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M R Franz

Publications and source records attributed to M R Franz.

At least 37 records · Page 2Linked to original sources
PubMed1998

Postrepolarization refractoriness versus conduction slowing caused by class I antiarrhythmic drugs: antiarrhythmic and proarrhythmic effects.

BACKGROUND: Conduction block may be both antiarrhythmic and proarrhythmic. Drug-induced postrepolarization refractoriness (PRR) may prevent premature excitation and tachyarrhythmia induction. The effects of propafenone and procainamide on these parameters, and their antiarrhythmic or proarrhythmic consequences, were investigated. METHODS AND RESULTS: In 11 isolated Langendorff-perfused rabbit hearts, monophasic action potentials (MAPs) were recorded simultaneously from six to seven different right and left ventricular sites, along with a volume-conducted ECG. All recordings were used to discern ventricular tachycardia (VT) or ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5) or 10-second burst stimulation at 25 to 200 Hz at baseline and after addition of procainamide (20 micromol/L) or propafenone (1 micromol/L) to the perfusate. MAPs were analyzed for action potential duration at 90% repolarization (APD90), conduction times (CT) between the pacing site and the other MAPs, and PRR (effective refractory period-APD90=PRR) and related to the induction of VT or VF. During steady-state pacing, procainamide and propafenone prolonged APD90 by 12% and 14%, respectively. Procainamide slowed mean CT by 40% during S2-S5 pacing, whereas propafenone slowed mean CT by up to 400% (P<0.001 versus baseline and procainamide). Wavelength was not changed significantly by procainamide but was shortened fourfold by propafenone at S5. Both drugs produced PRR, which was associated with a 70% decrease in VF inducibility with procainamide and elimination of VF with propafenone. Despite this protection from VF, monomorphic VT was induced with propafenone in 57% of burst stimulations. CONCLUSIONS: Drug-induced PRR protects against VF induction. Propafenone promotes slow monomorphic VT, probably by use-dependent conduction slowing and wavelength shortening.

Action Potentials↗
PubMed1998

Phase angle convergence of multiple monophasic action potential recordings precedes spontaneous termination of ventricular fibrillation.

AIMS: To elucidate the mechanism of spontaneous termination of ventricular fibrillation (VF) and to define an indicator of its occurrence, the phase angle, a novel measure to assess synchrony of activation, was evaluated. METHODS AND RESULTS: In 7 isolated rabbit hearts, 7 monophasic action potentials were recorded simultaneously. Ventricular fibrillation was induced by T wave shocks. Cycle lengths (CL) and phase angles between all 7 recordings were analyzed until spontaneous termination or shock-induced defibrillation. Average phase angle was calculated as activation time difference to a reference channel and expressed as a fraction of the reference channel's CL with 1 equaling a complete CL. Initial CLs and phase angles were similar in sustained and terminating episodes (CL: 141 +/- 16 ms vs 142 +/- 24 ms, phase angle: 0.244 +/- 0.11 vs 0.263 +/- 0.1, p = NS). During spontaneous termination, CL increased slightly by 7%. Average phase angle converged gradually over the last three activations before termination of ventricular fibrillation by 22-48% (p < 0.0005), eventually resulting in phase angles similar to paced rhythms directly prior to spontaneous termination of ventricular fibrillation. CONCLUSIONS: Gradual synchronization of activation is part of the electrophysiological mechanism resulting in spontaneous ventricular fibrillation termination and can be detected three activations before termination. Phase angle convergence may be useful to detect spontaneous termination of ventricular fibrillation.

Action Potentials↗
PubMed1998

Dispersion of ventricular repolarization in the voltage domain.

Dispersion of ventricular repolarization, assessed as QT dispersion in the ECG or by multiple monophasic action potential (MAP) recordings, is defined as the difference between the earliest and latest repolarization. It is thus measured in the time domain. However, myocardial refractoriness is primarily a function of the membrane potential during phase 3 repolarization. The purpose of this study, therefore, was to measure dispersion of ventricular repolarization in the voltage domain and to study its relation to VF inducibility. To further validate this concept, the effect of chronic amiodarone treatment on the voltage dispersion were assessed. MAPs were recorded simultaneously at 10 epicardial and endocardial sites in isolated rabbit hearts, both under baseline conditions (n = 8) and after chronic amiodarone treatment (n = 8). Repolarization dispersion in the voltage domain was calculated as the difference between the highest and lowest repolarization level of all 10 MAPs at 10-ms steps, starting from the MAP plateau level to complete repolarization. Plotting these voltage differences along the time axis resulted in a dispersion curve, which rose during early repolarization, reached a peak during phase 3 repolarization, and thereafter declined toward zero. There was a close correlation between VF vulnerability in response to electrical field stimuli and the time during which voltage dispersion was maximal (r = 0.828, P < 0.0001). Amiodarone caused a right-ward shift of both the dispersion curve (P = 0.007) and VF vulnerability (P = 0.025), but did not change the magnitude nor the shape of the voltage dispersion curve and its relation to VF vulnerability. Repolarization dispersion in the voltage domain describes an alternate approach for evaluating the heterogeneity of ventricular repolarization and may help to characterize arrhythmia susceptibility under experimental conditions.

Action Potentials↗
PubMed1998

Comparison of ECG variables of dispersion of ventricular repolarization with direct myocardial repolarization measurements in the human heart.

INTRODUCTION: QT dispersion (QTD) from the 12-lead ECG has been widely adopted as a noninvasive index of dispersion of ventricular repolarization (DVR). QTD, however, has never been validated by direct comparison with myocardial DVR in the human heart. METHODS AND RESULTS: Monophasic action potential (MAP) recordings obtained in an earlier study were retrospectively matched with 12-lead ECGs available from within 24 hours of the invasive procedure. MAPs were available from an average of 8+/-3 left endocardial sites in 4 patients with left ventricular hypertrophy (LVH) and 7 patients with normal ECGs, and 6+/-2 epicardial sites in 3 patients of each group during normal ventricular activation. Local repolarization time (RT) was determined as MAP duration at 90% repolarization plus the local activation time. Dispersion of RT was calculated as the difference between the earliest and latest RT. ECGs were digitized and analyzed with recently described interactive QTD analysis software. In addition to standard QTD (defined as QTmax-QTmin), all currently proposed ECG dispersion variables were compared and correlated with the invasive measurements of DVR. QTD exhibited a reasonable correlation with dispersion of RT (R = 0.67; P < 0.01). Several other variables designed to measure DVR exhibited a similar, but not better, correlation. Among them, the QT peak/QT end ratio in V3 (R = -0.72; P < 0.01) and averaged over all analyzable leads (R = -0.59; P < 0.01) exhibited a good correlation with dispersion of RT, which was further improved when endocardial measurements were considered alone. T area measures did not correlate with dispersion of RT, but discriminated LVH. CONCLUSION: DVR can be assessed by means of a 12-lead surface ECG. Several of the variables under study exhibit a similar accuracy in determination of true myocardial dispersion of repolarization. Variables involving the terminal part of repolarization, such as the QT peak/QT ratio, even from a single lead, may add to the determination of DVR from the human heart.

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PubMed1997

Effects of amiodarone on the circadian pattern of sudden cardiac death (Department of Veterans Affairs Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy).

Some antiarrhythmic drugs have been shown to influence the circadian pattern of sudden cardiac death (SCD). The effect of chronic amiodarone therapy on this pattern is unknown. This study determines the circadian pattern of deaths in the Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) and compares the distribution of SCD between the amiodarone and the placebo arms of the trial. CHF-STAT was a multicenter trial that determined whether amiodarone reduces mortality in patients with heart failure and asymptomatic ventricular arrhythmias. The time of death was retrospectively analyzed in patients who died from pump failure and SCD. In patients who died suddenly, the circadian pattern of deaths was compared between patients receiving amiodarone and those receiving placebo. In CHF-STAT, 274 patients died during follow-up. The time of death was available in 65 of the 74 patients who died from pump failure, and in 96 of the 139 patients who died suddenly. There was a circadian variation of all SCDs compared with other deaths with a distinct peak during the morning (p = 0.04). A similar morning peak of sudden cardiac death was found in both the amiodarone (n = 42) and the placebo (n = 54) groups, and the overall circadian pattern did not differ between them (p = 0.16). In contrast, death from pump failure occurred equally distributed over time. Thus, SCD occurs predominantly during the morning, whereas death from heart failure does not exhibit a morning peak. Amiodarone does not influence the circadian pattern of SCD.

Aged↗
PubMed1997

Effects of myocardial ischemia on ventricular fibrillation inducibility and defibrillation efficacy.

OBJECTIVES: This study investigated the effects of acute global ischemia on the vulnerable window, the upper limit of vulnerability and the defibrillation threshold. BACKGROUND: Myocardial ischemia, an important factor for arrhythmogenesis and sudden death, may affect the inducibility of ventricular fibrillation by T wave shocks as well as the defibrillation threshold. However, studies of the effect of ischemia on the defibrillation threshold remain inconclusive, and the effect of ischemia on recently established variables of ventricular fibrillation vulnerability is still unknown. METHODS: Ten isolated, perfused rabbit hearts were immersed in a tissue bath between two shock plate electrodes. Truncated 5-ms biphasic shocks were used to determine the vulnerable window, the upper limit of vulnerability and the defibrillation threshold. Measurements were performed during baseline and at 10 to 15 min of acute ischemia induced by an 80% reduction of coronary flow. The effects of ischemia were monitored by measuring the dispersion of ventricular activation and repolarization using multiple monophasic action potential recordings. RESULTS: Acute ischemia caused an increase in dispersion of activation (baseline vs. ischemia [mean +/- SD]: 22 +/- 6 vs. 34 +/- 10 ms, p < 0.001) and dispersion of repolarization (37 +/- 16 vs. 69 +/- 29 ms, p < 0.01). The width of the vulnerable window increased from 25 +/- 22 ms during baseline to 75 +/- 26 ms during ischemia (p = 0.001). The upper limit of vulnerability (baseline vs. ischemia: 294 +/- 44 vs. 274 +/- 53 V, p = 0.21) and the defibrillation threshold (271 +/- 33 vs. 268 +/- 42 V, p = 0.74) remained unchanged during ischemia. CONCLUSIONS: Acute global ischemia caused a threefold increase in the width of the vulnerable window. This increase was associated with increased heterogeneity of ventricular activation and repolarization. Despite these marked changes, the upper limit of vulnerability and the defibrillation threshold were not affected by acute myocardial ischemia. Thus, the previously reported similarity between both measures was maintained under these adverse conditions.

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PubMed1997

Induction of ventricular fibrillation by T-wave field-shocks in the isolated perfused rabbit heart: role of nonuniform shock responses.

OBJECTIVES: Single electrical field shocks are able to induce ventricular fibrillation (VF) if applied during the vulnerable period. During this period, a shock can either prolong the action potential duration or induce a new action potential. Whether the occurrence of different shock responses contributes to the induction of VF has not been investigated directly in the intact heart. METHODS: In 12 isolated Langendorff-perfused rabbit hearts seven monophasic action potentials (MAPs) were recorded simultaneously during the application of 838 T-wave shocks. Post-shock repolarization was assessed by classifying the shock-induced response in each MAP recording either as a full action potential or an action potential prolongation. Heterogeneity of post-shock repolarization was defined if both response patterns were present in different MAP recordings at the same time. The heterogeneity of post-shock activation was measured as the dispersion of the post-shock activation time (PS-AT). The arrhythmogeneity of a shock was quantified as the number of rapid shock-induced repetitive responses. RESULTS: Shocks inducing nonuniform repolarization were associated with greater arrhythmogeneity than shocks inducing uniform repolarization (17.6 +/- 30.0 versus 1.6 +/- 1.1 shock-induced repetitive responses, p < 0.001). The severity of the induced arrhythmia increased gradually with increasing nonuniformity of repolarization (p < 0.01 for a 10% increase), being maximal when the shock initiated near equal numbers of both full action potentials and action potential prolongations. The induction of severe arrhythmias by T-wave shocks was also associated with a higher dispersion of PS-AT (29 +/- 14 ms for the induction of VF, 19 +/- 12 ms for non-sustained arrhythmia, and 12 +/- 8 ms for no arrhythmic response, all p < 0.001). For VF inducing shocks, an increase in shock strength towards the upper limit of vulnerability decreased the dispersion of PS-AT from 34 +/- 15 ms to 23 +/- 11 ms (p < 0.001). CONCLUSIONS: Nonuniform post-shock repolarization and dispersed post-shock activation contribute to the induction of VF by T-wave shocks. A decreasing dispersion of PS-AT towards higher shock strengths may contribute to the decreased or abolished inducibility by shocks above the upper limit of vulnerability.

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PubMed1997

Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter.

OBJECTIVES: This study sought to determine whether chronic atrial fibrillation (AF) and atrial flutter in patients lead to electrical remodeling of the human atrial myocardium, manifested by an abnormal relation between atrial cycle length and action potential duration (APD). BACKGROUND: Experimental studies in goats and isolated human atrial tissue have shown that prolonged AF leads to persistent shortening of atrial refractoriness, a phenomenon referred to as electrical remodeling and which helps to explain why AF begets AF. Direct data on human in situ myocardium are still lacking. METHODS: Using monophasic action potential recordings at two right atrial sites simultaneously, we determined in 7 patients with chronic AF and 13 with chronic atrial flutter (3 weeks to 3 years in duration) the relation between paced cycle length and APD at 90% repolarization (APD90) 15 to 30 min after conversion to sinus rhythm. APD90 was measured during regularly paced cycle lengths (250 to 800 ms) to determine the steady state cycle length relation and during extrastimulus intervals (from 800 ms to refractoriness) at a basic cycle length of 600 ms to determine electrical restitution curves. The same pacing protocols and measurements were performed in nine control patients with sinus rhythm and no overt atrial disease. RESULTS: In control patients, steady state APD90 increased steadily with increases in cycle length from 250 to 800 ms, reaching a maximal value of 325 +/- 41 ms (mean +/- SD) at a cycle length of 800 ms. In patients with cardioversion from atrial flutter or AF, the steady state cycle length-APD90 relation was shifted downward and flattened at cycle lengths >400 ms, reaching only 219 +/- 44 and 245 +/- 39 ms, respectively, at the 800-ms cycle length (p < 0.005 vs. control). The early time course of electrical restitution (200- to 300-ms extrastimulus intervals) was similar between all three groups, but at extrastimulus intervals >350 ms, APD90 was shorter in both the AF and atrial flutter groups than in the control group (p < 0.05). There were no significant differences between patients with cardioversion from atrial flutter and those with cardioversion from AF. APD90 at a steady state cycle length of 600 ms showed no significant correlation with the duration of previous AF or atrial flutter. CONCLUSIONS: AF and atrial flutter lead to marked, quantitatively similar decreases in the right atrial APD during steady state pacing and extrastimulation a considerable time after cardioversion. These data confirm that both AF and atrial flutter lead to electrical remodeling in the human atrium, with a preponderance at longer cycle lengths. It may be prudent to abort both types of arrhythmias early to prevent electrical remodeling.

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PubMed1997

Effects of long-term amiodarone treatment on ventricular-fibrillation vulnerability and defibrillation efficacy in response to monophasic and biphasic shocks.

Antiarrhythmic drugs, most notably amiodarone, are often used to combat life-threatening tachyarrhythmias simultaneous with implantable cardioverter defibrillators. However, the effects of long-term amiodarone treatment on ventricular fibrillation (VF) vulnerability and the defibrillation threshold (DFT) remain incompletely understood. VF vulnerability and the DFF for monophasic and biphasic shocks were studied in 10 isolated perfused hearts of rabbits treated over the long term with amiodarone (50 mg/kg/day orally for 28 days) before the experiment. The results were compared with those of a control group (n = 10). Monophasic action potentials were recorded from 10 sites simultaneously to determine ventricular activation and repolarization. Myocardial tissue concentrations were 17.1 +/- 14.8 microg/g for amiodarone and 4.6 +/- 4.4 microg/g for desethylamiodarone. Amiodarone treatment prolonged action-potential duration by 12.9 ms (p = 0.025) and ventricular repolarization by 16.5 ms (p = 0.03) without changing ventricular activation and dispersion of repolarization. Amiodarone treatment caused a rightward shift of the vulnerable window for monophasic and biphasic shocks by 13-17 ms (p < 0.05). The width of the vulnerable window, the upper (ULV) and lower (LLV) limits of VF vulnerability, and the DFT remained unchanged. The fact that ULV and DFT remained unchanged suggests that the ULV still may be valid surrogate for the DFT during long-term amiodarone therapy.

Amiodarone↗
PubMed1997

Timing of the upper limit of vulnerability is different for monophasic and biphasic shocks: implications for the determination of the defibrillation threshold.

The upper limit of vulnerability (ULV) has been used in clinical studies to predict the DFT in patients with ICDs. Despite the ULV-DFT correlation, uncertainties about the optimal timing of the ULV determination remain. Previous studies using monophasic or biphasic shock waveforms reported differences in the ULV timing with respect to the electrocardiographic T wave. The purpose of this study was to directly compare the ULV timing for mono- versus biphasic T wave shocks. In ten isolated rabbit hearts, mono- and biphasic shocks were delivered randomly during the vulnerable window and at varying shock strengths to determine the ULV. The ULV timing was expressed as the coupling interval at the ULV, the myocardial repolarization state at the ULV measured by monophasic action potential recordings, and the relation between the ULV and the peak of the simultaneously recorded volume conducted T wave. The ULV for biphasic shocks occurred at longer coupling intervals than for monophasic shocks (188.0 +/- 9.5 ms vs 173.5 +/- 8.8 ms, P < 0.001). This resulted in a more repolarized myocardial state at the ULV for biphasic than for monophasic shocks (81.1% +/- 7.5% vs 66.9% +/- 9.0%, P = 0.002). The ULV for monophasic shocks occurred predominantly during the upslope of the T wave (8.0 +/- 9.7 ms before the peak of the T wave) whereas the ULV for biphasic shocks occurred at or after the peak of the T wave (5.9 +/- 9.3 ms after the peak of the T wave) (P < 0.001). Biphasic shocks delay the timing of the ULV as compared to monophasic shocks. This is important for the prediction of the DFT by ULV measurements.

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PubMed1997

Is dispersion of ventricular repolarization rate dependent?

QT dispersion has been adopted as a new index for the noninvasive assessment of the inhomogeneity of repolarization and has been evaluated in several clinical studies as an index of arrhythmia propensity. In most of these studies, indices of dispersion of repolarization were rate corrected by the Bazett formula calculating QT dispersion as QT cmax-QT cmin or JT dispersion as JT cmax-JT cmin, implying that dispersion of repolarization also changes with heart rate. This study aimed to determine in the electrically paced isolated heart whether dispersion of ventricular repolarization is rate dependent. Multiple (5-7) monophasic action potentials (MAPs) were recorded simultaneously from the epicardium and endocardium of both ventricles in 18 isolated Langendorff-perfused rabbit hearts. Hearts were paced from a right ventricular site at basic cycle lengths (CL) between 1,200 and 300 ms in 100-ms decrements. Action potential duration was measured at 90% repolarization (APD90), and recovery time (RT) was defined as the sum of APD90 and activation time in each of the simultaneous MAP recordings. The dispersion of APD90 and RT, respectively, were calculated as the maximal difference among all recordings. APD90 and RT shortened continuously throughout the range of paced steady-state CLs from 1,200 to 300 ms. APD90 was 197.6 +/- 6.1 ms at a CL of 1,200 ms and decreased to 148.5 +/- 2.5 ms at a CL of 300 ms (P < 0.0001). RT was 228.2 +/- 6.2 ms at a CL of 1,000 ms and decreased to 175.9 +/- 2.9 at a CL of 300 ms (P < 0.0001). In contrast, dispersion of APD90 and RT did not change significantly. Dispersion of APD90 was 24.8 +/- 2.3 ms at a CL of 1,200 ms, 26.1 +/- 1.9 msec at a CL of 1,000 ms, and 21.6 +/- 2.1 at a CL of 300 ms (NS). Dispersion of RT was 29.7 +/- 3.4 ms at a CL of 1,200 ms, 29.0 +/- 3.0 ms at a CL of 1,000 ms, and 32.7 +/- 3.2 ms at a CL of 300 ms (NS). In contrast to the duration of the QT interval, dispersion of ventricular repolarization does not change significantly with pacing induced changes in CL. Assuming that the rate-dependent behavior of action potential duration is similar between the rabbit and human heart, a rate correction of parameters of dispersion of repolarization is probably unnecessary.

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PubMed1997

Shock-induced dispersion of ventricular repolarization: implications for the induction of ventricular fibrillation and the upper limit of vulnerability.

INTRODUCTION: Shock-induced dispersion of ventricular repolarization (SIDR) caused by an electrical field stimulus has been suggested as a mechanism of ventricular fibrillation (VF) induction; however, this hypothesis has not been studied systematically in the intact heart. Likewise, the mechanism underlying the upper (ULV) and lower (LLV) limit of vulnerability remains unclear. METHODS AND RESULTS: In eight Langendorff-perfused rabbit hearts, monophasic action potentials were recorded simultaneously from ten different sites of both ventricles. Truncated biphasic T wave shocks were randomly delivered at various coupling intervals and strengths, exceeding the vulnerable window, ULV, and LLV, SIDR, defined as the difference between the longest and shortest postshock repolarization times, was 64 +/- 15 msec for shocks inducing VF. SIDR was 41 +/- 17 msec for shocks delivered above the ULV, and 33 +/- 14 and 27 +/- 8 msec for shocks delivered 10 msec before and after the vulnerable window, respectively (all P < 0.01 vs VF-inducing shocks). Although SIDR was larger for shocks delivered below the LLV (93 +/- 24 msec, P < 0.01 vs VF-inducing shocks), the repolarization extension was significantly smaller for shocks below the LLV (10.3% +/- 3.9% vs 16.3% +/- 4.9%, P < 0.01). CONCLUSION: SIDR is influenced by the shock timing and intensity. Large SIDR within the vulnerable window and an SIDR decrease toward its borders suggest that SIDR is essential for VF induction. The decrease in SIDR toward greater shock strengths may explain the ULV. Small repolarization extension for shocks below the LLV may explain why these shocks, despite producing large SIDR, fail to induce VF.

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PubMed1997

Electrophysiologic features of torsades de pointes: insights from a new isolated rabbit heart model.

INTRODUCTION: The exact electrophysiologic mechanism of torsades de pointes (TdP) is under intense investigation. No isolated animal heart model of this particular arrhythmia exists. METHODS AND RESULTS: In isolated rabbit hearts, TdP was induced by means of bradycardia in the presence of a high concentration of d-sotalol (10(-4) M) and shortly after lowering the concentration of potassium and magnesium in the perfusate. Multiple simultaneous epicardial and endocardial monophasic action potentials (MAPs) and volume-conducted 12-lead ECGs were recorded. d-Sotalol prolonged repolarization and increased dispersion of ventricular repolarization compared to baseline recordings. With the onset of low potassium and magnesium concentrations, repolarization was further prolonged and dispersion of repolarization was further increased followed by the occurrence of early afterdepolarizations (EADs) in the majority of MAP recordings, i.e., at both endocardial and epicardial locations of both ventricles. Upon increase of EAD amplitude, triggered arrhythmias with TdP of up to 42 beats ensued in 10 of 11 hearts studied. MAP duration at 90% repolarization (APD90), dispersion of APD90, and the incidence of EADs as well as dispersion of the QT interval and T wave area were significantly higher in beats triggering bigemini, couplets, or runs of TdP. CONCLUSION: TdP observed in this new isolated heart model was associated with markedly increased dispersion of ventricular repolarization and the occurrence of EADs in multiple locations of the heart. TdP is initiated when the amplitude of an EAD reaches threshold for initiation of the first beat of an episode.

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PubMed1997

Differential effects of D-sotalol, quinidine, and amiodarone on dispersion of ventricular repolarization in the isolated rabbit heart.

INTRODUCTION: Increased dispersion of ventricular repolarization has been suggested as a cause of proarrhythmic effects of Class IA or III antiarrhythmic drugs, such as d-sotalol, quinidine, and amiodarone. METHODS AND RESULTS: The influence of d-sotalol, quinidine, and amiodarone on the dispersion of monophasic action potential (MAP) durations was studied in 55 isolated Langendorff-perfused rabbit hearts at different pacing cycle lengths (CLs). MAP duration measured at 90% repolarization (APD90) was determined from 6 to 8 endocardial and epicardial MAP recordings with dispersion of ventricular repolarization defined as the range of APD90. The protocol was repeated 60 minutes after initiation of a perfusate containing increasing concentrations of d-sotalol (n = 12, 10[-6] M, 10[-5] M, and 5 x 10[-5] M) and quinidine (n = 8, 10[-6] M and 10[-5] M). Seventeen rabbits were fed with an aqueous solution of amiodarone (50 mg/kg per day over 4 weeks). The data of these experiments (n = 17) were compared with a series of 18 untreated control rabbits. Dispersion of ventricular repolarization was unchanged with the low concentration of d-sotalol (10[-6] M) but was increased-particularly at long CLs-with higher d-sotalol concentrations. With both concentrations of quinidine, dispersion of ventricular repolarization was increased in a rate-independent manner. Amiodarone did not affect dispersion of ventricular repolarization. CONCLUSIONS: Rate-dependent and concentration-dependent increases in dispersion of ventricular repolarization by d-sotalol and quinidine in this isolated rabbit heart model may help explain their proarrhythmic effects while the absence of an increase in dispersion of ventricular repolarization with amiodarone correlates with its clinically observed lower incidence of proarrhythmia.

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PubMed1996

Reduced arrhythmogenicity of biphasic versus monophasic T-wave shocks. Implications for defibrillation efficacy.

BACKGROUND: Biphasic waveforms defibrillate more effectively than monophasic waveforms; however, the mechanism remains unknown. The "upper-limit-of-vulnerability" hypothesis of defibrillation suggests that unsuccessful defibrillation is due to reinduction of ventricular fibrillation (VF). Thus, VF induction mechanisms may be important for the understanding of defibrillation mechanisms. We therefore compared myocardial VF vulnerability for monophasic versus biphasic shocks. METHODS AND RESULTS: In 10 Langendorff-perfused rabbit hearts, monophasic and biphasic T-wave shocks were randomly administered over a wide range of shock coupling intervals and shock strengths, and the two-dimensional coordinates within which VF was induced were used to calculate the area of vulnerability (AOV) for both shock waveforms. The arrhythmic response to biphasic shocks differed from that to monophasic shocks in three distinct ways: (1) the AOV was smaller (8.9 +/- 4.2 versus 13.9 +/- 6.0 area units, P < .02), (2) the transition zone between VF-inducing and nonarrhythmogenic shocks was narrower (14.7 +/- 4.8 versus 29.9 +/- 6.4 area units, P < .001), and (3) the entire AOV shifted toward longer coupling intervals (by 11.0 +/- 8.8 ms at the left border [P < .005] and 6.0 +/- 5.2 ms at the right border [P = .005] of the AOV). CONCLUSIONS: Biphasic shocks encounter a smaller AOV than monophasic shocks, a narrower transition zone from VF to no arrhythmia induction, and a lesser effectiveness in inducing VF at short coupling intervals. In keeping with the upper-limit-of-vulnerability hypothesis, these waveform-dependent differences in VF inducibility might help explain the lower defibrillation threshold for biphasic shocks.

Animals↗
PubMed1996

Effect of sustained load on dispersion of ventricular repolarization and conduction time in the isolated intact rabbit heart.

INTRODUCTION: It is well known that myocardial stretch can elicit ventricular arrhythmias in experimental models. However, previous reports have predominantly documented stretch-induced arrhythmias during short, pulsatile stretch. The arrhythmogenic mechanism of sustained static stretch is incompletely understood. METHODS AND RESULTS: To examine the influence of sustained load on several electrophysiologic parameters, a latex balloon was placed into the left ventricle of ten isolated Langendorff-perfused rabbit hearts and filled with a neutral volume of fluid. The heart was paced from a catheter inside the right ventricle (apicoseptal endocardial position), and the following parameters were studied during steady-state pacing with a cycle length of 500 msec (S1) and during extrastimulation (S2, base drive of 8 beats): monophasic action potential (MAP) durations at 90% repolarization (APD90) from 5 to 6 epicardial electrodes located on both ventricles and one right ventricular endocardial contact electrode; dispersion of APD90 (range of MAP durations from all electrodes); effective refractory period (ERP) and longest activation time (pacing stimulus to MAP upstroke). After baseline recordings, the balloon inside the left ventricle was filled with a volume of 1.0 mL of fluid by means of a servo-controlled pump. The ERP was significantly shortened from 198 +/- 9 msec at baseline to 183 +/- 8 msec during sustained load (P < 0.03). Similarly, the average APD90 was shortened from 180 +/- 5 msec at baseline to 175 +/- 6 msec during sustained load (P < 0.006) with steady-state pacing and from 178 +/- 6 msec to 170 +/- 8 msec during premature extrastimulation (P < 0.03). At the same time, dispersion of APD90 was increased from 27 +/- 5 msec to 38 +/- 6 msec (P < 0.002) during steady-state pacing and from 28 +/- 4 msec to 38 +/- 6 msec (P = 0.013) during premature extrastimulation. The longest activation time among all MAP recordings was increased from 39 +/- 2 msec to 43 +/- 3 msec (P = 0.003) during steady-state pacing and from 56 +/- 6 msec to 69 +/- 6 msec during premature extrastimulation (P < 0.003). CONCLUSIONS: Sustained load shortens the ERP and the mean APD90, and at the same time increases dispersion of APD90 and prolongs activation times. These findings provide additional insight into the arrhythmogenic mechanisms of sustained mechanical load.

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PubMed1996

Myocardial vulnerability to T wave shocks: relation to shock strength, shock coupling interval, and dispersion of ventricular repolarization.

INTRODUCTION: Induction of ventricular fibrillation (VF) by T wave shocks is of clinical interest due to the correlation between the upper limit of vulnerability (ULV) and the defibrillation threshold (DFT). However, the ULV has not yet been defined precisely in reference to the entire "area of vulnerability" (AOV), which is defined bifunctionally by both shock strengths and shock coupling intervals, nor has it been related to the dispersion of ventricular repolarization, considered to be an important determinant of vulnerability. METHODS AND RESULTS: In 11 isolated perfused rabbit hearts immersed in a tissue bath containing a 3-lead ECG recording system and two opposite plate electrodes for field shock administration, 7 monophasic action potentials (MAPs) were recorded simultaneously from different epicardial and endocardial regions of the right and left ventricles. An average of 90 +/- 25 monophasic waveform shocks of varying shock strengths and coupling intervals were delivered to each heart to determine the horizontal and vertical boundaries of the AOV. The AOV approximated a rhomboid with homogenous VF inducibility. The ULV and lower limit of vulnerability (LLV) represented discrete corners of the AOV with significant changes in VF inducibility if either shock coupling intervals or shock strength were changed by only 10 msec or 10 V, respectively (P < 0.001). The ULV occurred at 7 +/- 10 msec shorter coupling intervals than the LLV (P < 0.05), and VF-inducing shock strengths at the left corner of the AOV were 50 +/- 67 V higher as compared to the right corner (P < 0.01). The maximal range of VF-inducing coupling intervals coincided (within < 2 msec) with the dispersion of MAPs at 70% repolarization, and the ULV coupling interval coincided (within < 4 msec) with the longest repolarization at 50%. CONCLUSIONS: (1) VF vulnerability to monophasic T wave shocks is defined by an AOV that has the shape of a leftward tilted rhomboid. (2) Both the ULV and LLV are sharply defined upper and lower corners of the AOV rhomboid. (3) The width of the AOV corresponds to the dispersion of ventricular repolarization at the 70% level. (4) Considering the dispersion of ventricular repolarization may yield more precise ULV determinations and a better understanding of the correlation between the ULV and DFT.

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