Triggering mechanism for neurally mediated syncope induced by head-up tilt test: role of catecholamines and response to propranolol.

OBJECTIVES: We studied the triggering mechanism for neurally mediated syncope. BACKGROUND: Although increased transient sympathetic tone is thought to be necessary for the development of neurally mediated syncope, little is known about the triggering mechanism for neurally mediated syncope. METHODS: Plasma epinephrine (EP) and norepinephrine (NE) levels were assessed in 20 syncope patients during tilt test (80 degrees, 15 min) with and without isoproterenol (ISP, 0.01, 0.02 microg/kg/min). If syncope occurred, propranolol (0.1 mg/kg) was injected. RESULTS: Eight patients experienced syncope during tilting alone, and 9 patients required ISP for syncope. In the negative response without ISP, NE showed a small statistical 1.7-fold increase at end of tilting and EP did not change during tilting. When syncope occurred during tilting alone, a significant 11.7-fold increase in EP at syncope was registered concomitant with a small 2.5-fold increase in NE. When patients experienced syncope during tilting with ISP, a significant 5.0-fold increase in EP at syncope was registered concomitant with a small 1.7-fold increase in NE. In patients without ISP, propranolol did not interrupt syncope. In patients with ISP, six of eight receiving propranolol responded to tilting negatively. CONCLUSIONS: An increase of NE levels may result in inhibition of syncope and an EP surge may be a triggering mechanism for neurally mediated syncope. Comparatively low levels of EP may be enough to induce syncope during tilting with ISP compared with tilting alone. Propranolol is not effective in patients without ISP, but it frequently inhibits syncope in patients with ISP. Propranolol (0.1 mg/kg) may be insufficient to block the actions of high levels of circulating EP.

Neurally mediated syncope and arrhythmias: a study of syncopal patients using the head-up tilt test.

Understanding the causes of syncope in patients with arrhythmia is important in determining the therapeutic interventions. Neurally mediated syncope (NMS) was evaluated in 55 patients with various arrhythmias. The head-up tilt test with or without isoproterenol infusion induced NMS in 41 (74%) patients. When these patients was categorized into 3 types, depending on the development of syncope, vasodilatation was significant in a majority of patients. In 46% of patients with tachyarrythmias, NMS was accompanied by an increase in extrasystole. It was concluded that the evaluation of vasodilatation is important for the preventive strategy of NMS in patients with arrhythmias and that NMS may induce arrhythmias.

Uncommon electrocardiographic changes corresponding to symptoms during recurrent pulmonary embolism as documented by computed tomography scans.

Electrocardiographic (ECG) findings of pulmonary embolism (PE) include S1Q3T3 pattern, right bundle-branch block, right-axis deviation, and T-wave inversion in medial precordial leads. We report other uncommon ECG changes associated with various symptoms during recurrent PE as documented by computed tomography (CT) scans in a single patients. An 83-year-old woman was admitted with PE secondary to deep venous thrombosis in the left leg. During episodes of chest pain, ECG showed QTc prolongation (480 ms) with new T-wave inversion in leads III, aVF, and V1-V3, and ST-segment depression in leads V5-V6. Despite adequate anticoagulant therapy, recurrent episodes of PE occurred in the hospital. When the patient experienced sudden chest tightness, ECG showed a new S-wave notch in lead V1 and clock-wise rotation with sinus tachycardia. She also experienced transient syncope with hypotension. At this time, ECG showed transient atrioventricular junctional rhythm followed by sinus arrest, and CT scan showed a new massive embolus in the main pulmonary trunk with right ventricular dilatation, as demonstrated by echocardiography. The mechanism responsible for QTc prolongation with ST-T changes, the S-wave notch in lead V1 with clockwise rotation, or atrioventricular junctional rhythm with sinus arrest during PE may be associated with myocardial ischemia, acute right ventricular overload, or vagal reflex, respectively.

Long-term effects of pharmacological therapy for vasovagal syncope on the basis of reproducibility during head-up tilt testing.

The purpose of this study was to determine the efficacy of long-term pharmacological therapy selected on the basis of a head-up tilt test (HUT) in patients in whom reproducibility of the HUT response was demonstrable in the initial study. The HUT (80 degrees upright) was performed for 15 min with or without an infusion of isoproterenol (0.01-0.03 microgram/kg per min) in 54 patients with recurrent unexplained syncope. When vasovagal syncope was induced (positive response), the HUT was repeated to examine the test reproducibility. Vasovagal syncope was induced in 24 patients during HUT alone, and in 30 patients during the HUT with isoproterenol. Acute reproducibility was observed in 49/54 (91%) patients. In the tilt-positive patients, HUT was repeated after an intravenous administration of propranolol (0.1 mg/kg) or disopyramide (1 mg/kg) (acute test). Propranolol proved effective in 21 (80%) of 26 patients, and disopyramide in 13 (56%) of 23 patients. Thereafter, evaluation was done on the long-term clinical follow-up of the pharmacological intervention selected on the basis of the acute test in the 34 patients in whom the HUT could not induce vasovagal syncope after the oral administration of the pharmacological agent (propranolol 60 mg/day, disopyramide 300 mg/day). Thirty-two of 34 patients (94%) did not develop syncopal attacks during a 44 +/- 12-month period. Thus, in patients with unexplained syncope, HUT appears to have a high degree of acute reproducibility, and the acute drug response guided by HUT may be used to develop an effective long-term pharmacological therapy.

Decreasing parasympathetic tone activity and proarrhythmic effect after radiofrequency catheter ablation--differences in ablation site.

Holter ECG was used to evaluate changes in heart rate variability (HRV), indicators of the autonomic nervous system, and arrhythmia before and after radiofrequency (RF) catheter ablation in patients with symptomatic supraventricular tachycardia. Ablation targets in 43 patients included the atrioventricular (AV) nodal pathway (AVNRT, n = 17), a right free wall accessory pathway (n = 10), a septal accessory pathway (n = 6), and a left free wall accessory pathway (n = 10). The High frequency component (0.15 - 0.40 Hz) or pNN50 of HRV analysis, indicating parasympathetic activity, significantly decreased immediately after RF ablation in the AVNRT and septal accessory pathway groups, but not in the right or left wall groups. In contrast, in all four groups, ventricular premature contractions (VPCs) significantly increased in most of the patients, and ventricular tachycardia occurred in a few of the patients immediately after RF ablation. There was no serious arrhythmia. These alterations in HRV analysis and arrhythmia returned to the control level after 1 week or more. VPCs after RF ablation did not consistently increase as a result of the reduced parasympathetic tone activity, but at the lesion near the conduction system, the increase in VPCs was inhibited by higher parasympathetic tone activity, because the parasympathetic nerve fibers and receptors were distributed in these lesions.

Effects of nicorandil, a potassium channel opener, on idiopathic ventricular tachycardia.

OBJECTIVES: We assessed the effects of the adenosine triphosphate (ATP)-sensitive potassium channel opener, nicorandil, on ATP- and verapamil-responsive ventricular tachycardias (VTs). BACKGROUND: Adenosine- or ATP-sensitive VTs are thought to be due to a nonreentrant mechanism, presumably delayed afterdepolarization. We suggest that this potassium channel opener may suppress ATP- and verapamil-sensitive VTs. METHOD: The subjects included 13 patients with idiopathic VTs, 7 of whom had sustained VT and 6 of whom had nonsustained VT. We evaluated the effects of ATP, nicorandil and verapamil on VTs. RESULTS: Sustained VT: Verapamil had preventive effects on seven VTs. Four VTs were terminated by ATP, and of these, nicorandil terminated two and prevented exercise-induced VT in the two others. Three ATP-insensitive VTs, which were determined to be due to a reentry by an electrophysiologic study, were not terminated by nicorandil. Nonsustained VT: All six VTs were inhibited by ATP, and five of these were suppressed by nicorandil. Verapamil inhibited four of the five VTs. QT intervals and the corrected QT intervals were significantly shortened by nicorandil. CONCLUSIONS: Nicorandil suppresses ATP- and verapamil-responsive VTs. One of the mechanisms of suppression by nicorandil might be related to a reduction of calcium in the myocardium, because it reduces the action potential duration.

Slow ventricular tachycardia located in the epicardium of the left ventricular base and characterized by effects of adenosine triphosphate, nicorandil and verapamil.

A 31-year-old male with slow ventricular tachycardia (VT) developed a nonsustained VT with prolongation of the JT intervals after injection of contrast medium and saline into the marginal vein of the coronary sinus. The earliest activation site of the VT existed in the epicardium of the left ventricular base. Adenosine triphosphate prevented induction of VT and prolongation of JT intervals. Ventricular premature contractions showing the same morphology as the VT were also inhibited by nicorandil and verapamil. The mechanism of the VT was suggested to be abnormal automaticity due to an increase in the Ca++ current into cells after prolongation of the action potential duration induced by hypothermia.

Effects of adenosine triphosphate on ventriculoatrial conduction--usefulness and problems in assessment of catheter ablation of accessory pathways.

The effects of adenosine triphosphate (ATP) on ventriculoatrial (VA) conduction were examined before and after accessory pathway (AP) ablation, with emphasis on assessment of the complication of dual atrioventricular (AV) node pathway. By evaluating the differences in the response to ATP of APs and other pathways, we assessed the usefulness and problems of this method. Of 59 patients who underwent AP ablation, 31 showed pre-excitation and 28 had concealed APs. A dual AV node pathway was found in 9 patients (15.3%) before ablation. After ablation, a dual AV node pathway was newly found in 9 patients. Thus, the total number of patients with a dual AV node pathway was 18 (30.5%). VA conduction over APs was not blocked in 26 of 29 patients, but the remaining 3 APs were blocked transiently by ATP. ATP caused VA block over the AV node in 15 of 16 patients and a dual AV node pathway in all 11 patients. In contrast, VA conduction over the retrograde fast pathway was blocked in 9 of 14 patients with AV node re-entrant tachycardia. ATP has little effect on APs, so observation of the response to ATP provides a more reliable and useful means of evaluating successful ablation. With this method, however, it is important to consider the possibility of the presence of ATP-sensitive APs and ATP-resistant retrograde fast pathways. The influence of ablation-induced injury has not been fully clarified. It is therefore essential to take into account various data, including the comparison between data obtained before and after ablation.

Selective slow pathway ablation in atrioventricular nodal reentrant tachycardia--comparison of different methods and the site of slow pathway ablation.

The optimum potential of the slow pathway (SP) was investigated by determining the effectiveness and safety of high-radiofrequency catheter ablation to treat atrioventricular nodal reentrant tachycardia (AVNRT). The subjects consisted of 29 patients with AVNRT (11 men, with a mean age of 54 +/- 15 years). Three ablation methods were used: a) Method A used the earliest atrial activation site, which is retrograde to the slow pathway, b) Method SP used the SP potential, and c) Method SW, in which ablation was performed stepwise starting from the coronary sinus and moving toward the recording site of the His bundle potential. Five, 20, and 4 patients underwent Methods A, SP, and SW, respectively. The fewest number of applications was needed with Method SP (11 +/- 9, 6 +/- 4, and 13 +/- 9), and the delivered energy was also lowest with Method SP (9151 +/- 6119, 3712 +/- 2168, and 12183 +/- 4090 J, with Methods A, SP, and SW, respectively). In Method SP, the interval between the atrium and SP was significantly longer at sites which cured tachycardia, than at sites at which ablation was ineffective (88 +/- 26 vs 66 +/- 22 msec, p < 0.05). The SP potential showed a humped shape in 18 of 20 patients. Method SP was the most efficient ablation method for treating AVNRT.

Dipyridamole suppresses catecholamine- and Ca++ influx-sensitive ventricular arrhythmias.

To study the mechanism of ventricular arrhythmias, the effect of dipyridamole (DIP; 300 mg/day), an adenosine transport inhibitor, on ventricular premature contractions (VPCs) was assessed in 12 patients who showed VPCs (21312 +/- 12314/day) on Holter ECG in a controlled setting. The effects were compared with those of verapamil (240 mg/day) and bisoprolol (5 mg/day). DIP suppressed more than one-half the VPCs in 5 patients. The mean degree of reduction in these DIP-responders was 75 +/- 18%. Both verapamil and bisoprolol inhibited VPCs in all of the DIP-responders (verapamil: 71 +/- 15%, bisoprolol: 88 +/- 16%). Two of the 5 DIP-responders had sustained ventricular tachycardias (VT) that were terminated by intravenous DIP, ATP, acetylcholine, verapamil, and propranolol. In contrast, verapamil did not inhibit VPCs in any of the DIP-nonresponders. Bisoprolol also did not suppress VPCs in 3 of 6 DIP-non responders. heart rate was unaffected by DIP, but was suppressed by both verapamil and bisoprolol. In addition, DIP increased the serum concentration of adenosine (control 16.3 +/- 17.1 vs 22.3 +/- 19.0 pmol/ml after DIP, p < 0.05). The inhibitory effect of DIP may involve suppression of Ca+2 current through an extracellular increase in adenosine.

Sustained left ventricular tachycardia terminated by dipyridamole: cyclic AMP-mediated triggered activity as a possible mechanism.

Sustained VT in two patients was terminated by intravenous administration of dipyridamole, an adenosine transport inhibitor. VT was induced by rapid atrial or ventricular pacing, isoproterenol, or dibutyryl cyclic AMP infusion, or exercise. VT also was aborted by adenosine triphosphate or acetylcholine injection, or by vagal stimulation. VT was terminated or prevented by verapamil or propranolol. In addition, arrhythmias were prevented by oral administration of dipyridamole. These results suggest that VT is due to cyclic AMP-mediated triggered activity and that inhibition by dipyridamole may be due to a reduction in the intracellular concentration of cyclic AMP.

Histopathology of canine hearts subjected to catheter ablation using radiofrequency energy.

To investigate the pathologic changes of the myocardium and the adverse effects of radiofrequency (RF) catheter ablation, we observed canine hearts that had been ablated by RF energy. Catheter ablation was administered to three sites of the hearts of 46 dogs: endomyocardium, coronary sinus, and atrioventricular junction. The dogs were sacrificed 0-12 weeks after ablation and the lesions were stained with hematoxylin-eosin and Azan stain. Each ablated lesion was well demarcated from the adjacent normal tissue. The margin between the ablated lesion and normal tissue became clearer with time. The lesions were hemispherical and measured about 2 to 10 mm in diameter and 1 to 6 mm in depth. Histologic examination in the acute phase demonstrated the presence of coagulation necrosis of the myocardium, interstitial hemorrhage and edema, followed by infiltration of inflammatory cells. Granulation tissue replaced the normal myocardium. In the chronic phase, the lesions became fibrotic and fatty. A mural thrombus was found in 30% of the cases of endomyocardial ablation and 50% of the right ventricular lesions were transmural. Ablated lesions in the coronary sinus extended to the left atrium and left ventricle. Obstruction of the coronary sinus was observed in 8% of the ablated dogs. Most of the lesions with complete atrioventricular block were ablated at the His penetrating region of the conduction system. Thus, since the ablated lesions were clearly delineated, catheter ablation using RF energy appears to eliminate only the target area.

[Electrophysiologic effect of a new Ca(2+)-antagonist, TA-3090 on supraventricular tachycardia and conduction system].

We investigated the effect of a new Ca-antagonist, TA-3090 on supraventricular tachycardia (SVT) and conduction system, comparing it with the effect of Diltiazem Hydrochloride, in 11 patients who had paroxysmal SVT attacks. Seven of the 11 patients presented atrioventricular reentrant tachycardia (AVRT) via retrograde concealed conduction through an accessory pathway, and the others presented AV nodal reentrant tachycardia (AVNRT). After SVT was induced by means of programmed electrical stimulation at high right atrium, TA-3090 (0.1 mg/kg body weight) or Diltiazem (0.2 mg/kg) was administered intravenously for 3 minutes. TA-3090 terminated nine of 11 SVTs, while Diltiazem terminated four of 4 SVTs. On termination of SVT, both drugs interrupted A-H conduction during AVRT and the slow pathway during AVNRT. After TA injection, five of 11 SVTs could not be induced by programmed electrical stimulation, while two of 4 SVTs could not be induced after Diltiazem. In AVRT, three patients in which TA-3090 prevented SVT induction had a longer AV node effective refractory period than that of the others in which TA-3090 could not prevent SVT (330 +/- 46 vs 210 +/- 24 msec, p less than 0.01). However, SVT was induced more easily than before in three of the 11 patients treated with TA-3090 administration, and in one of the 4 patients treated with Diltiazem administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of multiple sclerosis with pure alexia].

We report here a case of multiple sclerosis (MS) showing pure alexia. The patient was a 28 year-old, right-handed male student of medicine. He had been healthy prior to college, but when he tried to read the newspaper one morning in January of 1983, he suddenly became aware that he could not. He could speak fluently and had no disturbances of auditory comprehension. No signs of abnormality were noted in his writing ability. Thereafter, the patient occasionally experienced difficulty in reading, together with right homonymous hemianopsia. These symptoms, however, usually vanished following sleep. In April, 1984, the patient experienced headache and ataxia when walking, followed by repeated remission and exacerbation of the symptoms. Corticosteroid therapy produced complete disappearance of the headache and ataxia. In September of 1985, he was hospitalized at our department due to the clouding of consciousness accompanied by convulsions. Neurologically, no abnormalities of the ocular fundus were noted and Babinski's sign was negative, but left hemiplegia was observed. Neuropsychologically, his intelligence was normal and he had no difficulty in writing, but paralexia was noted. There were no disorders of spontaneous speech or auditory comprehension. Examination by CT scan and magnetic resonance imaging revealed a number of lesions in the white substance of the cerebrum, including the left occipital lobe. The abnormal signs seen radiographically vanished when cortical hormones were administered. It has been thought that the symptoms of multiple sclerosis are due mainly to disorders of the white substance, and that MS seldom produces symptoms of aphasia, due to the fact that the lesions in this disease are generally small.(ABSTRACT TRUNCATED AT 250 WORDS)