The opposite polarity of the PQ segment compared to the P wave isointegral maps

The aim of our work was to study the opposite polarity of the PQ segment to the P wave body surface potential maps in different groups of patients. We constructed isointegral maps (IIM) in 26 healthy controls (C), 16 hypertensives (HT), 26 patients with arterial hypertension and left ventricular hypertrophy (LVH) and 15 patients with myocardial infarction (MI). We analyzed values and positions of map extrema and compared the polarity of maps using the correlation coefficient. The IIM P maxima appeared mainly over the precordium, the minima mainly in the right subclavicular area. The highest maxima were in the MI group, being significantly higher than in the HT and LVH groups. No differences concerning any values of other extrema were significant. The IIM PQ maxima were distributed over the upper half of the chest; the minima mainly over the middle sternum. A statistically significant opposite polarity between the IIM P and IIM PQ was found in 80 % of cases. The opposite polarity of the P wave and the PQ segment was proved in isointegral body surface maps. The extrema occurred in areas not examined by the standard chest leads. This has to be considered for diagnostic purposes.     

The effect of psychoemotional load on ventricular repolarization reflected in integral body surface potential maps

The aim of the present study was to investigate the reflection of psychoemotional stress in the body surface potential distribution as documented by isointegral maps of cardiac activation and recovery. In 72 young men (18.3+/- 7.3 y.) with no cardiovascular history body surface potential maps (BSPMs) at rest and during the test of mental arithmetic were recorded. The digitalized data for each point of the QRS, STT and QRST integral maps, for each subject in both situations, were processed and evaluated by methods of univariate as well as spatial mathematical and statistical modeling. The results showed during MA a significant decrease of repolarization integral values over the sternum and right precordium, which contributed to analogically localized decrements also in the QRST BSM. The decrease occurred in more than 2/3 of lead points. The most pronounced changes were observed in the right precordial area, where potentials decreased in more than in 70 % of subjects. In conclusion, the discriminative power of the difference STT and QRST integral maps was strong enough to distinguish the mental arithmetic induced changes in the superficial cardiac electric field. These adrenergic transient alterations in ventricular recovery may be of importance in subjects at risk for ventricular arrhythmias.     

ST segment body surface isointegral maps in patients with arterial hypertension

In this retrospective study we analysed changes of the ST segment in patients with arterial hypertension using multi-lead body surface mapping of the electric heart field as the ST segment often shows non-specific changes and is influenced by many different conditions. We constructed isointegral maps (IIM) of chosen intervals (the first 35 ms, the first 80 ms, and the whole ST segment) in 42 patients with arterial hypertension (with and without left ventricular hypertrophy) and in the control group involving 23 healthy persons. We analysed the position and values of map extrema. Spatial distribution of voltage integrals was similar in the control group and in the "pure" hypertensives. Patients with the left ventricular hypertrophy exhibited shifts of the integral minima. Despite our expectations, the highest extrema values were found in the control group and not in the left ventricular hypertrophy group. The extrema values were similar in all hypertensives, with or without left ventricular hypertrophy. Differences could be explained neither by the influence of the age, nor by the body habitus.     

Cardioelectric Field on the Bird Body Surface during Activation of Atrial Myocardium

Cardioelectric field (CEF) on the body surface of birds (hen and pigeon) at the period of atrial excitation was studied by the method of the 64-channel synchronous electrocardiotopography. At the period of the atrial depolarization in the birds the zone of CEF negative potentials on the body surface is located cranially with respect to the zone of positive potentials. At the initial moments of P wave the minimum is located in the cranial (hen) or middle (pigeon) third of the dorsal body surface, while the maximum—in the area of the heart projection onto the ventral (hen) or left-lateral (pigeon) body surface. The maximum and minimum of the potential reach the greatest value at the period of the middle part of the P wave (near the peak), their amplitude being higher in pigeons. The distribution dynamics of the CEF potentials on the body surface is similar in different bird species and is characterized by stability in mutual disposition of positive and negative zones. The interspecies and intraspecies CEF variability on the body surface at the period of the atrial activation seems to be due to differences in the heart disposition in the chest. At the period of the atrial myocardium activation, CEF on the bird body surface reflects adequately projection of the potential distribution on epicardium and the sequence of spreading of excitation in the atrial myocardium, including that in the presence of several fronts of depolarization waves.     

ECG body surface mapping (BSM) in type 1 diabetic patients

Diabetes mellitus is a risk factor of cardiovascular diseases. ECG of patients with diabetes mellitus type 1 (DM 1) shows tachycardia (block of parasympathetic innervation) and abnormal repolarization (increased QT interval and QT dispersion (QTd)) indicating a risk of ventricular tachycardia and sudden death in young people with DM 1. The aim of the present report was to measure 145 parameters of the heart electric field in 22 patients (14 men, 8 women) with DM 1 without complications (mean age 32.8+/-11.4 years) and in 22 controls (11 men, 11 women, mean age 30.1+/-3.4 years). The duration of diabetes was 13.9+/-7.8 years. The parameters were registered by the diagnostic system Cardiag 112.2 and statistically evaluated by the Student and Mann-Whitney test. Tachycardia (86.3+/-2.7 beats.min(-1)), shortening of both QRS (79.9+/-1.6 ms) and QT (349.0+/-5.9 ms) and increased QT dispersion (115+/-36 ms) were observed in DM 1 when compared with the controls (75.0+/-2.1 beats. min.(-1), QRS 89.9+/-2.7 ms, QT 374.0+/-4.4 ms, QTd 34.0+/-12.0 ms, p<0.01). The QTc was 415.2+/-4.1 ms in DM 1 and 401.4+/-6.6 ms in controls (NS). Other significant findings in DM 1 were: higher maximum of depolarization isopotential maps (DIPMmax) in the initial phase of QRS and less positive in the terminal phase, more negative minimum (DIPMmin) during QRS similarly as the minimum in depolarization isointegral maps (DIIMmin) and the minimum in isointegral map of the Q wave (Q-IIMmin), lower maximum in repolarization isopotential maps (RIPMmax) and less negative minimum (RIPMmin), more negative amplitude of Q wave (Q-IPMAM) and more pronounced spread of depolarization (activation time). Our results confirmed a decreased parasympathetic to sympathetic tone ratio (tachycardia, shortening of the activation time) and revealed different depolarization and repolarization patterns in DM 1. The differences in heart electric field parameters measured by the BSPM method in DM 1 and in the controls indicate the importance of ECG examination of diabetic patients type 1 in the prevention of cardiovascular diseases.     

A New Algorithm to Diagnose Atrial Ectopic Origin from Multi Lead ECG Systems - Insights from 3D Virtual Human Atria and Torso

Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms.     

Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition

Aging and glycolytic inhibition (GI) are known to alter intracellular calcium ion (Ca(i)(2+)) handling in cardiac myocytes, causing early afterpotentials (EADs) and delayed afterpotentials. We hypothesized that aging and GI interact synergistically in intact hearts to generate EADs and triggered activity leading to atrial fibrillation (AF). We studied isolated and Langendorff-perfused hearts of young (age 3-5 mo, N = 8) and old (age 27-29 mo, N = 14) rats subjected to GI (0 glucose + 10 mmol/l pyruvate). Epicardial atrial activation maps were constructed using optical action potentials, while simultaneously monitoring Ca(i)(2+) by means of dual-voltage and calcium-sensitive fluorescent dyes. During GI, spontaneous AF occurred in 13 of 14 old but in no young rats. AF was initiated by EAD-induced triggered activity at the left atrial pulmonary vein junction (LA-PVJ). The triggered activity initially propagated as single wave front, but within 1 s degenerated into multiple wavelets. The EADs and triggered activity in the old atria were associated with significantly elevated diastolic Ca(i)(2+) levels at the LA-PVJ, where the time constant tau of the Ca(i)(2+) transient decline and action potential duration were significantly (P < 0.01) prolonged compared with atrial sites 5 mm away from LA-PVJ. During GI and rapid atrial pacing, spatially discordant APD and Ca(i)(2+) transient alternans developed in the old but not young atria, leading to AF. Atria in old rats had significantly more fibrotic tissue than atria in young rats. We conclude that GI interacts with the aged and fibrotic atria to amplify Ca(i)(2+) handling abnormalities that facilitate EAD-mediated triggered activity and AF.     

A new method for regularization of the inverse problem of electrocardiography.

The inverse problem of electrocardiography (specifically, that part concerned with the computation of the ventricular surface activation isochrones) is shown to be formally equivalent to the problem of identification and measurement of discontinuities in derivatives of body surface potentials. This is based on the demonstration that such measurements allow localization of the relative extrema of the ventricular surface activation map (given a forward problem solution), which in turn restricts the space of admissible solution maps to a compact set. Although the inverse problem and the problem of identifying derivative discontinuities are both ill-posed, it is possible that the latter may be more easily or justifiably resolved with available information, particularly as current methods for regularizing the inverse problem typically rely on a regularization parameter chosen in an a posteriori fashion. An example of the power of the approach is the demonstration that a recent Uniform Dipole Layer Hypothesis-based method for producing the ventricular surface activation map is largely independent on that hypothesis and capable in principle of generating maps that are very similar in a precise sense to those that would result from the usual epicardial potential formulation (assuming the latter were capable of producing intrinsic deflections in computed epicardial electrograms sufficiently steep to accurately compute the activation map). This is consistent with the preliminary success of the former method, despite the significant inaccuracy of its underlying assumption.     

Electrocardiograms in five bipolar leads recorded from the body surface of three fish species (Cyprinus carpio, Oreochromis niloticus and Pagrus major) in fresh or sea-water

1. ECGs were recorded using five bipolar leads from the body surface of porgy Pagrus major and tilapia Oreochromis niloticus in fresh or sea-water, or held on a dry towel. 2. The maximum QRS amplitude was detected in lead V in both species being 54 +/- 25 microV in porgy and 241 +/- 78 microV in tilapia, respectively, when the fish were held on the dry towel. 3. Clear ECG waves could not be obtained from porgy in sea-water because of the porgy's small cardiac potential and leakage of the potential. However, clear ECG waves could be obtained in sea-water from the body surface of tilapia, with the average QRS amplitude being 35 +/- 8 microV. 4. The mean electrical P and QRS axes in tilapia were directed toward almost the same direction (frontal downward), whereas both P and QRS axes in most carp were in opposite directions. In porgy, the relationship between the P and QRS axes could not be identified due to the smaller amplitude of the P wave.     

窦房结优势起搏点兴奋向心房传导方式的探讨

本文采用同步双标测法,研究了窦房结(SN)优势起搏点兴奋向心房传导的规律。在14只麻醉狗心脏界沟部缝上一装有32个电极的电极板,标测优势起搏点(P点),最早起始负电位点(N点),心房激动过程图及最早激动点(O点)。在用异丙肾上腺索、心得安或刺激迷走神经使P点移位后,我们研究了P点位置与P—O、P—N的关系。在计60次实验中:(1)P—O、P—N多数并不重叠(分别为46次和40次);(2)随着P点从SN头部向尾部移位,O(N)点在P点头侧的出现率下降,在P点尾侧的出现率上升;(3)出现两个O点者23次,出现两个N点者11次,但P点始终只有一个。 本文提出了SN兴奋在SN内优先向头、尾两端扩布,再传向心房肌的窦房传导模式。并对心房激动多中心起源、界沟部兴奋超速传导等现象及Boiaeau的“心房综合起搏”假说进行了讨论。     

Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation

Atrial arrhythmias, and specifically atrial fibrillation (AF), induce rapid and irregular activation patterns that appear on the torso surface as abnormal P-waves in electrocardiograms and body surface potential maps (BSPM). In recent years both P-waves and the BSPM have been used to identify the mechanisms underlying AF, such as localizing ectopic foci or high-frequency rotors. However, the relationship between the activation of the different areas of the atria and the characteristics of the BSPM and P-wave signals are still far from being completely understood. In this work we developed a multi-scale framework, which combines a highly-detailed 3D atrial model and a torso model to study the relationship between atrial activation and surface signals in sinus rhythm. Using this multi scale model, it was revealed that the best places for recording P-waves are the frontal upper right and the frontal and rear left quadrants of the torso. Our results also suggest that only nine regions (of the twenty-one structures in which the atrial surface was divided) make a significant contribution to the BSPM and determine the main P-wave characteristics.     

Assessment of the P Wave Dispersion and Duration in Elite Women Basketball Players

Background

P wave dispersion is an independent predictor of atrial fibrillation. P wave dispersion is associated with inhomogeneous and discontinuous propagation of sinus impulses. The purpose of this study was to investigate P wave dispersion and transthoracic echocardiographic findings in elite women basketball players.

Methods

We recruited 27 well-trained woman athletes with a training history of many years (11.9 ± 3.6 years). All of the athletes were elite women basketball players and they were regularly maintaining sportive activities and training programs. Twenty-six age and sex matched healthy sedentary subjects consisted of control group. The difference between P maximum and P minimum durations was defined as P wave dispersion. The echocardiographic parameters were assessed in detail in the standard left lateral decubitus position.

Results

The body height, body weight, body surface area, metabolic equivalent, maximum P wave duration and P wave dispersion were increased in the elite basketball athletes as compared with healthy sedentary subjects. On the contrary; the heart rate, ejection fraction and interventricular septum thickness in diastole were decreased in athletes. The body height (p=0.006, r=0.37), body weight (p=0.04, r=0.28), body surface area (p=0.01, r=0.33) and heart rate (p=0.01, r=-0.32) were correlated with P wave dispersion.

Conclusions

P wave dispersion was increased in elite woman basketball players as compared with healthy sedentary subjects. P wave dispersion was correlated with heart rate, body height, body weight and body surface area.     

Noninvasive three-dimensional electrocardiographic imaging of ventricular activation sequence

Imaging the myocardial activation sequence is critical for improved diagnosis and treatment of life-threatening cardiac arrhythmias. It is desirable to reveal the underlying cardiac electrical activity throughout the three-dimensional (3-D) myocardium (rather than just the endocardial or epicardial surface) from noninvasive body surface potential measurements. A new 3-D electrocardiographic imaging technique (3-DEIT) based on the boundary element method (BEM) and multiobjective nonlinear optimization has been applied to reconstruct the cardiac activation sequences from body surface potential maps. Ultrafast computerized tomography scanning was performed for subsequent construction of the torso and heart models. Experimental studies were then conducted, during left and right ventricular pacing, in which noninvasive assessment of ventricular activation sequence by means of 3-DEIT was performed simultaneously with 3-D intracardiac mapping (up to 200 intramural sites) using specially designed plunge-needle electrodes in closed-chest rabbits. Estimated activation sequences from 3-DEIT were in good agreement with those constructed from simultaneously recorded intracardiac electrograms in the same animals. Averaged over 100 paced beats (from a total of 10 pacing sites), total activation times were comparable (53.3 +/- 8.1 vs. 49.8 +/- 5.2 ms), the localization error of site of initiation of activation was 5.73 +/- 1.77 mm, and the relative error between the estimated and measured activation sequences was 0.32 +/- 0.06. The present experimental results demonstrate that the 3-D paced ventricular activation sequence can be reconstructed by using noninvasive multisite body surface electrocardiographic measurements and imaging of heart-torso geometry. This new 3-D electrocardiographic imaging modality has the potential to guide catheter-based ablative interventions for the treatment of life-threatening cardiac arrhythmias.     

Spatial EMG potential distribution pattern of vastus lateralis muscle during isometric knee extension in young and elderly men

The aim of the present study was to compare spatial electromyographic (EMG) potential distribution during force production between elderly and young individuals using multi-channel surface EMG (SEMG). Thirteen elderly (72-79 years) and 13 young (21-27 years) healthy male volunteers performed ramp submaximal contraction during isometric knee extension from 0% to 65% of maximal voluntary contraction. During contraction, multi-channel EMG was recorded from the vastus lateralis muscle. To evaluate alteration in heterogeneity and pattern in spatial EMG potential distribution, coefficient of variation (CoV), modified entropy and correlation coefficients with initial torque level were calculated from multi-channel SEMG at 5% force increment. Increase in CoV and decrease in modified entropy of RMS with increase of exerted torque were significantly smaller in elderly group (p < 0.05) and correlation coefficients with initial torque level were significantly higher in elderly group than in young group at moderate torque levels (p < 0.05). These data suggest that the increase of heterogeneity and the change in the activation pattern are smaller in elderly individuals than in young individuals. We speculated that multi-channel SEMG pattern in elderly individual reflects neuromuscular activation strategy regulated predominantly by clustering of similar type of muscle fibers in aged muscle.     

Atrial Tachycardia Originating from the Cavo-Tricuspid Isthmus May Exhibit Narrow P Waves

An 83-year-old man underwent electrophysiological testing for focal atrial tachycardia (AT) exhibiting narrow P waves with negative deflections in the inferior leads. Catheter ablation at the cavo-tricuspid isthmus (CTI) successfully eliminated the AT. The propagation map during AT and pacing study from the successful ablation site demonstrated that the atrial activation throughout the CTI did not produce significant P wave deflections. Consequently, during AT, the left atrial activation time determined the P wave duration. This case demonstrates that AT originating from the CTI may exhibit narrow P waves which can be misinterpreted as AT originating from the inter-atrial septum.     

Characterization of fibrillatory rhythms by ensemble vector directional analysis

Recent studies have demonstrated that fibrillatory rhythms are not random phenomena but have definable patterns. However, standard mapping techniques may have limitations in their ability to identify the organization of fibrillation. The purpose of this study was to develop and apply a method, "ensemble vector mapping," for characterizing the spatiotemporal organization of fibrillation. Ventricular fibrillation was induced by burst pacing in normal mongrel dogs. In a separate protocol, atrial fibrillation was induced by epicardial aconitine application. Epicardial electrograms were recorded from a 112-electrode plaque array using a computerized mapping system. Vectors were created by summing orthogonal bipolar electrograms. The magnitude of the vectors was transformed using a logarithmic function, integrated over time, and normalized for local electrogram amplitude to produce an "ensemble vector" index whose magnitude is high when beat-to-beat activation direction is consistent and low when activation direction is variable. The mean index was 137 +/- 36 mV/s during ventricular pacing at a cycle length of 300 ms but only 39 +/- 23 mV/s during ventricular fibrillation (P < 0.001). The ensemble vector index was also lower during atrial fibrillation (60 +/- 54 mV/s) than during atrial pacing (115 +/- 27 mV/s, P < 0.01 vs. atrial fibrillation) but not as low as during ventricular fibrillation (P < 0.05, atrial vs. ventricular fibrillation). The index was also capable of distinguishing atrial tachycardia from atrial fibrillation. Ensemble vector mapping produces an objective assessment of the consistency of myocardial activation during fibrillation. The consistency of activation direction differs in different models of fibrillation and is higher during atrial than ventricular fibrillation. This technique has the potential to rapidly characterize repetitive activation patterns in fibrillatory rhythms and may help distinguish among different characteristics of fibrillatory rhythms.     

Age and anesthetic effects on murine electrocardiography

Murine models offer potential insights regarding human cardiac disease, but efficient and reliable methods for phenotype evaluation are necessary. We employed non-invasive electrocardiography (ECG) in mice, investigating statistical reliability of these parameters with respect to anesthetic and animal age. Mice (C57BL/6, 8 or 48 weeks) were anesthetized by ketamine/xylazine (K/X, 80/10 mg/kg ip) or by inhalation anesthetic (halothane, HAL; sevoflurane, SEV) and 6 lead ECGs were recorded. P wave duration and QT interval was significantly prolonged with K/X compared to HAL and SEV, indicating slowed atrial and ventricular conduction. P-R interval (atrio-ventricular conduction) was significantly increased in aged mice under all anesthetics. Heart rate was inversely correlated to QT interval and P wave duration. We also detected significant age effects with respect to optimal approaches for QT interval corrections. Power analysis showed 4-fold higher number of mice/group, were required for K/X, to achieve identical statistical sensitivity. These data demonstrate the importance of anesthetic selection for relevant and reliable ECG analysis in mice and illustrate the selective influences of anesthetics and age on cardiac conductance in this species.     

Electrocardiogram,vectocardiogram and body surface maps in patients with panic disorder

An increased risk of myocardial ischemic changes was demonstrated in patients suffering from panic disorder (PD). Using classical ECG methods, this risk cannot be evaluated in most patients. We measured the vectocardiogram (VCG) using Frank orthogonal leads and body surface maps (BSM) including 12-lead ECG. In our study of 11 PD patients (2 men, 9 women), without any seizures and pharmacological treatment and without cardiovascular symptoms, we found marked sinus tachycardia (heart rate 90.1 +/- 12.2 min(-1)) and a shorter R-R interval (678 +/- 93.6 ms) than in 27 controls (heart rate 73.6 +/- 7.7min(-1), R-R 822.7 +/- 86.4 ms) (5 men, 22 women) (p<0.001). The VCG measured spatial QRS-STT angle was more opened (70.3 +/- 24.5 degrees) than in the control group (49.5 +/- 19.5 degrees) (p<0.05). The maximum (extremum) in depolarization (DIAM max 30, 40) and repolarization (RIAM max 35) of body surface isoarea and isointegral (RIIM max) maps was less positive (p<0.001) and the minimum (DIAM min 40) was less negative than in the controls (p<0.05) even in the period free of a panic attack. Our results showed the changes in the heart electric field parameters occurred in PD patients when compared to the control group.     

The efficacy of the LinoxSmart DX ICD lead from a single center experience

PurposeThe Biotronik Linox^Smart DX implanted cardioverter defibrillator (ICD) lead is a novel VDD lead with the advantage of integrated atrial sensing dipole combined with a special augmentation and filtering mechanisms. We sought to determine the efficacy of the Biotronik Linox^Smart DX ICD lead.MethodsNon-randomized consecutive patients implanted with Biotronik Linox^Smart DX lead at Sheba Medical Center were included in this study. Electrical parameters and arrhythmic events were recorded during follow up of one year.ResultsSeventy-three patients (69 males (94.5%), mean age 61 ± 12 years) were included. All patients were successfully implanted with a Biotronic VR-T DX device and Linox^Smart DX ICD lead (DX-17 in 37% and DX-15 in 63% patients). Mean P wave amplitude at time of implantation was 3.66 ± 2.9 mV and improved significantly throughout the follow-up (5.29 ± 4.39 mV, p = 0.009). Appropriate atrial sensing (defined as P wave amplitude of ≥0.8 mV) rate of 100% at implantation significantly decreased to 89% (p = 0.015) at 12 months. Three out of 67 (4.5%) patients without a known history of atrial fibrillation had documented new onset paroxysmal atrial fibrillation. Appropriate shocks occurred in 4 (5.5%) patients. One patient with atrial sensing less than 0.4 mV had inappropriate shock.ConclusionsAmong patients implanted with the Biotronik Linox^Smart DX ICD lead in our single center, appropriate atrial sensing rate decreased over 12 months. Larger studies are needed to evaluate the reliability of long term appropriate atrial sensing.     

Chronic nicotine in hearts with healed ventricular myocardial infarction promotes atrial flutter that resembles typical human atrial flutter

The potential of chronic nicotine exposure for atrial fibrillation (AF) and atrial flutter (AFL) in hearts with and without chronic myocardial infarction (MI) remains poorly explored. MI was created in dogs by permanent occlusion of the left anterior descending coronary artery, and dogs were administered nicotine (5 mg.kg(-1).day(-1) sc) for 1 mo using osmotic minipumps. High-resolution epicardial (1,792 bipolar electrodes) and endocardial Halo catheters were used to map activation during induced atrial rhythms. Nicotine promoted inducible sustained AFL at a mean cycle length of 134 +/- 10 ms in all MI dogs (n = 6) requiring pacing and electrical shocks for termination. No AFL could be induced in MI dogs (n = 6), control (non-MI) dogs (n = 3) not exposed to nicotine, and dogs with no MI and exposed to nicotine (n = 3). Activation maps during AFL showed a single reentrant wavefront in the right atrium that rotated either clockwise (60%) or counterclockwise (40%) around the crista terminalis and through the isthmus. Ablation of the isthmus prevented the induction of AFL. Nicotine caused a significant (P < 0.01) but highly heterogeneous increase in atrial interstitial fibrosis (2- to 10-fold increase in left and right atria, respectively) in the MI group but only a 2-fold increase in the right atrium in the non-MI group. Nicotine also flattened (P < 0.05) the slope of the epicardial monophasic action potential duration (electrical restitution) curve of both atria in the MI but not in non-MI dogs. Two-dimensional simulation in an excitable matrix containing an isthmus and nicotine's restitutional and reduced gap junctional coupling (fibrosis) parameters replicated the experiments. Chronic nicotine in hearts with MI promotes AFL that closely resembles typical human AFL. Increased atrial interstitial fibrosis and flattened electrical restitution are important substrates for the AFL.