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PubMed1996

A new method for analysis of atrial activation during chronic atrial fibrillation in man.

To further clarify the mechanisms maintaining chronic atrial fibrillation (CAF), a method identifying preferable activation patterns of the atria during fibrillation, by time averaging of multiple discrete excitation vectors, was developed. Repeated recordings, each of 56 atrial bipolar electrograms simultaneously acquired during 8 s, were made at multiple sites in the right atrial free wall and the left atrial appendage in 16 patients with CAF using a 2.17 x 3.54 cm electrode array. The local activation times (LAT's) in each recording were estimated as the median activation time at the respective measurement point. By calculating the time difference between the LAT's at adjacent measurement points in two spatial dimensions, a direction vector was created for each activation wave passing each set of measurement points, a total of 42 sets. By time averaging of the individual direction vectors (typically n = 55) at each set of measurement points, preferable activation patterns were determined. Three types of activation patterns were found: 1) inconsistent activation (n = 5), 2) consistent activation with preferential propagation directions (n = 7) and 3) consistent activation with impulses originating from a localizable site within the recording area (n = 4). All activation patterns were reproducible and the two latter patterns were proven significant using statistical tests. We conclude that this new method is useful in further clarification of the mechanisms involved in the maintenance of atrial fibrillation.

Aged↗
PubMed2003

Expression of angiotensin II receptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease.

UNLABELLED: TIVES: We postulated a change of angiotensin II receptor subtype expression in patients with lone atrial fibrillation (AF) and AF with underlying mitral valve disease (MVD) both compared with sinus rhythm (SR). BACKGROUND: Atrial fibrillation is a progressive disease associated with electrical and structural remodeling. Angiotensin II (ANGII) is involved in the process of myocardial remodeling. Actions of ANGII are mediated by ANGII receptor subtypes 1 and 2 (AT(1) and AT(2)). METHODS: Left atrial (LA) and right atrial (RA) tissue samples were obtained from patients with AF or SR with or without underlying MVD. The AT(1) and AT(2) protein levels were measured by quantitative Western blotting techniques. RESULTS: The AT(1) protein level in the LA was significantly increased in patients with AF (all forms) compared with SR (p < 0.05), whereas AT(2) expression was not significantly altered. Comparison of the subgroups revealed a similar increase of AT(1) in both paroxysmal AF and chronic AF with or without MVD. Additionally, investigations of ANGII receptor subtypes in the RA did not exhibit any significant changes either in AT(1) or in AT(2) in patients with AF versus SR. Underlying MVD did not significantly affect AT(2) receptor subtype expression in LA. CONCLUSIONS: Atrial fibrillation is associated with an up-regulation of AT(1) in LA, but not in RA, and did not appear to influence the AT(2) expression in the atrium. Because we found an enhanced expression of AT(1)in the LA, we conclude that AT(1) might be involved in the pathogenesis of AF in the LA.

Adult↗
PubMed2001

Electrical conduits within the inferior atrial region exhibit preferential roles in interatrial activation.

Differences between conduction properties of interatrial conduits and their roles in initiation and maintenance of supraventricular arrhythmias remain unclear. Our objective was to determine details of interatrial activation in inferior atrial region and to correlate intra-atrial and interatrial activation patterns with the site of origin of atrial ectopic activation. In 9 dogs, basket-catheters carrying 64 electrodes were deployed into both the right atrium (RA) and left atrium (LA). A 10-electrode catheter was inserted into the coronary sinus (CS). Activation patterns of the RA, LA, and CS were compared during pacing in the CS, in RA inferoparaseptum posterior to Eustachian ridge-tendon of Todaro (TT), and in inferior RA near the CS ostium (anterior to TT). We found that pacing in proximal and middle CS resulted in a RA breakthrough invariably at the CS ostium, consistent with conduction through a CS-RA connection. Meanwhile, LA breakthrough emerged in inferoposterior region (inferior to mitral annulus), suggesting conduction through a CS-LA connection. While pacing in distal CS, LA breakthrough shifted to middle posterolateral wall. Whereas, the RA was activated by the LA directly through the septum. During pacing in RA inferoparaseptum posterior to TT, the LA was activated directly through the septum at 22 +/- 4 ms. Whereas, during pacing anterior to TT, the LA was activated through both the CS and the septum while earliest activation was delayed by 38 +/- 5 ms. In conclusion, both the interatrial septum and CS musculature form electrical conduits in inferior atrial region in canine. Differences in activation properties between the conduits in inferior interatrial region result in selective interatrial activation patterns during ectopic activation.

Animals↗
PubMed2001

Reduction in atrial defibrillation threshold by a single linear ablation lesion.

INTRODUCTION: This study investigated a hybrid approach to reduce the atrial defibrillation threshold (ADFT) by determining the effect of a single linear radiofrequency ablation (RFA) lesion on both the ADFT and activation patterns during atrial fibrillation (AF). METHODS AND RESULTS: In 18 open chest sheep (45 to 57 kg), coil defibrillation electrodes were placed in a superior vena cava/right ventricular configuration. AF was induced by burst pacing and maintained with acetyl beta-methylcholine (2 to 42 microL/min). ADFTs were obtained before and after a linear RFA lesion was created in the left atrium (LAL; n = 6), right atrium (RAL; n = 6), or neither atrium as a control (n = 6). In animals receiving an LAL, a 504-unipolar-electrode plaque was sutured to the LA. For animals receiving an RAL, two 504-electrode plaques were placed, one each on the LA and RA. From each plaque, activations were recorded before and after ADFT shocks, and organizational characteristics of activations were analyzed using algorithms that track individual wavefronts. In sham-treated controls, the ADFT did not change. In contrast, LAL reduced ADFT energy 29%, from 4.5 +/- 2.3 J to 3.2 +/- 2.0 J (P < 0.05). RAL reduced ADFT energy 25%, from 2.0 +/- 0.9 J to 1.5 +/- 0.7 J (P < 0.05). AF activation was substantially more organized after RFA than before RFA for both the RAL- and LAL-treated animals. CONCLUSION: A single RFA lesion in either the RA or LA reduces the ADFT in this sheep model. This decrease is associated with an increase in fibrillatory organization.

Animals↗
PubMed2000

Differences in organization between acute and chronic atrial fibrillation in dogs.

OBJECTIVES: The purpose of this study was to determine differences in acute and chronic atrial fibrillation (AF) "organization" in canine models. BACKGROUND: Electrophysiologic changes occur during atrial remodeling, but little is known about how remodeling affects AF organization. We hypothesized that atrial remodeling induced by long-term rapid atrial rates heterogeneously decreases AF organization. METHODS: In seven dogs, acute AF was induced by atrial burst pacing, and in eight dogs chronic AF was created by six weeks of continuous rapid atrial pacing. Atrial fibrillation was epicardially mapped from the right atria (RA) and left atria (LA). Atrial cycle length (CL), spatial organization and activation maps were compared. Spatial organization was quantified by an objective signal processing measure between multiple electrograms. RESULTS In acute AF, mean CL was slightly shorter in the LA (124 +/- 16 ms) than it was in the RA (131 +/- 14 ms) (p < 0.0001). In chronic AF, LA CL (96 +/- 14 ms) averaged 24 ms shorter than RA CL (121 +/- 18 ms) (p < 0.0001). Right atria and LA in acute AF had similar levels of organization. In chronic AF, the LA became approximately 25% more disorganized (p < 0.0001) while the RA did not change. In acute AF, a single broad wave front originating from the posterior and medial atrium dominated LA activation. In chronic AF, LA activation was more complex, sustaining multiple reentrant wavelets in the free wall and lateral appendage. CONCLUSIONS: Acute and chronic AF exhibit heterogeneous differences in CL, organization and activation patterns. The LA in chronic AF is faster and more disorganized than it is in acute AF. Differences in the models may be due to heterogeneous electrophysiologic remodeling and anatomic constraints. The design of future AF therapies may benefit by addressing the patient specific degree of atrial remodeling.

Acute Disease↗
PubMed2001

Potential ionic mechanism for repolarization differences between canine right and left atrium.

Experimental and clinical evidence suggests a critical role for the left atrium (LA) in atrial fibrillation (AF). In animal models, repolarization is faster in the LA than in the right atrium (RA), leading to more stable reentry circuits with a shorter intrinsic period in the LA. The ionic mechanisms underlying LA-RA repolarization differences are unknown. Therefore, we evaluated ionic currents and action potentials (APs) with the whole-cell patch clamp in isolated canine atrial myocytes. The density of the rapid delayed rectifier current (I(Kr)) was greater in the LA (eg, 1.83+/-0.10 pA/pF at +20 mV) than in the RA (1.15+/-0.07 pA/pF, P<0.01; n=16 cells per group). The slow and ultrarapid delayed rectifier, the inward rectifier, L-type Ca(2+), and transient outward K(+) currents were all comparable in the LA and RA. There were no differences in kinetic or voltage-dependent properties of currents in LA versus RA. Western blots of ether-a-go-go-related gene (ERG) protein in three RA and corresponding LA regions showed significantly greater ERG expression in LA. AP duration (APD) was shorter in the LA versus RA in both isolated cells and multicellular preparations, and the effective refractory period (ERP) was shorter in the LA compared with the RA in vivo. Dofetilide had significantly larger APD- and ERP-increasing effects in the LA compared with RA, and LA-RA repolarization differences were eliminated by exposure to dofetilide. We conclude that LA myocytes have larger I(Kr) than do RA myocytes, contributing importantly to the shorter APD and ERP in LA. The larger LA I(Kr) may participate in the ability of the LA to act as a "driver region" for AF, with potentially important implications for understanding AF mechanisms and antiarrhythmic therapy.

Action Potentials↗
PubMed1991

A noninvasive method of estimating mean pulmonary artery pressure in the pneumatic total artificial heart.

Accurate hemodynamic monitoring is essential for the clinical management of the recipient of a total artificial heart (TAH). The high incidence of pulmonary congestive disorders in this population complicates this already formidable task. Lack of diagnostic pulmonary artery pressure (PAP) information is recognized as a fundamental source of these problems. Because conventional methods of obtaining hemodynamic information are difficult to implement in TAH recipients, improvement of TAH case management depends on the development of innovative monitoring strategies. Noninvasive monitoring techniques have been developed for three (right atrial pressure, left atrial pressure, and aortic pressure) of the four auxiliary circulatory pressures used to quantify hemodynamic performance. Development of the fourth, for PAP, was the subject of this work. We developed a noninvasive, in vitro method of estimating mean PAP in the Jarvik-7 TAH (Symbion, Inc, Salt Lake City, UT) recipient. This information was obtained by analyzing the relationship between the pneumatic right drive pressure (RDP) and PAP waveforms produced by a Jarvik-7 (70 ml) connected to a Donovan mock circulation and driven by a Utahdrive System IIIe Controller (Symbion, Inc, Salt Lake City, UT). Total artificial heart driver parameters (i.e., heart rate, percent systole, and vacuum) were manipulated to produce a range of ventricular filling volumes (FV), from 40 to 60 ml, for three distinct states of the pulmonary vasculature: hypotensive, normal, and hypertensive. A unique multiple-linear regression equation was derived for each FV from the RDP-PAP relationship exhibited under these conditions. Comparison of computed estimates of PAP with actual measurements showed overall average correlations of greater than 0.92, with a standard error of the estimate of less than 1.9 mm Hg. The mean difference between actual and computed PAP measurements was -0.03 +/- 2.0 Hg. Estimations were accurate within 8.5% of true PAP values. Additional experimentation revealed that while the RDP-PAP relationships are dependent on FV, they are independent of the manner in which FV was obtained. Estimates proved useful over the clinical operating range of the pneumatic heart driver, as well as over the normal physiologic range of PAP in the human. This method is readily applicable to a computer-based monitoring implementation, although its effectiveness needs to be demonstrated in vivo.

Aorta↗
PubMed2006

Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling.

Several animal models of atrial fibrillation (AF) have been developed that demonstrate either atrial structural remodeling or atrial electrical remodeling, but the characteristics and spatiotemporal organization of the AF between the models have not been compared. Thirty-nine dogs were divided into five groups: rapid atrial pacing (RAP), chronic mitral regurgitation (MR), congestive heart failure (CHF), methylcholine (Meth), and control. Right and left atria (RA and LA, respectively) were simultaneously mapped during episodes of AF in each animal using high-density (240 electrodes) epicardial arrays. Multiple 30-s AF epochs were recorded in each dog. Fast Fourier transform was calculated every 1 s over a sliding 2-s window, and dominant frequency (DF) was determined. Stable, discrete, high-frequency areas were seen in none of the RAP or control dogs, four of nine MR dogs, four of six CHF dogs, and seven of nine Meth dogs in either the RA or LA or both. Average DFs in the Meth model were significantly greater than in all other models in both LA and RA except LA DFs in the RAP model. The RAP model was the only one with a consistent LA-to-RA DF gradient (9.5 +/- 0.2 vs. 8.3 +/- 0.3 Hz, P < 0.00005). The Meth model had a higher spatial and temporal variance of DFs and lower measured organization levels compared with the other AF models, and it was the only model to show a linear relationship between the highest DF and dispersion (R(2) = 0.86). These data indicate that structural remodeling of atria (models known to have predominantly altered conduction) leads to an AF characterized by a stable high-frequency area, whereas electrical remodeling of atria (models known to have predominantly shortened refractoriness without significant conduction abnormalities) leads to an AF characterized by multiple high-frequency areas and multiple wavelets.

Animals↗
PubMed1999

Vagal nerve activity recording in the awake condition for the control of an artificial heart system.

To detect useful information for an artificial heart control system, we paid attention to the autonomic nervous system. For stable recording, we used vagal nerve activity in chronic animal experiments using healthy adult goats in an awake condition because this nerve was sufficiently bold and large enough. Vagal nerve discharges were successfully recorded from awake goats. They were synchronized with respiration and responded to the hemodynamic changes induced by drug administration, suggesting that they may provide useful information for an artificial heart control algorithm. For automatic control, some time delay plays a vitally important role. Thus, predictive control for an artificial heart system may be desirable. It may be embodied by the use of autonomic nerve information.

Action Potentials↗
PubMed1996

An 8 1/2-year clinical experience with surgery for atrial fibrillation.

OBJECTIVE: The authors analyzed the clinical results during the first 8 1/2 years' experience with the Maze procedure for the surgical treatment of atrial fibrillation. SUMMARY BACKGROUND DATA: Atrial fibrillation occurs in 0.4% to 2% of the general population and in approximately 10% of patients older than 60 years of age. It is associated with significant morbidity and mortality. The irregular heartbeat causes discomfort, the loss of synchronous atrioventricular contraction compromises hemodynamics and the stasis of blood flow increases the vulnerability to thromboembolism. METHODS: From September 25, 1987 to March 1, 1996, 178 patients underwent the Maze procedure. Thirty-two patients underwent the Maze-I procedure, 15 underwent the Maze-II procedure, and 118 underwent the Maze-III procedure. Patients were analyzed for recurrence of atrial flutter and atrial fibrillation between 3 months and 8 1/2 years after surgery (n = 164). Patients were analyzed for atrial transport function, sinus nodule function, and postoperative pacemaker requirements. RESULTS: Ninety-three percent of all patients were arrhythmia free without any antiarrhythmic medication. Of the remaining patients with arrhythmia recurrence, all were converted to sinus rhythm with medical therapy. All patients were documented to have atrial transport function by either direct visualization, transesophageal echocardiography, or atrioventricular versus ventricular pacing at the same rate. Ninety-eight percent had documented right atrial function, and 94% had left atrial function. Of the 107 patients in this series who were documented to have a normal sinus node preoperatively, only 1 patient required a permanent pacemaker. CONCLUSION: The Maze procedure is an effective treatment for medically refractory atrial fibrillation in properly selected patients.

Adult↗
PubMed2005

Targeted modification of atrial electrophysiology by homogeneous transmural atrial gene transfer.

BACKGROUND: Safe and effective myocardial gene transfer remains elusive. Heterogeneous ventricular gene delivery has been achieved in small mammals but generally with methods not readily transferable to the clinic. Atrium-specific gene transfer has not yet been reported. We hypothesized that homogeneous atrial gene transfer could be achieved by direct application of adenoviral vectors to the epicardial surface, use of poloxamer gel to increase virus contact time, and mild trypsinization to increase virus penetration. METHODS AND RESULTS: We "painted" recombinant adenovirus encoding the reporter gene Escherichia coli beta-galactosidase directly onto porcine atria. Investigational variables included poloxamer use, trypsin concentration, and safety. Using the painting method, we modified the atrial phenotype with an adenovirus expressing HERG-G628S, a long-QT-syndrome mutant. Our results showed that application of virus with poloxamer alone resulted in diffuse epicardial gene transfer with negligible penetration into the myocardium. Dilute trypsin concentrations allowed complete transmural gene transfer. After trypsin exposure, echocardiographic left atrial diameter did not change. Left atrial function decreased on postoperative day 3 but returned to baseline by day 7. Tissue tensile strength was affected only in the 1% trypsin group. HERG-G628S gene transfer prolonged atrial action potential duration and refractory period without affecting ventricular electrophysiology. CONCLUSIONS: We show complete transmural atrial gene transfer by this novel painting method. Adaptation of the method could allow application to other tissue targets. Use with functional proteins in the atria could cure or even prevent diseases such as atrial fibrillation or sinus node dysfunction.

Action Potentials↗
PubMed2001

Inhibition of the Na(+)/H(+) exchanger delays the development of rapid pacing-induced atrial contractile dysfunction.

BACKGROUND: Atrial mechanical stunning due to atrial fibrillation may persist after restoration of sinus rhythm. Although the mechanism of rapid rate-related contractile dysfunction remains unknown, ischemia, pH changes, and calcium overload have been postulated as potential mechanisms. We hypothesized that blockade of the Na(+)/H(+) exchanger (NHE) would alter atrial contractile dysfunction from rapid rates. METHODS AND RESULTS: Twenty-three anesthetized dogs were studied and subjected to 5 hours of rapid right atrial pacing. Ten received an inhibitor of the NHE, 10 received saline, and 3 received nifedipine. All animals underwent placement of 2 sonomicrometers on the left atrium, transesophageal echocardiography, and invasive hemodynamic monitoring. All measurements were made in sinus rhythm. Except for baseline and postdrug measurements, reduction in left atrial fractional shortening was significantly less at all time points in the NHEI group than in the control and nifedipine groups (P:=0.05). The percent change from baseline of left atrial function at all time intervals as assessed by left atrial appendage contraction velocity (LAACV) was significantly less in the NHEI group than in the control (P:=0.05) group. LAACV was significantly preserved at all time intervals (except 300 minutes) in the NHEI group compared with the nifedipine group (P:=0.05). The only significant difference in hemodynamics among the groups was between the control and the nifedipine groups at 30 minutes after drug (P:=0.05). CONCLUSIONS: Treatment with HOE642 significantly blunts the decline in left atrial mechanical function from rapid atrial rates compared with both control and nifedipine-treated groups.

Analysis of Variance↗
PubMed1977

[Isolated mitral stenosis: systolic and diastolic dynamic geometry of the left ventricle. Integration with several hemodynamic parametres (author's transl)].

75 patients with isolated mitral stenosis were studied. Particular attention was paid to the integration of the parametres VTD, FE, mitral area, pulmonary artery pressure and dynamic systolic and diastolic geometry of the left ventricle. The existence of isolated MS with alteration of the left ventricular function not depending on the alterations of the preload and the forms with raised FE, was demonstrated. A classification into 6 groups was made, each characterized by special geometric modalities of contraction and relaxation. A significant compensation of several of the parametres of systolic mecanism (hyperkinesia) and diastolic (SERP) dynamic geometry was observed. It was therefore concluded that a more precise definition of the interaction of ventricular function with left atrial function is necessary.

Cardiomegaly↗
PubMed1995

P-pulmonale.

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Atrial Function, Left↗