Abrupt Changes In Cycle Length Research Articles

Representing variability and transmural differences in a model of human heart failure.

During heart failure (HF) at the cellular level, the electrophysiological properties of single myocytes get remodeled, which can trigger the occurrence of ventricular arrhythmias that could be manifested in many forms such as early afterdepolarizations (EADs) and alternans (ALTs). In this paper, based on experimentally observed human HF data, specific ionic and exchanger current strengths are modified from a recently developed human ventricular cell model: the O'Hara-Virág-Varró-Rudy (OVVR) model. A new transmural HF-OVVR model is developed that incorporates HF changes and variability of the observed remodeling. This new heterogeneous HF-OVVR model is able to replicate many of the failing action potential (AP) properties and the dynamics of both [Ca(2+)]i and [Na(+)]i in accordance with experimental data. Moreover, it is able to generate EADs for different cell types and exhibits ALTs at modest pacing rate for transmural cell types. We have assessed the HF-OVVR model through the examination of the AP duration and the major ionic currents' rate dependence in single myocytes. The evaluation of the model comes from utilizing the steady-state (S-S) and S1-S2 restitution curves and from probing the accommodation of the HF-OVVR model to an abrupt change in cycle length. In addition, we have investigated the effect of chosen currents on the AP properties, such as blocking the slow sodium current to shorten the AP duration and suppress the EADs, and have found good agreement with experimental observations. This study should help elucidate arrhythmogenic mechanisms at the cellular level and predict unseen properties under HF conditions. In addition, this AP cell model might be useful for modeling and simulating HF at the tissue and organ levels.

Electrophysiological properties under heart failure conditions in a human ventricular cell: a modeling study.

Heart failure (HF) is one of the major diseases across the world. During HF the electrophysiology of the failing heart is remodeled, which renders the heart more susceptible to ventricular arrhythmias. In this study, we quantitatively analyze the effects of electrophysiological remodeling of the major currents of human ventricular myocytes on the dynamics of the failing heart. We develop a HF model using a modified version of a recently published model of the human ventricular action potential, the O'Hara-Virag-Varro-Rudy (OVVR) model. The proposed HF model incorporates recently available HF clinical data. It can reproduce most of the action potential (AP) properties of failing myocytes, including action potential duration (APD), amplitude (APA), notch (APN), plateau (APP), resting membrane potential (RMP), and maximum upstroke velocity (dV/dtmax). In addition, the model reproduces the behavior of the [Na+], concentration and [Ca(2)+]i dynamics. Moreover, the HF model exhibits alternans with a fast pacing frequency and can induce early afterdepolarizations (EADs). Additionally, blocking the late sodium current shortens the APD and suppresses EADs, in agreement with experimental findings. The dynamics of the proposed model are assessed through investigating the rate dependence of the AP and the dynamics of the major currents. The steady-state (S-S) and S1-S2 restitution curves along with accommodation to an abrupt change in cycle length were evaluated. Our study should help to elucidate the roles of alterations in electrophysiological properties during HF. Also, this HF cellular model could be used to study HF in a realistic geometry and could be embedded into a model of HF electromechanics to investigate electrical and mechanical properties simultaneously during HF.

Regional differences in the dynamics of refractoriness in intact and hypertrophied in situ canine hearts

Functional re-entry is thought to represent the predominant mechanism underlying ventricular arrhythmias. Functional conduction block may be caused by regional dispersion of refractoriness (ERP). Dispersion of ERP may not be evident at baseline, but may occur with sudden changes in heart rate, as ventricular arrhythmias are commonly induced by short-long-short cycles. We examined the dynamics of local ERPs at two left ventricular (LV) sites in dogs with either no structural heart disease or biventricular hypertrophy (BVH). ERPs were determined at each of four bipoles of two adjacent needle electrodes in the LV apex and the lateral wall. The stimulation protocol included two different basic cycle lengths, one or two longer cycles after a train of 6 or 5 shorter cycles, and one shorter cycle after a train of 6 longer cycles. In normal dogs, a significant apicolateral ERP gradient was only evident with the longer basic cycle length. One shorter cycle was sufficient to dissolve that gradient. One longer cycle was enough to create a regional ERP gradient. Dynamic regional gradients occurred because the apex responded more markedly and more readily to abrupt changes in cycle length. BVH led to an increase in ERP at both LV sites and to an aggravation of regional ERP gradients. Dynamic ERP behavior seems to depend on topography and underlying pathology. Abrupt changes in heart rate might induce dynamic refractory gradients between various regions of the normal heart, but also between adjacent regions inhomogenously affected by hypertrophy.

Wide‐Complex Tachycardia with an Abrupt Change in Cycle Length:

Wide‐Complex Tachycardia with an Abrupt Change in Cycle Length:

Effect of rate and coupling interval on endocardial R wave amplitude variability in permanent ventricular sensing lead systems

Objectives. We have observed sensing errors in third generation implantable cardioverter-defibrillators that appear to be caused by variation in the R wave amplitude during sinus rhythm, particularly after premature beats. The purpose of this study was to quantify spontaneous R wave variability during sinus rhythm and to determine whether abrupt changes in cycle length further augment R wave amplitude variability.Background, Pacemaker sensing algorithms presume a relatively constant R wave signal to establish a sensing threshold. The concept of a fixed sensing threshold is not as applicable in third-generation cardioverter-defibrillators, which depend on automatic gain amplifiers to rapidly detect ventricular fibrillation. These devices may be susceptible to undersensing during sinus rhythm if significant variability in R wave signal characteristics occurs.Methods. Twelve patients with combination bradycardia pacing cardioverter-defibrillators were studied. The device used (Cadence, Ventritex) allowed recording of real time, telemetered electrograms from the sensing lead system. Measurements were made of the maximal range of the R wave amplitude during sinus rhythm and in response to abrupt changes in heart rate produced by premature atrial and ventricular stimuli.Results. The maximal range in R wave amplitude during sinus rhythm was 1.7 ± 1.3 mV, or 23.7 ± 19.2% of the mean R wave amplitude. The R wave amplitude variability increased with abrupt changes in cycle length, with a range of 2.8 ± 1.5 mV, or 38.8 ± 18.3% of the mean R wave amplitude (p < 0.05 compared with sinus rhythm). In most patients, R wave amplitude and coupling interval demonstrated an inverse proportional relation. Conclusions. There is substantial variability in the R wave amplitude during sinus rhythm measured by permanent ventricular sensing lead systems, and this variability is further augmented by abrupt changes in cycle length. This phenomenon may explain the occurrence of undersensing of sinus rhythm in implantable cardioverter-defibrillators with automatic gain sense amplifiers.

Effects of temperature on cycle length dependent changes and restitution of action potential duration in guinea pig ventricular muscle.

The aim was to investigate the effects of temperature on cycle length dependent changes of action potential duration and on restitution of action potential duration. Guinea pig papillary muscle action potentials were recorded using conventional microelectrode techniques. Action potential duration was measured at cycle lengths ranging from 500 to 2000 ms at both 27 degrees C and 37 degrees C. Restitution of action potential duration was determined by introducing an extra stimulus at progressively longer diastolic intervals from 40 to 9000 ms at pacing cycle lengths of 500, 1000, and 2000 ms. At 37 degrees C, action potential duration measured at 90% of repolarisation (APD90) during continuous pacing and the maximum value of APD90 achieved during restitution (APD90pl) decreased by 18(SEM 6) ms (n = 7) and 24(7) ms (n = 6), respectively, when pacing cycle length was reduced from 2000 to 500 ms. At 27 degrees C, the magnitude of the shortening of APD90 and APD90pl observed when pacing cycle length was similarly reduced was greater than at 37 degrees C, ie, 143(21) ms (n = 6) and 115(11) ms (n = 6), respectively. Thus the relation for restitution of action potential duration shifted downwards with reduction in pacing cycle length, and the magnitude of this shift was greater at 27 degrees C than at 37 degrees C. The difference between APD90 at the shortest diastolic interval (40 ms) and at diastolic interval of 100 ms (range of premature action potential durations) was much greater at 27 degrees C than at 37 degrees C at all three pacing cycle lengths. Reduction in temperature magnifies the cycle length dependent changes in action potential duration both during abrupt changes in cycle length, as with an extra stimulus, and during changes of steady state cycle length. This may indicate a greater dispersion of premature action potential durations during hypothermia, and hence predispose to hypothermia induced arrhythmias.

Differentiation of Arrhythmias by Measurement of Intracardiac Pressures in Man

Antitachycardia devices currently use sustained high rate, abrupt changes in cycle length, and probability density function to determine the onset of ventricular tachycardia. Hemodynamic changes occur with the onset of tachycardia and may provide a method of discriminating supraventricular from ventricular tachycardia. In this study, patients had atrial and ventricular pressures measured during rapid atrial and ventricular pacing. Right atrial pressure increased significantly with ventricular pacing but not with atrial pacing. Right ventricular pressures did not significantly differ with atrial or ventricular pacing. The change in atrial pressure compared to baseline was greater, with ventricular pacing compared to atrial pacing. Right ventricular pressure increased compared to baseline with atrial or ventricular pacing, but there was no significant difference between pacing modalities. Measurement of right atrial pressure might prove useful in discriminating supraventricular from ventricular tachycardia.

Concentration- and rate-dependent electrophysiological effects of restacorin on isolated canine purkinje fibres

The cellular electrophysiological effects of restacorin, a new antiarrhythmic agent were studied using conventional microelectrode techniques in isolated dog cardiac Purkinje fibres. Restacorin (1-30 mumol/l) decreased the maximum rate of rise of the action potential upstroke and action potential amplitude while action potential duration measured at 90% of repolarization was shortened in a concentration-dependent manner during pacing at a constant basic cycle length of 500 ms. The effect of 10 mumol/l restacorin on maximal rate of rise of the action potential upstroke and on action potential duration measured at 90% of repolarization were also studied while varying the constant pacing cycle length between 300 and 5000 ms. The results of these studies indicated a rate-dependent effect of restacorin on the action potential characteristics examined. After abrupt changes in cycle length, 10 mumol/l restacorin slowed the fast component of the relation for restitution of action potential duration from 155.3 +/- 5.2 ms (control, n = 6) to 217.1 +/- 17.8 ms (n = 6, P less than 0.05). In the presence of restacorin (10 mumol/l), a second slow component for recovery of maximal action potential upstroke rising velocity was expressed having a time constants of 8.5 +/- 1.2 s. The range of premature action potential durations was significantly decreased (by 57.1%, P less than 0.01) by 10 mumol/l restacorin. These results indicate that the cellular electrophysiological effects produced by restacorin in dog cardiac Purkinje fibres best resemble those produced by recognized class Ic antiarrhythmic drugs.

Differential Effects of Abrupt Cycle Length Changes on the Refractoriness of Accessory Pathway, His‐Purkinje System, Atrial and Ventricular Myocardium in Wolff‐Parkinson‐White Syndrome

We compared the response of the accessory pathway (AP), the atrial myocardium, the His-Purkinje system (HPS) and the ventricular myocardium during steady state (constant cycle length) and following an abrupt alteration in cycle length in 23 patients with Wolff-Parkinson-White syndrome. The durations of the anterograde and retrograde refractory periods were measured during constant drive cycle lengths of 600 and 400 ms (Method I) and during an abrupt change in cycle length of either short-to-long (400 to 600 ms) (Method II) or long-to-short (600 to 400 ms) (Method III) just before the extra stimulus. The mean durations of the anterograde effective refractory periods of the APs were 295 +/- 43, 243 +/- 39 and 273 +/- 37 ms at 600, 400 and 400 to 600 ms cycle lengths, respectively. For the atrial effective refractory periods at the three cycles, they were 238 +/- 18, 217 +/- 11 and 241 +/- 17 ms, respectively. During ventricular stimulation, the mean durations of the retrograde effective refractory periods of the APs were 263 +/- 25, 245 +/- 19 and 253 +/- 21 ms at cycle lengths of 600, 400 and 400 to 600 ms, respectively. For the relative refractory periods of the HPS, they were 335 +/- 29, 239 +/- 23 and 367 +/- 38 ms, respectively and, for the effective refractory periods of the ventricular myocardium, they were 227 +/- 17, 206 +/- 15 and 215 +/- 18 ms, respectively. The retrograde effective refractory period of the HPS could be measured in only five patients at the three cycles (600, 400 and 400 to 600 ms) and the mean values were 265 +/- 57, 225 +/- 14 and 305 +/- 27 ms, respectively. With Method III, AP and ventricular myocardium responded in a cumulative manner while HPS demonstrated paradoxical effect. Compared to Method I, changes with Methods II and III were statistically significant for all variables measured. During all three cycles, the retrograde effective refractory period of the HPS exceeded the effective refractory period of the AP; and the HPS demonstrated progressive conduction delay while the AP responded to no or minimal delays when the V1V2 intervals were similar. An abrupt cycle length change of the short-to-long type facilitated the induction of orthodromic tachycardia during ventricular pacing.(ABSTRACT TRUNCATED AT 400 WORDS)

Atrioventricular Nodal Conduction and Refractoriness Following Abrupt Changes in Cycle Length

The properties of the atrioventricular (AV) nodal conduction and effective refractory period in man are generally evaluated at a constant basic cycle length (CL) and, in most cases, they demonstrate an inverse relationship to the drive cycle. The response of AV node to abrupt change in CL is less defined. We therefore studied the effects of abrupt changes in CL on AV nodal conduction time and refractoriness in 18 patients. AV nodal conduction time, and effective and functional refractory periods were measured during: (1) a constant long CL, (2) a constant short CL, and (3) after an abrupt increase in CL just prior to the introduction of extrastimuli. In 10 of the 18 patients a constant long CL of 600 ms, a constant short CL of 400 ms and a sudden short-to-long change in CL (400 to 600 ms) were tested. AV nodal conduction times (A2H2) were measured at the shortest and longest comparable A1A2 intervals. The mean value of the shortest A2H2 intervals for constant CL of 600 ms was 144 +/- 18 ms; for a constant CL of 400 ms it was 162 +/- 17 ms; after a sudden short-to-long change in CL (400 to 600 ms) it was 142 +/- 14 ms. The mean value of the longest A2H2 intervals at a constant CL of 600 ms was 185 +/- 18 ms; at a constant CL of 400 ms it was 236 +/- 26 ms (p less than 0.01) and after a short-to-long change in CL (400 to 600 ms) 199 +/- 21 ms. AV nodal effective refractory periods measured at the same three CLs had mean values of 279 +/- 13 ms; 300 +/- 15 ms and 294 +/- 13 ms, respectively. Similar results were obtained when other CLs such as 700 to 900, 500 to 900, and 400 to 700 ms were tested. The data suggest that after abrupt short-to-long changes in CL, AV nodal function curves shift from long constant CL toward short constant CL as the coupling intervals decrease, indicating a cumulative pattern. Although the return to baseline conduction time after the fast basic rate is known to be slow, the limitation of this effect to the very early premature beat in the human has not been reported previously.

Electrical restitution process in dispersed canine cardiac Purkinje and ventricular cells.

Rate-dependent changes in cardiac action potential duration (APD) have been related to ion accumulation and depletion in restricted extracellular spaces. Isolated cardiac cells lack intercellular clefts and thus are less likely than intact tissue to experience ionic transients immediately outside the plasma membrane. Furthermore, isolated Purkinje cells lack the T tubules found in ventricular tissue and cells, which also can be a site of ion accumulation and depletion. We therefore employed single canine ventricular and Purkinje cells to investigate the contribution of restricted spaces to the electrical restitution process. In both cell types, abrupt changes in cycle length do not alter resting potential, but APD alters with a time constant of approximately 1 min. In addition, both preparations exhibit two components to the electrical restitution process of the APD. The rapid component has a time constant of 66 +/- 17 ms in the ventricle cells and 186 +/- 43 ms in the Purkinje cells. The slower component is both smaller and more variable. These values are similar to those reported in intact canine ventricular and Purkinje tissue. Thus the restitution process of APD, as measured in these isolated cardiac cells, is not markedly dependent on the presence or absence of restricted extracellular spaces.

Effects of abrupt changes in cycle length on atrial refractory periods in man

While the electrophysiologic effects of sudden changes in cycle length on the His-Purkinje System and ventricular myocardial refractoriness are better known, the behavior of atrial myocardium in this regard is poorly understood. The effects of an abrupt long to short cycle length change (11 patients: group A) and/or short to long cycle length alteration (18 patients: group B) on the atrial effective and functional refractory period were assessed during electrophysiologic studies. The values thus obtained were compared to those observed during the scanning of both constant long and constant short cycle lengths of the same duration. In group A the effective and functional refractory periods of the right atrium measured 250 ± 38 msec and 296 ± 31 msec during a constant long cycle length of 709 ± 80 msec, whereas the same parameters had values of 228 ± 30 msec and 260 ± 32 msec, respectively, at a constant short cycle length of 436 ± 81 msec. With an abrupt change in cycle length from long to short (a change of 273 ± 75 msec), the effective and functional atrial refractory periods were 225 ± 29 and 267 ± 29 msec in that order, and these values closely approximated those seen with a constant short cycle length. Similarly, the two atrial refractory period parameters in group B measured 218 ± 16 msec and 262 ± 19 msec during a constant short cycle length of 414 ± 68 msec and were 236 ± 17 msec and 284 ± 21 msec, respectively, at a constant long cycle length of 689 ± 92 msec. With a sudden short to long cycle length change of 275 ± 91 msec, the effective and functional atrial refractory periods measured 238 ± 15 and 284 ± 22 msec, respectively. The latter set of values are again quite similar to those obtained at a constant long cycle length. These data suggest that refractoriness of the human atrial myocardium adjusts abruptly and appropriately to the duration of the last cycle length. This behavior is indeed unique when compared to ventricular myocardium, which shows a cumulative effect of several preceding cycles, and His-Purkinje system, where the refractoriness overshoots in the direction of cycle length change.

Triggered rhythms in atrial muscle

Intracellular and extracellular recording techniques were used to study triggered activity in tissues isolated from the inferior right atrium of the dog. In the presence of norepinephrine (>10 −7 M) single stimuli or short rapid pacing elicited action potentials with delayed after-depolarizations, leading to single or repetitive non-driven beats. Most commonly, during sustained triggered activity action potential and electrogram configurations remained constant. In addition, cycle length changed gradually, initially decreasing and then increasing before activity stopped. However in some preparations, once sustained triggered activity was initiated there were abrupt spontaneous changes in action potential and electrogram configurations that were coincident with abrupt spontaneous changes in cycle length. When quiescent, short rapid pacing caitiated triggered activity with a relatively short cycle length that abruptly shifted to a longer cycle length before stopping. During sustained triggered activity, short rapid pacing caused an abrupt decrease in cycle length that was coincident with changes in action potential and electrogram configurations. The present results indicate that abrupt changes in cycle length can occur during bouts of triggered activity resulting in unique patterns of arrhythmias. These rhythms may be due to interactions and shifts between multiple sites of triggered pacemaker activity.

Frequency-Dependent Effects of Several Class I Antiarrhythmic Drugs on &amp;OV0312;max of Action Potential Upstroke in Canine Cardiac Purkinje Fibers

Vmax of the action potential upstroke in canine cardiac Purkinje fibers was studied in the presence of seven class I antiarrhythmic drugs--lidocaine (4 micrograms/ml), mexiletine (4 micrograms/ml), propranolol (0.9 micrograms/ml), procainamide (30 micrograms/ml), quinidine (5 micrograms/ml), flecainide (4 micrograms/ml), and disopyramide (3.1 micrograms/ml)--at constant cycle lengths (CCL) and after abrupt changes in cycle length (ACCL). The time constant of Vmax recovery after ACCL at a basic cycle length of 500 ms was 0.09 +/- 0.01 s for lidocaine, 0.18 +/- 0.03 s for mexiletine, 1.35 +/- 0.20 s for propranolol, 4.4 +/- 0.8 s for procainamide, 8.3 +/- 1.2 s for quinidine, 11.0 +/- 0.9 s for flecainide, and 37.9 +/- 9.4 s for disopyramide. These values were similar to those reported by others in guinea pig papillary muscle, and, with the exception of flecainide, conformed to the scheme proposed by Courtney (J Mol Cell Cardiol 1980; 12:1273-86) based on the molecular weight and lipid solubility hypothesis. Each drug altered the Vmax differently at CCL from after ACCL at the same diastolic intervals. The magnitude of these differences and the range of diastolic intervals at which they were present varied among different drugs. These observations explain differences in the drug effects on the Vmax of the regularly and prematurely occurring depolarizations. In the presence of lidocaine and mexiletine, the recovery kinetics of Vmax were not altered by CCL within the 300-1,500-ms range, and the magnitude of Vmax depression was not influenced by action potential duration within the 200-270-ms range.

Facilitation of macroreentry within the His-Purkinje system with abrupt changes in cycle length.

We have recently described the ability of abrupt short-to-long changes in atrial cycle length (CL) to prolong refractoriness of the His-Purkinje system (HPS) and increase the likelihood of aberrant ventricular conduction. We have also shown similar functional behavior in retrograde refractoriness of the HPS during changes in ventricular CL. To further assess these characteristics we evaluated the effect of abrupt short-to-long change in ventricular CL on the phenomenon of macroreentry within the HPS (Re-HPS) in 20 patients in whom Re-HPS occurred during application of a ventricular extrastimulus (V2) at a constant ventricular CL (method I) and/or with abrupt short-to-long change in CL (method II). For both methods V2 was coupled to a CL of identical duration, designated the reference CL (CLR). In method I the CLs preceding (CLP) the CLR equaled CLR, whereas in method II CLP was less than CLR. The results showed a dramatic increase in occurrence of Re-HPS with abrupt short-to-long change in CL with Re-HPS occurring in 19 patients with this method compared with in 11 patients during constant CL. In 10 patients manifesting Re-HPS with both methods the associated retrograde conduction (V2H2) delays were equal or less during abrupt short-to-long changes in CL and, remarkably, there were concomitantly shorter antegrade conduction (H2V3) delays compared with at a constant CL. Moreover, despite the resulting shorter V2V3, additional Re-HPS beats were also more likely to occur with abrupt short-to-long change in CL compared with at a constant CL.(ABSTRACT TRUNCATED AT 250 WORDS)

Divergence between refractoriness of His-Purkinje system and ventricular muscle with abrupt changes in cycle length.

The concept that refractoriness of the His-Purkinje system (HPS) and ventricular muscle both vary directly with cycle length is based on observations during the use of constant cycle length. During abrupt changes in ventricular cycle length, refractoriness of the ventricular muscle is known to reflect the cumulative durations of preceding cycle lengths. The effect of such changes on retrograde refractoriness of the HPS is not known. In this study refractoriness of ventricular muscle and of the HPS was evaluated in 30 patients with normal intraventricular conduction by the ventricular extrastimulus (V2) technique during constant cycle length (method I) and during abrupt cycle length changes (method II). During method II the cycle length immediately before V2 was identical to the constant cycle length of method I and therefore was designated as the reference cycle length (CLR); however, the cycle length preceding (CLP) CLR was either longer than CLR (method IIA) by 100 to 300 msec in 11 patients or shorter than CLR (method IIB) by 100 to 300 msec in 30 patients. Results showed that compared with method I, method IIA shortened the relative refractory period (RRP) of the HPS from 350 +/- 29 to 344 +/- 29 msec (p less than .04), whereas the effective refractory period (ERP) of the ventricular muscle increased from 225 +/- 21 to 233 +/- 20 msec (p less than .0001). In contrast, compared with method I, method IIB lengthened the RRP of the HPS from 335 +/- 30 to 351 +/- 35 msec (p less than .0001), whereas ERP of the ventricular muscle decreased from 223 +/- 23 to 213 +/- 22 msec (p less than .0001). Similar to the inverse relationship between CLP and RRP of the HPS, ERP of the HPS was prolonged with short CLP (method IIB) compared with long CLP (method IIA). The results indicate a marked divergence between refractoriness of the HPS and of ventricular muscle during abrupt cycle length changes; these results were not previously anticipated. Whereas ventricular muscle responded to cumulative effects of preceding cycle lengths and varied directly with CLP, the HPS appeared to respond to directional and/or dynamic changes in cycle length and varied inversely with CLP. Moreover, in contrast to ventricular muscle, the HPS appeared to be responsive to rate of change in cycle length whereby short-to-long change in cycle length had a greater effect than long-to-short change in cycle length.

Effects of abrupt changes in cycle length on refractoriness of the His-Purkinje system in man.

Abrupt changes in cycle length (CL) occur frequently in the clinical setting of atrial fibrillation. However, the effects of such changes on the His-Purkinje system (HPS) have not previously been considered during aberrant ventricular conduction (VAb). In 12 patients who manifested VAb with atrial premature stimulation (A2) during sinus rhythm, the relative refractory period (RRP) of the HPS was evaluated during a constant atrial CL (method I) and during abrupt changes in the CL (method II), wherein the A2 was coupled to an atrial CL (last A1A1) comparable to method I. This last A1A1 during method II was preceded by a series of constant atrial CLs 100-200 msec longer (method IIA) in 11 of 12 patients, or 109-300 msec shorter (method IIB) in all 12 patients. Although abrupt changes in the atrial CL using method IIA resulted in a longer HH interval (by 0-30 msec; mean 13.2 +/- 9.2 msec) preceding the A2, the RRP-HPS was 5-20 msec shorter (mean 9.3 +/- 5.3 msec) compared with method I in eight patients. The effect of abrupt changes was further evaluated in nine patients using method III, with a constant atrial CL, with a duration equal to the last H1H1 interval of method IIA. The VAb that occurred with method III was not manifested with method IIA in seven of nine patients, and in two patients the RRP-HPS was the same or less. Conversely, method IIB resulted in a shorter HH interval (by 0.110 msec; mean 28.9 +/- 21.1 msec) preceding A2, but in 10 patients, RRP-HPS was 5-40 msec longer (mean 20.7 +/- 10.5 msec) than that of method I and in two, VAb was only manifested using method IIB. Further scanning with method III, derived from the HH interval immediately preceding A2 of method IIB, was performed in seven patients and compared with method IIB. Prolongation in the RRP-HPS was shown using the latter method. The results indicate that abrupt changes in CL influence the functional behavior of the HPS in a manner not anticipated. Such changes may have important implications in determining the occurrence of VAb during atrial fibrillation.

Simultaneous recording of monophasic action potentials and contractile force from the human heart.

Cardiac monophasic action potentials (MAPs) and contractility have been simultaneously measured in man while the heart rate was being changed by right atrial pacing. A new non-suction electrode was used for safe and long-term recording of MAPs from the endomyocardium. Abrupt changes in cycle-length were followed first by a fast, then a slow response in the adaptation of MAP-duration and of contractility (LV dp/dt max) to the new steady state. After increasing the heart rate then slow phase of MAP shortening appears to be related to the slow staircase of contractility, whereas after the step decrease of frequency no such a relation could be observed. The consistency of these results with those obtained in corresponding in-vitro experiments indicates that this methodical approach may be suitable for assessing the process of E-C coupling in the human heart.