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.     

Long-Term Results of Cryoablation with a New Cryoprobe to Eliminate Chronic Atrial Fibrillation Associated with Mitral Valve Disease

The purpose of this study was to examine the performance of a new cryoprobe in the treatment of chronic atrial fibrillation (AF) associated with mitral valve disease. The study included 66 patients undergoing mitral valve replacement. The mean AF duration was 9.0 ± 9.0 years and mean left atrial (LA) was diameter 57 ± 10 mm. Cryoablation (−60°C) was applied to four pulmonary vein (PV) orifices over 2–3 minute. The spherical tip (2-cm in diameter) of the cryoprobe is capable of ablating the left atrium near the PV, as well as the PV ostium with a single cryoablation. After cryoablation, mitral valve surgery or a combined surgical procedure were performed in 66 patients. There were no intraoperative complications. Sinus rhythm was restored in 60 patients (91%) immediately after the operation. Recurrent AF was treated with antiarrhythmic drugs and/or direct current cardioversion in 43 patients (72%). At discharge, 48 patients (72%) were in sinus rhythm. During a mean follow-up period of 31 ± 16 months, 40 patients (61%) were in sinus rhythm with (29) or without antiarrhythmic drugs (11). In patients in sinus rhythm at the end of the follow-up period, the duration of preoperative AF duration was significantly shorter (P < 0.05) and the preoperative LA diameter and cardiothoracic ratio were significantly smaller than in patients who were in AF (both for P < 0.005). Using this new cryoprobe, sinus rhythm was restored and maintained in 61% of patients with chronic AF and mitral valve disease with a 12–15 minute cryoablation procedure.     

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.     

Deficiency of endogenous prostanoids in gastric and duodenal ulcer diseases

The levels of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (PGF₁α) and thromboxane B₂ (TXB₂) in endoscopic biopsy specimens from the gastric and duodenal mucosa of healthy volunteers and ulcer patients were measured by radio-immunoassay. The PGE₂ and PGF₁α levels in the mucosa of the corpus of the stomach were lower and the TXB₂ level was higher in 10 patients with gastric ulcer in the corpus than in the 16 healthy subjects. The PGE₂ level in the antral mucosa of 14 patients with gastric ulcer in the antrum was lower than in the controls. In 18 patients with duodenal ulcer, PGE₂ deficiency was more widespread in the entire gastric and duodenal mucosa while the reduced PGF₁α level was limited in the gastric corpus. Lower levels of PGE₂ in patients with antral or duodenal ulcer and of PGE₂ and PGF₁α in patients with corpus ulcer in the anatomical mucosal area including the ulcer site may predispose the mucosa to ulceration.     

New Electrophysiologic Features and Catheter Ablation of Atrioventricular and Atriofascicular Accessory Pathways:

Catheter Ablation for Mahaim Pathways. Introduction : Several modalities of catheter ablation have been proposed to eliminate Mahaim pathway conduction. However, limited research has been reported on the electrophysiologic nature of this pathway in its entity.
Methods and Results : In seven patients, electrophysiologic study was performed, and radiofrequency energy was applied to investigate the electrophysiologic clues for successful ablation. In all seven patients, the Mahaim pathway was diagnosed as a right-sided atriofascicular or atrioventricular pathway with decremental properties. In two patients, two different kinds of electrograms were recorded through the ablation catheter positioned at the Mahaim pathway location: one was suggestive of conduction over the decremental portion, demonstrating a dulled potential; and the other of nondecremental conduction, demonstrating a spiked potential. All but one of the Mahaim pathways were eliminated successfully at the atrial origin where the spiked Mahaim potential was recorded. Radiofrequency energy application was performed at the slow potential site resulting in failure to eliminate the conduction over the Mahaim pathway. Conduction block at the site between the slow and fast potential recording sites was provoked by intravenous administration of adenosine, concomitant with a decrease in the amplitude of the Mahaim potential. In one patient, the clinical arrhythmia was a sustained monomorphic ventricular tachycardia originating from the ventricular end of the Mahaim fiber.
Conclusion : The identification of Mahaim spiked potentials may be the optimal method to permit their successful ablation. Detailed electrophysiologic assessment is indispensable for successful ablation of tachycardias associated with Mahaim fibers because tachycardias unassociated with Mahaim fibers can occur despite complete elimination of the Mahaim fiber.     

Hepatic HCV-RNA as a predictor of outcome after interferon therapy in patients with chronic hepatitis C

Measurement of serum HCV-RNA is a useful index for evaluating the antiviral effect of interferon therapy in chronic hepatitis C. In the present study, we investigated whether the detection of hepatic HCV-RNA after interferon treatment, using a polymerase chain reaction assay, predicted long-term response to therapy in patients with chronic hepatitis C. Thirty-three patients underwent liver biopsies before and after interferon therapy. Histology and clinical courses were compared after treatment. Before therapy, serum and hepatic HCV-RNA was detected in specimens from 32 (97%) and 33 (100%) patients, respectively. Serum HCV-RNA became undetectable in samples from 22 (67%) patients; however, in 10 of these patients (45%), serum HCV-RNA levels relapsed after therapy. Hepatic HCV-RNA became undetectable in 14 patients after therapy and the serum aminotransferase concentration remained within normal limits during and following (24–92 weeks) therapy in 12 of these patients (86%). All 11 patients with detectable hepatic HCV-RNA also had serum HCV-RNA and elevated aminotransferase concentrations refractory to therapy. The absence of hepatic HCV-RNA at the end of interferon treatment thus predicted a long-term complete response to therapy with a sensitivity of 100%, a specificity of 90% and an accuracy of 94%. We conclude that hepatic rather than serum HCV-RNA is a more useful index for the prediction of the long-term efficacy of interferon therapy.     

Verapamil-Sensitive Left Anterior Fascicular Ventricular Tachycardia: Results of Radiofrequency Ablation in Six Patients

Verapamil-Sensitive Left Anterior Fascicular VT. Introduction: Verapamil-sensitive left ventricular tachycardia (VT) with a right bundle branch block (RBBB) configuration and left-axis deviation bas been demonstrated to arise from the left posterior fascicle, and can be cured by catheter ablation guided by Purkinje potentials. Verapamil-sensitive VT with an RBBB configuration and right-axis deviation is rare, and may originate in the left anterior fascicle. Methods and Results: Six patients (five men and one woman, mean age 54 ± 15 years) with a history of sustained VT with an RBBB configuration and right-axis deviation underwent electrophysiologic study and radiofrequency (RF) ablation. VT was slowed and terminated by intravenous administration of verapamil in all six patients. Left ventricular endocardial mapping during VT identified the earliest ventricular activation in the anterolateral wall of the left ventricle in all patients. RF current delivered to this site suppressed the VT in three patients (ablation at the VT exit). The fused Purkinje potential was recorded at that site, and preceded the QRS complex by 35, 30, and 20 msec, with pace mapping showing an optimal match between the paced rhythm and the clinical VT. In the remaining three patients, RF catheter ablation at the site of the earliest ventricular activation was unsuccessful. In these three patients, Purkinje potential was recorded in the diastolic phase during VT at the mid-anterior left ventricular septum. The Purkinje potential preceded the QRS during VT by 66, 56, and 63 msec, and catheter ablation at these sites was successful (ablation at the zone of slow conduction). During 19 to 46 months of follow-up (mean 32 ± 9 months), one patient in the group of ablation at the VT exit bad sustained VT with a left bundle branch block configuration and an inferior axis, and one patient in the group of ablation at the zone of slow conduction experienced typical idiopathic VT with an RBBB configuration and left-axis deviation. Conclusion: Verapamil-sensitive VT with an RBBB configuration and right-axis deviation originates close to the anterior fascicle. RF catheter ablation can be performed successfully from the VT exit site or the zone of slow conduction where the Purkinje potential was recorded in the diastolic phase.     

Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis

Abstract We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vascodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease.