Functional mathematical model of dual pathway AV nodal conduction.

Dual atrioventricular (AV) nodal pathway physiology is described as two different wave fronts that propagate from the atria to the His bundle: one with a longer effective refractory period [fast pathway (FP)] and a second with a shorter effective refractory period [slow pathway (SP)]. By using His electrogram alternance, we have developed a mathematical model of AV conduction that incorporates dual AV nodal pathway physiology. Experiments were performed on five rabbit atrial-AV nodal preparations to develop and test the presented model. His electrogram alternances from the inferior margin of the His bundle were used to identify fast and slow wave front propagations. The ability to predict AV conduction time and the interaction between FP and SP wave fronts have been analyzed during regular and irregular atrial rhythms (e.g., atrial fibrillation). In addition, the role of dual AV nodal pathway wave fronts in the generation of Wenckebach periodicities has been illustrated. Finally, AV node ablative modifications have been evaluated. The model accurately reproduced interactions between FP and SP during regular and irregular atrial pacing protocols. In all experiments, specificity and sensitivity higher than 85% were obtained in the prediction of the pathway responsible for conduction. It has been shown that, during atrial fibrillation, the SP ablation significantly increased the mean HH interval (204 ± 39 vs. 274 ± 50 ms, P < 0.05), whereas FP ablation did not produce significant slowing of ventricular rate. The presented mathematical model can help in understanding some of the intriguing AV node mechanisms and should be considered as a step forward in the studies of AV nodal conduction.

The dual pathway electrophysiology of the atrioventricular conduction. A new look at an old phenomenon.

Although we soon will be marking the 100th anniversary of the discovery of the atrioventricular (AV) node, the mysteries of this most complex of all parts of the conduction system of the heart remain. We are still battling controversies related to the precise morphology of the AV node and its atrial approaches. We are still debating the exact reentrant pathways of the AV nodal reentrant tachycardia. We are still uncertain if the so-called dual AV nodal electrophysiology encompasses two or more pathways, and what exactly makes these pathways in the absence of distinct insulated cables between the atrium and the AV node. It may be just surprising, in view of the above limitations, that current level of knowledge has nevertheless made possible some of the most spectacular successes in the modern cardiac electrophysiology. Thus, the cases of typical AVNRT are cured with a very high rate of success by radiofrequency ablations, increasing the quality of life of thousands of patients. AV nodal modifications are being performed to slow the ventricular rate during atrial fibrillation, although more progress is needed in this endeavor. The goal of the present review is to outline the major anatomic and electrophysiologic efforts in understanding the mechanisms underlying the dual pathway AV nodal propagation and to trace some novel approaches that promise to widen the horizon of the experimental and clinical fields.

Preload-adjusted maximal power: a novel index of left ventricular contractility in atrial fibrillation.

BACKGROUND: Left ventricular contractility in atrial fibrillation is known to change in a beat to beat fashion, but there is no gold standard for contractility indices in atrial fibrillation, especially those measured non-invasively. OBJECTIVE: To determine whether the non-invasive index of contractility "preload-adjusted PWR(max)" (maximal ventricular power divided by the square of end diastolic volume) can accurately measure left ventricular contractility in a beat to beat fashion in atrial fibrillation. METHODS: Atrial fibrillation was induced experimentally using 60 Hz stimulation of the atrium and maintained in 12 sheep; four received diltiazem, four digoxin, and four no drugs (control). Aortic flow, left ventricular volume, and left ventricular pressure were monitored simultaneously. Preload-adjusted PWR(max), the slope of the end systolic pressure-volume relation (E(max)), and the maximum rate of change of left ventricular pressure (dP/dt(max)) were calculated in a beat to beat fashion. RESULTS: Preload-adjusted PWR(max) correlated linearly with load independent E(max) (p < 0.0001) and curvilinearly with load dependent dP/dt(max) (p < 0.0001), which suggested the load independence of preload-adjusted PWR(max). After five minutes of diltiazem administration, preload-adjusted PWR(max), dP/dt(max), and E(max) fell significantly (p < 0.0001) to 62%, 64%, and 61% of baseline, respectively. Changes were not significant after five minutes of digoxin (103%, 98%, and 102%) or in controls (97%, 96%, and 95%). CONCLUSIONS: Preload-adjusted PWR(max) correlates linearly with E(max) and is a useful measure of contractility even in atrial fibrillation. Non-invasive application of this method, in combination with echocardiography and tonometry, may yield important information for optimising the treatment of patients with atrial fibrillation.

Single capacitive discharge utilizing an auxiliary shock in the coronary venous system reduces the defibrillation threshold.

UNLABELLED: Auxiliary shocks (AS) from electrodes sutured to the left ventricle (LV) prior to primary biphasic shocks (PS) have been shown to reduce defibrillation thresholds (DFT). Two capacitors are required to generate these waveforms. We investigate delivery of AS from one capacitor using a novel waveform. The epicardial surface of the LV is accessed transvenously via the middle cardiac vein (MCV) avoiding a thoracotomy. METHODS: A defibrillation electrode was placed in the right ventricle (RV) and superior vena cava (SVC) in 12 pigs (37+/-2 kg). A 50x1.8 mm electrode was inserted in the MCV through a guide catheter. A can was placed in the left pectoral region. A monophasic AS (100 microF, 1.5 J) was delivered along one pathway before switching to deliver a biphasic waveform (40% tilt, 2 ms phase 2) along another. DFTs (PS+AS) were assessed using a binary search. Two configurations not incorporating AS acted as controls. DFTs were compared using repeated measures analysis of variance. RESULTS: DFTs of the four novel configurations (AS/PS) were: RV-->Can/MCV-->Can=14.9+/-3.7 J, MCV-->Can/RV-->Can=17.2+/-5.7 J, RV-->SVC+Can/MCV-->SVC+Can=13.4+/-4.6 J, MCV-->SVC+Can/RV-->SVC+Can=17.1+/-5.9 J. Delivering AS in the RV followed by PS in the MCV reduced the DFT (RV-->Can (19.9+/-7.3 J, P<0.01) and RV-->SVC+Can (19.2+/-6.0 J, P<0.05)). CONCLUSIONS: Delivering AS prior to PS in the MCV reduces the DFT by up to a third compared to conventional configurations of RV-->Can and RV-->SVC+Can. This is possible using only a single capacitor and an entirely transvenous approach to the LV.

Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs.

Although the atrioventricular node (AVN) plays a vital role in blocking many of the atrial impulses from reaching the ventricles during atrial fibrillation (AF), a rapid irregular ventricular rate nevertheless persists. The goals of the present study were to explore the feasibility of novel epicardial selective vagal nerve stimulation for slowing of the ventricular rate during AF and to characterize the hemodynamic benefits in vivo. Electrophysiological-echocardiographic experiments were performed on 11 anesthetized open-chest dogs. Hemodynamic measurements were performed during three distinct periods: 1) sinus rate, 2) AF, and 3) AF with vagal nerve stimulation. AF was associated with significant deterioration of all measured parameters (P < 0.025). The vagal nerve stimulation produced slowing of the ventricular rate, significant reversal of the pressure and contractile indexes (P < 0.025), and a sharp reduction in one-half of the abortive ventricular contractions. The present study provides comprehensive evidence that slowing of the ventricular rate during AF by selective ganglionic stimulation of the vagal nerves that innervate the AVN successfully improved the hemodynamic responses.

His electrogram alternans reveal dual-wavefront inputs into and longitudinal dissociation within the bundle of His.

BACKGROUND: His electrogram (HE) amplitude and morphology changes were observed in our previous studies during transition from "fast" to "slow" atrioventricular nodal (AVN) conduction. This phenomenon and its significance for the dual-AVN electrophysiology are not well recognized and have not been studied. METHODS AND RESULTS: Experiments were performed on 17 healthy rabbit atrial-AVN preparations during standard programmed electrical pacing. HEs were mapped along the His bundle with roving surface electrodes, along with recording of cellular action potentials (APs). HEs recorded from the superior margin of the His bundle were of greater amplitude during basic beats and decreased substantially, by 42+/-19% (P<0.01), when premature A(1)A(2) shortened to 178+/-20 ms. In contrast, the HEs from the inferior margin increased dramatically, 2.9+/-1.7 times (P<0.01), during short A(1)A(2) and remained high until AVN block occurred. In addition, during long A(1)A(2), the superior HEs consistently preceded the inferior by 1.9+/-0.7 ms. In contrast, at short A(1)A(2), the superior HEs occurred 2.7+/-0.8 ms after the inferior. Cellular AP recordings demonstrated clearly the presence of and the transition between early (fast) and late (slow) excitation wavefronts that accompanied HE alternans. CONCLUSIONS: The morphological-electrophysiological evidence from the AV junction suggests that fast and slow wavefronts reach the His bundle differently, producing functional longitudinal dissociation into 2 domains. The characteristic HE alternans recorded from these domains are a new sensitive tool to determine the presence of distinctly different wavefronts and their participation in the conduction during reentrant or other arrhythmias. These findings provide further understanding of the mechanisms of dual-AVN electrophysiology.

Assessment of LV systolic function in atrial fibrillation using an index of preceding cardiac cycles.

The clinical assessment of left ventricular (LV) systolic function during atrial fibrillation (AF) is unreliable and difficult because of beat-to-beat variability. We evaluated an index for the estimation of LV systolic function in AF that is based on the relationship between the preceding (R-R1) and prepreceding (R-R2) R-R intervals. LV Doppler stroke volume (SV), ejection fraction (EF), peak aortic flow rate (AoF) and the maximum value of the first derivative of the LV pressure curve (dP/dt(max)) were evaluated in 13 healthy open-chest dogs during triggered AF. All parameters showed a significantly strong positive linear relationship with the ratio of R-R1/R-R2 (r = 0.65, 0.74, 0.75, and 0.70 for SV, EF, AoF, and dP/dt(max), respectively). The calculated value of LV systolic parameters at R-R1/R-R2 = 1 in the linear regression line showed a good relationship and an agreement with the measured average value of the parameter over all cardiac cycles (SV, 12.1 vs. 12.8 ml; EF, 49.6 vs. 51.2%; AoF, 1.37 vs. 1.48 l/min; and dP/dt(max), 2,323 vs. 2,454 mmHg/s). Using the LV systolic parameters estimated at R-R1/R-R2 = 1 in the linear regression line allows the LV contractile function to be accurately and reproducibly evaluated during AF and obviates the less-reliable process of averaging multiple cardiac cycles.

Anatomic-electrophysiological correlations concerning the pathways for atrioventricular conduction.

The remarkable success of radiofrequency ablation in recent decades in curing atrioventricular nodal reentrant tachycardias has intensified efforts to provide a solid theoretical basis for understanding the mechanisms of atrioventricular transmission. These efforts, which were made by both anatomists and electrophysiologists, frequently resulted in seemingly controversial observations. Quantitatively and qualitatively, our understanding of the mysteries of propagation through the inhomogeneous and extremely complex atrioventricular conduction axis is much deeper than it was at the beginning of the past century. We must go back to the initial sources, nonetheless, in an attempt to provide a common ground for evaluating the morphological and electrophysiological principles of junctional arrhythmias. In this review, we provide an account of the initial descriptions, which still provide an appropriate foundation for interpreting recent electrophysiological findings.

New approach to biphasic waveforms for internal defibrillation: fully discharging capacitors.

INTRODUCTION: The use of two independent, fully discharging capacitors for each phase of a biphasic defibrillation waveform may lead to the design of a simpler, smaller, internal defibrillator. The goal of this study was to determine the optimal combination of capacitor sizes for such a waveform. METHODS AND RESULTS: Eight full-discharge (95/95% tilt), biphasic waveforms produced by several combinations of phase-1 capacitors (30, 60, and 90 microF) and phase-2 capacitors (1/3, 2/3, and 1.0 times the phase-1 capacitor) were tested and compared to a single-capacitor waveform (120 microF, 65/65% tilt) in a pig ventricular fibrillation model (n = 12, 23+/-2 kg). In the full-discharge waveforms, phase-2 peak voltage was equal to phase-1 peak voltage. Shocks were delivered between a right ventricular lead and a left pectoral can electrode. E50s and V50s were determined using a ten-step Bayesian process. Full-discharge waveforms with phase-2 capacitors of < or =40 microF had the same E50 (6.7+/-1.7 J to 7.3+/-3.9 J) as the single-capacitor truncated waveform (7.3+/-3.7 J), whereas waveforms with phase-2 capacitors of > or =60 microF had an extremely high E50 (14.5+/-10.8 J or greater, P < 0.05). Moreover, of the former set of energy-efficient waveforms, those with phase-1 capacitors of > or =60 microF additionally exhibited V50s that were equivalent to the V50 of the single-capacitor waveform (344+/-65 V to 407+/-50 V vs 339+/-83 V). CONCLUSION: Defibrillation efficacy can be maintained in a full-discharge, two-capacitor waveform with the proper choice of capacitors.

Surface potentials from the region of the atrioventricular node and their relation to dual pathway electrophysiology.

BACKGROUND: Clinical applications of the principles of dual atrioventricular nodal (AVN) electrophysiology in the treatment of AVN reentrant tachycardias rely on empirical findings, such as discontinued conduction curves or the presence of specific catheter-recorded signals. However, neither the shape of the conduction curve nor the surface electrograms have been validated as functionally related to the presence of slow or fast wavefronts. METHODS AND RESULTS: We performed in vitro studies using 10 rabbit atrial-AVN preparations. A bipolar roving electrode was used to explore the endocardial surface of the triangle of Koch during programmed electrical stimulation. Microelectrodes were impaled in AVN cells to correlate surface and intracellular responses. In 7 preparations, a specific area near the compact cell region produced surface electrograms that were dissociated in 2 distinct components, with progressive shortening of prematurity. Similar dissociation was demonstrated during Wenckebach periodicity and increased vagal tone. Cellular recordings supported the presence of early ("fast") and late ("slow") wavefronts, with different refractory properties. Although the fast-slow transition was a basis for discontinued propagation, the AVN conduction curves were smooth in the majority of cases. CONCLUSIONS: Exploration of the triangle of Koch during programmed pacing reveals the presence of dual-wavefront surface potentials. Clinical confirmation of these AVN potentials could provide a new, sensitive tool in defining dual AVN electrophysiology.

Fully discharging phases. A new approach to biphasic waveforms for external defibrillation.

BACKGROUND: Phase-2 voltage and maximum pulse width are dependent on phase-1 pulse characteristics in a single-capacitor biphasic waveform. The use of 2 separate output capacitors avoids these limitations and may allow waveforms with lower defibrillation thresholds. A previous report also suggested that the optimal tilt may be >70%. This study was designed to determine an optimal biphasic waveform by use of a combination of 2 separate and fully (95% tilt) discharging capacitors. METHODS AND RESULTS: We performed 2 external defibrillation studies in a pig ventricular fibrillation model. In group 1, 9 waveforms from a combination of 3 phase-1 capacitor values (30, 60, and 120 microF) and 3 phase-2 capacitor values (0=monophasic, 1/3, and 1.0 times the phase-1 capacitor) were tested. Biphasic waveforms with phase-2 capacitors of 1/3 times that of phase 1 provided the highest defibrillation efficacy (stored energy and voltage) compared with corresponding monophasic and biphasic waveforms with the same capacitors in both phases except for waveforms with a 30-microF phase-1 capacitor. In group 2, 10 biphasic waveforms from a combination of 2 phase-1 capacitor values (30 and 60 microF) and 5 phase-2 capacitor values (10, 20, 30, 40, and 50 microF) were tested. In this range, phase-2 capacitor size was more critical for the 30-microF phase-1 than for the 60-microF phase-1 capacitor. The optimal combinations of fully discharging capacitors for defibrillation were 60/20 and 60/30 microF. Conclusions-Phase-2 capacitor size plays an important role in reducing defibrillation energy in biphasic waveforms when 2 separate and fully discharging capacitors are used.

Biventricular shocking leads improve defibrillation efficacy.

INTRODUCTION: A single lead active can configuration has been widely used in patients with life-threatening ventricular arrhythmias. Occasionally, however, such a defibrillation lead configuration may not achieve adequate defibrillation threshold (DFT). The purpose of this study was to determine whether addition of a left ventricular (LV) lead can improve defibrillation efficacy. METHODS AND RESULTS: Three transvenous defibrillation leads (8.3-French with a 5-cm long unipolar coil) were placed in the right ventricle (RV), LV, and superior vena cava (SVC), along with an active can (92 cm2) in the left subpectoral area. The DFT stored energy of seven combinations of these defibrillation leads were compared in a pig ventricular fibrillation model using a biphasic defibrillation waveform (125 microF, 6.5/3.5 msec). A biventricular leads active can configuration in which the RV and LV leads were of the same polarity reduced the DFT stored energy by approximately 35% when compared to a single RV lead active can configuration (9.6 +/- 3.0 J vs 15.0 +/- 7.2 J, respectively, P = 0.02). Moreover, adding a SVC lead further reduced the DFT energy (8.4 +/- 3.3 J). CONCLUSION: A biventricular leads active can configuration can significantly improve defibrillation efficacy as compared to a single lead active can configuration. In such a defibrillation lead configuration, the polarity of RV and LV leads should be the same.

Autonomic modification of the atrioventricular node during atrial fibrillation: role in the slowing of ventricular rate.

BACKGROUND: Postganglionic vagal stimulation (PGVS) by short bursts of subthreshold current evokes release of acetylcholine from myocardial nerve terminals. PGVS applied to the atrioventricular node (AVN) slows nodal conduction. However, little is known about the ability of PGVS to control ventricular rate (VR) during atrial fibrillation (AF). METHODS AND RESULTS: To quantify the effects and establish the mechanism of PGVS on the AVN, AF was simulated by random high right atrial pacing in 11 atrial-AVN rabbit heart preparations. Microelectrode recordings of cellular action potentials (APs) were obtained from different AVN regions. Five intensities and 5 modes of PGVS delivery were evaluated. PGVS resulted in cellular hyperpolarization, along with depressed and highly heterogeneous intranodal conduction. Compact nodal AP exhibited decremental amplitude and dV/dt and multiple-hump components, and at high PGVS intensities, a high degree of concealed conduction resulted in a dramatic slowing of the VR. Progressive increase of PGVS intensity and/or rate of delivery showed a significant logarithmic correlation with a decrease in VR (P<0.001). Strong PGVS reduced the mean VR from 234 to 92 bpm (P<0.001). The PGVS effects on the cellular responses and VR during AF were fully reproduced in a model of direct acetylcholine injection into the compact AVN via micropipette. CONCLUSIONS: These studies confirmed that PGVS applied during AF could produce substantial VR slowing because of acetylcholine-induced depression of conduction in the AVN.

Atrioventricular nodal conduction during atrial fibrillation: role of atrial input modification.

BACKGROUND: Posteroseptal ablation of the atrioventricular node (AVN) has been proposed as a means to slow the ventricular rate during atrial fibrillation (AF). The suggested mechanism is elimination of the AVN "slow pathway." On the basis of the unpredictable success of the procedure, we hypothesize that, in fact, the slow pathway is preserved. Therefore, the slowing of the ventricular rate results from reduced bombardment of the AVN. METHODS AND RESULTS: In 8 rabbit heart atrial-AVN preparations, cooling of the posterior and/or the anterior AVN approaches revealed nonspecific effects on the slow and fast pathway portions of the AVN conduction curve. In 13 other preparations, simulated AF during posterior cooling (n=6) prolonged the His-His (H-H) intervals but did not reveal specific slow pathway injury. In the remaining 7 preparations, AF was applied before and after posteroseptal surgical cuts. During AF with posterior origin, the cuts resulted in longer mean H-H along with slowing of the AVN bombardment rate. However, there was no change in the minimum observed H-H, suggesting an intact slow pathway. During AF with anterior origin, the mean and the shortest H-H remained unchanged before and after the cuts in all preparations. This was associated with the maintenance of high-rate AVN bombardment. CONCLUSIONS: Posteroseptal ablation does not eliminate the slow pathway. Ventricular rate slowing can be obtained if the ablation procedure results in a posteroanterior intra-atrial block leading to a reduction of the rate of AV nodal bombardment.

Role of the differential bombardment of atrial inputs to the atrioventricular node as a factor influencing ventricular rate during high atrial rate.

OBJECTIVES: The role of the atrial inputs for the conduction through the atrioventricular node (AVN) at slow rates and during reentrant tachycardia is well acknowledged, although still controversial. However, the relationship between the sequence and rate of atrial engagement of the AVN inputs and the resulting ventricular rate during high atrial rate remains unclear. This study provides quantitative description of complex AVN input-output correlations determining the ventricular rate during random high atrial rate. METHODS AND RESULTS: 12 rabbit heart preparations were used to evaluate the ventricular rate during programmed regular high atrial rate pacing or random pacing from eight atrial sites. Electrograms were recorded at the posterior (P) and anterior (A) AVN inputs, and at the bundle of His along with nodal cellular action potentials. Lorenz-plots and input-output-rate correlations were used to quantify the ventricular rate under different pacing protocols. Small alternations in the sequence of activation of P and A resulted in substantial changes of the organization of the intranodal cellular responses and the ventricular rate. The ventricular rate was shown to be significantly dependent on the site of high rate pacing (P < 0.01) and on the resulting mean rate of inputs activation. Furthermore, the asymmetry between P- and A-bombardment was an important determinant, so that high ventricular rate was associated with large difference between the inputs rates and vice versa (P < 0.05). CONCLUSIONS: The prevailing ventricular rate during high atrial rate is a complex dynamic parameter that depends not only on the global mean atrial rate but, in a major part, on the differential bombardment of the AVN inputs and on the site of initiation of the atrial wave fronts.

High-resolution, three-dimensional fluorescent imaging reveals multilayer conduction pattern in the atrioventricular node.

BACKGROUND: The atrioventricular node (AVN) is the only normal electrical link between the upper and lower chambers of the heart. The AVN modulates transmission of impulses, thus coordinating the contraction of the atria and ventricles. METHODS AND RESULTS: Structural and functional complexity, combined with the absence of adequate experimental techniques, has complicated attempts to directly evaluate the three-dimensional electrical activity of the AVN. Thus, despite a century of research by conventional electrophysiologic and histologic methods, even the existence of conduction through AVN is still debated. CONCLUSIONS: Using a novel combination of microelectrode recordings and high resolution fluorescent imaging with voltage-sensitive dyes, we have for the first time clearly demonstrated three-dimensional conduction through the AVN.

Virtual electrode-induced phase singularity: a basic mechanism of defibrillation failure.

Delivery of a strong electric shock to the heart remains the only effective therapy against ventricular fibrillation. Despite significant improvements in implantable cardioverter defibrillator (ICD) therapy, the fundamental mechanisms of defibrillation remain poorly understood. We have recently demonstrated that a monophasic defibrillation shock produces a highly nonuniform epicardial polarization pattern, referred to as a virtual electrode pattern (VEP). The VEP consists of large adjacent areas of strong positive and negative polarization. We sought to determine whether the VEP may be responsible for defibrillation failure by creating dispersion of postshock repolarization and reentry. Truncated exponential biphasic and monophasic shocks were delivered from a bipolar ICD lead in Langendorff-perfused rabbit hearts. Epicardial electrical activity was mapped during and after defibrillation shocks and shocks applied at the plateau phase of a normal action potential produced by ventricular pacing. A high-resolution fluorescence mapping system with 256 recording sites and a voltage-sensitive dye were used. Biphasic shocks with a weak second phase (<20% leading-edge voltage of the second phase with respect to the leading-edge voltage of the first phase) produced VEPs similar to monophasic shocks. Biphasic shocks with a strong second phase (>70%) produced VEPs of reversed polarity. Both of these waveforms resulted in extra beats and arrhythmias. However, biphasic waveforms with intermediate second-phase voltages (20% to 70% of first-phase voltage) produced no VEP, because of an asymmetric reversal of the first-phase polarization. Therefore, there was no substrate for postshock dispersion of repolarization. Shocks producing strong VEPs resulted in postshock reentrant arrhythmias via a mechanism of phase singularity. Points of phase singularity were created by the shock in the intersection of areas of positive, negative, and no polarization, which were set by the shock to excited, excitable, and refractory states, respectively. Shock-induced VEPs may reinduce arrhythmias via a phase-singularity mechanism. Strong shocks may overcome the preshock electrical activity and create phase singularities, regardless of the preshock phase distribution. Optimal defibrillation waveforms did not produce VEPs because of an asymmetric effect of phase reversal on membrane polarization.

Voltage-sensitive dye RH421 increases contractility of cardiac muscle.

Voltage-sensitive dyes and imaging techniques have proved to be indispensable tools for use in in vitro electrophysiological studies. To avoid motion artifacts in optical recordings, electromechanical uncouplers such as 2,3-butanedione monoxime (BDM) are required. In this study, we sought to determine whether the voltage-sensitive dye RH421 had an effect on the contractility of heart muscle, either alone or in the presence of BDM. Ventricular contractility was studied in (i) isolated rat myocytes and (ii) Langendorff-perfused rat hearts under control conditions, and during perfusion with RH421 or RH421 + BDM. The following results were obtained. (i) The amplitude of cell shortening increased progressively from 6.24 +/- 0.64 to 9.95 +/- 1.02 microm during 15 min of superfusion with 5 microM RH421 (n = 11), and further increased to 12.54 +/- 0.97 microm during washout. In seven cells first perfused with 15 mM BDM and then with 15 mM BDM + 5 microM RH421, the amplitude of the cell shortening first decreased from 5.17 +/- 0.51 to 0.41 +/- 0.19 microm, then the amplitude increased to 2.63 +/- 0.25 microm. (ii) Left ventricular pressure (LVP) of the heart (n = 7) was reduced by 15 mM BDM from 60.7 +/- 2.5 to 2.8 +/- 0.5 mmHg (1 mmHg = 133.3 Pa). LVP increased to 12.8 +/- 1.1 mmHg during subsequent perfusion with 10 microM RH421 in the presence of BDM and did not change (LVP = 12.4 +/- 2.4 mmHg) during washout of the dye. Therefore, RH421 increased the contractility of rat hearts and isolated myocytes with and without BDM.

Iridium oxide-coated defibrillation electrode: reduced shock polarization and improved defibrillation efficacy.

BACKGROUND: Transvenous implantable cardioverter-defibrillator (ICD) leads are designed to deliver electric shocks to the heart for termination of ventricular dysrhythmias. However, the efficiency of different lead materials has not been well studied. This study compares an ICD lead coated with iridium oxide (IROX), a material that reduces shock-induced polarization, with an otherwise identical, uncoated lead. METHODS AND RESULTS: The defibrillation threshold (DFT) was determined in 13 swine with both IROX-coated and uncoated ICD leads paired with an uncoated "can" electrode. The leads were exchanged through a Teflon sheath to reproduce the intracardiac position. The delivered energy DFT of the IROX-coated lead was 15.9+/-5.4 J and was significantly lower than the delivered energy DFT of the uncoated lead (19.1+/-5.1 J; P<.006). The initial lead impedance was equivalent in both leads (IROX, 41.7+/-5.8 omega; uncoated, 41.3+/-4.7 omega; P=NS) at DFT. However, the impedance rose by 7.3+/-2.0 omega during the first phase and by 3.7+/-2 omega during the second phase with the uncoated lead, whereas the corresponding impedance change was 1.0+/-0.3 omega during phase 1 and 1.6+/-0.5 omega during phase 2 (P<.01 each phase) when the IROX-coated lead was used. CONCLUSIONS: This study shows that an IROX coating of this lead system significantly lowers the DFT energy in the swine model. The blunting of the impedance rise by the IROX coating that is seen is consistent with a reduction in electrode polarization.