Slow conduction through an arc of block: A basis for arrhythmia formation postmyocardial infarction.

INTRODUCTION: The electrophysiologic basis for characteristic rate-dependent, constant-late-coupled (390 + 54 milliseconds) premature ventricular beats (PVBs) present 4-5 days following coronary artery occlusion were examined in 108 anesthetized dogs. METHODS AND RESULTS: Fractionated/double potentials were observed in injured zone bipolar and composite electrograms at prolonged sinus cycle lengths (1,296 ± 396 milliseconds). At shorter cycle lengths, conduction of the delayed potential decremented, separating from the initial electrogram by a progressively prolonged isoelectric interval. With sufficient delay of the second potential following an isoelectric interval, a PVB was initiated. Both metastable and stable constant-coupled PVBs were associated with Wenckebach-like patterns of delayed activation following an isoelectric interval. Signal-averaging from the infarct border confirmed the presence of an isoelectric interval preceding the PVBs (N = 15). Pacing from the site of double potential formation accurately reproduced the surface ECG morphology (N = 15) of spontaneous PVBs. Closely-spaced epicardial mapping demonstrated delayed activation across an isoelectric interval representing "an arc of conduction block." Rate-dependent very slow antegrade conduction through a zone of apparent conduction block (N = 8) produced decremental activation delays until the delay was sufficient to excite epicardium distal to the original "arc of conduction block," resulting in PVB formation. CONCLUSION: The present experiments demonstrate double potential formation and rate-dependent constant-coupled late PVB formation in infarcted dog hearts. Electrode recordings demonstrate a prolonged isoelectric period preceding PVB formation consistent with very slow conduction (<70 mm/s) across a line of apparent conduction block and may represent a new mechanism of PVB formation following myocardial infarction.

Bi-ventricular pacing improves pump function only with adequate myocardial perfusion in canine hearts with pseudo-left bundle branch block.

Bi-ventricular (BiV) pacing is an effective therapy for the treatment of cardiac electromechanical (EM) dysfunction. The reason(s), however, for therapy non-response in approximately one-third of the subjects remains unclear, especially as it relates to myocardial perfusion and pacing location. In this study, we examined how acute BiV pacing response may be related to underlying myocardial perfusion coupled with pacing near or distant to the area of perfusion. In 10 open-chest anesthetized canines, coronary blood flow to the left ventricular (LV) anterior wall (AW: n = 5) and lateral wall (LW: n = 5) was controlled during four pacing conditions: right atrial, right ventricular (pseudo-left bundle branch block; [pseudo-LBBB]), BiV-LW and BiV-AW. Local EM function (piezo-electrical crystals and electrodes), along with global hemodynamic parameters, were measured during all pacing conditions at three coronary perfusion rates (≥0.40 mL/min/g, 0.20-0.40 mL/min/g and <0.20 mL/min/g). A positive BiV therapy response was assessed by a significant increase in the maximum cardiac output compared with the pseudo-LBBB condition. Despite no improvement in QRS duration, BiV-LW pacing improved LV function compared with the pseudo-LBBB pacing condition (P value <0.01). This improvement with BiV-LW pacing was seen above a certain myocardial perfusion threshold and was independent of any increases in regional coronary blood flow with BiV pacing. At lower myocardial perfusion rates, LV function was not improved with BiV pacing at any location. This study underscores the significance of even mild ischemia on BiV pacing response.

Cardiac late potential signals and sources.

Most studies of cardiac late potentials (LPs) recorded from the body surface use signal processing definitions to characterize these abnormal ventricular potentials. For many years, the focus of the clinical studies have been on those signals that outlast the QRS complex; however, cardiac mapping studies have clearly identified that the such abnormal activation occurs during the QRS complex as well and can be distinguished from normal QRS potentials using advanced signal processing tools. Thus, both the abnormal intra-QRS potentials and the LP represent a continuum of the same signal sources. The electrogram recordings of these signals are often characterized as multiphasic with ambiguous/multiple depolarization times spanning tens of milliseconds within very short distances (<1.0 mm). The biophysical basis for these ambiguities does not fit conventional theories of cardiac propagation. This work examines the role that myofibroblasts (MFs) may play in facilitating conduction and producing very long conduction delays (10-30 milliseconds) between populations of close but isolated regions of normal cells. The prerequisite element of this hypothesis is that the MF can express gap junction proteins that align with the corresponding proteins in the myocardial cells. Membrane responsiveness studies of the MF did not detect, as expected, any ion channels capable of producing significant transmembrane currents or depolarizing potentials. However, in tissue-cultured preparations of neonatal mouse myocytes, a nonconducting gap (200-400 µm) was seeded with MF, and this gap was electrotonically bridged by the MF resulting in conduction velocities of 0.1 m/s. Such passive cell mediation of cardiac conduction would provide a biophysical explanation of LP as well as forming the basis of several hypothesized mechanisms of cardiac arrhythmias, such as microreentry. A fiber model using a series of coupled Luo-Rudy cardiac cell models was interspersed with a simple resistor-capacitor model of the MF, which then demonstrated a range of conduction disorders including excessive delays (>30 milliseconds) and decremental conduction. Hence, the role of this passive cell coupling in the generation of abnormal patterns of conduction as well as arrhythmogenesis has yet to be fully determined but may in fact define another mechanism of cardiac conduction.

Uniform action potential repolarization within the sarcolemma of in situ ventricular cardiomyocytes.

Previous studies have speculated, based on indirect evidence, that the action potential at the transverse (t)-tubules is longer than at the surface membrane in mammalian ventricular cardiomyocytes. To date, no technique has enabled recording of electrical activity selectively at the t-tubules to directly examine this hypothesis. We used confocal line-scan imaging in conjunction with the fast response voltage-sensitive dyes ANNINE-6 and ANNINE-6plus to resolve action potential-related changes in fractional dye fluorescence (DeltaF/F) at the t-tubule and surface membranes of in situ mouse ventricular cardiomyocytes. Peak DeltaF/F during action potential phase 0 depolarization averaged -21% for both dyes. The shape and time course of optical action potentials measured with the water-soluble ANNINE-6plus were indistinguishable from those of action potentials recorded with intracellular microelectrodes in the absence of the dye. In contrast, optical action potentials measured with the water-insoluble ANNINE-6 were significantly prolonged compared to the electrical recordings obtained from dye-free hearts, suggesting electrophysiological effects of ANNINE-6 and/or its solvents. With either dye, the kinetics of action potential-dependent changes in DeltaF/F during repolarization were found to be similar at the t-tubular and surface membranes. This study provides what to our knowledge are the first direct measurements of t-tubule electrical activity in ventricular cardiomyocytes, which support the concept that action potential duration is uniform throughout the sarcolemma of individual cells.

A single moving dipole model of ventricular depolarization.

Modeling abnormal depolarization of the ventricles may provide a means to localize sites of arrhythmia foci from the body surface recordings. In this paper, we present a single moving dipole (SMD) model of the ventricular depolarization. The model can reproduce characteristic QRS patterns comparable to the clinical recordings when it is located in an inhomogeneous torso model. Our approach involves estimating a series of dipole moments based on vectocardiograms and estimating trajectories based on the three-dimensional isochrone of the ventricular activation. The patterns of body surface potential isochrones are consistent with those from previous studies. The SMD model was also used to simulate posterior wall infarction, which matched the criteria for this diagnosis. In conclusion, our SMD model provided a base for further ventricular depolarization studies and this equivalent dipole approach might be useful in investigating ventricular arrhythmias and their site of origin.

High-resolution analysis of ambulatory electrocardiograms to detect possible mechanisms of premature ventricular beats.

For generations of electrocardiogram (ECG) analysis, the presence of premature ventricular beats (PVBs) has been characterized as a common event in the ECG without regard to the mechanism which has caused the PVB in the first place. At best, the coupling interval with the preceding sinus beat may be noted. This viewpoint persisted throughout the era of automated ECG analysis, as well as influencing the treatment of more life threatening events by PVB suppression strategies alone. This study proposed three hypotheses which would link the PVB to a specific mechanism or milieu. Each of these hypotheses requires significant signal processing of the continuously recorded high resolution ECG. Data are presented which demonstrate that abnormal intra-QRS potentials may be linked to a reentrant mechanism for the PVBs and that many patients have significant changes in these potentials in the sinus beats preceding the PVB. Changes in the characteristics of the repolarization as measured in the T/U wave period were also observed and could be linked to triggered activity mechanism for some PVBs. Finally, the role of subclinical ST segment changes also indicates that low grade ischemia may play a role in modulating either PVB mechanism. The data generated by this study suggest that a new view toward PVB mechanism as measured by ECG characteristics may warrant a more rational approach to renewed interest identifying the malignant PVBs and their eventual clinical management.