as 6 minutes on a screen. Today, the computer incorporated in the monitor can scrutinize each cardiac cycle in real time. The system produces a statistical report based on every heart beat and also performs data reduction and storage of electrocardiograph samples. To assess real-time analysis we examined data collected from the Circadian CircaMed ambulatory electrocardiography system. We found that it could detect and quantify simple or complex ventricular ectopic beats, brady- or tachyarrhythmic events, and ST-segment deviation. One hundred fifty patients 21 to 85 years old with symptoms or clinical finding suggestive of ischemia, cardiac arrhythmia, or conductive defects were referred to our electrocardiography laboratory for ambulatory monitoring. The results demonstrate that this system can detect the full range of cardiac disease found with the traditional method. Of the 150 patients, ambulatory electrocardiographic tests were positive in 93 (62%). In addition, we developed a methodology for lead placement when using two bipolar leads, as is typical for ambulatory electrocardiography. We present a procedure for determining the optimum lead placement that is based on the patient's history and a 12-lead electrocardiogram.

Meiotic recombination between dispersed repeated genes is associated with heteroduplex formation.

In Saccharomyces cerevisiae, recombination events occurring between allelic genes located on homologous chromosomes are often associated with heteroduplex formation. We found that recombination events between repeated genes on nonhomologous chromosomes (ectopic events) are also associated with the formation of heteroduplexes, indicating that classical and ectopic recombination events involve similar mechanisms.

Meiotic Recombination between Dispersed Repeated Genes Is Associated with Heteroduplex Formation

In Saccharomyces cerevisiae, recombination events occurring between allelic genes located on homologous chromosomes are often associated with heteroduplex formation. We found that recombination events between repeated genes on nonhomologous chromosomes (ectopic events) are also associated with the formation of heteroduplexes, indicating that classical and ectopic recombination events involve similar mechanisms.

Electrophysiological specificity of antiarrhythmic drugs: Is it necessary?

AbstractMany factors have been identified in the genesis of cardiac arrhythmias. The relative importance of any given factor over another can vary from individual to individual, and may change with time. Successful antiarrhythmic drug therapy, therefore, must be effective against a multifaceted and evolving matrix. Clinically, the more successful antiarrhythmic agents have complex pharmacological profiles. For example, quinidine and amiodarone have several mechanistic actions which contribute to their antiarrhythmic efficacy. Multiple unfocused actions often result in side effects such as proarrhythmia, which has been demonstrated for both the above agents. Another approach to treating arrhythmias is to use different, selective agents in combination. Using programmed electrical stimulation techniques in dogs, we demonstrated that propranolol was ineffective in preventing reentrant tachycardia. However, subtherapeutic doses of the class III agent sematilide when combined with propranolol prevented reentry. A multivalent approach may also be useful in solving the problem of proarrhythmia. Using standard microelectrode techniques in vitro, we demonstrated that clofilium produced early after depolarizations, as well as an increase in triggered activity. In vivo, clofilium increased the number of ectopic events in infarcted dogs. The addition of a class I or a class IV antiarrhythmic agent in these animals was effective in suppressing the increased ectopic activity. These data suggest that combination therapy, by combining either single agents with selective actions or developing agents with multiple, focused actions may be an effective way to increase antiarrhythmic efficacy and decrease side effects.

Beyond pure parasystole: promises and problems in modeling complex arrhythmias.

The dynamics of pure parasystole, a cardiac arrhythmia in which two competing pacemakers fire independently, have recently been fully characterized. This model is now extended in an attempt to account for the more complex dynamics occurring with modulated parasystole, in which there exists nonlinear interaction between the sinus node and the ectopic ventricular focus. Theoretical analysis of modulated parasystole reveals three types of dynamics: entrainment, quasiperiodicity, and chaos. Rhythms associated with quasiperiodicity obey a set of rules derived from pure parasystole. This model is applied to the interpretation of continuous electrocardiographic data sets from three patients with complicated patterns of ventricular ectopic activity. We describe several new statistical properties of these records, related to the number of intervening sinus beats between ectopic events, that are essential in characterizing the dynamics and testing mathematical models. Detailed comparison between data and theory in these cases show substantial areas of agreement as well as potentially important discrepancies. These findings have implications for understanding the dynamics of the heartbeat in normal and pathological conditions.