Plasma Globotriaosylsphingosine Level as a Primary Screening Target for Fabry Disease in Patients With Left Ventricular Hypertrophy.

Background: Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.

Methods and results: Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25-79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.

Functional, morphological and electrocardiographical abnormalities in patients with apical hypertrophic cardiomyopathy and apical aneurysm: correlation with cardiac MR.

Objective: The prognosis of apical hypertrophic cardiomyopathy (APH) has been benign, but apical myocardial injury has prognostic importance. We studied functional, morphological and electrocardiographical abnormalities in patients with APH and with apical aneurysm and sought to find parameters that relate to apical myocardial injury.

Study Design: a multicentre trans-sectional study.

Arrhythmogenic effects of arsenic trioxide in patients with acute promyelocytic leukemia and an electrophysiological study in isolated guinea pig papillary muscles.

Background: Arsenic trioxide (As(2)O (3)) is a new promising regimen for patients with a relapse of acute promyelocytic leukemia (APL), but causes life-threatening arrhythmias. This study aimed to investigate the incidence and mechanism of arrythmogenesis caused by As(2)O(3).

Methods And Results: Standard 12-lead ECGs were monitored throughout As(2)O(3) therapy in 20 APL patients.

A selective inhibitor of Na+/Ca2+ exchanger, SEA0400, preserves cardiac function and high-energy phosphates against ischemia/reperfusion injury.

The Ca2+ overload by Ca2+ influx via Na+/Ca2+ exchanger (NCX) is a critical mechanism in myocardial ischemia/reperfusion injury. We investigated protective effects of a novel selective inhibitor of NCX, SEA0400, on cardiac function and energy metabolism during ischemia and reperfusion. Langendorff-perfused rat hearts were exposed to 35 minutes global ischemia and 40 minutes reperfusion.

Usefulness of delayed enhancement magnetic resonance imaging for detecting cardiac rupture caused by small myocardial infarction in a case of cardiac tamponade.

Delayed enhancement magnetic resonance imaging (DE-MRI) has excellent spatial resolution and compared with other cardiac imaging techniques it can detect a small myocardial infarction (MI) or a subendocardial infarction. A 76-year-old man was admitted for loss of consciousness because of cardiac tamponade. The cause of tamponade was unknown, but electrocardiography and blood test suggested a recent MI.

[Usefulness of lung and right ventricular thallium-201 uptake during single photon emission computed tomography in exercise testing of patients with coronary artery disease].

Objectives: Increased pulmonary or right ventricular 201Tl uptake during the exercise test has been used as a marker of multivessel coronary artery disease. The most useful method for assessing the severity of coronary artery disease was evaluated among conventional evaluation of single photon emission computed tomography (SPECT), measurement of lung to heart uptake ratio (L/H), and right ventricular to left ventricular uptake ratio (RV/LV) on 201Tl images during exercise testing.

Methods: Regions-of-interest (4 X 4 pixels) were placed at the lung and the heart, and L/H was defined as mean lung uptake/mean heart uptake.

Different actions of cardioprotective agents on mitochondrial Ca2+ regulation in a Ca2+ paradox-induced Ca2+ overload.

Background: Mitochondrial Ca2+ overload is a major cause of irreversible cell injury during various metabolic stresses. The protective effects of various agents that affect mitochondrial function against Ca2+ overload during Ca2+ paradox were investigated in rat ventricular myocytes.

Methods And Results: On Ca2+ repletion following Ca2+ depletion, [Ca2+]i increased rapidly, and 90 of 210 cells (43%) died.

Modification of sarcoplasmic reticulum (SR) Ca2+ release by FK506 induces defective excitation-contraction coupling only when SR Ca2+ recycling is disturbed.

This study examined whether the effects of FK506-binding protein dissociation from sarcoplasmic reticulum (SR) Ca(2+) release channels on excitation-contraction (EC) coupling changed when SR Ca(2+) reuptake and (or) the trans-sarcolemmal Ca(2+) extrusion were altered. The steady-state twitch Ca(2+) transient (CaT), cell shortening, post-rest caffeine-induced CaT, and Ca(2+) sparks were measured in rat ventricular myocytes using laser-scanning confocal microscopy. In the normal condition, 50 micromol FK506/L significantly increased steady-state CaT, cell shortening, and post-rest caffeine-induced CaT.

Coronary ectasia with slow flow related to apical hypertrophic cardiomyopathy--a case report.

Coronary ectasia (CE) has been reported to be associated with a high risk of coronary events and caused by several etiologies. The authors present a patient with CE who was noted to have an ECG abnormality in routine health check. Coronary angiography revealed diffuse ectasia in all 3 coronary arteries.

Mitochondrial membrane potential modulates regulation of mitochondrial Ca2+ in rat ventricular myocytes.

Although recent studies focused on the contribution of mitochondrial Ca2+ to the mechanisms of ischemia-reperfusion injury, the regulation of mitochondrial Ca2+ under pathophysiological conditions remains largely unclear. By using saponin-permeabilized rat myocytes, we measured mitochondrial membrane potential (DeltaPsi(m)) and mitochondrial Ca2+ concentration ([Ca2+](m)) at the physiological range of cytosolic Ca2+ concentration ([Ca2+](c); 300 nM) and investigated the regulation of [Ca2+](m) during both normal and dissipated DeltaPsi(m). When DeltaPsi(m) was partially depolarized by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP, 0.

Usefulness of stress myocardial perfusion imaging for evaluating asymptomatic patients after coronary stent implantation.

Background: Stent implantation in coronary angioplasty has reduced the rate of restenosis, but many patients still undergo follow-up coronary angiography (CAG). The present study was a multi-center retrospective analysis of the usefulness of stress single photon emission computed tomography (SPECT) compared with follow-up CAG in stent-implanted patients who remained asymptomatic during the follow-up period.

Methods And Results: The study group of 103 patients underwent both SPECT and CAG at 4-9 months after stent implantation.

Difference in the cardioprotective mechanisms between ischemic preconditioning and pharmacological preconditioning by diazoxide in rat hearts.

Background: Recent studies have implicated the opening of mitochondrial K(ATP) (mitoK(ATP)) channels and the production of reactive oxygen species (ROS) in the cardioprotective mechanism of ischemic preconditioning (IPC).

Methods And Results: The involvement of mitoK(ATP) channels and ROS in the cardioprotective effects of both IPC and the mitoK(ATP) channel opener diazoxide (DZ) was investigated in ischemic/reperfused rat hearts. The effects of IPC and DZ on myocardial high-energy phosphate concentrations and intracellular pH (pH(i)) were also examined using (31)P nuclear magnetic resonance spectroscopy.

A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding affinity to protein kinase C.

Dilated cardiomyopathy is characterized by ventricular dilation with systolic dysfunction of cardiac muscle. Recent genetic studies have revealed that mutations in genes for cytoskeleton proteins distributed in the Z-disc and/or intercalated discs of the cardiac muscle are major predictors of cardiomyopathy. However, as mutations in these genes can account for only a part of the patient population, there should be another disease-causing gene(s) for cardiomyopathy.

Effects of cytochrome P450 inhibitors on agonist-induced Ca2+ responses and production of NO and PGI2 in vascular endothelial cells.

Production of endothelium-dependent vascular relaxing factors, such as nitric oxide (NO) and prostaglandin I2 (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), is regulated in part by changes in intracellular Ca2+ concentration ([Ca2+]i) in vascular endothelial cells (ECs). Cytochrome P450 (CYP), shown to mediate endothelium-dependent hyperpolarization via epoxyeicosatrienoic acids, is one of the candidates for EDHF. In this study we tested the hypotheses that CYP might be involved in EC Ca2+ signaling and that CYP activity might be linked with production of vasodilating factors other than EDHF.

Importance of Ca2+ influx by Na+/Ca2+ exchange under normal and sodium-loaded conditions in mammalian ventricles.

Na+/Ca2+ exchange (NCX) is a major Ca2+ extrusion system in cardiac myocytes, but can also mediate Ca2+ influx and trigger sarcoplasmic reticulum Ca2+ release. Under conditions such as digitalis toxicity or ischemia/reperfusion, increased [Na+]i may lead to a rise in [Ca2+]i through NCX, causing Ca2+ overload and triggered arrhythmias. Here we used an agent which selectively blocks Ca2+ influx by NCX, KB-R7943 (KBR), and assessed twitch contractions and Ca2+ transients in rat and guinea pig ventricular myocytes loaded with indo-1.

Protective effects of hydrogen peroxide against ischemia/reperfusion injury in perfused rat hearts.

Among the several mechanisms proposed for ischemic preconditioning (IPC), generation of reactive oxygen species (ROS) is reported to be involved in the cardioprotective effects of IPC. The present study was designed to investigate whether repetitive exposure to hydrogen peroxide (H(2)O(2)) can protect the myocardium against subsequent ischemia/reperfusion injury, and whether the H(2)O(2)-induced cardioprotection is related to the preservation of energy metabolism. Langendorff-perfused rat hearts were exposed to two, 5 min episodes of IPC or to various concentrations of H(2)O(2) twice and then to 35 min global ischemia and 40 min reperfusion.

CaMKII-dependent reactivation of SR Ca(2+) uptake and contractile recovery during intracellular acidosis.

In hearts, intracellular acidosis disturbs contractile performance by decreasing myofibrillar Ca(2+) response, but contraction recovers at prolonged acidosis. We examined the mechanism and physiological implication of the contractile recovery during acidosis in rat ventricular myocytes. During the initial 4 min of acidosis, the twitch cell shortening decreased from 2.

Sildenafil for primary and secondary pulmonary hypertension.

Background: Sildenafil is a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, an enzyme that is abundant in both lung and penile tissues. Sildenafil is widely used to dilate penile arteries, suggesting that it may also dilate pulmonary arteries in patients with pulmonary hypertension. However, the long-term hemodynamic effects and safety of the drug in pulmonary hypertension are not known.