Deficiency of Testosterone Associates with the Substrate of Atrial Fibrillation in the Rat Model

Background: Since the prevalence of atrial fibrillation (AF) increases progressively with aging, especially in men, we hypothesized that testosterone might affect the occurrence of AF.
Methods and Results: We examined the electrophysiological properties of the atria in isolated-perfused hearts of sham-operated male (SM), female (SF), orchiectomized male with and without administration of testosterone (ORCH-T and ORCH), and ovariectomized female (OVX) Sprague-Dawley rats. An electrophysiological study revealed that repetitive atrial responses induced by electrical stimuli significantly increased in ORCH rats without changes in other electrophysiological properties and were abolished by administration of testosterone. To investigate the underlying mechanisms, we evaluated the expression level of calcium-handling proteins. In ORCH rats, the immunoreactive protein level of ryanodine receptor type 2 (RyR2) and sodium–calcium exchanger significantly increased as compared with SM and ORCH-T rats without alterations in the level of FK506-binding protein (FKBP12.6), sarcoendoplasmic reticulum Ca-ATPase, and phospholamban. Immunoprecipitation analysis demonstrated decreased binding of FKBP12.6 to RyR2 in ORCH rats, which was prevented by testosterone. In contrast, the expression levels of these proteins showed no significant differences between SF and OVX rats.
Conclusion: Deficiency of testosterone was arrhythmogenic in rat atria possibly through less binding of FKBP12.6 to RyR2, which could induce feasible calcium leakage from the sarcoendoplasmic reticulum. These results would explain, at least in part, the increase in the prevalence of AF in accordance with the decline of testosterone particularly in elderly men.     

Experimental Study About Removal of the Implanted Tined Polyurethane Ventricular Lead by Radiofrequency Waves Through the Lead

Polyurethane pacemaker leads are widely used nowadays. However, only a few studies have been done to investigate the fixation mechanism of polyurethane leads. To elucidate how pacemaker leads are fixed at the early phase after implantation, polyurethane-insulated tined ventricular leads were implanted in seven mongrel dogs. One to 4 months later, tips of the leads were anchored among the trabeculae and the distal part of the leads were encapsulated by whitish fibrous tissue. It was found that not organized thrombi, but cell reaction with various stages of inflammatory cells was responsible for forming the fibrous tissue. We attempted to remove the lead by delivering radiofrequency wave through the lead. However, no lead could be removed.     

Effects of Chronotropic Responsive Cardiac Pacing on Ventilatory Response to Exercise in Patients with Complete AV Block

To identify the effect of chronotropic responsive cardiac pacing on the ventilatory response to exercise, ten selected patients with complete atrioventricular block underwent paired cardiopulmonary exercise tests in fixed rate ventricular (WI) and dual chamber (DDD) or rate responsive ventricular (VVIR) pacing modes. Compared to VVI pacing, DDD or VVIR pacing increased peak oxygen uptake (P < 0.005) and augmented anaerobic threshold (P < 0.001), In eight patients, dyspnea was the major symptom limiting exercise with VAT pacing and this was markedly attenuated with DDD or VVIR pacing. In all patients, ventilation (VE) and the ratio of ventilation to CO₂ production (VE/VCO₂) were consistently higher with VVI pacing during exercise. To compare the response of the two pacing modes at the same workloads in an aerobic condition, we measured ventilatory variables 1 minute prior to the anaerobic threshold obtained with VVI pacing. When DDD or VVIR pacing was compared with VVI pacing, VE and VE/VCO₂ significantly decreased from 20.5 ± 5.3 L/min to 18.3 ± 5.0 L/min (P < 0.005) and from 35.9 ± 5.8 to 31.9 ± 5.0 (P < 0.003), respectively. Respiratory frequency rose significantly more with VVI pacing (P < 0.001) despite an unchanged tidal vohame. Although peak VE did not differ between the two pacing modes, VE/VCO₂ at the peak exercise increased significantly more with VVI pacing (P < 0.005). Respiratory frequency also rose more with VVI pacing (P < 0.005) and tidal volume did not change. This study suggests that chronotropic responsive cardiac pacing attenuates the exertional dyspnea by improving the ventilatory response to exercise as well as increasing the cardiac output in patients with complete atrioventricular block.     

Clonal and non-clonal karyotypically abnormal cells in haemophagocytic lymphohistiocytosis

We studied chromosomes in bone marrow (BM) or peripheral blood cells of nine patients with haemophagocytic lymphohistiocytosis (HLH); three of them had a family history of HLH and four others underwent concurrent Epstein-Barr virus (EBV) infection. In addition to a large population of normal mitotic cells, karyotypically abnormal clonal cells were found in two patients, abnormal clonal cells and a nonclonal (single) abnormal cell in one, and nonclonal abnormal cells in three. All the six patients with chromosome abnormalities died of progressive disease; one of them also had EBV infection and EBV-associated clonal proliferation. Two of three patients with EBV infection and only normal mitotic cells in BM completely recovered from the disease.
Although HLH did not show histological and/or haema-tological evidence of a neoplastic disease, clonal chromosome abnormalities and the fatal clinical outcome found in some of the patients suggest that the disease may be heterogenous and include malignancy. HLH patients with karyotypically abnormal clonal cells in BM should warrant more intensive chemotherapy than that presently being applied to them and should be considered as candidates for BM transplantation.     

Epinephrine-Induced Ventricular Premature Complexes Due to Early Afterdepolarizations and Effects of Verapamil and Propranolol in a Patient with Congenital Long QT Syndrome

Epinephrine-Induced VPCs and EADs in Congenital LQTS. We report a patient with congenital long QT syndrome in whom early afterdcpolarizations (RAl)s) were demonstrated on monophasic action potential (MAP) recordings in the left ventricular mid-base inferior wall. Epinephrine infusion at 5 fig/mm increased the amplitude of the EADs and the late component of the T(U) wave. Epinephrine also induced ventricular premature complexes (VPCs) with right hundle branch block morphology and left-axis deviation that occurred from the peak of the EADs. Verapamil injection (5 nig) during continuous epinephrine infusion abolished all VPCs with a slight reduction in the amplitude of the EADs. Propranolol injection (5 mg) in addition to verapamil further reduced the amplitude of the EADs and the late component of the T(U) wave. These findings suggest that the epinephrinc-induced VPCs were closely related to triggered rhythm arising from the EADs, and that both verapumil and propranoloi were effective for the suppression of VPCs and EADs.     

Increased Dispersion of Repolarization Time Determined by Monophasic Action Potentials in Two Patients with Familial Idiopathic Ventricular Fibrillation

Increased Dispersion of RT in Familial Idiopathic VF. Introduction: The role of increased dispersion of repolarization in the genesis of torsades de pointes in patients with long QT syndrome has been clarified, but its role in the genesis of idiopathic ventricular fibrillation (VF) is not yet known. To investigate the pathogenesis of VF, we recorded monophasic action potentials (MAPs) from two siblings (48- and 36-year-old males) with familial idiopathic VF. Methods and Results: The elder brother (patient I) showed a late r’ wave in lead V¹ and ST segment elevation in leads V¹ through V³. The younger brother (patient 2) had late r’ waves and ST segment elevation in leads II, III, and aVF, and the configurations were very similar to those of patient I. MAPs were recorded from several sites in the right ventricular (RV) and left ventricular (LV) endocardium during constant right atrial pacing. The repolarization time (RT) was defined as the sum of the activation time (AT) and action potential duration (APD) at 90% repolarization. In patient 1, marked prolongation of the AT (140 msec) and the RT (380 msec) was recorded in the RV septum of the outflow tract, and the RT dispersion was markedly increased (125 msec). In contrast, patient 2 showed prolongation of the AT (80 msec) and RT (310 msec), and fractionated electrograms in the RV floor of the inflow tract. The RT dispersion was also increased (80 msec). VF and nonsustained polymorphic ventricular tachycardia were induced by double premature stimulation in patients 1 and 2, respectively. Chronic amiodarone therapy decreased the RT dispersion and suppressed the induction of ventricular tachyarrhythmias in patient 2, although late r’ waves and slight ST segment elevation were unmasked in leads V₁, and V₂. Conclusion: Our data suggest that the increased dispersion of the RT, which was due mainly to a localized conduction delay in the RV, created an arrhythmogenic substrate in the two patients with familial idiopathic VF.     

Human herpesvirus-6-associated exanthema in a patient with acute lymphocytic leukaemia

We report the first case of human herpesvirus-6 (HHV-6) associated exanthema in a patient with acute lymphocytic leukaemia (ALL). We analysed DNA extracted from an exanthematous lesion using the polymerase chain reaction (PCR). DNA was positive for HHV-6 but negative for herpes simplex virus, varicella zoster virus, and cytomegalovirus. Immunohistochemical staining of the skin with monoclonal antibody against HHV-6 confirmed the infection. The possibility of HHV-6 infection should be considered when an atypical skin rash is seen in patients with ALL.     

Lack of Teratogenicity of 3-Chloro-4-(Dichloromethyl)-5-Hydroxy-2 (5H)-Furanone (MX) in Embryonic Mouse Palate Culture in vitro

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5 H )-furanone (MX) is known as a by-product of wood pulp manufacture and a contaminant of chlorinated drinking water. Since our previous studies (Teramoto et al., 1998, 1999) demonstrated in a micromass in vitro test a strong inhibitory effect of MX on rat embryo cell differentiation, the potential teratogenicity was investigated in this study by using a suspension organ culture system. Twelve-day mouse embryo palatal explants were cultivated for 72 hr in the MX-containing medium at a concentration of 0, 1, 10, 100 or 300 μg/ml and examined for closure of the palatal shelves. All control explants showed almost complete closure of the palatal shelves. Similar results were also obtained in the MX-treated explants at concentrations up to and including 100 μg/ml. Immunohistochemistry revealed no difference between the control and MX-treated explants in distribution of PCNA-and TUNEL-positive cells in the palatal mesenchyme and medial edge epithelium, respectively. When the MX concentration was raised to 300 μg/ml, palatal shelves remained wide open. However, histopathology revealed extensive pyknosis of the mesenchymal cells and loss of the epithelium. These results may indicate that MX is cytotoxic against the mouse palate at a high concentration, and that it has no cleft-palate inducing effects in mice.     

Catheter Ablation of Atrial Fibrillation in Patients With Valvular Heart Disease: Long‐Term Follow‐Up Results

AF Ablation in Patients With Valvular Heart Disease . Background: The purpose of this study is to evaluate the efficacy of atrial fibrillation (AF) ablation in patients with moderate valvular heart disease (VHD). Methods: In total, 534 consecutive patients who underwent AF ablation were enrolled. Patients with a history of valve surgery or other structural heart disease were excluded. Patients with clinically moderate VHD (group‐1, n = 45) were compared with those without VHD (control group‐2, n = 436). Ipsilateral pulmonary vein antrum isolation (PVAI) was performed with a double Lasso technique in all the patients. Left atrial (LA) linear ablation was undertaken in persistent AF patients, if AF was inducible after PVAI. Results: Patients in group‐1 were significantly older and had a larger LA. PVAI was successfully achieved in all the patients. Patients in group‐1 received LA linear ablation more frequently during the index procedure. After a median of 26 months from the index procedure, the freedom from AF was significantly lower in group‐1 than group‐2 off antiarrhythmic drugs (AADs) (47% vs 69%, P = 0.002). Although there were more number of total procedures in group‐1 than group‐2, the freedom from AF was lower at median 24 months after the last procedure (78% vs 87%, P = 0.038). There was no significant difference in the freedom from AF on AADs (91% vs 95%, P = 0.356) or complication rate between the 2 groups. Atrial tachycardia following the index procedure was observed more frequently in group‐1 (P = 0.001). Conclusion: The patients with VHD undergoing AF ablation are less likely to remain in sinus rhythm at long term without AADs than those without VHD. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1193‐1198, November 2010)