Antimelanoma differentiation-associated protein 5 antibody level is a novel tool for monitoring disease activity in rapidly progressive interstitial lung disease with dermatomyositis.

BACKGROUND: Antimelanoma differentiation-associated protein (anti-MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). OBJECTIVES: We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. METHODS: Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti-MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide. RESULTS: All patients achieved RP-ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti-MDA5 antibody levels at remission. Six (50%) patients became anti-MDA5 antibody negative after therapy. After a mean follow-up of 31 months, RP-ILD relapse was observed in four (33%) patients in both the anti-MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti-MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti-MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti-MDA5 antibody exhibited symptoms of relapse during follow-up. Therefore, reincrease in anti-MDA5 antibody levels was associated with relapse. CONCLUSIONS: The anti-MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP-ILD relapse in patients with CADM or DM.

New quantitative methods for evaluation of dynamic changes in QT interval on 24 hour Holter ECG recordings: QT interval in idiopathic ventricular fibrillation and long QT syndrome.

OBJECTIVES: To introduce a nomogram of the normal QT interval at various heart rates measured from 24 hour Holter ECG recordings in healthy subjects with respect to age and sex and to use the nomogram to characterise dynamic changes in QT interval in patients with idiopathic ventricular fibrillation (IVF) and the long QT syndrome (LQT). METHODS: The study group consisted of 422 subjects: 249 healthy men ranging in age from 21-88 years (mean (SD) 47 (20) years) and 173 healthy women ranging in age from 21-85 years (47 (19) years). In addition, seven men with IVF ranging in age from 33-53 years (43 (9) years) and five women with LQT ranging in age from 20-55 years (37 (14) years) were studied. For each subject, QT interval and heart rate were determined automatically from 24 hour Holter ECG digital data-namely, QT interval was measured from signal averaged ECG waves obtained by averaging consecutive sinus beats during each 15 second period over 24 hours. Data were grouped and averaged at an interval of 5 beats/min for heart rates ranging from 46-120 beats/min. RESULTS: In healthy subjects aged < 50 years and > or = 50 years QT intervals were longer in women than in men. QT intervals were longer in both men and women aged > or = 50 years than in ages < 50 years. From these findings a nomogram of QT interval at varying heart rates adjusted for age (younger group aged < 50 years or older group aged > or = 50 years) and sex was determined. In patients with IVF, QT intervals were significantly shorter at slower heart rates than normal values obtained from the nomogram. In patients with LQT, QT intervals were significantly longer at both faster and slower heart rates than normal values. CONCLUSIONS: The nomogram of QT interval at varying heart rates adjusted for sex and age could be used to assess dynamic changes of QT interval of various pathological conditions. For example, patients with IVF had shorter QT interval at slower heart rates, a finding suggestive of arrhythmogenicity of this specific syndrome at night. Patients with LQT had prolonged QT interval at specific heart rate ranges depending on their genotype.

Modulation of ventricular repolarization and R-R interval is altered in patients with globally impaired cardiac 123I-MIBG uptake.

BACKGROUND: Cardiac (123)I-metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. METHODS: Twenty-nine patients with prior myocardial infarction were divided into two groups by a heart-to-mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M >or= 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holter recording and a standard 12-lead electrocardiography were used for evaluation of HRV, QT-RR relation, and QT dispersion. RESULTS: Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT-RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 +/- 25 msec) than in group II (43 +/- 19 msec) and group III (28 +/- 9 msec). CONCLUSION: These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.

Spectral characteristics of human atrial fibrillation waves of the right atrial free wall with respect to the duration of atrial fibrillation and effect of class I antiarrhythmic drugs.

The aim of this study was to use fast Fourier transform analysis to clarify the characteristics of human atrial fibrillation (AF) waves with respect to the duration of AF and the effect of class I antiarrhythmic drugs. Twenty-two patients (10 paroxysmal AF, 12 persistent AF) without organic heart disease were studied by conventional electrophysiological methods. Electrograms were recorded from the right atrial free wall during AF and spectral analysis was performed for 35s (16 consecutive 4096-ms epochs with 50% overlap) and the fibrillation cycle length (FCL) was calculated from the peak frequency. Mean FCL and SD were determined from 16-epoch data, and the temporal variability of FCL was defined as the SD of FCL. Paroxysmal AF had a longer mean FCL than persistent AF (178+/-26ms vs 139+/-16 ms, p<0.001) and AF duration had a significant inverse correlation with mean FCL (r=-0.79, p<0.001). The temporal variability of FCL was significantly greater in paroxysmal AF than in persistent AF (p<0.05) and there was a significant positive correlation between the mean FCL and the temporal variability of FCL (r=0.66, p<0.001). In 8 of 18 patients given a class I antiarrhythmic drug (cibenzoline or procainamide), AF was terminated and in those patients the mean FCLs before administration of class I drugs were significantly greater than in patients without AF termination. With respect to mean FCL before drug administration, conversion occurred in 100% of patients with FCL > or =168 ms and in 17% of those with FCL <168 ms. A longer duration of AF shortens the mean FCL, which is consistent with atrial electrical remodeling. Class I drugs prolong the mean FCL above a critical level and will terminate AF, which can be estimated from the mean FCL before drug administration.

Spontaneous onset of torsade de pointes in long-QT syndrome and the role of sympathovagal imbalance.

The net effects of sympathetic and vagal activity on the QT interval and the mode of spontaneous onset of torsade de pointes (TdP) are still unclear in long-QT syndrome. Two patients with long-QT syndrome had syncope while undergoing Holter ECG investigation. The spontaneous onset of TdP in these patients was analyzed with respect to the relation between the RR and QT intervals. Both patients were high-school students (16- and 17-year-old boys) who had been diagnosed as long-QT syndrome and followed up without medical treatment because they had had neither a history of syncope nor arrhythmia induction by treadmill exercise tests. The first episode of syncope in both patients occurred during ordinary daily life and was not related to exercise or psychological stress. The dynamic changes between the RR and QT intervals associated with the spontaneous onset of TdP were analyzed by Holter ECG. Both patients showed sinus tachycardia followed by abrupt sinus bradycardia immediately before the onset of TdP. The enhanced rate of the adaptive response of the QT interval that occurred during the deceleration of the heart rate preceded the onset of TdP. These observations suggest that the complex situation that follows sympathovagal imbalance may have an important role in the dynamic change in the QT interval and initiation of TdP in patients with long-QT syndrome.

[Abnormal Q wave in the right precordial leads unmasked during right bundle branch block in a patient with anteroseptal myocardial infarction: a case report].

Electrocardiography in a 77-year-old woman showed small R waves in leads V1-V3 3 hours after the onset of acute anteroseptal myocardial infarction. Abnormal Q waves appeared in leads V1-V3 only during intermittent right bundle branch block. The normal septal force disappeared after transmural septal infarction and a small force of right ventricle origin became apparent as a small R wave in V1. Right bundle branch block delayed activation of right ventricle, and thereby deleted the initial R wave and unmasked the Q wave of the septal infarction. Appearance of a Q wave in leads V1-V3 with right bundle branch block should not be assumed to reflect the extension of myocardial infarction.

Electrophysiological mechanisms of conversion of typical to atypical atrioventricular nodal reentrant tachycardia occurring after radiofrequency catheter ablation of the slow pathway.

This report presents an adult patient with conversion of typical to atypical atrioventricular nodal reentrant tachycardia (AVNRT) after slow pathway ablation. Application of radiofrequency energy (3 times) in the posteroseptal region changed the pattern of the atrioventricular (AV) node conduction curve from discontinuous to continuous, but did not change the continuous retrograde conduction curve. After ablation of the slow pathway, atrial extrastimulation induced atypical AVNRT. During tachycardia, the earliest atrial activation site changed from the His bundle region to the coronary sinus ostium. One additional radiofrequency current applied 5 mm upward from the initial ablation site made atypical AVNRT noninducible. These findings suggest that the mechanism of atypical AVNRT after slow pathway ablation is antegrade fast pathway conduction along with retrograde conduction through another slow pathway connected with the ablated antegrade slow pathway at a distal site. The loss of concealed conduction over the antegrade slow pathway may play an important role in the initiation of atypical AVNRT after slow pathway ablation.

Changes in autonomic nervous activity after catheter ablation of right ventricular outflow tract tachycardia.

Idiopathic right ventricular outflow tract (RVOT) tachycardia is prone to occur when sympathetic nervous activity increases. The effects of catheter ablation on the arrhythmia may be modified by changes in the sympathovagal balance induced by the ablation. In 8 patients with RVOT tachycardia, analyses of heart rate variability (HRV) were performed before, early (1-3 days, POST1) and late (7-14 days, POST2) after the ablation. From 24-h ambulatory Holter monitoring, RR intervals of a 2-h period during sleep (00.00-06.00 h) were analyzed. MSSD and pNN50 were increased along with a decrease in the frequency of ventricular arrhythmias at both POST1 and POST2 after successful ablation. In contrast, high frequency power (HF) was increased, and low frequency power (LF) and LF/HF were decreased only at POST2 in the 8 patients. In 4 patients in whom the initial ablation had been unsuccessful, the indices of HRV did not change significantly after the unsuccessful ablation, but after successful ablation they changed as in the other 4 patients. After successful catheter ablation of the RVOT tachycardia, sympathetic nervous activity was decreased and parasympathetic nervous activity was increased along with decrease in the frequency of ventricular arrhythmias. The presence of ventricular tachyarrhythmia could, therefore, elicit sympathetic predominance and consequently modify arrhythmogenesis.

Circadian variation of idiopathic ventricular tachycardia originating from right ventricular outflow tract.

We determined circadian variation of isolated ventricular premature complexes (VPCs), 2 to 4 consecutive VPCs, and ventricular tachycardia (5 consecutive VPCs) originating from the right ventricular outflow tract in patients without apparent structural heart diseases. There was apparent circadian variation with 2 prominent peaks for these ventricular arrhythmias, and blockade abolished ventricular tachycardia and attenuated the circadian variation of consecutive VPCs.

ST segment elevation in the right precordial leads induced with class IC antiarrhythmic drugs: insight into the mechanism of Brugada syndrome.

We evaluated two patients without previous episodes of syncope who showed characteristic ECG changes similar to Brugada syndrome following administration of Class IC drugs, flecainide and pilsicainide, but not following Class IA drugs. Patient 1 had frequent episodes of paroxysmal atrial fibrillation resistant to Class IA drugs. After treatment with flecainide, the ECG showed a marked ST elevation in leads V2 and V3, and the coved-type configuration of ST segment in lead V2. A signal-averaged ECG showed late potentials that became more prominent after flecainide. Pilsicainide, a Class IC drug, induced the same ST segment elevation as flecainide, but procainamide did not. Patient 2 also had frequent episodes of paroxysmal atrial fibrillation. Pilsicainide changed atrial fibrillation to atrial flutter with 2:1 ventricular response, and the ECG showed right bundle branch block and a marked coved-type ST elevation in leads V1 and V2. After termination of atrial flutter, ST segment elevation in leads V1 and V2 continued. In this patient, procainamide and quinidine did not induce this type of ECG change. In conclusion, strong Na channel blocking drugs induce ST segment elevation similar to Brugada syndrome even in patients without any history of syncope or ventricular fibrillation.

Successful radiofrequency catheter ablation of incessant ventricular tachycardia with a delta wave-like beginning of the QRS complex.

Ventricular tachycardia with a delta wave-like beginning of the QRS complex is considered to be refractory to endocardial catheter ablation because it originates from the epicardial region. A 45-year-old woman had incessant ventricular tachycardia with a delta wave-like beginning of the QRS complex which was resistant to several antiarrhythmic drugs. The origin of the arrhythmia was at the mitral annulus on the antero-lateral left ventricular wall. The earliest endocardial activation preceded the QRS complex by 18 msec. After 7 sec of endocardial radiofrequency application ventricular tachycardia was terminated. During a 2 year follow-up ventricular tachycardia did not recur and only small numbers of premature ventricular contractions (< 100/day) were noted. VT with delta wave-like QRS morphology which originates from the basal region of the ventricle may be treated successfully with radiofrequency catheter ablation using an endocardial approach.

Role of sympathovagal balance in the initiation of idiopathic ventricular tachycardia originating from right ventricular outflow tract.

VT originating from the right ventricular outflow tract (RVOT) is prone to occur when sympathetic nervous activity is increased. beta-Blockade is, therefore, effective in suppressing this VT. The purpose of this study was to determine the role of sympathovagal balance assessed by heart rate variability (HRV) in the spontaneous initiation of repetitive premature ventricular contractions (PVCs) and VT (five or more consecutive PVCs) arising from RVOT in seven patients without structural heart diseases. Frequency-domain measures of HRV were determined by analyzing 24-hour Holter electrocardiographic recording with the maximum entropy method over a 1,280-second period immediately before the onset of 35 single PVCs, 26 episodes of 2-4 consecutive PVCs, and 21 episodes of VT. High frequency component (HF: 0.15-0.40 Hz) was used as an index of parasympathetic activity, and the ratio of low frequency component (LF: 0.04-0.15 Hz) to HF (LF/HF ratio), as an index of sympathovagal balance. NN50(%), a time-domain variable of parasympathetic activity, was also determined. Mean RR interval and any measures of HRV did not change significantly before single PVCs. Mean RR interval shortened and HF decreased prior to repetitive PVCs and VT. The LF/HF ratio, however, increased only before the onset of VT. NN50(%) tended to decrease before repetitive PVCs and decreased significantly before VT. With propranolol (30-60 mg/day), frequency of repetitive PVCs was suppressed from 2,048 +/- 1,201 to 746 +/- 658/day and VT was totally abolished, but frequency of single PVCs did not change significantly. In conclusion, sympathetic predominance plays an important role in the initiation of repetitive PVCs and VT originating from RVOT in patients without structural heart diseases.

Essential pathway of reentry in the canine model of atrial flutter. Analysis using radiofrequency ablation.

In humans, the isthmus in the low right atrium between the tricuspid annulus and the inferior vena cava or the coronary sinus ostium is a well-established target of catheter ablation of common atrial flutter. In the canine model of atrial flutter with a Y-shaped incision, the tricuspid annulus was thought to constitute the essential reentrant pathway. The present study was designed to determine whether the supravalvular tissue around the tricuspid annulus is essential to atrial flutter in the canine model with an intercaval obstacle on the basis of the results of radiofrequency ablation. Epicardial approach of radiofrequency ablation was tested in 4 groups of dogs. Group A (5 dogs): Single application of radiofrequency energy (20 W) for 5 sec to the mid right atrial free wall. Group B (9 dogs): One to two applications to the tricuspid annulus. A ligature was also placed encircling the tricuspid annulus from the supravalvular atrial tissue to the subvalvular ventricular tissue. Group C (9 dogs): Linear transverse applications to the mid right atrial free wall between the tricuspid annulus and the intercaval obstacle. Group D (10 dogs): The isthmus between the inferior vena cava and the tricuspid annulus was ablated. After the experiment, the heart was excised for anatomical and histological studies. Atrial flutter was never abolished in all dogs in Groups A and B. A ligature encircling the tricuspid annulus also failed to terminate atrial flutter in 2 dogs tested. In contrast, atrial flutter was successfully abolished in 6 dogs (67%) of Group C and in 7 dogs (70%) of Group D. Total energy delivered was significantly higher in Group C than in Group D (364 +/- 133 versus 139 +/- 65 joules, p < 0.003). The total energy required for successful ablation was related to the cross sectional area of the ablation site (r = 0.55, p < 0.05). These results indicate that the tricuspid annulus is not an essential part of the reentrant pathway in the canine model of atrial flutter with an intercaval obstacle. The entire atrial tissue between the anatomical barriers could be involved in the reentrant pathway, and should therefore be ablated transmurally for successful ablation.

Electrophysiologic effects of SD-3212, a new class I antiarrhythmic drug, on canine atrial flutter and atrial action-potential characteristics.

SD-3212 (levo-semotiadil fumarate) is a newly developed compound that exhibits potent antiarrhythmic activity because of its inhibitory action on sodium and calcium channels. In animal models, SD-3212 suppressed ventricular tachyarrhythmias, but the effects of this drug on atrial tachyarrhythmias have not been reported. We investigated the electrophysiologic effects of SD-3212 on canine atrial flutter induced after placement of the intercaval obstacle and on atrial action-potential characteristics. In all seven dogs, SD-3212 (1.9 +/- 0.3 mg/kg) terminated atrial flutter after significant increase in atrial flutter cycle length from 126 +/- 5 to 166 +/- 14 ms (increase, 31 +/- 8%; p < 0.005). SD-3212 increased right atrial effective refractory period (RAERP) significantly from 126 +/- 7 to 149 +/- 11 ms at a basic cycle length of 300 ms. The increases in RAERP after SD-3212 at basic cycle lengths of 300, 200, and 150 ms did not differ (increase, 18 +/- 4%, 17 +/- 3%, and 19 +/- 3%, respectively). Interatrial conduction time (IACT) was prolonged after SD-3212 from 63 +/- 4 to 81 +/- 6 ms (increase, 31 +/- 6%) at a basic cycle length of 150 ms. Prolongation of IACT was frequency dependent. The plasma concentration of SD-3212 after the termination of atrial flutter was 187 +/- 56 ng/ml in four dogs tested. In vitro study by using standard microelectrode techniques showed SD-3212 at concentrations of 1-3 microM significantly prolonged action-potential duration at 90% repolarization. Vmax was decreased by SD-3212 in a concentration-dependent manner (0.3-3 microM), and the inhibitory effect on Vmax was greatest at the highest stimulation frequency of 3.3 Hz. These results indicate that a new antiarrhythmic drug, SD-3212, is effective in interrupting canine atrial flutter, possibly by suppressing atrial conduction, and might be effective for the treatment of clinical atrial tachyarrhythmias.

Left ventricular dimensions and autonomic balance during head-up tilt differ between patients with isoproterenol-dependent and isoproterenol-independent neurally mediated syncope.

OBJECTIVES: This study sought to elucidate differences in mechanisms of neurally mediated syncope between patients with syncope induced by head-up tilt alone and those requiring isoproterenol infusion to induce syncope during head-up tilt. BACKGROUND: Some patients with neurally mediated syncope require isoproterenol to induce syncope during head-up tilt (isoproterenol dependent), and others do not (isoproterenol independent). Differences in mechanisms between these two groups have not been well elucidated. METHODS: A 60 degrees head-up tilt test was performed in 13 patients with isoproterenol-independent syncope (Group I, mean [+/- SD] age 28 +/- 12 years), 14 patients with isoproterenol-dependent syncope (Group II, mean age 34 +/- 14 years) and 20 control subjects without syncope (Group III, mean age 32 +/- 12 years). Left ventricular size and contractility were determined by echocardiography, and sympathovagal balance was determined with power spectral analysis of heart rate variability using a maximal entropy method. RESULTS: Group I patients had smaller left ventricular dimensions than Group II and III during baseline tilt. During head-up tilt with isoproterenol infusion (0.01 to 0.04 microgram/kg body weight per min), left ventricular dimensions decreased to the same extent in Groups II and III, but fractional shortening was greater in Group II than in Group III at the end of the tilt. The ratio of low (0.05 to 0.15 Hz) to high frequency (0.15 to 1.0 Hz) component became greater in Group I than in Groups II and III during the last period of baseline tilt. However, the ratio was greater in Group II than in Group III during the last period of the tilt with isoproterenol. CONCLUSIONS: Patients with isoproterenol-independent syncope had an exaggerated decrease in left ventricular size and sympathetic predominance preceding syncope during head-up tilt. In contrast, in patients with isoproterenol-dependent syncope, similar changes in autonomic nervous balance were evident only during isoproterenol infusion in addition to head-up tilt.

Electrophysiologic effects of intravenous E-4031, a novel class III antiarrhythmic agent, in patients with supraventricular tachyarrhythmias.

The electrophysiologic effects of intravenous (i.v.) E-4031, a new class III antiarrhythmic drug, were evaluated in 15 patients with supraventricular tachyarrhythmias [11 men, 4 women; mean age 41 +/- 19 (SD) years]. Eleven patients had accessory atrioventricular (AV) pathways, and 4 patients with no accessory pathway had paroxysmal atrial fibrillation. Electrophysiologic studies were performed before and after E-4031 administration (loading infusion 9 micrograms/kg for 5 min + maintenance infusion 0.15 microgram/kg/min). QT and QTc intervals were significantly prolonged by E-4031 from 0.40 +/- 0.03 (mean +/- SD) to 0.46 +/- 0.03 s (p < 0.0001) and from 0.43 +/- 0.03 to 0.49 +/- 0.04 s (p < 0.0001), respectively. No effect was observed on RR interval, PR interval, QRS duration, or AH and HV intervals. The effective refractory periods (ERPs) of the right atrium and ventricle were significantly prolonged from 219 +/- 27 to 236 +/- 26 ms (p < 0.001) and from 230 +/- 12 to 249 +/- 11 ms (p < 0.001), respectively. The ERP of the AV node did not change significantly after E-4031 administration. In patients with ventricular preexcitation, E-4031 significantly prolonged the ERP of the antegrade accessory pathway conduction from 340 +/- 101 to 362 +/- 106 ms (p < 0.001), but not retrograde accessory pathway conduction. AV reentrant tachycardia was induced in 3 of 11 patients with an accessory pathway, and repetitive atrial firing was induced in 3 of 4 patients with paroxysmal atrial fibrillation. E-4031 could prevent repetitive atrial firing in only 1 patient and could not prevent induction of AV reentrant tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute ischemia on anisotropic conduction in canine ventricular muscle.

The effects of acute ischemia on conduction velocities in the longitudinal (theta L) and transverse (theta T) fiber axis were determined from epicardial activation patterns, recorded with 48 bipolar electrodes (plaque electrode, 25 x 35 mm) on the left anterior ventricular wall of eight dogs and the posterior wall of seven dogs. During left ventricular stimulation (cycle length = 300 msec) in the center of the plaque electrode, theta L, theta T, and the ratio of longitudinal to transverse conduction velocities (theta L/T) were measured before and 2 to 5 minutes after occlusion of the left anterior descending coronary artery or the left circumflex coronary artery. During the control state theta L was greater than theta T demonstrating anisotropic properties of cardiac muscle, not only in the anterior but also in the posterior wall. During acute ischemia theta L and theta T were decreased from the control value and theta T was decreased by a greater extent than theta L resulting in an increase in theta L/T from 1.83 +/- 0.31 (mean +/- SD) to 2.19 +/- 0.36 in the anterior wall and from 1.58 +/- 0.17 to 1.92 +/- 0.28 in the posterior wall. During ventricular fibrillation some lines of conduction block were parallel to the long axis of epicardial muscle fiber bundle and the others were perpendicular. In conclusion, acute ischemia increased anisotropic conduction (theta L/T) in the epicardial ventricular muscle mainly due to greater reduction in theta T, in the anterior and the posterior wall. This augmented anisotropic ventricular conduction may have some relation to the initiation of ventricular fibrillation during acute ischemia.

Effects of diltiazem on concealed atrioventricular nodal conduction in relation to ventricular response during atrial fibrillation in anesthetized dogs.

By means of a new quantitative index for concealed conduction, we evaluated the effects of diltiazem on atrioventricular (AV) node concealment and correlated this index with the variability of the ventricular response during atrial fibrillation in 16 anesthetized mongrel dogs. After determination of the atrial effective refractory period (ERP), AV nodal ERP (AVNERP), concealment zone, and concealment index (AVNERP of blocked atrial extrasystole/AVNERP of conducted atrial extrasystole), the R-R intervals during atrial fibrillation induced by electrical stimulation were measured. Both low (0.1 mg/kg) and medium (0.2 to 0.4 mg/kg) doses of diltiazem prolonged the AVNERP and increased the mean R-R interval during atrial fibrillation. Only medium doses of diltiazem increased the degree of concealed conduction in the AV node and accentuated the variability of R-R intervals. There was a good positive correlation between the variability of the ventricular response during atrial fibrillation and the concealment index. In conclusion, medium doses of diltiazem are more effective in reducing heart rate during atrial fibrillation than a low dose. However, medium doses also increase the degree of concealed conduction in the AV node and enhance the irregularity of the ventricular response during atrial fibrillation. Measurement of the concealment index is useful for quantitating the degree of concealed conduction in the AV node, which is actually an important determinant of the ventricular response during atrial fibrillation.