Global Repolarization Sequence of the Ventricular Endocardium: Monophasic Action Potential Mapping in Swine and Humans

The aim of this study was to evaluate the global sequence of repolarization over the ventricular endocardium. Disturbances in myocardial repolarization are associated with the genesis of arrhythmias. However, little is known about the global sequence of repolarization. Monophasic action potentials (MAPs) were recordedfrom 61 +/- 18 LV and/or RV sites in ten healthy pigs and from 43 +/- 15 LV or RV sites in eight patients using the CARTO system. Local activation time (AT), end-of-repolarization (EOR) time, and MAP duration were calculated and three-dimensional global maps of AT, EOR, and MAP duration constructed. LV maps were obtained from all ten pigs and RV maps from three pigs. Five RV maps and five LV maps were obtained from the eight patients. (1) EOR sequence was recognizable in 12 of 13 pig maps and in all the patient maps. (2) EOR followed the sequence of activation in 12 of 13 pig maps and 8 of 10 patient maps. (3) The longest MAPs were recorded in or near the earliest activation area, and the shortest ones in or near the latest activation area in all the pig maps and in nine often and eight often patient maps, respectively. (4) In all maps, MAP duration and AT were negatively correlated, and EOR and AT positively correlated. In conclusion, repolarization gradients exist over the pig and the human ventricular endocardium. The activation sequence is a determinant for the repolarization sequence. The magnitude of the progressive MAP shortening with progressively later activation, relative to local AT, is a critical factor governing the direction and pattern of the EOR.     

Atrial refractoriness and action potential duration after sudden reversal of atrioventricular sequence

To address the potential of atrioventricular (AV) asynchrony to provoke cardiac arrhythmias, atrial electrophysiology was examined during normal and reversed AV interval in anesthetized pigs. A new automatic stimulation technique was adapted to monitor rapid changes in the effective refractory period (ERP), using continuous AV sequential pacing, incremental extrastimulus interval scanning, and automatic detection of capture. Right atrial ERP using 2-8 ms stimulus interval increments and right atrial and ventricular monophasic action potential (MAP) duration were determined simultaneously when the AV interval was changed from normal (+80 ms) to reversed (-40 ms) and back. During reversed AV interval the peak right atrial pressure increased from 8 +/- 3 to 14 +/- 4 mmHg (P < 0.001) and mean arterial pressure decreased from 86 +/- 18 to 65 +/- 21 mmHg (P < 0.001). At new steady state, atrial ERP and MAP duration at 90% level of repolarization were lengthened by 22 +/- 16 and 42 +/- 12 ms respectively (P < 0.001). Ventricular MAP duration did not change. A statistically significant lengthening in atrial ERP could be demonstrated in 5-10 seconds. After reversion of the AV sequence, the ratio of atrial ERP to MAP duration decreased from 1.27 to 0.94 (P < 0.001) on average for 15 seconds, the change being thought to favor reentry. Thus atrial wall stress from contraction during ventricular systole even for a short period of time modifies atrial electrophysiology. Deficient AV synchrony may immediately contribute to the development of atrial arrhythmias.     

The recording of monophasic action potentials with fractal-coated iridium electrodes in humans

The present study was designed to evaluate the feasibility of the recording of monophasic action potentials (MAP) with fractal-coated iridium electrodes in a clinical setting. In 18 patients who underwent an electrophysiological study for various arrhythmias, we performed MAP recordings with both 1.3-mm2 and 6-mm2 tip surface area fractal-coated iridium and standard silver--silver chloride (Ag/AgCl) electrodes in the high right atrium and two ventricular positions. Amplitude and MAP duration at 90%, 50%, and 25% of repolarization were calculated during steady-state pacing at 600, 500, and 400 ms cycle lengths with extrastimuli application. Morphology comparisons of MAP signals recorded with both types of electrodes were performed by regression analysis using 5% of the repolarization segments of the MAP trajectory. Differences between MAP duration at 90%, 50%, and 25% of repolarization recorded with fractal-coated and Ag/AgCl electrodes were statistically insignificant. Amplitude values recorded with 6-mm2 tip electrodes were significantly smaller than those recorded with Ag/AgCl electrodes for all comparisons. During steady-state pacing, the correlation coefficients between Ag/AgCl and fractal-coated 1.3-mm2 and 6-mm2 tip electrodes were within the range of 0.93-0.999 and 0.87-0.999, respectively. The correlation of MAP amplitude and duration at 90%, 50%, and 25% of repolarization following the extrastimulus S2, recorded with both types of electrodes, was significantly weaker for right atrial recordings (r value range 0.78-0.92) as compared to ventricular recordings (r value range 0.92-0.99). The MAP sensing features of fractal-coated iridium and Ag/AgCl electrodes are comparable. The best results for recording of MAPs with fractal-coated electrodes can be achieved with small surface area tip electrodes.     

Correlation of electrotonic monophasic action potential shortening with short-term memory in human atrium

To determine the presence of memory in human atria, we recorded monophasic action potential (MAP) at the high right atrium (HRA) in 21 patients. After reaching a steady state at 600 ms, HRA pacing was switched to the coronary sinus (CS) pacing to alter the activation sequence. After 20 minutes of CS pacing, pacing was continued at HRA to record the memory effect of CS pacing. Atrial memory was defined as the change in HRA MAP duration (MAPd) after 20 minutes of altered activation sequence. Baseline MAPd was 229 +/- 31 ms, which was shortened to 226 +/- 24 ms immediately after CS pacing. After 20 minutes of CS pacing, HRA MAPd during HRA pacing was 220 +/- 28 ms, which was significantly shorter than the baseline MAPd (P = 0.003). The degree of atrial memory was associated with the degree of initial electrotonic MAPd changes caused by the altered activation sequence. These results suggest that memory phenomenon exists in human atria, and it can be expressed as a change in MAPd.     

Effects of epinephrine on right ventricular monophasic action potentials in the LQT1 versus LQT2 form of long QT syndrome: preferential enhancement of "triangulation" in LQT1

AIMS: To explore effects of epinephrine and phenylephrine on the behavior of right ventricular monophasic action potentials (MAPs) in symptomatic LQT1 and LQT2 patients. METHODS AND RESULTS: We recorded endocardial MAPs from right interventricular septum at baseline and during epinephrine and phenylephrine infusions in six symptomatic DNA-verified LQT1 (QTc 528 +/- 83) and five LQT2 patients (QTc 527 +/- 72) and in five control patients (QTc 381 +/- 22). We measured MAP durations at 90% and at 50% levels of repolarization and their difference (MAP50 to MAP90, a measure of MAP morphologic "triangulation"), during atrial pacing to characterize rate dependence of MAPs and repolarization phase 3 durations, respectively. Restitution kinetics were determined during atrioventricular sequential pacing, using the approach of empirical restitution rate. Epinephrine prolonged MAP50-to-MAP90 duration and increased the rate dependence of MAP90 duration and increased restitution rate in type LQT1, but not in LQT2 patients nor in control subjects. Phenylephrine did not change MAP behavior. During epinephrine administration, both LQT1 and LQT2 patients had a ratio of the restitution rate of MAP to diastolic interval >1.0 at short diastolic intervals. CONCLUSION: Symptomatic LQT1 patients with prolonged baseline QTc intervals showed beta-adrenergic-induced changes in MAPs (triangulation) known to be arrhythmogenic, thus giving insight to the difference in clinical triggers of life-threatening arrhythmias between LQT1- and LQT2-affected individuals.     

Heart rate variability is a useful parameter for evaluation of anticholinergic effect associated with inducibility of atrial fibrillation

BACKGROUND: Disopyramide is thought to have an advantageous effect for atrial fibrillation (AF) associated with vagal activity because of its anticholinergic effect. METHOD: We used a canine vagal nerve stimulation (VNS) model. The monophasic action potential (MAP) duration at 90% repolarization (MAP(90)), the intraatrial conduction time, the induciblity of AF by electrical stimulation, and the amplitude of high-frequency component (HF-amp) of the heart rate variability (HRV) were evaluated before and after the administration of disopyramide (1 mg/kg) (group D, n = 8) or pilsicainide (1 mg/kg) (group P, n = 5). RESULTS: In group D, HF-amp decreased in the baseline condition from 1.1 +/- 0.6 to 0.6 +/- 0.4 ms and the degree of VNS-induced augmentation of HF-amp was attenuated from +492% to +127%. VNS-induced shortening of MAP(90) was also attenuated in the right atrium (from -30 +/- 15% to -10 +/- 6%) and in the left atrium (from -15 +/- 9% to -6 +/- 6%). In group P, little effect was shown in these parameters. The vagotonic AF became noninducible in all eight experiments in group D, while in only one of five in group P. CONCLUSION: The beneficial effect of disopyramide for vagotonic AF is based on the decrease of basal vagal tone and attenuation of the effect of vagal stimulation in the atrial myocardium. HRV is a useful parameter for evaluation of the effect of antiarrhythmic drugs on the autonomic nerve system, and the evaluation of variability may be useful for testing drug efficacy for arrhythmias.     

Monophasic action potential recordings in response to rapid transient elevation of extracellular potassium and their modification by beta-adrenoceptor blockade in the anaesthetized dog

1. Monophasic action potentials (MAPs) were recorded simultaneously from the endocardium and the epicardium in open-chested dogs (n = 16) during bolus intravenous injections of potassium chloride at 0.1 mmol/kg and 0.2 mmol/kg. MAP duration was measured at 90% repolarization. Local conduction was measured as the delay between the pacing artefact and upstroke of the MAP. 2. The animals were anaesthetized with alpha-chloralose and urethane. Heart block was created by atrioventricular nodal ablation with 0.1% (v/v) formalin. Infra-nodal pacing was established. 3. Bolus injections of potassium chloride at 0.1 mmol/kg shortened MAP duration. The effect was maximal at 15 s after the injection [epicardium: 171.5 +/- 3.0 (control) and 148.9 +/- 5.2 ms at 15 s (P less than 0.001); endocardium: 178.7 +/- 4.4 (control) and 165.6 +/- 5.3 ms (P less than 0.001)]. The shortening on the epicardium was significantly greater than on the endocardium (P less than 0.05). 4. Local conduction time showed no significant change [epicardium: 37.8 +/- 1.8 (control) and 41.2 +/- 2.4 at 15 s; endocardium: 41.1 +/- 1.6 (control) and 45.0 +/- 3.4 at 15 s]. 5. After beta-adrenoceptor blockade, MAP duration shortened, exhibiting a maximum effect at 20 s after a bolus injection of potassium chloride at 0.1 mmol/kg [epicardium: 184.7 +/- 7.1 (control) and 130.7 +/- 9.0 ms at 20 s (P less than 0.001); endocardium 192.0 +/- 7.4 (control) and 148.6 +/- 10.8 ms at 20 s (P less than 0.001)]. The greater shortening observed on the epicardial surface did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous Recording of Atrial and Ventricular Monophasic Action Potentials: Monophasic Action Potential Duration During Atrial Pacing, Ventricular Pacing, and Ventricular Fibrillation

A newly developed transvenous suction electrode was used in dogs to record monophasic action potentials (MAPs) from the right atrium and right ventricle simultaneously. Continuous MAP recordings could be made from the same endocardial site for test periods of 1.5 hours. Left ventricular pacing at increasing heart rates resulted in a statistically significant decrease of right ventricular MAP duration. A high degree of correlation was found between right ventricular MAP duration at 90% of repolarization and the QT interval during both right atrial and left ventricular pacing. At the onset of ventricular fibrillation (VF), right ventricular MAP duration shortened to 25% of the value obtained during left ventricular pacing at a cycle length of 250 ms. A cyclic alternation in amplitude of the right ventricular MAPs was observed during VF. Fast Fourier Transform Analysis of right ventricular MAPs during VF showed a significant dominant frequency at 12 Hz, with no levels of interest beyond this frequency. This observation might prove to be useful in elaborating a new algorithm for the automatic detection of ventricular fibrillation.     

Action potential remodeling in the human right atrium with chronic lone atrial fibrillation

It has been shown in animal experiments that recurrent induction of atrial fibrillation (AF) or long-lasting atrial pacing causes a shortening of the atrial effective refractory period (ERP) and action potential duration (APD) and a loss of their physiological adaptation to rate. Much remains to be clarified as to the electrical remodeling in human patients with chronic AF. We recorded monophasic action potentials (MAPs) from the right atrium at pacing cycle lengths (CLs) of 300, 333, 400, 500, 600, and 750 ms after external cardioversion in 13 patients with chronic lone AF. Their configuration was compared with those obtained from 13 control patients. APDs at 50% and 90% repolarization (APD50, APD90) at the shortest CL (300 ms) in control and AF patients were 131 +/- 14, 211 +/- 19 ms and 136 +/- 12, 210 +/- 22 ms, respectively (mean +/- SD). APDs in control patients increased linearly with increases of CL, reaching maximal values of 174 +/- 30 ms (APD50) and 277 +/- 38 ms (APD90) at a CL of 750 ms. In AF patients, the steady-state CL-APD relation was shifted downward and flattened at CLs > 500 ms; APD50 and APD90 at a CL of 750 ms were 158 +/- 19 ms, 232 +/- 28 ms, respectively. APD90s at CLs of 600 and 750 ms were significantly shorter in AF than in control patients. No statistically significant difference was obtained in APD50 between the two groups at any CL tested. MAP configuration in AF patients was characterized by an acceleration of the late repolarization. The difference between APD90 and APD50 (APD90-50) in control patients was increased with increases of CL, reaching a plateau at a CL of 600 ms. This CL dependent slowing of the late repolarization of MAPs was abolished in AF patients. The atrial ERP, measured at CLs of 400 and 600 ms, showed changes parallel to those of APD90. ERP at a CL of 600 ms in AF patients (224 +/- 13 ms) was significantly shorter than that in control patients (247 +/- 25 ms). We conclude that chronic lone AF leads to electrical remodeling in the human atrium, which causes a loss of rate response of the late repolarization of action potential, leading to a shortening of APD and ERP at slower heart rates.     

急性心房压力增高对心房肌电生理性质的影响

目的:探讨急性心房压力增高对心房肌电生理性质的影响及其与房性心律失常的关系。方法:12只杂种成年犬,在阻断自主神经状态下行心外膜电生理检查,分成基础对照组,单纯升压组及胺碘酮 升压组,分别测量心房不同位点的单相动作电位(MAP)及房颤诱发率。结果:与基础对照相比,单纯升压组MAPD90明显延长,MAPD90离散度(△MAPD90)增大,RT离散度(△RT)增大,房颤诱发率增加。胺碘酮 升压组MAPD90延长,但△MAPD90减小,△RT在慢频率起搏时减小,但起搏频率增快时逐渐增大,房颤诱发率虽高于对基础对照,但与单纯升压组相比无统计学差异。结论:1)急性心房压力增高后△RT增大,这可能是此时房颤诱发率增高的电生理基础;2)胺碘酮静脉制剂在房压增高时不能有效降低房颤诱发率,推测与这时△RT在快频率起搏时增大有关。     

Transmural Mapping of Myocardial Refractoriness and Endocardial Dispersion of Repolarization in an Ovine Model of Chronic Myocardial Infarction

Background: Myocardial refractoriness and repolarization is an important electrophysiological property that, when altered, increases the risk of arrhythmogenesis. These electrophysiological changes associated with chronic myocardial infarction (MI) have not been studied in detail. We assessed the influence of left ventricular (LV) scarring on local refractoriness, repolarization, and electrogram characteristics. Methods: MI was induced in five sheep by percutaneous left anterior descending artery occlusion for 3 hours. Mapping was performed at 19 ± 6 weeks post‐MI. A total of 20 quadripolar transmural needles were deployed at thoracotomy in the LV within and surrounding scar. Bipolar pacing was performed from each needle to assess the effective refractory period (ERP) of the subendocardium and subepicardium. The activation (AT) and repolarization (RT) times, and modified activation recovery interval (ARI_m) were determined from endocardial unipolar electrograms recorded in sinus rhythm simultaneously from all needles. Scarring was quantified histologically and compared with electrophysiological characteristics. Results: Increased scarring corresponded with increased ERP (P < 0.01), decreased subendocardial electrogram amplitude (P < 0.001), and slope (P < 0.001). ERP did not differ between endocardium and epicardium (P > 0.05). The ARI_m and RT were prolonged during early myocardial activation (P < 0.001). After adjusting for AT, the RT and ARI_m were prolonged in areas of scarring (P < 0.001). After adjusting for electrogram amplitude, the ARI_m was prolonged in dense scar (P < 0.05). Conclusions: We confirmed histologically that scarring contributes to prolongation of repolarization, increased refractoriness, and reductions in conduction and voltage post‐MI. Prolongation of repolarization may be further augmented when local activation is earliest or electrogram voltage is decreased within scar.     

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 fT_cmax-fT_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 ond 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.     

Basic assessment of paced activation sequence mapping: implications for practical use

Some experiences support the use of atrial paced activation sequence mapping, but there is no systematic study assessing its spatial resolution, reproducibility, and influence of pacing parameters. The aim of this study was to evaluate these issues by using a 24-pole catheter positioned at the atrial aspect of the tricuspid and mitral annuli in 15 patients. Bipolar pacing was performed at two sites (right and left atria), 2 cycle lengths (300 and 500 ms) and two outputs (twice and tenfold the late diastolic threshold voltage for 2-ms pulses). The elapsed time between the atrial activation at the two dipoles adjacent to the pacing dipole (activation time [AT]) was measured during each pacing sequence. Changes in cycle length did not modify the AT. The increase in voltage slightly modified the AT (maximum -2 ms at the RA; 95% CI -3 to -1 ms) due to a greater shortening of the conduction time to the dipole located next to the anode. The 95% limits of the intraobserver and interobserver agreements in the AT measurement were -2 to 3 ms and -3 to 3 ms, respectively. The spatial resolution was studied in ten patients by measuring the AT during pacing from each dipole of a 20-pole catheter with a 1-3-1 mm interelectrode distance. The mean AT change was 10 +/- 4 ms per 6 mm of pacing site displacement (95% CI 8-11 ms, range 2.5-20 ms). In conclusion, paced atrial activation sequence analysis is reproducible, accurate, and relatively independent of pacing parameters.     

Inverse Relation of Body-Surface Activation-Recovery Interval and Recovery Time to Activation Time in Normal Subjects: Stronger Correlation and More Heterogeneous Distribution in Activation-Recovery Interval Than in Recovery Time

The activation-recovery interval (ARI), measured directly from the myocardium, has shown a good correlation with the action potential duration (APD) in experiments. APD has been reported to be inversely related to the activation time (AT). However, no studies have examined the correlation between the body-surface ARI and AT in normal subjects. Fifty normal subjects (25 men and 25 women) were studied to elucidate the relationship between the body-surface ARI and AT. The body-surface AT was defined as the duration between the QRS onset and the minimum dV/dt of the QRS wave, and ARI as the interval between the minimum dV/dt of the QRS wave and the maximum dV/dt of the T wave in each lead of an 87 unipolar lead system. We also measured the recovery time (RT) defined as the duration between the QRS onset and the maximum dV/dt of the T wave. ARI was inversely correlated with AT (r = -0.73). RT was also inversely correlated with AT (r = -0.61), however, RT had a less heterogeneous distribution than ARI (148 ms vs 159 ms). There were no differences between male and female subjects in the relation between ARI and RT or in the body-surface distribution of ARI and RT. These findings suggest that the body-surface ARI may reflect recovery properties over the cardiac surface and that APD may distribute inhomogsneously over the human cardiac surface with a longer RT over an area with a shorter AT. ARI calculated from body-surface ECG may be a useful noninvasive and repeatedly measurable estimate of APD.     

Origin of electrical activation within the right atrial and left ventricular walls: differentiation by electrogram characteristics using the noncontact mapping system

Clinical data using the noncontact mapping system (Ensite 3000) suggest that characteristics of the reconstructed unipolar electrograms may predict the origin of electrical activation within the atrial and ventricular walls (endocardial vs myocardial vs epicardial origin). Experimental data are lacking. In ten open-chest pigs (mean body weight 62 kg) cardiac pacing was performed at a cycle length of 600 ms with a pulse width of 2 ms and twice diastolic threshold from the endo-, the myo-, and the epicardium, respectively. Pacing was undertaken at three right atrial and three left ventricular sites, and cardiac activation was recorded with the Ensite system. Reconstructed unipolar electrograms at the location of earliest endocardial activation assessed by color coded isopotential maps were analyzed systematically for differences in morphology. The positive predictive value of atrial electrograms exhibiting an initial R wave during pacing for a subendocardial origin (i.e., myocardial or epicardial) was 0.96. The negative predictive value was 0.48. Electrograms generated during myocardial pacing exhibited increased maximal negative voltage and maximal dV/dt (-3 +/- 1.8 mV, -798 +/- 860 mV/ms, respectively) than the electrograms obtained during endocardial (-2 +/- 1 mV, -377 +/- 251 mV/ms, respectively) and epicardial pacing (-2.1 +/- 0.7 mV, -440 +/- 401 mV/ms, respectively, P<0.01 for both parameters). During pacing at the left ventricular wall, occurrence of an initial R wave did not differ significantly between electrograms reconstructed during endocardial and subendocardial pacing. All other characteristics of the unipolar ventricular electrograms analyzed, except latency, did not differ significantly when compared to stimulation depth. Morphological characteristics of unipolar electrograms generated by the noncontact mapping system during pacing of the atrium allowed for discrimination of an endocardial versus a subendocardial origin of activation. At the ventricular level, characteristics of unipolar electrograms did not predict the origin of cardiac activation in this experimental setting.     

Effect of IKr blocker nifekalant on atrial action potential duration after successful internal cardioversion of chronic atrial fibrillation

BACKGROUND: Chronic atrial fibrillation (AF) is characterized by a marked decrease in the atrial effective refractory period (ERP) and in the ERP adaptation to rate as well as a decrease in the atrial conduction velocity. Little information is available about the ionic mechanisms underlying AF in humans. MATERIALS AND METHODS: We studied the effect of IKr blocker nifekalant on the rate-dependent changes in atrial action potential duration in 11 patients after successful internal cardioversion of chronic AF of >2 months duration and in 7 patients without AF. In AF patients, right atrial (RA) monophasic action potential (MAP) was recorded at pacing cycle lengths (CLs) of 800-250 ms before and after administration of nifekalant. In control patients, RAMAP was recorded at CLs of 600 and 350 ms before and after administration of nifekalant. RESULTS: Nifekalant significantly increased RAMAPD at 90% repolarization (RAMAPD90) at CLs of 800-300 ms in the AF patients. The increase in RAMAPD90 by nifekalant became significantly smaller at shorter CLs (42.5 +/- 12.4 ms at a CL of 600 ms vs 32.8 +/- 14.5 ms at a CL of 350 ms, P < 0.05). Effect of nifekalant on RAPMAPD was attenuated at CL of 600 ms in AF patients in comparison to control patients (increase in RAMAPD in control; 73.0 +/- 36.6 ms vs increase in RAMAPD in AF; 42.5 +/- 12.4 ms, P < 0.05); however, it was similar at a CL of 350 ms between control and AF patients. CONCLUSIONS: Electrophysiological effects of nifekalant are significantly attenuated in the chronically remodeled human atrium at slower heart rates, but the beneficial effect of RAMAPD prolongation by IKr blocker was well-preserved even at shorter CLs after chronic AF.     

Comparison of effects of dextran-70 and Ringer's acetate on pulmonary function, hemodynamics, and survival in experimental septic shock

The effects of dextran-70 with NaCl vs. Ringer's acetate on hemodynamics, gas exchange, oxygen transport, and survival were evaluated in a porcine model of pulmonary and circulatory insufficiency induced by a continuous iv endotoxin infusion over 6 h. Dextran and Ringer's acetate were infused continuously to maintain baseline mean left atrial pressure (LAP) throughout the endotoxin period. Twelve pigs receiving endotoxin + Ringer's acetate displayed a progressive 45% decline in cardiac output (Qt) and a two-peaked increase in pulmonary vascular resistance (PVR) with a late increase of 250%. Venous admixture (Qva/Qt) increased progressively more than six-fold and extravascular lung water (EVLW) increased by 55%. Mean arterial BP (MAP) fell by 25%, oxygen delivery by 40%, base excess (BE) ranged between -4.5 and -9 mmol/L at the end of the endotoxin period and four of 12 animals died. Polymorphonuclear cell count (PMN) fell rapidly by 90% and was decreased severely throughout the endotoxin period. By contrast, the 12 pigs that received endotoxin + dextran maintained Qt near baseline and PVR was significantly lower in this group. Qva/Qt increased progressively more than four-fold, but it was significantly lower than in the Ringer's acetate group as was the increase in EVLW (23%). MAP only decreased by 10%, oxygen delivery only decreased by 20%. BE ranged between -1.0 and -3.0 mmol/L at the end of the endotoxin period and all animals survived. PMN fell by 90% at 0.5 h but subsequently tended to return toward baseline, and PMN were significantly increased compared with the Ringer's acetate group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate reinitiation of atrial tachyarrhythmias after spontaneous restoration of sinus rhythm in patients with an implanted monitoring device

Immediate reinitiation of atrial tachyarrhythmia (IRAT) has been observed after cardioversion. After spontaneous restoration of sinus rhythm (SR), incidence and characteristics of IRAT have not been described. Therefore, in patients with atrial tachyarrhythmias (ATs) and bradycardia, a pacemaker with dedicated memory functions was implanted. Devices were interrogated after 1 month and stored episodes of AT were analyzed: incidence of IRAT, duration and rate of the preceding episode, sinus rate before AT, coupling interval of atrial premature beats (APBs) initiating AT, and incidence of repetitive APBs. A potential association with IRAT was assessed for clinical characteristics. In 36 of 68 patients, stored electrograms confirmed correct detection of AT onset and termination in 545 episodes. IRAT was present in 212 (39%, 24 patients) episodes of AT. Episodes of AT preceding IRAT were longer than those before non-IRAT (156 vs 46 s, P < 0.001), and occurred during a higher atrial rate before onset of AT (cycle length 775 +/- 111 vs 856 +/- 133 ms, P < 0.001). The coupling interval of APBs initiating IRAT was shorter (502 +/- 83 vs 538 +/- 89 ms; P < 0.001) while the percentage of episodes with repetitive APBs before AT onset and the median atrial cycle length of the preceding AT were not different. On stepwise logistic regression analysis, none of the clinical factors evaluated independently predicted IRAT. In conclusion, IRAT is frequent after spontaneous restoration of SR. Changes of atrial electrophysiological properties promoting IRAT may already develop during AT of short duration.     

Chronic amiodarone effects on epicardial conduction and repolarization in the isolated porcine heart

Amiodarone is a potent antiarrhythmic agent with complex chronic effects, notably on repolarization and conduction, that are not fully understood. Its low arrhythmogenic potential has been related to a lack of increase in repolarization dispersion. Since its effects are not documented in pigs we conducted a mapping study of activation and repolarization in isolated perfused porcine hearts. Amio20 female pigs (n = 7) received amiodarone 20 mg/kg per day over 4 weeks while Amio50 female pigs (n = 7) received 50 mg/kg per day over 4 weeks. Concentrations of the drug encompassed values found in clinical studies. Then, activation patterns and activation-to-recovery intervals (ARI) were mapped epicardially from 128 unipolar electrograms in isolated perfused hearts in corroboration of epicardial action potential recordings. Mean ARI was longer in Amio20 experiments compared to the seven control hearts (325 +/- 11 ms vs 288 +/- 5 ms at 1,000 ms), whereas ARI dispersion was not different, being comprised between 7 and 11 ms and generating smooth gradients. In Amio50 experiments, mean ARI was further prolonged (390 +/- 10 ms at 1,500 ms) with an exaggerated reverse rate dependence concomitant with a depressant effect on the plateau of the action potential. Again, ARI dispersion did not differ from controls. Finally, the drug depressed the maximal rate of depolarization (Vmax) and slowed conduction in a rate dependent and concentration dependent fashion. In conclusion, chronic amiodarone induces Class I and Class III antiarrhythmic effects in ventricular porcine epicardium that are concentration dependent but does not affect dispersion of repolarization. This may partly explain its low arrhythmogenic potential.     

The acute effects of biatrial pacing on atrial depolarization and repolarization

Permanent biatrial and/or multisite atrial pacing may prevent atrial fibrillation (AF), but the effects on atrial electrophysiology remain incompletely understood. Acute biatrial pacing was studied in 20 patients with and 28 without (controls) a history of atrial fibrillation and/or flutter. Twelve-lead electrocardiograms were recorded during pacing from the high right atrium (RA), from the distal coronary sinus (LA), and biatrial pacing. P wave duration was measured in each lead and the difference between maximum and minimum P duration was termed P wave dispersion. Effective refractory periods (ERPs) were measured during each pacing mode. The dispersion of P wave duration was 35 +/- 14 ms in controls and 40 +/- 29 ms in AF patients (P = 0.17). Compared to RA pacing, LA pacing shortened P duration in controls (127 +/- 18 to 107 +/- 16 ms, P < 0.05) and biatrial pacing markedly shortened P duration in controls (127 +/- 18 to 93 +/- 14 ms, P < 0.05) and AF patients (114 +/- 43 to 97 +/- 21 ms, P < 0.05). P wave dispersion was unaffected. In controls, the LA ERP was longer than the RA ERP. This phenomenon was not present in AF patients, whose LA ERP was shorter than that of controls. Biatrial pacing had no effect on atrial ERPs or the dispersion of atrial refractoriness. In conclusion, acute biatrial pacing does not affect atrial repolarization but it does cause a marked shortening of global biatrial depolarization. Distal coronary sinus pacing produces a shorter P wave than RA pacing. There is substantial dispersion in the surface P wave of the electrocardiogram, the significance of which awaits further study.