Transmural mechanics at left ventricular epicardial pacing site

Left ventricular (LV) epicardial pacing acutely reduces wall thickening at the pacing site. Because LV epicardial pacing also reduces transverse shear deformation, which is related to myocardial sheet shear, we hypothesized that impaired end-systolic wall thickening at the pacing site is due to reduction in myocardial sheet shear deformation, resulting in a reduced contribution of sheet shear to wall thickening. We also hypothesized that epicardial pacing would reverse the transmural mechanical activation sequence and thereby mitigate normal transmural deformation. To test these hypotheses, we investigated the effects of LV epicardial pacing on transmural fiber-sheet mechanics by determining three-dimensional finite deformation during normal atrioventricular conduction and LV epicardial pacing in the anterior wall of normal dog hearts in vivo. Our measurements indicate that impaired end-systolic wall thickening at the pacing site was not due to selective reduction of sheet shear, but rather resulted from overall depression of fiber-sheet deformation, and relative contributions of sheet strains to wall thickening were maintained. These findings suggest lack of effective end-systolic myocardial deformation at the pacing site, most likely because the pacing site initiates contraction significantly earlier than the rest of the ventricle. Epicardial pacing also induced reversal of the transmural mechanical activation sequence, which depressed sheet extension and wall thickening early in the cardiac cycle, whereas transverse shear and sheet shear deformation were not affected. These findings suggest that normal sheet extension and wall thickening immediately after activation may require normal transmural activation sequence, whereas sheet shear deformation may be determined by local anatomy.     

Ventricular Pacing on the Prognosis of Patients with Pacemaker Implantation

Excessive right ventricular apex pacing has significant adverse effects on the cardiac function and hence, it is necessary to clinically optimize pacing parameters and advocate suitable physiological pacing to safeguard the cardiac function after pacemaker implant. Minimizing ventricular pacing is an atrioventricular node priority function, to encourage ventricular self conduction and to reduce unnecessary right ventricular pacing. Minimized ventricular pacing reduces ventricular pacing by encouraging self atrioventricular conduction function and extending the AV interval. This study is a prospective cohort study to evaluate the changes of cardiac function in patients and serum amino-terminal natriuretic peptide (NT-proBNP) before and after pacing, and the risk of atrial fibrillation with different CUM% VP. The study has shown that the cardiac function will deteriorate with an increase in pacing rate.     

Ventricular pacing – Electromechanical consequences and valvular function

Although great strides have been made in the areas of ventricular pacing, it is still appreciated that dyssynchrony can be malignant, and that appropriately placed pacing leads may ameliorate mechanical dyssynchrony. However, the unknowns at present include:1. The mechanisms by which ventricular pacing itself can induce dyssynchrony;2. Whether or not various pacing locations can decrease the deleterious effects caused by ventricular pacing;3. The impact of novel methods of pacing, such as atrioventricular septal, lead-less, and far-field surface stimulation;4. The utility of ECG and echocardiography in predicting response to therapy and/or development of dyssynchrony in the setting of cardiac resynchronization therapy (CRT) lead placement;5. The impact of ventricular pacing-induced dyssynchrony on valvular function, and how lead position correlates to potential improvement.This review examines the existing literature to put these issues into context, to provide a basis for understanding how electrical, mechanical, and functional aspects of the heart can be distorted with ventricular pacing. We highlight the central role of the mitral valve and its function as it relates to pacing strategies, especially in the setting of CRT. We also provide future directions for improved pacing modalities via alternative pacing sites and speculate over mechanisms on how lead position may affect the critical function of the mitral valve and thus overall efficacy of CRT.     

ICC pacing mechanisms in intact mouse intestine differ from those in cultured or dissected intestine

Pacing of mouse intestine is driven by spontaneous activity of a network of interstitial cells of Cajal in the myenteric plexus (ICC-MP). So far, highly dissected circular muscle (CM) strips from control and mutant mice lacking ICC-MP and isolated, cultured ICC from newborn control mice were used to analyze its properties. Using intact circular and longitudinal segments of intestine, we recently reported that there were both significant similarities and differences between pacing studied in segments and from isolated, dissected tissues. Here, we report additional similarities and differences in our model from those in highly reduced systems. Similar to cultured or dissected intestine, blockade of sarcoplasmic-endoplasmic reticulum Ca(2+) pumps with thapsigargin or cyclopiazonic acid reduced pacing frequency, but thapsigargin was less effective than in isolated, cultured ICC. Moreover, inhibition of inositol 1,4,5-trisphosphate (IP(3)) receptors with xestospongin C, a putative inhibitor of IP(3) receptors, failed to affect pacing but successfully blocked increased pacing frequency by phorbol ester. 2-Aminoethoxy-diphenylborate, a putative blocker of IP(3)-mediated calcium release, caused a significant decrease in the amplitude and frequency of contractions. The mitochondrial uncoupler carbonyl cyanide p-trifluormethoxyphenylhydrazone blocked pacing and KCl-induced contractions at a concentration of 1 microM. The cyclic nucleotide agonists sodium nitroprusside (SNP), forskolin, and 8-bromo-cGMP inhibited pacing in CM. In longitudinal muscle (LM), SNP and forskolin had little effect on pacing. Furthermore, dibutyryl-cAMP did not affect pacing in CM or LM. These results suggest that pacing in intact intestine is under partly similar regulatory control as in more reduced systems. However, pacing in intact intestine is not affected by xestospongin C, which abolishes pacing in isolated, cultured ICC and exhibits attenuated responses to thapsigargin. Also, major differences between LM and CM suggest a separate pacemaker may drive LM.     

Endocardial transvenous pacing in patients with surgically palliated univentricular hearts: A review on different techniques,problems and management

Fontan surgery and its modifications have improved survival in various forms of univentricular hearts. A regular atrial rhythm with atrioventricular synchrony is one of the most important prerequisite for the long-term effective functioning of this preload dependent circulation. A significant proportion of these survivors need various forms of pacing for bradyarrhythmias, often due to sinus nodal dysfunction and sometimes due to atrioventricular nodal block. The diversion of the venous flows away from the cardiac chambers following this surgery takes away the simpler endocardial pacing options through the superior vena cava. The added risks of thromboembolism associated with endocardial leads in systemic ventricles have made epicardial pacing as the procedure of choice. However challenges in epicardial pacing include surgical adhesions, increased pacing thresholds leading to early battery depletion and frequent lead fractures. When epicardial pacing fails, endocardial lead placement is equally challenging due to lack of access to the cardiac chambers in Fontan circulation. This review discusses the univentricular heart morphologies that may warrant pacing, issues about epicardial pacing, different techniques for endocardial pacing in patients with disconnected superior vena cava, pacing in different modifications of Fontan surgeries, issues of systemic thromboembolism with endocardial leads, atrioventricular valve regurgitation attributed to pacing leads and device infections. In a vast majority of patients following Glenn shunt and Senning surgery, an epicardial pacing and lead replacement is always feasible though technically very difficult. This article highlights the different options of transatrial and transventricular endocardial pacing.     

Novel Technique of Dual Chamber Pacing Through Minithoracotomy and Transatrial Endocardial Active Fixation Lead Insertion for Epicardial Pacing Lead Malfunction

Epicardial pacing lead fixation is employed in patients with cavopulmonary anastamosis (Glenn shunts) when they need permanent pacing. Epicardial pacing in these patients may malfunction due to high pacing thresholds or diaphragmatic pacing. A novel technique of transatrial insertion of two endocardial screw-in pacing leads through right anterolateral minithoracotomy could achieve synchronous atrioventricular pacing in a patient with Ebsteins anomaly with symptomatic sinoatrial and atrioventricular nodal disease.     

Motion energy as a control variable for adapting stimulation frequency

An activity sensing rate-responsive pacing system is presented which adaptively controls heart rate to adjust cardiac output in response to increased metabolic demand, and more optimally restore homeostasis of the intact cardiovascular system. The current use of ventricular demand and DDD universal pacing systems, although rate and multi-parameter and multi-function programmable, are fixed at these programmed settings. These devices are adequate for patients at rest or during moderate exertion, but are suboptimal for physically active patients whose physiology requires increased oxygen supply to meet an increased cardiac demand. In the past, these patients may have experienced fatigue or dyspnea out of proportion to their cardiovascular disease. The Ergos rate-adaptive single- and dual-chamber pacing system is a second generation pulse generator which is rate responsive to a patient's increased physiologic demand by sensing a motion signal which reflects increased work load and the need for a compensating increase in heart rate. Ergos offers increased assistance to patients with sinus bradycardia who may require the rate-responsiveness with the additional advantage of AV synchrony. Clinical results show the effectiveness of the presented sensor control by motion energy for rate adaptive pacing therapy.     

Transvenous implantation of a ventricular pacing lead in a patient with an artificial tricuspid valve prosthesis

The preference for treatment of symptomatic bradycardia is transvenous right ventricular pacing combined with atrial synchronisation if applicable. In the case of congenital anomalies where no conduit is present between the peripheral veins and the right ventricle, it is not possible to place the ventricular pacing lead in the right ventricle. Also the presence of an artificial valve in the tricuspid position excludes placement of an endocardial right ventricular pacing lead. Since the introduction of biventricular pacing, new guiding catheters and leads used as a transvenous route for left ventricular pacing are available. We report implantation of a ventricular pacing lead in the great cardiac vein for permanent ventricular pacing in a patient with a tricuspid valve prosthesis.     

Selective His-bundle pacing in an adult with atrioventricular canal defect via retrograde His localization

Adult congenital heart disease patients may undergo numerous fluoroscopically guided procedures including pacemaker implantation during their lifetime. One alternative to traditional pacemaker setup which may improve long-term pacing outcomes is His bundle pacing. Given the altered His-bundle location, and given increased radiation exposure over a lifetime, we used 3-dimensional mapping to locate the His and to minimize fluoroscopy for placement of a His-bundle pacemaker system in a 31-year old patient with atrioventricular canal defect and complete heart block with 100% RV pacing and epicardial lead fracture.MethodsAn Octapolar Livewire catheter (Abbott, Minneapolis, USA) was used for mapping and location of the His bundle from a right femoral venous access on the EnSite Precision system 3-dimensional mapping system (Abbott Medical, Abbott Park, IL). The same map was used to guide 3830 lead placement into the posterior-inferior His-bundle position.ResultsSuccessful placement of a His-bundle pacing system with thresholds of 1Volt@0.4ms for both the atrial and ventricular leads with selective His-bundle pacing noted. Ten-month follow-up demonstrated His-bundle capture at 0.75V@0.4ms with stable impedance, sensing and with 100% right ventricular pacing a projected longevity of 12 years total.ConclusionsSuccessful placement of selective His-bundle pacing can be achieved in an adult patient with atrioventricular canal defect using 3-dimensional mapping.     

Adverse effects of atrioventricular synchronous right ventricular pacing on left ventricular sympathetic activity, efficiency, and hemodynamic status

Right ventricular (RV) pacing is now recognized to play a role in the development of heart failure in patients with and without underlying left ventricular (LV) dysfunction. We used the cardiac norepinephrine spillover method to test the hypothesis that RV pacing is associated with cardiac sympathetic activation. We studied 8 patients with normal LV function using temporary right atrial and ventricular pacing wires. All measurements were carried out during a fixed atrial pacing rate. The radiotracer norepinephrine spillover technique was employed to measure total body and cardiac sympathetic activity while changes in LV performance were evaluated with a high-fidelity manometer catheter. Atrioventricular synchronous RV pacing, compared with atrial pacing alone, was associated with a 65% increase in cardiac norepinephrine spillover, an increase in LV end-diastolic pressure, and a reduction in myocardial efficiency. These responses may play a role in the development of heart failure and poor outcomes that are associated with chronic RV pacing.     

A Low-Cost Simulation Model for R-Wave Synchronized Atrial Pacing in Pediatric Patients with Postoperative Junctional Ectopic Tachycardia

Background

Postoperative junctional ectopic tachycardia (JET) occurs frequently after pediatric cardiac surgery. R-wave synchronized atrial (AVT) pacing is used to re-establish atrioventricular synchrony. AVT pacing is complex, with technical pitfalls. We sought to establish and to test a low-cost simulation model suitable for training and analysis in AVT pacing.

Methods

A simulation model was developed based on a JET simulator, a simulation doll, a cardiac monitor, and a pacemaker. A computer program simulated electrocardiograms. Ten experienced pediatric cardiologists tested the model. Their performance was analyzed using a testing protocol with 10 working steps.

Results

Four testers found the simulation model realistic; 6 found it very realistic. Nine claimed that the trial had improved their skills. All testers considered the model useful in teaching AVT pacing. The simulation test identified 5 working steps in which major mistakes in performance test may impede safe and effective AVT pacing and thus permitted specific training. The components of the model (exclusive monitor and pacemaker) cost less than $50. Assembly and training-session expenses were trivial.

Conclusions

A realistic, low-cost simulation model of AVT pacing is described. The model is suitable for teaching and analyzing AVT pacing technique.     

Permanent parahisian pacing

Right Ventricular Apical permanent pacing could have negative hemodynamic effects. A physiologic pacing modality should preserve a correct atrio-ventricular and interventricular synchronization. This can be obtained through biventricular pacing, left ventricular pacing, or from alternative right ventricular pacing sites. Direct His Bundle Pacing (DHBP) was documented as reliable and effective for preventing the desynchronization and negative effects of right ventricular apical pacing. It is, however, a complex method that requires longer average implant times, cannot be carried out on all patients and presents high pacing thresholds. On the contrary, the parahisian pacing, with simpler feasibility and reliability criteria, seems to guarantee an early invasion of the His-Purkinje conduction system, with a physiological ventricular activation, very similar to the one that can be obtained with direct His bundle pacing. We present our experience on 68 patients who underwent a permanent right ventricular pacing in hisian/parahisian region, for advanced AV block and narrow QRS. In the first 17 patients we performed a double-blind randomized controlled study, with two 6-months cross-over periods in parahisian and apical pacing, documenting a significant improvement of NYHA class, exercise tolerance, quality of life score, mitral and tricuspidal regurgitation degree, and interventricular mechanical delay. In the subsequent 51 patients, in a mean follow of 21 months/patient, the pacing threshold remained stable (0.7+/-0.5 V implant; 0.9+/-0.7 V follow-up; p=0.08). The ejection fraction maintained medium-long term stable values, confirming the fact that the parahisian pacing can prevent deterioration of the left ventricular function. Parahisian pacing, therefore, has proven to be a reliable method, easy to apply and effective in preventing the negative effects induced by non-physiological right ventricular apical pacing.     

Left ventricular endocardial or triventricular pacing to optimize cardiac resynchronization therapy in a chronic canine model of ischemic heart failure

Cardiac resynchronization therapy (CRT) is a proven treatment for heart failure but ~30% of patients appear to not benefit from the therapy. Left ventricular (LV) endocardial and multisite epicardial [triventricular (TriV)] pacing have been proposed as alternatives to traditional LV transvenous epicardial pacing, but no study has directly compared the hemodynamic effects of these approaches. Left bundle branch block ablation and repeated microembolizations were performed in dogs to induce electrical dysynchrony and to reduce LV ejection fraction to <35%. LVdP/dt(max) and other hemodynamic indexes were measured with a conductance catheter during LV epicardial, LV endocardial, biventricular (BiV) epicardial, BiV endocardial, and TriV pacing performed at three atrioventricular delays. LV endocardial pacing was obtained with a clinically available pacing system. The optimal site was defined as the site that increased dP/dt(max) by the largest percentage. Implantation of the endocardial lead was feasible in all canines (n = 8) without increased mitral regurgitation seen with transesophageal echocardiography and with full access to the different LV endocardial pacing sites. BiV endocardial pacing increased dP/dt(max) more than BiV epicardial and TriV pacing on average (P < 0.01) and at the optimal site (P < 0.01). There were no significant differences between BiV epicardial and TriV pacing. BiV endocardial pacing was superior to BiV epicardial and to TriV pacing in terms of acute hemodynamic response. Further investigation is needed to confirm the chronic benefit of this approach in humans.     

Left ventricular pacing in patients with congestive heart failure

Cardiac resynchronisation therapy (CRT) using biventricular (BIV) pacing has proved its effectiveness to correct myocardial asynchrony and improve clinical status of patients with severe congestive heart failure (CHF) and widened QRS. Despite a different effect on left ventricular electrical dispersion, left univentricular (LV) pacing is able to achieve the same mechanical synchronisation as BIV pacing in experimental studies and in humans. This results in clinical benefits of LV pacing at mid-term follow-up, with significant improvement in functional class, quality of life and exercise tolerance at the same extent as those observed with BIV stimulation in non randomised studies. Furthermore these benefits are obtained at lesser costs and with conventional dual-chamber devices. However, LV pacing has to be compared to BIV pacing in randomised trials before being definitely considered as a cost-effective alternative to BIV pacing.     

心室不同部位起搏对正常犬和扩张型心肌病心力衰竭犬模型在体心肌跨室壁复极离散的影响

实验以正常犬和扩张型心肌病心力衰竭犬(dilated cardiomyopathy congestive heart failure,DCM-CHF)模型为对象、以心肌跨室壁复极离散的相关参数为指标,研究左心室心外膜起搏、双心室起搏(模拟临床上心室再同步治疗的方法)后的心肌电生理特性变化。实验以快速右心室起搏的方法制备DCM-CHF犬模型;正常犬和DCM-CHF犬均经射频消融希氏束制备三度房室传导阻滞模型;采用同步记录犬体表心电图和内膜下、中层、外膜下三层心肌单相动作电位(monophasic action potentials,MAP)的方法,测定不同部位起搏时的QT间期、Tpeak-Tend(Tp-Te)间期和三层心肌的单相动作电位时程(MAP duration,MAPD)、跨室壁复极离散度(transmural dispersion of repolaization,TDR)。结果显示:在正常犬,左室心外膜与双心室起搏后三层心肌的MAPD均延长,同时TDR增大(左室心外膜起搏47.16 ms、双心室起搏37.54 ms、右室心内膜起搏26.75 ms,P<0.001),体表心电图Tp-Te间期的变化与之平行;在DCM-CHF犬较正常犬已表现出中层心肌MAPD延长(276.30 ms vs 257.35 ms,P<0.0001)和TDR(33.8 ms vs 27.58 ms,P=0.002)增大的基础上,左室心外膜参与起搏后仍进一步使三层心肌的MAPD延长和TDR增大。研究结果提示,左室心外膜起搏和双心室起搏后使内膜下、中层     

Decreased connexin43 expression in the mouse heart potentiates pacing-induced remodeling of repolarizing currents

Gap junction redistribution and reduced expression, a phenomenon termed gap junction remodeling (GJR), is often seen in diseased hearts and may predispose toward arrhythmias. We have recently shown that short-term pacing in the mouse is associated with changes in connexin43 (Cx43) expression and localization but not with increased inducibility into sustained arrhythmias. We hypothesized that short-term pacing, if imposed on murine hearts with decreased Cx43 abundance, could serve as a model for evaluating the electrophysiological effects of GJR. We paced wild-type (normal Cx43 abundance) and heterozygous Cx43 knockout (Cx43+/-; 66% mean reduction in Cx43) mice for 6 h at 10-15% above their average sinus rate. We investigated the electrophysiological effects of pacing on the whole animal using programmed electrical stimulation and in isolated ventricular myocytes with patch-clamp studies. Cx43+/- myocytes had significantly shorter action potential durations (APD) and increased steady-state (Iss) and inward rectifier (I(K1)) potassium currents compared with those of wild-type littermate cells. In Cx43+/- hearts, pacing resulted in a significant prolongation of ventricular effective refractory period and APD and significant diminution of Iss compared with unpaced Cx43+/- hearts. However, these changes were not seen in paced wild-type mice. These data suggest that Cx43 abundance plays a critical role in regulating currents involved in myocardial repolarization and their response to pacing. Our study may aid in understanding how dyssynchronous activation of diseased, Cx43-deficient myocardial tissue can lead to electrophysiological changes, which may contribute to the worsened prognosis often associated with pacing in the failing heart.     

The downside of right ventricular apical pacing

The right ventricular (RV) apex has been the standard pacing site since the development of implantable pacemaker technology. Although RV pacing was initially only utilized for the treatment of severe bradyarrhythmias usually due to complete heart block, today the indications for and implantation of RV pacing devices is dramatically larger. Recently, the adverse effects of chronic RV apical pacing have been described including an increased risk of heart failure and death. This review details the detrimental effects of RV apical pacing and their shared hemodynamic pathophysiology. In particular, the role of RV apical pacing induced ventricular dyssynchrony is highlighted with a specific focus on differential outcome based upon QRS morphology at implant.     

Coronary flow reserve in stress-echo lab. From pathophysiologic toy to diagnostic tool

Background

High-rate pacing is a valid stress test to be used in conjunction with echocardiography; it is independent of physical exercise and does not require drug administration. There are two main applications of pacing stress in the echo lab: the noninvasive detection of coronary artery disease through induction of a regional transient dysfunction; and the assessment of contractile reserve through peak systolic pressure/end-systolic volume relationship at increasing heart rates to assess global left ventricular contractility.

Methods

The pathophysiologic rationale of pacing stress for noninvasive detection of coronary artery disease is obvious, with the stress determined by a controlled increase in heart rate, which is a major determinant of myocardial oxygen demand, and thereby tachycardia may exceed a fixed coronary flow reserve in the presence of hemodynamically significant coronary artery disease. The use of pacing stress echo to assess left ventricular contractile reserve is less established, but promising. Positive inotropic interventions are mirrored by smaller end-systolic volumes and higher end-systolic pressures. An increased heart rate progressively increases the force of ventricular contraction (Bowditch treppe or staircase phenomenon). To build the force-frequency relationship, the force is determined at different heart rate steps as the ratio of the systolic pressure (cuff sphygmomanometer)/end-systolic volume index (biplane Simpson rule). The heart rate is determined from ECG.

Conclusion

Two-dimensional echocardiography during pacing is a useful tool in the detection of coronary artery disease. Because of its safety and ease of repeatability noninvasive pacing stress echo can be the first-line stress test in patients with permanent pacemaker. The force-frequency can be defined as up- sloping (normal) when the peak stress pacing systolic pressure/end-systolic volume index is higher than baseline and intermediate stress values, biphasic with an initial up- sloping followed by a later down-sloping trend, or flat or negative when peak stress pacing systolic pressure/end-systolic volume index is equal or lower than baseline stress values. This approach is certainly highly feasible and allows a conceptually immaculate definition of contractility with prognostic usefulness, but its therapeutic implications remains to be established. Bowditch treppe, assessed with pacing stress, can be used to assess the optimal stimulation frequency and to optimise the patient's chronotropic response in programming rate-adaptive pacemakers.     

Sodium-, chloride-, and mibefradil-sensitive calcium channels in intestinal pacing in wild-type and W/WV mice

Pacing of intestinal smooth muscle is driven by a network of cells found in the myenteric plexus called the interstitial cells of Cajal (ICC-MP), which produce a rhythmic pacemaker current. Using intact segments of circular (CM) and longitudinal (LM) muscle from wild-type and W/WV mice, we found that sodium-, chloride-, and mibefradil-sensitive ion channel currents are required for normal pacing to occur. Application of 30 micromol/L and 300 micromol/L lidocaine, 1 mmol/L 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), 50 nmol/L and 500 nmol/L mibefradil, or low sodium Krebs significantly reduced pacing frequency in LM and CM. However, simultaneously applying DIDS and lidocaine or low sodium Krebs solution did not completely block pacing nor did it have an additive effect. Lidocaine and low sodium Krebs solution also abolished the gradient of pacing frequencies (higher proximally) found throughout the intestine, resulting in a uniform contraction frequency of 30-40/min. In W/WV mice, which lack ICC-MP, application of DIDS and lidocaine had no effect on the robust pacing in LM segments. In conclusion we found that sodium-, chloride-, and mibefradil-sensitive channel activities were required for normal pacing and to maintain the pacing gradient found throughout the intestines in wild-type but not W/WV mice.     

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation

Chronic rapid atrial pacing (RAP) leads to changes that perpetuate atrial fibrillation (AF). Chronic atrial dilatation due to mitral regurgitation (MR) also increases AF inducibility, but it is not clear whether the underlying mechanism is similar. Therefore, we have investigated atrial electrophysiology in a canine MR model (mitral valve avulsion, 1 mo) using high-resolution optical mapping and compared it with control dogs and with the canine RAP model (6-8 wk of atrial pacing at 600 beats/min, atrioventricular block, and ventricular pacing at 100 beats/min). At followup, optical action potentials were recorded using a 16 x 16 photodiode array from 2 x 2-cm left atrial (LA) and right atrial (RA) areas in perfused preparations, with pacing electrodes around the field of view to study direction dependency of conduction. Action potential duration at 80% repolarization (APD(80)) was not different between control and MR but was reduced in RAP atria. Conduction velocities during normal pacing were not different between groups. However, the MR LA showed increased conduction heterogeneity during pacing at short cycle lengths and during premature extrastimuli, which frequently caused pronounced regional conduction slowing. Conduction in the MR LA during extrastimulation also displayed a marked dependence on propagation direction. These phenomena were not observed in the MR RA and in control and RAP atria. Thus both models form distinctly different AF substrates; in RAP dogs, the decrease in APD(80) may stabilize reentry. In MR dogs, regional LA conduction slowing and increased directional dependency, allowing unidirectional conduction block and preferential paths of conduction, may account for increased AF inducibility.