Wedensky facilitation in canine right bundle branch

The phenomenon of Wedensky facilitation was investigated in canine specialized conduction fibers. A segment of block was produced by an electrical depolarizing current of sufficient intensity to result in non-conduction of impulses. A subthreshold stimulus was applied to the preparation distal to the segment of block with a bipolar stimulating electrode. Electrotonic potentials which originated at the proximal block boundary and traversed the segment of block were demonstrated with an intracellular microelectrode. Synchronization of the previously subthreshold distal stimulus with the peak of the transmitted electrotonic potential demonstrated facilitation by conversion of the distal stimulus to a 1:1 response. Temporal variation of the distal stimulus to coincide with different portions of the electrotonic potential demonstrated loss of facilitation when the stimulus preceded, or followed the electrotonic peak voltage.     

Slow recovery of excitability and the Wenckebach phenomenon in the single guinea pig ventricular myocyte

The cellular mechanisms of Wenckebach periodicity were investigated in single, enzymatically dissociated guinea pig ventricular myocytes, as well as in computer reconstructions of transmembrane potential of the ventricular cell. When depolarizing current pulses of the appropriate magnitude were delivered repetitively to a well-polarized myocyte, rate-dependent activation failure was observed. Such behavior accurately mimicked the Wenckebach phenomenon in cardiac activation and was the consequence of variations in cell excitability during the diastolic phase of the cardiac cycle. The recovery of cell excitability during diastole was studied through the application of single test pulses of fixed amplitude and duration at variable delays with respect to a basic train of normal action potentials. The results show that recovery of excitability is a slow process that can greatly outlast action potential duration (i.e., postrepolarization refractoriness). Two distinct types of subthreshold responses were recorded when activation failure occurred: one was tetrodotoxin- and cobalt-insensitive (type 1) and the other was sensitive to sodium-channel blockade (type 2). Type 1 responses, which were commonly associated with the typical structure of the Wenckebach phenomenon (Mobitz type 1 block), were found to be the result of the nonlinear conductance properties of the inward rectifier current, IK1. Type 2 sodium-channel-mediated responses were associated with the so-called "millisecond Wenckebach." These responses may be implicated in the mechanism of Mobitz type 2 rate-dependent block. Single-cell voltage-clamp experiments suggest that variations in excitability during diastole are a consequence of the slow deactivation kinetics of the delayed rectifier, IK. Computer simulations of the ventricular cell response to depolarizing current pulses reproduced very closely all the response patterns obtained in the experimental preparation. It is concluded that postrepolarization refractoriness and Wenckebach periodicity are properties of normal cardiac excitable cells and can be explained in terms of the voltage dependence and slow kinetics of potassium outward currents. The conditions for the occurrence of intermittent activation failure during diastole will depend on the frequency and magnitude of the driving stimulus.     

电紧张调整性T波改变的临床观察

目的 :观察各种原因所致电张调整性T波改变的临床表现和持续时间。方法 :对显性预激射频消融后 5 8例、特发性室性心动速终止后 5例及右室起搏 （VVI）恢复自主心律后 2 6例的进行动态心电图观察。结果 :显性预激消融后 2 6例 ,特发性室性心动速终止后 5例及VVI起搏恢复自主心律后 2 2例显示不同程度电张调整性T波改变 ,前二者持续约 1周 ,后者持续约 2周 ,均未经治疗自动恢复正常。结论 :电张调整性T波改变是心肌正常的电生理特性 ,一般持续 1～ 2周自动恢复正常。     

The phenomenon of accommodation in the ventricular myocardium

Summary The ventricular and auricular myocardium was found to possess an ability to accommodate to applied electrical current pulses.Accommodation to cathodal current flow was observed even when nonpolarizable electrodes were employed and also when tests were made with chronically implanted metal electrodes in intact anesthetized dogs.Accommodation tended to attain its maximum within 40 to 45 msec after the beginning of the conditioning pulse. It reduced the facilitatory action of the conditioning pulse by 50 to 60%.Post-cathodal and post-anodal changes in excitability occurred. They were of 10 to 15 msec duration following a 70 msec conditioning current flow. They were of lesser magnitude then the average residual facilitation remaining just before termination of conditioning stimuli.Evidence that various circumstances can modify the ability of cardiac tissue to accommodate to intrinsic and applied stimuli was discussed. The possible importance of this phenomenon to the maintenance of effective action of the heart under abnormal circumstances was considered.With 1 figure in 5 detailsSupported by a grant from the Life Insurance Medical Research Fund.-In honor of Prof.B. Kisch's, M.D. 70th birthday.     

ATX-II effects on the apparent location of M cells in a computational model of a human left ventricular wedge

Introduction: The apparent location of the myocytes (M cells) with the longest action potential duration (APD) in a canine left ventricular (LV) wedge have been reported to shift after application of a sea anemone toxin, ATX‐II. This toxin slows inactivation of I_Na and thus prolongs APD. Thus, M cells may exhibit dynamic functional states, rather than being a static, anatomically discrete, myocyte population. In this study, we attempted to further define and understand this phenomenon using a mathematical model of the human ventricular myocyte action potential incorporated into an in silico “wedge” preparation. Our simulations demonstrate that even under conditions of a fixed population and ratio of epicardial, M, and endocardial myocytes, the apparent anatomical position (transmural location) of the myocytes with the longest APD can shift following ATX‐II treatment. This arises because the ATX‐II effect, modeled as a small increase in the late or persistent Na⁺ current, and consequent prolongation of APD significantly changes the electrotonic interactions between ventricular myocytes in this LV wedge preparation. Methods and Results: This LV wedge model is based on bidomain equations. It corresponds to a rectangular tissue immersed in a passive and isotropic medium that represents the superfusion bath. In this theoretical work, the three known different and discrete populations of myocytes in the human left ventricle have been included: the epicardial, M, and endocardial cells. The effects of ATX‐II on I_Na were simulated by altering the voltage‐dependent steady‐state inactivation of the parameters h (fast gate) and j (slow gate). As a result, in these ATX‐II simulations a persistent late Na⁺ current was generated in all three types of ventricular myocytes. However, the APDs were prolonged in a heterogeneous pattern. Our simulations demonstrate that after the ATX‐II effects develop, alterations in transmural electrotonic interactions can produce changes in the transmural location of myocytes with the longest APD. Conclusions: The combination of intercellular electrotonic interactions, which tend to reduce and smooth out the discrete transmural APD variations, and the heterogeneous effects of ATX‐II, which preferentially prolong the APD of M cells, can shift the location of the ventricular myocytes. This shift results in significantly altered transmural patterns of action potential durations, which would be expected to change localized refractory period and excitability. These cellular changes give rise to alterations in the corresponding surface electrograms and may change the overall substrates for conduction and rhythm disturbances.     

阈下条件电刺激对患者心脏不应期和起搏节律的影响

目的研究阈下条件电刺激对心脏不应期的影响。方法通过右心电极导管法,在24例心律失常患者中,观察阈下条件单个刺激（Ss）和串刺激（St）对心房或心室不应期和心房或心室起搏节律的影响。结果在SlS2间期中加发St,可使人心房及心室相对不应期和有效不应期延长;且随St强度的增加,不应期延长量增加。在SlS2间期中加发Ss,只有6/18例,心房相对不应期延长;另6/18例,心室相对及有效不应期延长。另外,St和Ss可抑制心房及心室起搏节律。结论阈下条件电刺激具有抑制心肌兴奋性的作用。     

Distribution and three-dimensional structure of intercellular junctions in canine myocardium

Electrotonic coupling of cardiac myocytes at gap junctions may influence patterns of conduction in myocardium. To delineate the three-dimensional structure and distribution of intercellular junctions, we analyzed serial ultrathin sections of canine myocardium with transmission electron microscopy and disaggregated myocytes with scanning electron microscopy. Morphometric analysis of left ventricular myocardium sectioned in three orthogonal planes revealed that 80% of total gap junctional membrane occurred in large, ribbon-like gap junctions oriented transversely at cell end processes. The remaining 20% of gap junctional membrane was contained in small gap junctions located within plicate segments (interdigitating regions of cell-to-cell adhesion) of intercalated disks. In serial ultrathin sections, all gap junctions were contiguous with plicate segments. Thus, true "lateral" gap junctions do not exist in working ventricular myocytes and would not likely be able to withstand shear forces created by laterally sliding cells. Examination of serial plastic sections with light microscopy revealed complex overlapping of myocytes such that individual myocytes were connected at intercalated disks to an average of 9.1 +/- 2.2 other myocytes. These observations provide an improved understanding of the extent and distribution of cell junctions and should facilitate experimental and model studies of conduction in myocardium.     

Electrical Activity of the Crayfish Myocardium

Passive and Active Electrical Responses . Introduction: The purpose of this investigation was to study the electrical activity of the crayfish myocardium. Methods and Results: In isolated crayfish hearts, intracellularly injected hyperpolarizing pulses propagate electrotonically to distances up to 1 mm, and the myocardium behaves as an irregular functional syncytium. Conclusion: The existence of low-resistance intercellular connections provides a basis for the analysis and interpretation of many of the results obtained in this article, and makes it possible to propose the following tentative conclusions: (1) in the crayfish myocardium, not all muscle cells are innervated, yet many sites in the crayfish myocardium receive the same polyneural innervation; (2) in many records, the burst of junction potentials that follow each action potential are electrotonic in nature; (3) the cardiac muscle fibers of the crayfish heart are electrically excitable, and the generated action potentials do propagate actively at least for short distances; (4) the gaps between the innervated sites are filled with noninnervated but connected muscle cells that are passively and actively engaged; and (5) an exaggerated richness of innervation is not needed since the crayfish heart can provide effective and quasisynchronous mechanical systoles because of its efficiently combined characteristics.     

Role of Potassium Currents on Cell Excitability in Cardiac Ventricular Myocytes

Potassium Currents and Cell Excitability. Ventricular cell excitability has been mostly associated with the ability of sodium currents to generate an action potential upstroke. However, even in the presence of normal sodium currents, a cell will not generate an active response if it is unable to depolarize from the resting potential to the activation threshold. This article summarizes recent data demonstrating that potassium currents can act as important modulators of cell excitability. In fact, potassium currents can play a major role in determining the dynamics of Wenckebach periodicity, hysteresis of excitability, and active facilitation in ventricular myocytes. The article discusses the specific roles that the inward rectifier, I_Kb the delayed rectifier, I_K, and the ATP-sensitive, I_K-ATP currents play on the dynamic modulation of cell excitation. (J Cardiovasc Electrophysiol, Vol. 3, pp. 474–486. October 1992)     

The influence of atrial activity on ventricular capture by failing artificial pacemakers. I. Report of two new cases and review of the literature.

Atrial activity can influence the ability of a failing artificial pacemaker to excite the heart. An appropriately timed atrial beat may cause failure in excitation by pacemaker stimuli which are usually successful in ventricular capture. Conversely, stimuli which usually fail in excitation may be made to succeed by an appropriately timed atrial beat. Two case reports and a review of the literature are presented. Alternative mechanisms for this influence of atrial activity are electrotonic effects (Wedensky facilitation or inhibition) and mechanical effects (motion of the pacing catheter or ventricular myocardium). The authors consider the latter mechanism preferable.     

Hysteresis in the excitability of isolated guinea pig ventricular myocytes.

Hysteresis phenomena were demonstrated in the excitability of single, enzymatically dissociated guinea pig ventricular myocytes. Membrane potentials were recorded with patch pipettes in the whole-cell current-clamp configuration. Repetitive stimulation with depolarizing current pulses of constant cycle length and duration but varying strength led to predictable excitation (1:1) and nonexcitation (1:0) patterns depending on current strength. However, transition between patterns depended on the direction of current strength change, and stable hysteresis loops were obtained in stimulus-response pattern versus current strength plots in 31 cells. Increase of pulse duration and decrease of stimulation rate contributed to a reduction in hysteresis loop areas. In addition, at the abrupt transitions from 1:0 to 1:1 patterns, a latency adaptation phenomenon was consistently observed. Bath application of tetrodotoxin (30 microM) produced no change of hysteresis, whereas hysteresis was substantially decreased in cobalt (2 mM) superfusion experiments. Analysis of the changes in amplitude and shape of the subthreshold responses during the transitions from one stable pattern to the other suggested that activity led to an increase in membrane resistance, particularly in the voltage domain between resting and threshold potentials. We therefore modeled the dynamic behavior of the single cells, using an analytical solution aimed at calculating the recovery of activation latency as a function of diastolic membrane resistance. Numerical iteration of the analytical model equations closely reproduced the experimental hysteresis loops in both qualitative and quantitative ways. The effect of stimulation frequency on the model was similar to the experimental findings. The overall study suggests that the excitability pattern of guinea pig ventricular myocytes is responsible for hysteresis and bistabilities when current intensity is allowed to fluctuate around threshold levels.     

Active components of excitability in K-depolarized ventricular muscle

The steady-state and dynamic characteristics of excitability were assessed in isolated guinea pig papillary muscles depolarized with elevated [K+]o to resting potentials near -60 mV. Transmembrane potentials were recorded from fibers during application of low-amplitude current pulses used to analyze net changes in active membrane components of excitability in terms of elicited local responses and measure threshold current (Ith). Generated local responses were blocked entirely by tetrodotoxin and lidocaine, which increased steady-state Ith by more than 200%. In the absence of Na+ channel-blocking agents, local responses showed marked but characteristic attenuation in a time- and voltage-dependent manner by preceding subthreshold depolarizations, which concomitantly reduced excitability. However, local responses and excitability were also modulated by small changes in [Ca2+]o (+/- 0.7 mmol) and reduced by exposure to slow channel blockers and to Cs+. Thus these data suggest that while the Na+ channel is the primary active component of excitability in partially depolarized ventricular muscle, Ca2+ -mediated and Cs+ -sensitive conductances may also participate, although to a lesser extent. These findings may help explain the frequency-dependence of excitability and conduction under conditions of ischemia in the intact heart.     

Characteristics of junctional regions between Purkinje and ventricular muscle cells of canine ventricular subendocardium

The normal cardiac activation sequence requires propagation of the action potential from the subendocardial Purkinje network into the underlying ventricular muscle cells. This process occurs at specific junctional sites distributed over the endocardial surface of both ventricles. At these junctional sites, action potentials can be recorded from cells that appear to be interposed between the Purkinje cells and the ventricular muscle cells. The action potential upstrokes recorded from these "transitional" cells have characteristic double phases produced by electrotonic interactions with the Purkinje cells and the ventricular muscle cells. We have shown that these junctional regions in the canine subendocardium appear to be fixed anatomic sites with locations independent of the activation sequence of the Purkinje network. In addition, the activation delay between the Purkinje cells and the ventricular muscle cells at a junctional site and the patterns of the action potential upstrokes of transitional cells at a junctional site are independent of the activation sequence of the Purkinje network. We have also demonstrated that at some locations there are multiple Purkinje activation signals recorded with a surface electrode and that these multiple activation signals represent discrete groups of Purkinje cells, some of which contribute to the junctional process while others appear to be substantially uncoupled from neighboring Purkinje cell groups and the underlying transitional cells.     

Identification and properties of ATP-sensitive potassium channels in myocytes from rabbit Purkinje fibres

OBJECTIVE: Our goal was to identify the ATP-sensitive potassium (KATP) channels in cardiac Purkinje cells and to document the functional properties that might distinguish them from KATP channels in other parts of the heart. METHODS: Single Purkinje cells and ventricular myocytes were isolated from rabbit heart. Standard patch-clamp techniques were used to record action potential waveforms. and whole-cell and single-channel currents. RESULTS: The KATP channel opener levcromakalim (10 microM) caused marked shortening of the Purkinje cell action potential. Under whole-cell voltage-clamp, levcromakalim induced an outward current, which was blocked by glibenclamide (5 microM), in both Purkinje cells and ventricular myocytes. Metabolic poisoning of Purkinje cells with NaCN and 2-deoxyglucose caused a significant shortening of the action potential (control 376 +/- 51 ms; 6 min NaCN/2-deoxyglucose 153 +/- 21 ms). This effect was reversed with the application of glibenclamide. Inside-out membrane patches from Purkinje cells showed unitary current fluctuations which were inhibited by cytoplasmic ATP with an IC50 of 119 microM and a Hill coefficient of 2.1. This reflects approximately five-fold lower sensitivity to ATP inhibition than for KATP channels from ventricular myocytes under the same conditions. The slope conductance of Purkinje cell KATP channels, with symmetric, 140 mM K+, was 60.1 +/- 2.0 pS (mean +/- SEM). Single-channel fluctuations showed mean open and closed times of 3.6 +/- 1.5 ms and 0.41 +/- 0.2 ms, respectively, at -60 mV and approximately 21 degrees C. At positive potentials. KATP channels exhibited weak inward rectification that was dependent on the concentration of internal Mg2+. Computer simulations, based on the above results, predict significant shortening of the Purkinje cell action potential via activation of KATP channels in the range 1-5 mM cytoplasmic ATP. CONCLUSIONS: Purkinje cell KATP channels may represent a molecular isoform distinct from that present in ventricular myocytes. The presence of KATP channels in the Purkinje network suggests that they may have an important influence on cardiac rhythm and conduction during periods of ischemia.     

AV Nodal Function During Atrial Fibrillation:

AVN Function in Atrial Fibrillation. The irregular ventricular rhythm that accompanies atrial fibrillation (AF) has been explained in terms of concealed conduction within the AV node (AVN). However, the cellular basis of concealed conduction in AF remains poorly understood. Our hypothesis is that electrotonic modulation of AVN propagation by atrial impulses blocked repetitively within the AVN is responsible for changes in function that lead to irregular ventricular rhythms in patients with AF. We have tested this idea using two different simplified computer ionic models of the AVN. The first (“black-box”) model consisted of three cells: one representing the atrium, another one representing the AVN, and a third one representing the ventricle. The black-box model was used to establish the rules of behavior and predictions to be tested in a second, more elaborate model of the AVN. The latter (“nine-cell” model) incorporated a linear array of nine cells separated into three different regions. The first region of two cells represented the atrium; the second region of five cells represented the AV node; and the third region of two cells represented the ventricle. Cells were connected by appropriate coupling resistances. During regular atrial pacing, both models reproduced very closely the frequency dependence of AV conduction and refractoriness seen in patients and experimental animals. In addition, atrial impulses blocked within the AV node led to electrotonic inhibition or facilitation of propagaticm of immediately succeeding impulses. During simulated AF, using the nine-cell model, random variations in the atrial (A-A) interval yielded variations in the ventricular (V-V) interval but there was no scaling, i.e., the V-V intervals were not multiples of the A-A intervals. As such, the model simulated the statistical behavior of the ventricles in patients with AF, including: (1) the ventricular rhythm was random; and (2) the coefficient of variation (standard deviation/mean) of the ventricular rhythm was relatively constant at any given mean V-V interval. Analysis of cell responses revealed that repetitive atrial input at random A-A intervals resulted in complex patterns of concealment within the AVN cells. Consequently, the effects of electrotonic modulation were also random, which resulted in a smearing of the AV conduction curve over A-A intervals that were larger than those predicted for 1:1 AV conduction. Hence, during AF, electrotonic modulation acts in concert with the frequency dependence of AVN conduction to result in complex patterns of ventricular activation. Finally, similarly to what was shown in patients, VVI pacing of the ventricle in the nine-cell model at the appropriate frequency led to blockade of nearly all anterograde (i.e., A-V) impulses. The essential feature here was that the retrograde impulse invading the AVN cells was followed by refractoriness with slow recovery of excitability, setting the stage for electrotonic inhibition of anterograde impulses. Overall, the results provide insight into the cellular mechanisms underlying AVN function and irregular ventricular response during AF.     

The influence of atrial systole on ventricular capture by failing artificial pacemakers. II. Experimental observations

The mechanism by which atrial systole influences the efficacy of ventricular capture by a failing pacemaker was investigated in 12 dogs with atrioventricular heart block. Atrial systole caused facilitation of ventricular capture in eight dogs, and inhibition of capture in 10 dogs. Interpolating atrial extrasystoles caused an enhancement or depression of the hemodynamic performance of the atrial systole that affected the efficacy of the pacemaker stimulus. These interpolation experiments showed that atrial systole influenced the efficacy of capture by a mechanical mechanism and not by an electrotonic mechanism. Atrial systole probably caused motion of the endocardial pacing catheter and/or ventricular myocardium. This motion increased or decreased the contact between the pacing electrode and the endocardium with subsequent changes in the efficacy of capture. In three dogs with pacing through epicardial electrodes, atrial systole had no effect on the efficacy of capture.     

On the mechanism of ouabain toxicity in purkinje and ventricular muscle fibers at rest and during activity

Purkinje and ventricular muscle fibers were loaded with 42 potassium, and tissue radioactivity was measured. At the same time, trans-membrane potentials were recorded. Changes in K fluxes were estimated from the change in tissue radioactivity with the preparation at rest or stimulated electrically. The same procedures were repeated in the presence of ouabain. The results obtained show that ouabain causes (1) a small decrease (about 5 percent) in K uptake in both Purkinje and ventricular muscle fibers at rest; (2) a reduction of about 50 percent of K uptake in stimulated Purkinje fibers; (3) the disappearance of the small increase in K uptake found in stimulated ventricular muscle fibers; (4) a small reduction of K efflux in stimulated Purkinje fibers; (5) a pronounced reduction in K efflux in resting ventricular muscle fibers; and (6) a more frequent inexcitability in Purkinje than in ventricular muscle fibers, although the concentration of ouabain was far smaller for Purkinje fibers. It is concluded that (a) an active fiber is more sensitive than a resting fiber to ouabain toxicity because the usual increase in ionic fluxes (and therefore of active ion transport) with activity is reduced or abolished by ouabain; and (b) Purkinje fibers are more sensitive to ouabain than ventricular muscle fibers because the increase in active ion transport with the onset of stimulation is almost an order of magnitude greater in Purkinje fibers.     

Overdrive suppression of conduction at the canine Purkinje-muscle junction

We have shown previously that overdrive suppression of conduction in depolarized His-Purkinje tissue requires conduction asymmetry. In this study we examined whether overdrive suppression of conduction can occur at the Purkinje-muscle junction, where natural asymmetry of conduction exists. Canine Purkinje-muscle preparations were superfused with hyperkalemic Tyrode's solution (KCl 8 to 12 mM), and action potentials were recorded from Purkinje, junctional, and muscle cells. Initially, the Purkinje fiber was paced at the shortest cycle length at which 1:1 anterograde Purkinje-muscle conduction occurred. The papillary muscle then was paced for 10 to 50 beats at shorter cycle lengths during which, because of conduction asymmetry at the Purkinje-muscle junction, 1:1 retrograde muscle-Purkinje conduction also occurred. After overdrive papillary muscle pacing, Purkinje fiber pacing at the same cycle length that previously resulted in 1:1 conduction now produced transient Purkinje-muscle conduction block (overdrive suppression of conduction). The degree and duration of overdrive suppression of conduction were proportional to the rate and duration of overdrive pacing. After overdrive pacing, Purkinje cell action potential amplitude and Vmax recovered within 300 msec, yet conduction block persisted for up to 7 sec. In contrast, excitability in papillary muscle cells near the Purkinje-muscle junction increased continuously after overdrive pacing. These data suggest that rapid activation of Purkinje cells during overdrive pacing was not required for overdrive suppression of conduction and that restoration of conduction after overdrive pacing was determined primarily by recovery of excitability in papillary muscle cells. Transient Purkinje-muscle conduction block after periods of rapid ventricular rates might account for overdrive-induced conduction disturbances normally attributed to bundle branch block.     

Phase dependency of electrotonic spread of hyperpolarizing current pulses in the rabbit sinoatrial node

Electrotonic current spread in the SA node of the rabbit was measured by means of hyperpolarizing current pulses (1 to 10 microA, 60 ms), which were injected intracellularly through a K(+)-perfused suction electrode. The pulses were applied at the beginning, middle or end of the diastolic depolarization phase. The resulting membrane potential change of nodal fibers was measured with microelectrodes. Space constants were calculated by fitting single exponential curves to the data. The input resistance (Rin) of fibers at different sites in the SA node was measured by means of a double barrel microelectrode (current pulses 5.5 to 11 nA, 60 ms) to detect a change in the internal resistance during the diastolic depolarization phase. During diastole the average electrotonic potential increased by 30% (P less than 0.001), the increase of the space constant ranged from 9 to 183% (P less than 0.05). Rin however, did not change during diastole. It is concluded that the electrotonic spread increased phase dependently, due to an increase of membrane resistance; the internal resistance was not phase dependent.     

Subthreshold Parameters of Cardiac Tissue in a Bi-Layer Computer Model of Heart Failure

Current density threshold and liminal area are subthreshold parameters of the cardiac tissue that indicate its susceptibility to external and internal stimulations. Extensive experimental and theoretical research has been conducted to quantify these two parameters in normal conditions for both animal and human models. Here we employed a 2D numerical model of human cardiac tissue to assess these subthreshold parameters under the pathological conditions of heart failure and fibrosis. Stimuli were applied over an area ranging from 0.04 to 1 mm² using various pulse durations. The current density threshold decreased with increasing stimulation area or pulse duration. No significant changes were found in both parameters between control conditions and heart failure in the atrial tissue, while in the ventricular tissue, heart failure resulted in significantly reduced excitability with higher stimulation current magnitudes needed for excitation and larger liminal areas. This results from the specific ionic remodeling in ventricular heart failure that affects both subthreshold active currents such as I_K1 and connexin 43 conductance. In fibrosis, increased fibroblast to myocyte coupling coefficient had a non-linear influence on current density thresholds, with an initial increase of current magnitude followed by a relaxation phase down to the current magnitude threshold for the control condition with no fibrosis. The results show that subthreshold excitation properties of the myocardium are influenced in a complex, non-linear manner by cardiac pathologies. Such observations may contribute to our understanding of impulse capturing properties, relevant, for example, for the generation of ectopic foci-originated arrhythmias and for the efficient design of cardiac stimulating electrodes.