Hyaluronan metabolism in overloaded temporomandibular joint.

This study aimed to examine hyaluronan (HA) metabolism in relation to the onset and progression of temporomandibular joint osteoarthritis (TMJ-OA) induced by mechanical overloading. Two-month-old and 6-month-old C57BL/6N mice were divided into experimental and untreated control groups (n = 5/group). A sliding plate was attached to the maxillary incisors of the experimental mice for 10 days to overload the condylar cartilage in TMJ. In experimental group, profound cartilage degradation was detected in haematoxylin-eosin, Safranin-O-Fast Green-stained sections. It was also shown that the cartilage degradation was greater in older mice in both the control and the experimental groups. The number of HABP-positive cells was decreased by mechanical overloading and with age. The reduction of HA expression was correlated with the progression of cartilage degradation induced by mechanical overloading. The absolute quantification of the mRNA expression related to HA synthesis and HA degradation was also performed in each group. The mRNA expression levels of HA synthase (HAS) 2 and 3 were lower in the experimental group compared with the control group in the younger mice. In contrast, the mRNA expression levels of the HA degradation gene, HYAL2 and KIAA1199, were higher in the experimental group compared with the control group in the older mice. Thus, mechanical overload differently affected the balance of HA degradation and HA synthesis in the older and younger mice, respectively. In conclusion, mechanical overloading affects HA metabolism and it might initiate or amplify the condylar cartilage degradation.

Prevalence and epidemiological traits of HIV infections in populations with high-risk behaviours as revealed by genetic analysis of HBV.

The prevalence and epidemiological traits of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) infections in high-risk populations (HRPs) remained unclarified in Japan. We determined the prevalence of HIV, HBV and Treponema pallidum (TP) and the viral genotypes in HRPs who attended primary sexually transmitted infection (STI) clinics in Osaka province during 2006-2011. Of 7898 specimens, 133 (1·7%) were HIV positive, which was significantly higher than the figures reported by Japanese Red Cross (0·0019%) and public health centres (0·27%) in Japan. The frequency of HIV-1 subtype B was 88·7%, followed by CRF01_AE (2·3%) and C (0·8%), which were almost identical to the national trend. HBV seroprevalence was surprisingly high in the HIV-positive group (63·2%), which was significantly higher than that in the HIV-negative group (25·6%). By contrast, there was no statistical correlation between HIV and TP infection. Interestingly, the distinct HBV genotypes Ae and G were prevalent in the HIV-positive population (60·0% and 20·0%, respectively), although both were rarely detected during nationwide surveillance. The transmission of HIV and HBV appeared to occur largely within a closed community early in life. Of note, about one-quarter of HIV-positive cases would have remained untested if health professionals had not motivated individuals to undergo HIV testing. This is the first evidence-based assessment of HIV positivity and HIV/HBV co-infection in HRPs at primary STIs in Japan and the effect of the involvement of health professionals in the diagnosis of HIV infections in asymptomatic carriers. The genotyping of HBV provided valuable information for understanding HIV epidemical traits.

Squamous cell carcinoma arising in mature cystic teratoma of the ovary: an immunohistochemical analysis of its tumorigenesis.

AIMS: Squamous cell carcinoma (SCC) is the most common form of malignant transformation in mature cystic teratoma (MCT) of the ovary. Some investigators have suggested the possibility of origin from columnar epithelium. The aim of this study was to analyse such tumours immunohistochemically to elucidate their histogenesis. METHODS AND RESULTS: The expression of cytokeratin (CK) 10 and CK18 was examined in 21 samples of SCC arising in MCT. The expression of CK10 and CK18 was also assessed in SCCs arising in different organs (skin, vulva, lung and uterine cervix) for the purpose of comparison. SCC in MCT expressed CK10 in 7/21 cases [33.3%, 95% confidence interval (CI) 0.12-0.53] and CK18 in 14/21 cases (66.7%, 95% CI 0.46-0.87). SCC in MCT expressed CK10 less frequently, but CK18 more frequently, as is the case in SCCs of the uterine cervix (CK10, 20%; CK18, 70%) and the lung (CK10, 5%; CK18, 90%), both of which are derived from columnar epithelium by squamous metaplasia. CONCLUSIONS: SCC in MCT may be derived from metaplastic squamous epithelium.

Treatment with human chorionic gonadotropin for PADAM: a preliminary report.

The purpose of this study was to evaluate the efficacy and safety of human chorionic gonadotropin (hCG) for patients with partial androgen deficiency of the aging male (PADAM). Twenty-one patients over 50 years of age with PADAM symptoms were included in this study. Laboratory and endocrinologic profiles were reviewed as appropriate, and PADAM symptoms were judged by means of several questionnaires such as the Aging Males' Symptoms (AMS) scale, short version of the International Index of Erectile Function (IIEF-5), and the Self-rating Depression Scale (SDS). Laboratory and endocrinologic values and symptom scores were evaluated and compared before and after treatment by hCG injection. The treatment period was 8.0 +/- 5.0 months (3.0-24.0 months). Serum concentrations of testosterone, including total testosterone, calculated free testosterone, and calculated bioavailable testosterone, increased significantly. AMS total scores and subscores decreased significantly after treatment. However, IIEF-5 and SDS scores did not improve. With respect to adverse effects, laboratory tests showed that only red blood cell count, hematocrit and hemoglobin level increased significantly after treatment, however, these values remained within the normal range. No adverse effect was identified after treatment. We conclude that hCG injection may be considered as a treatment for PADAM.

Comparative study on evaluation methods for serum testosterone level for PADAM diagnosis.

The International Society for the Study of the Aging Male (ISSAM) recommends that a diagnosis be based on a patient's total testosterone (TT), calculated free testosterone (cFT), or calculated bioavailable testosterone (cBT) for partial androgen deficiency of the aging male (PADAM). The purpose of this study was to confirm whether hypogonadism of patients with PADAM is related to symptoms and clarify which criteria of testosterone recommended by ISSAM is suitable for Japanese patients. A total of 90 patients with PADAM symptoms were included in this study. Endocrinologic profiles were reviewed as appropriate, and PADAM symptoms were judged by means of several questionnaires. Laboratory values and symptoms were compared between patients with and without hypogonadism. Even when any criterion of testosterone was used for diagnosis of hypogonadism, AMS (total and subscales), IIEF-5, or SDS scores of PADAM symptoms did not differ significantly between patients classified as having and not having hypogonadism. No other endocrinologic variables than testosterone differed significantly between them, either. PADAM symptoms are not related to testosterone level and it is still obscure whether ISSAM's criterion can be adopted for Japanese patients with PADAM. Other pathology needs to be addressed for evaluation and diagnosis of PADAM in Japan.

Effects of verapamil and lidocaine on two components of the re-entry circuit of verapamil-senstitive idiopathic left ventricular tachycardia.

OBJECTIVES: We characterized pharmacologically the slow conduction zone of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) with regard to the late diastolic potential (LDP). BACKGROUND: We showed that the slow conduction zone of ILVT could be divided into two components by LDP; that is, the distal component with a tachycardia-dependent conduction delay property and the proximal one without it. METHODS: Electrophysiologic studies were performed in eight consecutive patients. The LDP was recorded during left ventricular (LV) mapping during ILVT. Entrainment was performed from the right ventricular outflow tract while recording LDP. The effects of lidocaine (1 mg/kg body weight) and verapamil (0.5 or 1.0 mg) were examined during entrainment. RESULTS: The LDPs preceding the Purkinje potential (PP) were serially recorded from the upper third to the middle of the LV septum along the narrow longitudinal line. The ventricular tachycardia (VT) cycle length increased after lidocaine (p < 0.05), and further after verapamil (p < 0.05). The increments in the VT cycle length after administration of the drugs strongly correlated with those in LDP-PP (r > 0.9 for both drugs). The interval from the ventricular potential to LDP was unchanged after administration of the drugs. In one patient, verapamil terminated VT by local conduction block between LDP and PP. The LDP-PP measured during entrainment increased after lidocaine, and further after verapamil, whereas the interval from the stimulus to LDP remained unchanged. CONCLUSIONS: The component distal to LDP is mainly calcium channel-dependent and partly depressed sodium channel-dependent. The proximal component is considered to be sodium channel-dependent (normal).

Immunocytochemical localization of beta-citryl-L-glutamate in primary neuronal cells and in the differentiation of P19 mouse embryonal carcinoma cells into neuronal cells.

The immunocytochemical localization of beta-citryl-L-glutamate (beta-CG) in primary neuronal cells and in the differentiation of P19 cells was examined. 1: Cells with the morphological features of neurons in the primary culture were specifically stained with the anti-beta-CG antibody both in neurites and in the cell body. 2: The neuronal cells differentiated from P19 cells were distinctly stained with the anti-beta-CG antibody both in neurites and in the cell body, while the non-neuronal cells were not. 3: The concentration of beta-CG was low in the P19 cells, but increased significantly with the differentiation of P19 cells into neurons. It was shown that beta-CG was localized exclusively in neurons. These findings suggest that beta-CG plays functional roles in the differentiation and growth of neuron.

NO is involved in MCh-induced accentuated antagonism via type II PDE in the canine blood-perfused SA node.

The possible role of type II (cGMP-stimulated cAMP hydrolysis) phosphodiesterase (PDE) in the accentuated antagonism of muscarinic effects on heart rate during beta-stimulation via endogenous nitric oxide (NO) was evaluated. The canine isolated sinoatrial node preparation was cross circulated with arterial blood of a support dog. The sinoatrial rate of the preparation was 96 +/- 5 beats/min (n = 16) at control. Methacholine (MCh; 0.01-1 microg) injected into the right coronary artery in a bolus fashion caused dose-dependent decreases in sinoatrial rate. Under an intra-arterial infusion of isoproterenol (1 microM), resulting in approximately 50% increase in sinoatrial rate, MCh-induced decreases were markedly augmented from -18 +/- 3% to -44 +/- 4% at 0.3 mg of MCh. When N(G)-nitro-L-arginine methyl ester (100 microM) or N(G)-monomethyl-L-arginine (100 microM) were continuously infused, the augmented MCh-induced decreases in sinoatrial rate were significantly suppressed (-29 +/- 3% or -25 +/- 3%, respectively, P < 0.01). Pretreatment with either 3-isobutyl-1-methylxanthine (IBMX; 20 microM), a non-selective PDE inhibitor, or amrinone (20 microM), a selective type III (cGMP inhibited cAMP hydrolysis) PDE inhibitor, doubled the isoproterenol-induced increase in the sinoatrial rate. However, the augmented MCh-induced decreases in sinoatrial rate were significantly depressed by IBMX (from -23 +/- 5% to -14 +/- 1%, P < 0.01) but not by amrinone (to -20 +/- 3%). These results suggest that MCh-induced accentuated antagonism in the sinoatrial node pacemaker activity can be modulated by endogenous NO via an activation of the type II cyclic GMP-stimulated cAMP PDE.

Electrogram characteristics indicative of a recurrent conduction site after ablation of the inferior vena cava-tricuspid annulus isthmus: a study in the canine blood-perfused atrioventricular preparation.

Analysis of the electrograms recorded along the ablation line can identify a recurrent conduction site after ablation of the isthmus between the inferior vena cava (IVC) and tricuspid annulus (TA) for atrial flutter. The present study examined the relationship between the activation sequence and electrogram characteristics using a model of recurrent conduction in the isthmus. The canine heart was isolated (n=8) and cross-circulated with the arterial blood of a support dog. A plaque electrode was placed at the isthmus, and 42 bipolar electrograms (filtered and unfiltered) were recorded during pacing at 120beats/min from the lateral right atrium before and after creating a narrow gap by 2 discontinuous incisions from the TA to the IVC. All bipolar electrodes, with the cathode in the TA side and the anode in the IVC side, were placed perpendicular to the TA. Before creating the incisions, the wavefront (WF) from the pacing impulse traveled uniformly in the isthmus and almost in parallel to the TA, and the filtered electrogram at each site showed a single potential. After creating the incisions, the WF propagated through the gap and spread radially to the area distal to the incisions. In close proximity to the incision lines opposite to the pacing site, the WF advanced from the gap towards the TA and IVC perpendicularly to the TA. Filtered electrograms on the incision lines showed double or split potentials, whereas those on the gap showed a single or fractionated potential. In unfiltered electrograms recorded from the TA to the IVC in close proximity to the incision lines opposite the pacing site, reversal of electrogram polarity was noted at the gap. A single or fractionated potential between double potentials indicates a gap between lines of conduction block. Electrogram polarity reversal along the ablation line indicates the presence of 2 opposing WF arising from the gap.

Purification and characterization of factor VII inhibitor found in a patient with life threatening bleeding.

We recently observed a patient with acquired inhibitor-induced F.VII deficiency whose plasma level of F.VII was < 1.0%. However, the biochemical nature of the inhibitor has not yet been clarified. In the present study, we purified the F.VII inhibitor from the patient's plasma by using activated F.VII (F.VIIa)-conjugated gel and characterized the inhibitor. The results showed that the inhibitor comprised two kinds of antibodies: one was eluted with EDTA (antibody 1) and the other with glycine-HCl buffer (pH 2.3) (antibody 2) from the F.VIIa affinity gel. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis of these inhibitors demonstrated that both antibodies had features of immunoglobulin G1 (IgG1) with kappa and lambda-light chains. Antibody 1 bound to the immobilized F.VIIa with a high affinity in the presence of calcium ion, while antibody 2 bound to the F.VIIa very weakly and the binding was independent of calcium ion. Immunoblotting analysis demonstrated that antibody 1 bound to the light chain of F.VIIa after reduction with 2-mercaptoethanol, while it did not react with either the gamma-carboxyglutamic acid (Gla)-domainless light chain of F.VIIa or the heavy chain with the protease domain. Antibody 1 markedly inhibited the activity of tissue factor-F.VIIa complex. Based on these observations, it is suggested that F.VIIa autoantibody (antibody 1) recognizes the calcium-dependent conformation within or near the Gla domain and inhibits F.VIIa activity by interacting with the light chain.

Atrial ectopy originating from the posteroinferior atrium during radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia.

Atrial ectopy sometimes appears during RF ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, its origin, characteristics, and significance are still unclear. To examine these issues, we analyzed 67 consecutive patients with AVNRT (60 with slow-fast AVNRT and 7 with fast-slow AVNRT), which was successfully eliminated by RF ablation to the sites with a slow potential in 63 patients and with the earliest activations of retrograde slow pathway conduction in 4 patients. During successful RF ablation, junctional ectopy with the activation sequence showing H-A-V at the His-bundle region appeared in 52 patients (group A) and atrial ectopy with negative P waves in the inferior leads preceding the QRS and the activation sequence showing A-H-V at the His-bundle region appeared in 15 patients (group B). Atrial ectopy was associated with (10 patients) or without junctional ectopy (5 patients). Before RF ablation, retrograde slow pathway conduction induced during ventricular burst and/or extrastimulus pacing was more frequently demonstrated in group B than in group A (9/15 [60%] vs 1/52 [2%], P < 0.001). Successful ablation site in group A was distributed between the His-bundle region and coronary sinus ostium, while that in group B was confined mostly to the site anterior to the coronary sinus ostium. In group B, atrial ectopy also appeared in 21% of the unsuccessful RF ablations. In conclusion, atrial ectopy is relatively common during slow pathway ablation and observed in 8% of RF applications overall and 22% of RF applications that successfully eliminated inducible AVNRT. Atrial ectopy appears to be closely related to successful slow pathway ablation among patients with manifest retrograde slow pathway function.

Prolonged nocturnal penile tumescence caused by epinastine.

PURPOSE: We report a case of prolonged nocturnal penile tumescence (NPT) caused by the antiallergic agent epinastine. METHODS/RESULTS: We measured NPT using Rigiscan-Plus (DacoMed, Minneapolis, MN, USA) with or without the patient having taken epinastine. CONCLUSIONS: Considering its pharmacological effects on cyclic nucleotides, epinastine may have an effect on erectile function.

Significance of late diastolic potential preceding Purkinje potential in verapamil-sensitive idiopathic left ventricular tachycardia.

BACKGROUND: Verapamil-sensitive idiopathic left ventricular tachycardia (VT) is due to reentry with an excitable gap. A late diastolic potential (LDP) is recorded during endocardial mapping of this VT, but its relation to the reentry circuit and significance in radiofrequency (RF) ablation remain to be elucidated. METHODS AND RESULTS: Sixteen consecutive patients with this specific VT were studied (12 men and 4 women; mean age, 32 years). In all patients, sustained VT was induced and during left ventricular endocardial mapping, LDP preceding Purkinje potential (PP) was recorded at the basal (11 patients), middle (3 patients), or apical septum (2 patients). The area with LDP recording was confined to a small region (0.5 to 1.0 cm2) in each patient and was included in the area where PP was recorded (2 to 3 cm2). The relative activation times of LDP, PP, and local ventricular potential (V) at the LDP recording site to the onset of QRS complex were -50.4+/-18.9, -15.2+/-9.6, and 3.0+/-13.3 ms, respectively. The earliest ventricular activation site during VT was identified at the posteroapical septum and was more apical in the septum than the region with LDP in every patient. In 9 patients, VT entrainment was done by pacing from the right ventricular outflow tract while recording LDP. During entrainment, LDP was orthodromically captured, and as the pacing rate was increased, the LDP-to-PP interval was prolonged, whereas stimulus-to-LDP and PP-to-V interval were constant. In 3 patients, the pressure applied to the catheter tip at the LDP region resulted in conduction block between LDP and PP and in VT termination. RF energy application at the LDP recording site successfully eliminated VT. CONCLUSIONS: LDP was suggested to represent the excitation at the entrance to the specialized area with a conduction delay in response to the increase in the rate within the critical slow conduction zone participating in the reentry circuit of this VT. LDP can be a useful marker for successful RF ablation for this VT.

Effects of pilsicainide and propafenone on vagally induced atrial fibrillation: role of suppressant effect in conductivity.

The effects of pilsicainide on vagally induced atrial fibrillation and on electrophysiological parameters were compared with those of propafenone in alpha-chloralose-anesthetized dogs. Conduction velocity, effective refractory period, wavelength, averaged atrial fibrillation cycle length and activation sequence in the right atrial free wall were determined before and after drug administration. Pilsicainide (2 mg/kg/5 min and 3 mg/kg/h)(n=10) or propafenone (2 mg/kg/15 min and 4 mg/kg/h)(n=10) was intravenously infused during stable atrial fibrillation sustaining > 30 min. Pilsicainide terminated atrial fibrillation in nine dogs, while propafenone did so in three (p < 0.01). After the drug, conduction velocity was suppressed more in the pilsicainide than in the propafenone group(p < 0.01). There was no difference in effective refractory period after drug between the two groups. Mean wavelength was prolonged from 46.0 to 70.4 mm in the pilsicainide group and from 45.0 to 110.8 mm in the propafenone (p < 0.01 vs. pilsicainide). Activation mapping during atrial fibrillation showed Type II or III atrial fibrillation as previously defined [Konings, K.T.S., Kirchhof, C.J.H.J., Smeets, J.R.L.M., Wellens, H.J.J., Penn, O.C., Allessie, M.A., 1994. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. Vol. 89, pp. 511-521.] before the drug, and changed to Type I before atrial fibrillation termination. Thus, pilsicainide was more effective to terminate vagally induced atrial fibrillation than was propafenone despite a greater effect of propafenone than of pilsicainide on wavelength. In this canine atrial fibrillation model, the suppression of conduction velocity may play an important role in changing the activation pattern of atrial fibrillation and thus, terminating atrial fibrillation.

Influence of chronic nitric oxide inhibition of coronary blood flow regulation: a study of the role of endogenous adenosine in anesthetized, open-chested dogs.

The effect of chronic inhibition of endothelium-derived nitric oxide (NO) synthesis on the regulation of coronary blood flow (CBF) is yet to be elucidated. A chronic canine model of inhibited NO synthesis was created and the role of adenosine in the regulation of coronary blood flow in this model was examined. Dogs were fed a diet supplemented with 40 mg/kg per day N(G)-nitro-L-arginine methyl ester (L-NAME group, n=8) or a regular diet without L-NAME supplementation (control group, n=8) for 4 weeks. The experiments were performed in an anesthetized, open-chest state and the results were compared in the L-NAME and control groups. Chronic L-NAME treatment significantly increased arterial pressure. Neither basal CBF in the left anterior descending artery nor heart rate differed between the L-NAME and control groups. In the L-NAME group, the response of CBF to intracoronary acetylcholine and adenosine was blunted, but that to glyceryl trinitrate was not. In addition, myocardial reactive hyperemia following 20 sec coronary occlusion was blunted in the L-NAME group. During atrial pacing at a rate 60 beats/min faster than the sinus rate, CBF increased to a similar degree in the L-NAME and control groups, and systolic wall thickening (SWT) changed similarly in both groups. Intracoronary 8-phenyltheophylline (8-PT), an adenosine receptor blocker, decreased basal CBF in the L-NAME group but not in the control group. In the L-NAME group, pacing-induced increase in CBF was abolished and SWT deteriorated after 8-PT administration. Basal myocardial adenosine release was significantly increased in the L-NAME group compared with the control group. It is concluded that in anesthetized, open-chest dogs with chronic inhibition of NO synthesis, adenosine may play a compensatory role in the regulation of coronary blood flow, as concomitant blockade of adenosine causes deterioration of coronary circulation and cardiac function.

Slow potential-guided radiofrequency catheter ablation in atrioventricular nodal reentrant tachycardia: characteristics of the potential associated with successful ablation.

To examine the characteristics of Haïssaguerre's slow potential (SP) specific to effective catheter ablation of the slow pathway in AV nodal reentrant tachycardia, the properties of SP and its recording site were analyzed in 52 patients who underwent successful SP-guided ablation. The properties of SP included the ratio of the amplitude of SP to that of atrial potential (A)(SP/A), the SP duration, the interval between His-bundle potential (HP) and SP (HP-SP), the interval between A and SP (A-SP), the interval between SP and ventricular potential (V) (SP-V), and the ratio of A-SP to the interval between A and the V (A-SP/A-V). The SP recording site was determined by the ratio of the amplitude of A to that of V (A/V) and by the relative position of the ablation catheter on X ray (right anterior oblique projection), expressed as the ratio of the distance between the coronary sinus ostium and SP site to that between the coronary sinus ostium and HP recording site (relative SP position). Twenty-eight slow pathways were ablated with a single energy application, while the other 24 required applications > or = 2. In all successful applications, SP/A, SP duration, HP-SP, A-SP, SP-V, A-SP/A-V, A/V, and relative SP position were 51% +/- 25%, 28 +/- 5 ms, -11 +/- 9 ms, 57 +/- 25 ms, 68 +/- 13 ms, 46% +/- 9%, 15% +/- 13%, and 51% +/- 13%, respectively. A significant correlation was observed between the relative SP position and A-SP, and between the relative SP position and A-SP/A-V (r = 0.60 and 0.37, respectively), while it was not between the relative SP position and HP-SP, nor between the relative SP position and SP-V. When the characteristics of SP were comparatively analyzed between the effective and ineffective applications in 24 patients in whom applications > or = 2 were required, there was no difference observed in HP-SP, A-SP, SP-V, A-SP/A-V, and A/V. However, SP/A, SP duration, and the relative SP position in the effective applications were all greater than those in the ineffective ones (56% +/- 20% vs 35% +/- 18%, P < 0.001; 29 +/- 4 vs 26 +/- 5 ms, P < 0.01; and 52% +/- 15% vs 33% +/- 11%, P < 0.001, respectively). These results indicate that SP with an amplitude over a half of A amplitude and recorded at the mid-septum of the tricuspid annulus can be a marker for successful slow pathway ablation. Although the local atrial electrogram appears late as the SP recording site shifts to the lower position, the timing of SP relative to HP and V remained unchanged, suggesting that SP is independent of the local atrial activation.

The upper turnover site in the reentry circuit of common atrial flutter.

The upper turnover site of the reentry circuit of common atrial flutter was examined with the uses of atrial activation mapping and extrastimulus techniques during atrial flutter. The findings suggest that it is anterior to the orifice of the superior vena cava, i.e., between the superior vena cava and tricuspid annulus.

Characteristics of slow conduction zone demonstrated during entrainment of idiopathic ventricular tachycardia of left ventricular origin.

Idiopathic ventricular tachycardia (VT) with the right bundle branch block pattern and left-axis deviation has been shown to be due to reentry, but the property of the slow conduction zone within the reentry circuit is little understood. In 7 patients (mean VT cycle length [CL]: 361 +/- 49 ms), rapid pacing from the right ventricular outflow tract was performed during VT while recording electrograms at the early activation site in the left ventricle and at the right ventricular apex; also, conduction times from the pacing site to these recording sits (St-A and St-B intervals, respectively) were measured. Both constant fusion (except for the last paced beat) and progressive fusion were seen in all patients, indicating VT entrainment. The left ventricular site was captured orthodromically with an St-A of 394 +/- 57 ms at the pacing CL of 351 +/- 47 ms during entrainment, while the right ventricular apex was captured directly with an St-B interval of 63 +/- 19 ms. The St-A interval was gradually prolonged with the shortening of the pacing CL, whereas the St-B interval remained unchanged. VT was interrupted in all patients at the pacing CL of 279 +/- 39 ms. The effects of intravenous lidocaine (1 mg/kg) and verapamil (1 mg) were examined in 5 and 7 patients, respectively. Neither drug terminated VT but the VT-CL was increased to 369 +/- 57 ms after lidocaine (p <0.05) and to 413 +/- 69 ms after verapamil (p <0.05) (p <0.05 vs after lidocaine). The St-A interval was significantly increased after lidocaine (p <0.05) and after verapamil (p <0.05), while the St-B interval remained unchanged. A significant correlation between changes in St-A interval and VT-CL after verapamil was noted (p <0.001). In conclusion, the slow conduction zone of this VT shows tachycardia-dependent conduction delay, and the mechanism of this slow conduction involves mainly calcium channel-dependent conduction and partly depressed sodium channel-dependent conduction.