Yoshino Minoura

Microvolt T-Wave Alternans as a Predictor of Ventricular Tachyarrhythmias A Prospective Study Using Atrial Pacing

Background—Microvolt T-wave alternans (TWA) is reported to be closely associated with sudden cardiac death (SCD) and ventricular tachycardia (VT). Animal experiments revealed that microvolt TWA is highly dependent on heart rate. The purpose of this study was to determine whether patients with TWA at relatively low heart rates have increased vulnerability to ventricular tachyarrhythmias. Methods and Results—Subjects were 248 consecutive patients (158 men, 90 women; mean age, 59±17 years) who underwent electrophysiological study from 1997 to 2000. TWA recording was made in sinus rhythm and at atrial pacing rates of 90, 100, 110, and 120 bpm with the Cambridge Heart CH2000 system. Alternans voltage (Valt) was measured when the alternans ratio was >3 for a period of >1 minute in VM, X, Y, Z, or 2 adjacent precordial leads. Study end point was the first appearance of VT, ventricular fibrillation (VF), appropriate implantable cardioverter-defibrillator therapy with pacing or shocks, or SCD. During the 37±12-month follow-up period, 22 patients had sustained VT, and 5 patients died of SCD. In patients with >1.9-μV Valt at rates of 90, 100, and 110 bpm, the incidence of VT/VF/SCD was 56%, 28%, and 18%, respectively. Valt of >2.9 μV at a heart rate of 90 bpm had a 70% positive predictive value for VT/VF/SCD. However, when Valt was <0.9 μV at a rate of 120 bpm, negative predictive value was 100%. Conclusions—Patients with TWA at relatively low heart rates are susceptible to ventricular tachyarrhythmias.

Effect of Wenxin Keli and quinidine to suppress arrhythmogenesis in an experimental model of Brugada syndrome

BACKGROUND Wenxin Keli (WK), a Chinese herb extract, is reported to be effective in the treatment of atrial and ventricular cardiac arrhythmias. Recent studies suggest that WK inhibits the transient potassium outward current (I(to)). OBJECTIVE To examine the effectiveness of WK, alone and in combination with quinidine, to suppress arrhythmogenesis in an experimental model of Brugada syndrome (BrS). METHODS Action potential and electrocardiographic recordings were obtained from epicardial and endocardial sites of coronary-perfused canine right ventricular wedge preparations. The Ito agonist NS5806 (10-15 μM) was used to pharmacologically mimic a genetic predisposition to BrS. RESULTS The Ito agonist induced Phase 2 reentry (P2R) in 13/19 preparations and polymorphic ventricular tachycardia (pVT) in 11/19 wedge preparations. WK (10 g/L) suppressed P2R and pVT in 100% (3/3) of preparations. A lower concentration of WK (5 g/L) suppressed P2R in 60% (3/5) and pVT in 50% (2/4), but in combination with a low concentration of quinidine (5 μM), was 100% effective in suppressing P2R and pVT. Quinidine alone suppressed P2R and pVT in 60% (3/5) and 50% (2/4), respectively, and in combination with WK (5 g/L) suppressed P2R and pVT by 80% (4/5) and 75% (3/4), respectively. WK reduced Ito, the L-type calcium current, and contractility in single cardiomyocytes, but dose-dependently increased contractility in intact wedge preparations, an effect mimicked by tyramine. CONCLUSIONS Our data provide support for the hypothesis that WK, particularly in combination with quinidine, effectively suppresses arrhythmogenesis in an experimental model of BrS via inhibition of Ito and indirect adrenergic sympathomimetic effects.

A temporal window of vulnerability for development of atrial fibrillation with advancing heart failure.

Heart failure (HF) is associated with development of AF and life‐threatening ventricular tachycardia and fibrillation (VT/VF). Vulnerability to development of AF and VT/VF at different stages of HF and the underlying pathophysiological mechanisms are poorly defined. The present study was designed to determine the time‐course of development of electrical and structural remodelling of the atria and ventricles, and their contribution to induction of AF and VT/VF in a canine model of HF.

Effects of α2-adorenoceptor agonist dexmedetomidine on respiratory rhythm generation of newborn rats.

Dexmedetomidine, an α2-adrenoceptor agonist which has a slight side effect on breathing, is clinically used as an analgesic and sedative agent. Previous studies have shown depressing or modest effects of α2-adorenoceptor agonists on respiratory rhythm generation in newborn rat preparation in vitro. In contrast, it was recently reported that dexmedetomidine induced long-lasting activation of respiratory rhythm in brainstem-spinal cord preparation isolated from neonatal mice. In the present study, we examined whether dexmedetomidine induces any effects on respiratory rhythm in brainstem-spinal cord preparation isolated from newborn rats. We also examined the effects of dexmedetomidine on reflex response in the spinal cord, which is presumed to be an indication of nociceptive response. We found that the administration of dexmedetomidine, at the range of 0.1-10μM, dose-dependently depressed respiratory rhythm and that the inhibitory effect was reversed by atipamezole, an α2-adorenoceptor antagonist. Spinal cord reflex responses were depressed by the application of dexmedetomidine at the range of 0.1-1nM, a lower concentration than that affecting respiratory rhythm. The inhibitory effect was also reversed by atipamezole. Our findings provide neuronal mechanisms that support the clinical use of dexmedetomidine, which shows sedative and antinociceptive effects with minimal side effects on breathing.

Electrophysiological responses of sympathetic preganglionic neurons to ANG II and aldosterone

The intermediolateral cell column (IML) of the spinal cord is an important area where sympathetic impulses propagate to peripheral sympathetic organs. ANG II and aldosterone are important components of the renin-angiotensin-aldosterone system (RAAS), which activate the sympathetic nervous system. Each is partly synthesized in the brain and plays a paracrine role in the regulation of blood pressure independently of RAAS in the periphery. Our purpose in the present study was to clarify the contributions of sympathetic preganglionic neurons in the IML (IML neurons) and the effects of ANG II and aldosterone on the sympathetic nervous system. To examine responses to ANG II and aldosterone, we intracellularly recorded 104 IML neurons using a whole cell patch-clamp technique in spinal cord slice preparations. IML neurons were classified into two types: silent and firing. Both neuron types were significantly depolarized by ANG II, and candesartan inhibited this depolarization. After pretreatment with TTX, firing neurons (but not silent neurons) were significantly depolarized by ANG II. Aldosterone significantly increased the number of excitatory postsynaptic potentials (EPSPs) in both neuron types, but this response disappeared after pretreatment with TTX. ANG II and aldosterone had no synergistic effects on the IML neurons. The silent neurons had large cell soma, and many more dendrites than the firing neurons. These results suggest that ANG II acts presynaptically and postsynaptically in IML neurons, while aldosterone acts mainly presynaptically. Thus, the physiological effects of these substances are likely to be transmitted via specific membrane receptors of IML and/or presynaptic neurons.

Single center experience in Japanese patients with syncope

BACKGROUND AND PURPOSE The present diagnostic method and features of syncope in Japan are unclear. Implantable loop recorder (ILR) and head-up tilt tests have recently become available for diagnosing syncope. The examination method and rates of diagnosing syncope may vary. This study aimed to clarify the present diagnostic method and features of syncope in a single Japanese medical center. METHODS AND RESULTS We retrospectively reviewed the medical records of consecutive patients who were seen at our hospital from January 1, 2009, to December 31, 2012. A total of 547 patients (328 men, 60.4±21.5 years) with syncope were seen at our hospital. Reflex syncope was diagnosed in 29.1% of the cases, orthostatic hypotension in 11.7%, cardiac syncope in 34.0%, and unexplained syncope in 23.9% by initial and early evaluations. The number of patients with situational syncope and orthostatic hypotension that could be diagnosed in the initial evaluation of the first examination was significantly greater than that in subsequent evaluations. Forty-three percent of the unexplained syncope patients received an ILR. The consent rate for ILR implantations in the unexplained syncope patients with a suspected arrhythmia nature was 53.1%. The cumulative ILR diagnostic rates were 47% and 65% at 1 and 2 years after the ILR implantation, respectively. The estimated ILR diagnostic rates were significantly greater than that for conventional test without using an ILR. When patients with unexplained syncope could be diagnosed, the recurrent symptoms were greatly reduced. CONCLUSIONS Syncope is induced by various causes in Japan. It is important that we understand the characteristics of each syncope cause. The consent rate for implanting an ILR in appropriate unexplained syncope patients is low. We need to educate these patients about the importance of making a diagnosis of syncope.

Recurrence of atrial fibrillation within three months after pulmonary vein isolation for patients with paroxysmal atrial fibrillation: Analysis using external loop recorder with auto-trigger function

Pulmonary vein isolation (PVI) via catheter ablation has been shown to be a highly effective treatment option for patients with symptomatic paroxysmal atrial fibrillation (AF). The recurrence of AF within 3 months after PVI is not considered to be the result of ablation procedure failure, because early recurrence of AF is not always associated with late recurrence. We examined the usefulness of an external loop recorder with an auto‐trigger function (ELR‐AUTO) for the detection of atrial fibrillation following PVI to characterize early recurrence and to determine the implications of AF occurrence within 3 months after PVI.

Drug-induced Brugada syndrome

Brugada syndrome (BrS) is an inherited cardiac disorder that is associated with an electrocardiogram pattern of ST segment elevation on right precordial leads and a high incidence of sudden death. Diagnosis requires documentation of a coved‐type ST segment that occurs spontaneously or in the presence of a class IA or IC antiarrhythmic agent. A wide variety of other drugs, including antianginals, antidepressants, antipsychotics, and antihistamines, have been reported to unmask or induce the electrocardiographic and arrhythmic manifestations of BrS. This review focuses on drug‐induced BrS phenotypes, prevalence, and underlying mechanisms.

Interaction between novel oscillation within the ventromedial hypothalamus and the sympathetic nervous system

The ventromedial hypothalamus (VMH) is known to play an important role in feeding behavior and the control of sympathetic nerve activity (SNA). We report the identification of novel neuron groups that showed oscillations on both sides of the VMH in hypothalamus slice preparations from juvenile rats of postnatal days 5-14. We detected spontaneous rhythmic burst activity with a frequency of around 0.06Hz typically in the dorsolateral region of the VMH (i.e., VMH oscillation) using optical recordings (voltage and calcium imaging), field potential recordings and intracellular membrane potential recordings. The oscillation was also confirmed after isolation of the VMH from other hypothalamic structures. The frequency of oscillation was increased by lowering the glucose concentration of the superfusate. To evaluate the relation between VMH oscillation and SNA, we simultaneously recorded VMH oscillation, SNA from the thoracic sympathetic nerve trunk and phrenic nerve discharge (Phr) in the decerebrate and arterially perfused in situ preparation from juvenile rats of postnatal days 5-11. Power spectral analysis in the arterially perfused in situ rat preparation revealed similar peak values to those of slice preparations within the low-frequency range between the VMH oscillation and sympathetic nerve trunk activity. In addition, we analyzed cross-correlations between the VMH, SNA and Phr. The results revealed that a predominant positive correlation of the VMH activity with the SNA existed with an average time lag of 2.4s, suggesting the presence of functional couplings between the VMH and SNA (and respiratory center) in the lower brainstem and spinal cord. We hypothesize that the VMH oscillation might be involved in low-frequency modulation of the SNA.

Daily Dysfunction of Autonomic Regulation Based on Ambulatory Blood Pressure Monitoring in Patients with Neurally Mediated Reflex Syncope.

The onset of neurally mediated reflex syncope (NMRS) is associated with dysfunction of the autonomic regulatory system. Yet relatively little is known about the daily conditions of the autonomic regulation system in patients with NMRS. This study elucidated characteristics of daily autonomic function using ambulatory blood pressure monitoring (ABPM) and evaluated the utility of ABPM for NMRS diagnosis.