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M R Franz

Publications and source records attributed to M R Franz.

At least 55 records · Page 3Linked to original sources
PubMed1996

[In vivo registration of monophasic action potentials--new possible applications in clinical electrophysiology].

Monophasic action potential (MAP) recordings have gained a more important role during the recent years. A new application for their use in the clinical laboratory is the precise differentiation between ventricular tachycardias and ventricular fibrillation. A correct diagnosis of the arrhythmic episode may be of relevance for the determination of the defibrillation threshold during implantation and testing of implantable cardioverter defibrillators. Diagnostic studies and ablation procedures of triggered arrhythmias represent another indication for MAP recordings. The focus of enhanced automaticity can be located by the detection of afterdepolarizations which allows a reliable ablation using a MAP-ablation combination catheter. Recently, a new phenomenon has been reported regarding the relationship between ventricular repolarization and excitability during programmed electrical stimulation in humans. Each additional extrastimulus was able to capture the myocardium at a less complete repolarization level than the previous one. This "facilitation of excitability" phenomenon or "encroachment" was correlated with the initiation of ventricular tachyarrhythmias. The involved mechanism can be modulated pharmacologically and might therefore play a role in the antiarrhythmic treatment of patients with ventricular arrhythmias.

Cardiac Pacing, Artificial↗
PubMed1996

The vulnerable period for low and high energy T-wave shocks: role of dispersion of repolarisation and effect of d-sotalol.

INTRODUCTION: The induction of ventricular fibrillation (VF) by T-wave shocks has been related to dispersion of repolarisation, but only indirect evidence of this hypothesis exists. The effects of drugs prolonging repolarisation like d-sotalol on the vulnerability to T-wave shocks remain unknown. METHODS: In 9 isolated rabbit heart, 7 monophasic action potentials (MAPs) and an ECG were recorded simultaneously. Vulnerable periods were determined using two different shock strengths, one close to the fibrillation threshold and the other close to the upper limit of vulnerability, at baseline and after action potential prolongation by d-sotalol. RESULTS: The vulnerable period had a duration of 30 +/- 14 ms for the lower and 34 +/- 12 ms for the higher shock strength (P = NS). Coupling intervals of the vulnerable periods were 13 +/- 10 ms shorter for higher shock strengths as compared to lower shock strengths (P < 0.005). The vulnerable period for low shock strengths coincided with dispersion of MAPs at 90% repolarisation (r = 0.87-0.92, P < 0.005), and the vulnerable period for high shock strengths coincided with dispersion at 70% repolarisation (r = 0.82-0.93, P < 0.005). ECG parameters predicted the vulnerable periods less precisely than MAP repolarisation (r < or = 0.72). d-Sotalol prolonged MAP durations by an average of 33 ms at 70% and 39 ms at 90% repolarisation but did not alter the described relations, nor did it reduce dispersion of repolarisation or duration of the vulnerable periods. CONCLUSIONS: Dispersion of repolarisation determines vulnerable periods and might be part of the arrhythmogenic substrate promoting induction of VF by T-wave shocks. The coupling intervals of the vulnerable periods depend on the applied shock strength as well as repolarisation, with shock strengths close to the fibrillation threshold inducing VF during dispersion at 90% repolarisation and shock strengths close to the upper limit of vulnerability inducing VF during dispersion at 70% repolarisation. d-Sotalol reduces neither vulnerability to T-wave shocks nor dispersion of repolarisation in this isolated heart model.

Action Potentials↗
PubMed1996

Stretch-induced voltage changes in the isolated beating heart: importance of the timing of stretch and implications for stretch-activated ion channels.

OBJECTIVES: It is now well recognized that myocardial stretch can cause arrhythmias due to stretch-induced depolarizations. The effects of transient stretch applied during the various phases of the cardiac action potential have not been investigated. This study (1) examined the effects of short stretch pulses and sustained stretch on the monophasic action potential (MPA) repolarization time course and diastolic potential, (2) examined the arrhythmic response to differently timed stretch pulses, and (3) tested by comparison with computer simulations whether these effects are compatible with stretch-activated channel characteristics known from patch-clamp studies. METHODS: We studied the MAP changes elicited by short transient stretch pulses applied at different times during the cardiac cycle to 8 isolated Langendorff-perfused rabbit hearts. The left ventricle (LV) was instrumented with a fluid-filled balloon, the volume of which was altered rapidly and precisely by means of a computer-controlled linear motor-driven piston. MAPs were recorded simultaneously from one right ventricular (RV) and two LV sites while short volume pulses of increasing amplitude were applied to the LV at variable delays after the last of 8 regular electrical pacing stimuli. The effect of pulsatile volume pulses applied at different phases of electrical systole and diastole was compared to the effect of sustained stretch pulses (60 s duration) of the same amplitude. The experimental results were compared with computer simulations of stretch-induced effects on the action potential to further validate the experimentally measured effects with theoretical predictions based on the Oxford Heart model with added stretch channel terms. RESULTS: Stretch pulses applied during early systole caused a brief transient repolarization during the LV MAP plateau phase, with a maximal amplitude of 24 +/- 10% of the total MAP amplitude. Stretch pulses at the end of the MAP caused a transient depolarization, with a maximal amplitude of 13 +/- 5%. These oppositely polarized stretch effects crossed over during a transitional range of repolarization (mean 65 +/- 9% of repolarization) when stretch produced neither transient repolarizations nor depolarizations. Only stretch pulses applied at a mean repolarization level of 77 +/- 5% or later led to arrhythmias, preceded by transient depolarizations. No corresponding de- or repolarizations were seen in MAPs recorded simultaneously from the unstretched RV. The effects of long pulses on the MAP waveform were nearly identical to an overlay plot of the effects of many differently timed short transient pulses. When the stretch-induced voltage changes in the MAP were plotted against the repolarization level at which they were produced, a linear relationship was found (mean correlation coefficient r = 0.97; P < 0.0001) with a reversal at approximately half the total MAP amplitude. The computer simulations of the influence of stretch-activated channels reproduced both the effects of short and sustained stretch seen in the MAP recordings. CONCLUSIONS: We demonstrated in the isolated beating heart that the electrophysiologic effects of sudden myocardial stretch depend on the timing of the stretch relative to electrical systole or diastole. These findings are in agreement with patch clamp studies on stretch-activated ion channels which showed a linear current/voltage relation with a reversal potential between -20 and -30 mV. Only stretch pulses applied at the end of the action potential or during diastole elicit ectopic beats as a result of transient depolarizations, while stretch pulses applied during phase 2 and 3 cause transient repolarizations or no effect, respectively.

Action Potentials↗
PubMed1995

Relation between repolarization and refractoriness during programmed electrical stimulation in the human right ventricle. Implications for ventricular tachycardia induction.

BACKGROUND: Although programmed electrical stimulation is widely used for provoking sustained ventricular tachycardia (VT), the mechanism by which repetitive extrastimulation evokes VT is still little understood. Specifically, it is not clear why several closely coupled extrastimuli are frequently required to induce VT. Although regularly paced human ventricular myocardium exhibits a near constant relation between myocardial repolarization and refractoriness, the effect of repetitive extrastimulation on the relation between repolarization and excitability in the human heart and its relevance for arrhythmia induction by programmed stimulation are unknown. We hypothesized that the induction of VT by repetitive extrastimulation is facilitated by an altered relation between repolarization and refractoriness, and this leads to disturbances in ventricular impulse propagation, which trigger the onset of VT. METHODS AND RESULTS: Twenty-one patients undergoing routine electrophysiological study were paced from the right ventricular apex and outflow tract endocardium with monophasic action potential-pacing catheters placed at both sites simultaneously Monophasic action potential durations (APDs) and effective refractory periods (ERPs) were measured simultaneously at each site, during regular stimulation (S1-S1) at 400-ms cycle length and during three consecutive extrastimuli (S2 through S4) at the closest coupling intervals at which all three extrastimuli still resulted in capture. Measurements further included the repolarization level at which the earliest capture occurred, the ratio between ERP and APD, and the propagation time between the pacing and distant recording site. APD and ERP both shortened progressively with each extrastimulus. APD at 90% repolarization decreased from a baseline (S1) of 238.1 +/- 19.7 ms by 14.9% at S2, 18.9% at S3, and 22.9% at S4 (P < .0001, S1 versus S4). ERP decreased from 233.1 +/- 19.7 ms (S1) to 180.0 +/- 41.9 ms (S3) (P < .0001, S1 versus S3). While ERP shortening occurred mainly on the basis of APD shortening, there was an additional factor that contributed to ERP shortening independent of APD shortening. Each consecutive extrastimulus was able to elicit a propagated response at earlier repolarization levels than the previous one: the earliest capture for S2 occurred at 85.5 +/- 10.2% of complete repolarization, for S3 at 83.9 +/- 10.5%, and for S4 at 78.4 +/- 11.2% (P < .05 for S2 versus S3; P < .05 for S3 versus S4; P < .01 for S2 versus S4). This progressive "encroachment" of the earliest capture stimulus onto the preceding repolarization phase (at progressively less repolarized levels) correlated with a progressive delay of impulse propagation between the pacing site and the second recording site: propagation time increased from baseline (S1) by 10.5 +/- 1.3% with S2 to 19.0 +/- 1.6% with S3 and to 22.5 +/- 2.8% with S4 (P < .05, S4 versus S1). VT was induced in 11 of 21 patients. Nine of these had VT induced only when significant encroachment of extrastimuli on the preceding repolarization phase (< 81.3 +/- 7.0%) and associated conduction slowing (> 16.6 +/- 1.8%) were present. CONCLUSIONS: Repetitive extrastimulation not only shortens APD and subsequently ERP but also alters the ERP/APD relation by allowing capture to occur at progressively less complete repolarization levels. This progressive encroachment onto the preceding repolarization phase is associated with impaired impulse propagation and a high incidence of VT induction. This may help explain how repetitive, closely coupled extrastimulation induces ventricular tachycardia in the human heart.

Aged↗
PubMed1995

Sudden cardiac death and polymorphous ventricular tachycardia in patients with normal QT intervals and normal systolic cardiac function.

This study delineates the clinical spectrum of 15 patients with polymorphic ventricular tachycardia and normal QT intervals in the absence of apparent structural heart disease, adverse drug effects, or electrolyte disturbances. Patients presented with either palpitations (n = 2), presyncope (n = 5), syncope (n = 4), no symptoms (n = 1), or aborted sudden death (n = 3). Mean age was 41 years (range 20 to 64), and mean follow-up 38 months (range 4 to 109). Left ventricular function was normal as determined by either echocardiogram (n = 9) or left ventriculography (n = 9). Episodes of polymorphic ventricular tachycardia (VT) were analyzed in terms of the preceding interval, and the relation of the initiating coupling interval to the QT interval (coupling interval/QT interval = polymorphic VT index). The mean QT for the group as a whole was 0.41 +/- 0.02 second. Patients could be separated into 3 distinct groups. Four patients had polymorphic VT reproducibly induced by exercise and initiated by late-coupled beats (mean polymorphic VT index 1.27 +/- 0.21). Isoproterenol induced polymorphic VT in 3 of 4 patients, and all 4 responded to chronic beta blockade. Two patients had polymorphic VT during episodes of coronary artery spasm, and both responded to calcium channel blockade. Polymorphic VT unrelated to exertion or coronary vasospasm occurred in 9 patients. Tachycardia onset was initiated by closely coupled beats (mean polymorphic VT index 0.95 +/- 0.16), and was preceded by a pause in 4 patients, and no pause in 5 patients. Sudden death occurred in 5 of 9 patients with the shortest polymorphic VT indexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Electrocardiographic indexes of dispersion of ventricular repolarization: an isolated heart validation study.

OBJECTIVES: This study tested the correlation of QT and JT dispersion and other potentially useful electrocardiographic (ECG) indexes with dispersion of repolarization and recovery time. BACKGROUND: Dispersion of ventricular repolarization is currently being assessed noninvasively from the surface ECG by means of QT and JT dispersion, although their correlation with dispersion of repolarization as measured directly from the myocardium is not well established. METHODS: Multiple monophasic action potentials were recorded simultaneously with a 12-lead ECG from isolated Langendorff-perfused rabbit hearts. The QT and JT dispersion was compared with the dispersion of monophasic action potential duration at 90% repolarization (APD90) and with dispersion of recovery time. As new ECG indexes, total T wave area, T wave area after the peak (late T wave area) and T peak to T end interval were also tested. RESULTS: The QT and JT dispersion showed a significant correlation with the dispersion of APD90 and the dispersion of recovery time (r values between 0.58 and 0.64, respectively, p < 0.001). However, total T wave area showed better correlation, respectively, with dispersion of APD90 and recovery time (r = 0.79 and r = 0.82, p < 0.0001), as did late T wave area (r = 0.81 and r = 0.81, p < 0.0001) and T peak to T end interval (r = 0.81 and r = 0.82, p < 0.0001). CONCLUSIONS: The JT and QT dispersion correlate significantly with dispersion of APD90 and recovery time. The ECG assessment of dispersion of repolarization can be improved by three new ECG dispersion indexes: T peak to T end interval, total T wave area and late T wave area. These new indexes should be tested clinically.

Action Potentials↗
PubMed1995

Prolongation of conduction time during premature stimulation in the human atrium is primarily caused by local stimulus response latency.

BACKGROUND: Conventional clinical electrophysiological techniques cannot accurately differentiate between local stimulus response latency and propagation time of the atrial response. The purpose of this study was to identify and distinguish local stimulus response latency from impulse propagation time in the human right atrium during programmed electrical stimulation. METHODS: Pacing was performed from two atrial sites (high and low right atrium) in 19 patients, using monophasic action potential recording/pacing combination catheters (interelectrode distance < 2 mm). Local stimulus response latency (interval between stimulus artifact and upstroke of the local monophasic action potential), and propagation time (interval between local and remote monophasic action potential upstroke) were evaluated at a basic cycle length (S1-S1) of 600 ms and as a function of the extrastimulus proximity (interval between extrastimulus and effective refractory period). Data are presented as means +/- SEM. RESULTS: During basic stimulation, local latency was very small (3.8 +/- 1.7 ms). During premature extrastimulation (proximity < 70 ms), local latency increased progressively with decreasing coupling intervals. Prolongation of local latency was most pronounced during stimulation close to the effective refractory period with local stimulus response latency increasing to 18.3 +/- 1.4 ms (380 +/- 7.9%) at 10 ms proximity (P < 0.002) and to 27.9 +/- 3.7 ms (630 +/- 13.2%) at 5 ms proximity, respectively (P < 0.0001). The impulse propagation time between the stimulation site and the remote recording site was on average 54.5 +/- 14.3 ms during basic stimulation, and increased up to 62.1 +/- 13.5 ms (14.0 +/- 8.4%), which was not significant. CONCLUSIONS: The intra-atrial impulse propagation remained essentially unchanged during the entire range of premature stimulation. Local stimulus response latency was negligible and constant during late coupling intervals but increased dramatically when extrastimulation approached the preceding repolarization phase. This has the following clinical impact: first, local stimulus response latency during premature extrastimulation curbs the targeted atrial response interval second, local stimulus response latency, not propagation time, seems responsible for the greater functional than effective refractory period during electrical stimulation; third, local stimulus response latency should be considered in pace mapping for accurate comparison of conduction time before pacing with that during pacing.

Aged↗
PubMed1995

Terfenadine increases the QT interval in isolated guinea pig heart.

Torsades de pointes ventricular tachycardia (VT) has been reported in patients taking the nonsedating antihistamine, terfenadine. We performed electrophysiologic studies of 14 isolated guinea pig hearts using the Langendorff technique to assess whether terfenadine exerted actions that could be responsible for inducing the arrhythmia. Twelve hearts were perfused with an oxygenated Tyrode's solution containing a 2-microM preparation of either racemic, R-, or S-terfenadine. QT interval (QT), monophasic action potential duration (APD), and ventricular effective refractory periods (ERP) were measured at a fixed range of cycle lengths (CL). At 400-ms CL, both isomers and racemate prolonged QT and APD by 8% and ERP was increased by 14%. Infusion of vehicle, dimethyl sulfoxide (DMSO), alone in two hearts caused a slight decrease in QT and APD, suggesting that the direct effect of terfenadine on QT may have been underestimated. One-way analysis of variance (ANOVA) showed no statistical difference in effect on QT, APD, or ERP for the three forms of terfenadine (p < 0.05). These results support the conclusion that terfenadine induces torsades de pointes because of direct actions in delaying cardiac repolarization. The lack of stereospecificity in this action indicates that chirally pure formulations are not likely to have greater safety than the racemate.

Action Potentials↗
PubMed1995

Computer analysis of monophasic action potentials: manual validation and clinically pertinent applications.

Monophasic action potential (MAP) recordings are increasingly being used in a variety of clinical and experimental situations but their manual measurement is cumbersome, especially when hundreds or thousands of beats must be analyzed to monitor the exact time course of action potential duration (APD) changes following heart rate alterations, during surveillance of APD alternans, or during the onset and stabilization of Class III drug effects. To facilitate this task we developed a computer program that automates programmed electrical stimulation, digitizes at 1-kHz sampling frequency MAP recordings up to 8 channels simultaneously, analyzes all APDs at repolarization levels from 10%-90% in 10% decrements (APD10-90), and automatically outputs the analyzed numerical data into spreadsheets for graphical display or statistical analysis. To validate the computer algorithm, two independent observers manually analyzed 585 concurrent MAP recordings at a paper speed of 100 mm/s. Cycle length measurements by the computer were precise to 0.4 +/- 0.5 ms as compared to the computer determined paced cycle length. Computer measurements of APD20, 50, and 90 differed from manual measurements by 2.0 +/- 8.8 ms, 0.7 +/- 7.9 ms, and 0.2 +/- 8.5 ms, respectively, for observer 1; and by 12.2 +/- 8.3 ms, 5.8 +/- 7.5 ms, and 1.4 +/- 10.1 ms, respectively, for observer 2. Inter-observer variability (IOV) was 10.3 +/- 11.1 (APD20), 5.1 +/- 9.0 ms (APD50), and 1.2 +/- 7.8 ms (APD90), which was similar to computer/observer-2 differences and significantly greater (0.001) than computer/observer-1 differences. This indicates that the computer analysis was at least as precise as manual measurements when compared to IOV, and more precise when comparing computer/observer-1 differences to IOV. While providing equal or greater precision, computer-aided analysis of 100 MAP signals took approximately 1 minute while manual analysis of the same data set took between 2.5 and 4 hours. The pacing and analysis software was subsequently applied to experiments that mimic clinically pertinent examples of MAP recordings: (1) automatic generation, analysis, and graphical display of electrical restitution curves at multiple ventricular sites simultaneously; (2) evaluation of myocardial pharmacokinetics by monitoring the progression of Class III antiarrhythmic drug effects by continuous MAP recordings, and displaying differences in drug action between multiple sites; (3) depiction of the adaptation time course of APD to abrupt changes in paced cycle length; and (4) quantitative analysis of APD alternans during myocardial ischemia. The results show that our computerized algorithm greatly facilitates the generation of cardiac electrophysiological, and clinically important, data.

Action Potentials↗
PubMed1994

Prolongation of monophasic action potential duration and the refractory period in the human heart by tedisamil, a new potassium-blocking agent.

The effect of intravenous tedisamil (0.3 mg.kg-1), a newly developed potassium-blocking agent, on ventricular repolarization was studied in 10 patients (three women, seven men; mean age 53 +/- 8 years) with coronary artery disease (stenoses < or = 60%). Left ventricular monophasic action potentials, effective refractory periods and surface electrocardiograms were recorded during sinus rhythm and during constant atrial pacing at cycle lengths of 600, 500 and 400 ms. Under tedisamil there was a 12% reduction of heart rate and in parallel a prolongation of QTc interval (+10%) and left ventricular monophasic action potential duration (+16% at 90% repolarization). QRS duration remained unchanged. Tedisamil increased the duration of monophasic action potentials during constant atrial pacing, indicating a direct prolongation effect on left ventricular repolarization independent of sinus node activity. By increasing the atrial pacing rate this prolonging effect diminished. Left ventricular effective refractory periods also increased in a frequency-dependent fashion with a greater prolongation effect at long cycle lengths as compared to short cycle lengths. The ratio between effective refractory period and monophasic action potential duration, however, remained constant, independent of heart rate. We conclude that tedisamil is bradycardiac at the dose tested and has a reverse use dependent prolongation effect on left ventricular repolarization and refractoriness. The electrophysiologic profile is consistent with a class III antiarrhythmic classification.

Action Potentials↗
PubMed1994

Dispersion and delay of electrical restitution in the globally ischaemic heart.

Alternans of action potential duration (APD) has been shown to be a precursor of ventricular fibrillation in ischaemic myocardium. We postulated that magnitude of alternans of APD during ischaemia depends not only on the severity of ischaemia but also on disturbed beat-to-beat restitution of APD. Monophasic action potentials were recorded simultaneously from right (RV) and left ventricular (LV) epicardial sites of isolated rabbit hearts. The inter-beat time courses of APD recovery were determined both during normal flow and ischaemia by interposing single cycle length changes ranging from 200 to 800 ms (= electrical restitution) simultaneously at the three recording sites. During normal perfusion, electrical restitution curves showed a steep initial recovery of APD, attaining steady-state values at extrastimulus cycle lengths of only 298 +/- 12 ms, with a high degree of uniformity between the three recording sites (inter-site variability < 2%). Ischaemia produced a marked slowing of electrical restitution which, on average, reached a plateau at extrastimulus cycle lengths of 415 +/- 45 ms, 650 +/- 72 ms and > 800 ms at 2 min, 5 min and 9 min of ischaemia, respectively (each P < 0.001 vs control). In addition, ischaemia resulted in a large inter-site variability, with RV and LV restitution curves deviating from each other by as much as 28.5% (P < 0.0001 vs baseline). We conclude that global ischaemia not only leads to a delayed but also non-uniform electrical restitution.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

New classification of moricizine and propafenone based on electrophysiologic and electrocardiographic data from isolated rabbit heart.

Because the classification of propafenone and moricizine is not clear, we measured in 20 specifically equipped isolated rabbit hearts QRS duration, QT interval, action potential duration at 90% of repolarization (APD90), effective refractory period (ERP), conduction time (CT), and rise velocity (Rv) of the monophasic action potentials (AP) during exposure to moricizine and propafenone in comparison with procainamide. Propafenone and procainamide prolonged APD90 and JT. All drugs increased ERP. Propafenone demonstrated marked tonic sodium channel block. Onset of use-dependent kinetics (tau on), defined as change in Rv as fraction per beat at 300 ms cycle length (CL), were 0.047 +/- 0.004/beat for procainamide, 0.050 +/- 0.004/beat for propafenone, and 0.022 +/- 0.003/beat for miricizine. Recovery kinetics, defined as recovery of Rv after cessation of pacing, had a time constant of 5.3 +/- 0.7 s for procainamide, 6.3 +/- 0.8 s for propafenone, and 25.0 +/- 1.3 s for moricizine. Based on these data, moricizine must be classified as a Ic agent, whereas propafenone demonstrates pronounced tonic sodium channel block, in addition to its phasic block, which is similar to class Ia kinetics.

Action Potentials↗
PubMed1994

Bridging the gap between basic and clinical electrophysiology: what can be learned from monophasic action potential recordings?

With rapid advances occurring in both basic and clinical electrophysiology, the gap between the two disciplines appears to be widening rather than narrowing. In most instances, we cannot apply the knowledge derived from cellular studies directly to clinical practice. Monophasic action potential (MAP) recording by contact electrode technique allows us to measure basic electrophysiological phenomena in the human heart and thus provides an important bridge between basic and clinical electrophysiology. MAP recordings produce the time course of cellular repolarization during cycle length changes and antiarrhythmic drug administration, lending insights into use dependency and reverse use dependency of antiarrhythmic drug effects in the clinical electrophysiology laboratory. The ability to deliver electrical stimuli at the MAP recording site further allows one to investigate drug-induced postrepolarization refractoriness. MAP recordings provide precise local activation times, important for mapping of abnormal ventricular activation, and detect areas of abnormal repolarization due to ischemia or scarring. MAP recordings are uniquely suited to detect early and delayed afterdepolarizations in the human heart, thereby helping to unravel the arrhythmia mechanisms in the long QT syndrome. By embedding the MAP electrode in a radiofrequency electrode, arrhythmogenic foci may be both detected and ablated. In many instances, MAP recordings are more accurate than ECG tracings in defining and distinguishing ventricular fibrillation and ventricular tachycardia. This can be of clinical importance during testing of the implantable cardioverter/defibrillator. An area of growing interest is stretch-activated arrhythmias. Here, MAP recordings are of particular value because no other method is available to record mechanically induced electrophysiological changes in the vigorously beating heart. It can be expected that MAP recordings will, in the future, provide this important bridge between "cell and bedside" also in atrial tachyarrhythmias, such as in atrial fibrillation and flutter.

Action Potentials↗
PubMed1993

Ischaemia induced alternans of action potential duration in the intact-heart: dependence on coronary flow, preload and cycle length.

Clinical and experimental evidence relate action potential duration (APD) alternans to ischaemic heart disease and ventricular arrhythmias. The present investigation was performed to study the quantitative relationship between APD alternans and the degree of ischaemia, loading conditions and cycle length (CL) in an intact heart. Monophasic action potentials (MAP) were simultaneously recorded by contact electrodes from two left (LV) and one right ventricular (RV) sites in 20 Langendorff-perfused rabbit hearts. The preparations were subjected to global ischaemia at flow rates ranging from 40% of normal flow to complete cessation of flow. Pacing was performed at either constant or regularly changing CL. The magnitude of APD alternans was expressed as beat-to-beat differences in action potential duration of two consecutive MAPs. During normal perfusion, neither very fast pacing at a CL of 200 ms nor periodical rate switches resulted in persistent APD alternans. Pacing at a constant CL of 800 ms did not induce APD alternans at complete cessation of flow for 6 min. However, alternans developed progressively at a constant CL of 400 ms after 2.8 +/- 0.3 min of complete ischaemia at the pre-loaded LV, and after 4.6 +/- 0.4 min at the unloaded RV (P < 0.01). The reduction of preload at the LV from 15 to 5 mmHg end-diastolic pressure delayed development of APD alternans from 2.8 +/- 03 min to 4.3 +/- 0.4 min (P < 0.05) at 400 ms CL. Following graded underperfusion of 40%, 20% and 10% of initial flow, persistent APD alternans developed in relation to the degree of flow reduction and increased progressively with duration of ischaemia. APD alternans at the LV always preceded the onset of APD alternans at the RV. In experiments with identical flow rates the shortest CL of 200 ms resulted in the greatest and earliest initiation of APD alternans compared to the longer CL (P < 0.01, P < 0.001). An increase in CL from 400 to 800 ms immediately abolished APD alternans, generated by the shorter CL, at any time during the 6 min period of complete ischaemia. Similarly, increasing the cycle length from 200 or 400 to 600 ms eliminated APD alternans up to 6 min of ischaemia and significantly reduced its magnitude between 7 and 10 min within a few beats. We conclude that persistent APD alternans is a characteristic findings in the rabbit heart during global ischaemia4 It is a sensitive parameter of the severity of ischaemia and depends.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Increased dispersion of ventricular repolarization and ventricular tachyarrhythmias in the globally ischaemic rabbit heart.

Contemporary concepts of ischaemic ventricular tachyarrhythmias (VTA) are based on increased electrophysiological heterogeneity of the myocardium. We developed a multi-site monophasic action potential recording system for an isolated rabbit heart to study the effects of global ischaemia on the electrophysiological properties at different ventricular sites simultaneously. The hearts were paced from the right ventricle (RV), and conduction time (CT), action potential duration (APD) and total repolarization time (TRT = [CT + APD]) were measured during normal perfusion and ischaemia. The dispersion of these parameters was calculated as the maximal difference between simultaneous recordings. Inducibility of VTA by programmed extrastimulation (ES) was investigated under normal and ischaemic conditions. During global ischaemia, CT increased progressively, showing a faster and greater increase at the left ventricle (LV) than at the RV. After 10 min the prolongation of CT reached a plateau at the LV while it continued to rise in the RV. The dispersion of CT increased from 14.5 +/- 2.7 ms during normal perfusion to a maximum of 79.8 +/- 17.2 ms after 14 min of ischaemia (P < 0.0001). APD was uniform at the three sites (190.9 +/- 10.2, 185.0 +/- 8.6 and 179.3 +/- 9.8 ms, ns) during normal perfusion but changed non-uniformly during ischaemia. There was a transient lengthening of APD until 1 and 3 min of ischaemia at the LV sites followed by a rapid shortening of APD. At the RV site, APD continued to increase until 5 min of ischaemia and then shortened gradually. Consequently, dispersion of APD showed a rapid initial rise from 17.7 +/- 2.7 ms to 77.8 +/- 10.2 ms (P < 0.0001) followed by a slower final increase. TRT was uniform during normal perfusion (210.4 +/- 10.3, 213.1 +/- 7.8, 212.1 +/- 10.3 ms, ns) but became non-uniform during global ischaemia. The dispersion of TRT increased from 15.4 +/- 4.2 ms to 92.6 +/- 23.2 ms (P < 0.0001) during 14 min of global ischaemia. Both CT and APD contributed independently to TRT and could either augment or partially compensate for the ischaemic alterations of the other parameter. ES induced VTA only during ischaemia (3.7 +/- 1.1 VTA per heart, P < 0.0001) at coupling intervals between 220 and 380 ms. The dispersion of TRT of the last regular beat preceding VTA was 67.7 +/- 17.4 ms (P < 0.001). ES which triggered VTA showed a more than two-fold increase of CT dispersion compared to the last steady state beat (122.7 +/- 29.4%, P = 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Relation between repolarization and refractoriness in the human ventricle: cycle length dependence and effect of procainamide.

The cycle length dependence of the action potential duration and the effective refractory period of the right ventricular endocardium were investigated in 24 patients undergoing electrophysiologic studies for suspected ventricular tachycardia. The action potential duration at 90% repolarization and the effective refractory period at twice diastolic threshold strength were measured at the same catheter site at steady state cycle lengths of 350 to 600 ms. Both measurements decreased linearly with decreasing cycle length, maintaining a parallel relation. When the relation between action potential duration and effective refractory period was expressed as the effective refractory period-action potential duration difference, nearly constant values (range -12 to -15 ms) were obtained at all cycle lengths. To determine whether sodium channel blocking drugs influence the effective refractory period-action potential duration relation in humans, measurements of these two variables were obtained in 15 patients before and during the infusion of procainamide. Procainamide prolonged the action potential duration at each cycle length by a near constant amount over baseline values (p less than 0.001). Procainamide also increased the effective refractory period at each cycle length but with a greater incremental increase at the shorter cycle lengths. The rate-dependent increase in the effective refractory period-action potential duration difference became significant at cycle lengths less than or equal to 400 ms; at these high rates, the effective refractory period-action potential duration difference became positive (1.6 ms, p less than 0.01 compared with baseline). Thus, in the human ventricle, the action potential duration and the effective refractory period have a close relation that remains fixed over a wide range of cycle lengths.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗