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https://www.readbyqxmd.com/read/28815597/cardiac-action-potential-repolarization-re-visited-early-repolarization-shows-all-or-none-behaviour
#1
Beatriz Trenor, Karen Cardona, Javier Saiz, Denis Noble, Wayne Giles
In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, action potential height and duration are key physiological variables. In addition, rate-dependent changes in ventricular action potential duration (APD), and variations in APD at a fixed heart rate, are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for Safety Pharmacology decisions...
August 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28808886/assessment-of-pharmacokinetic-interactions-between-obeticholic-acid-and-caffeine-midazolam-warfarin-dextromethorphan-omeprazole-rosuvastatin-and-digoxin-in-phase-1-studies-in-healthy-subjects
#2
Jeffrey E Edwards, Lise Eliot, Andrew Parkinson, Sharon Karan, Leigh MacConell
INTRODUCTION: Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. METHODS: Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28808762/relationships-between-more-than-90-coronary-luminal-narrowing-induced-by-ergonovine-provocation-test-and-ecg-ischemic-change-as-well-as-chest-symptoms
#3
Shozo Sueda, Hiroaki Kohno
In the clinic, patients with ≥90% luminal narrowing during ergonovine (ER) testing had variable response. We investigated ischemic findings and chest symptoms in patients with ≥90% luminal narrowing when performing ER tests, retrospectively. We performed 1210 ER tests over 26 years (1991-2016). We analyzed chest symptoms and positive ischemic ECG changes during ER tests. More than 90% luminal narrowing was found in 352 patients (29.1%) including 211 patients in the right coronary artery (RCA) and 217 patients in the left coronary artery (LCA)...
August 14, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28799823/lack-of-qt-prolongation-for-2-o-methoxyethyl-modified-antisense-oligonucleotides-based-on-retrospective-exposure-response-analysis-of-ten-phase-1-dose-escalation-placebo-controlled-studies-in-healthy-subjects
#4
Rosie Z Yu, Rudy Gunawan, Richard S Geary, Steven G Hughes, Scott P Henry, Yanfeng Wang
The potential of QT prolongation of ten 2'-O-methoxyethyl-modified (2'-MOE) antisense oligonucleotides (ASOs) was evaluated retrospectively via exposure/response (ER) analysis using data from Phase 1 clinical studies in healthy subjects. All Phase 1 studies were double-blind, placebo-controlled, single and multiple ascending dose studies designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the ASOs in healthy subjects. The active doses in these studies ranged from 50 to 450 mg administered by subcutaneous (SC) injection in single and multiple ascending dose cohorts...
August 11, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28792295/medical-care-at-a-large-vertical-running-event
#5
Christopher J Nash, Christopher T Richards, Gina Schwieger, Sanjeev Malik, George T Chiampas
OBJECTIVE: Vertical running events, during which participants race up the stairwells of skyscrapers, are becoming increasingly popular. Such events have unique and specific operational and clinical considerations for event medical directors, but descriptions of the medical care provided at these events are lacking. We sought to perform a descriptive analysis of the medical care delivered at a single, large vertical running event. METHODS: A retrospective chart review of medical encounters at a large vertical running event from 2011-2017 was performed...
August 9, 2017: Prehospital Emergency Care
https://www.readbyqxmd.com/read/28791335/internalization-of-rat-fsh-and-lh-cg-receptors-by-rec-ecg-in-cho-k1-cells
#6
Jong-Ju Park, Hun-Ki Seong, Jeong-Soo Kim, Byambaragchaa Munkhzaya, Myung-Hwa Kang, Kwan-Sik Min
Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn(56) of the α-subunit...
June 2017: Balsaeng'gwa Saengsig
https://www.readbyqxmd.com/read/28765984/-acute-chest-pain
#7
REVIEW
M Möckel, T Störk
Patients presenting with acute chest pain are a challenge for attending physicians in private practice and specialists for emergency and acute medicine in hospitals because a wide spectrum of diagnoses may be the cause, ranging from acute myocardial infarction (AMI) to harmless muscular tension. The evaluation of patients with acute chest pain follows basic principles independent of the setting: A thorough clinical investigation by the responsible physician including medical history and physical examination, followed by a 12-channel electrocardiogram (ECG) and further focused diagnostics...
August 1, 2017: Der Internist
https://www.readbyqxmd.com/read/28762918/-noninvasive-electrophysiological-mapping-in-patients-with-complete-left-bundle-branch-block-and-different-modes-of-biventricular-pacing
#8
S V Zubarev, M P Chmelevsky, M A Budanova, M A Trukshina, T A Lyubimtseva, V K Lebedeva, D S Lebedev
OBJECTIVE: to investigate possibilities of noninvasive electrophysiological mapping (NEM) during biventricular (BiV) pacing and to compare the results with data of 12 lead ECG and tissue Doppler echocardiography (TDI). MATERIAL AND METHODS: The study included 25 patients with complete left bundle branch block (LBBB) and implanted cardiac resynchronization therapy (CRT) system. Twenty-two patients were CRT responders, three other patients did not demonstrate a clear effect...
May 2017: Kardiologiia
https://www.readbyqxmd.com/read/28762476/use-of-early-clinical-trial-data-to-support-thorough-qt-study-waiver-for-upadacitinib-and-utility-of-food-effect-to-demonstrate-ecg-assay-sensitivity
#9
Mohamed-Eslam F Mohamed, Jiewei Zeng, Ping Jiang, Balakrishna Hosmane, Ahmed A Othman
Exposure-response analyses of QT data from early-stage clinical studies represent a valuable tool to assess the QT prolongation potential for drugs in development in lieu of stand-alone thorough QT (TQT) studies. However, demonstrating adequate ECG assay sensitivity can be challenging in the absence of a positive pharmacological control. Upadacitinib is a Janus Kinase 1 inhibitor currently being evaluated in Phase 3 rheumatoid arthritis trials. Exposure-response analyses to evaluate the QT prolongation potential for upadacitinib from Phase 1 trials and the utility of the effect of food on QTcF to demonstrate ECG assay sensitivity are presented...
August 1, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28758412/onset-of-depressed-heart-work-is-correlated-with-the-increased-heart-rate-and-shorten-qt-interval-in-high-carbohydrate-fed-overweight-rats
#10
Aysegul Toy Durak, Yusuf Olgar, Erkan Tuncay, Irem Karaomerlioglu, Gizem Kayki Mutlu, Ebru Arioglu Inan, Vecdi Melih Altan, Belma Turan
Mechanical activity of the heart is adversely affected with metabolic syndrome (MetS) characterized with increased body-mass and marked insulin-resistance. Herein, we examined effects of high-carbohydrate intake on cardiac functional abnormalities via evaluating in situ heart-work, heart-rate and electrocardiograms (ECG) in rats. MetS is induced in Wistar male rats by adding 32% sucrose for 22-24 weeks and confirmed with insulin-resistance, increased body-weight, blood glucose and insulin, systolic and diastolic blood pressures besides significant left ventricular integrity-lost and increased connective-tissue around myofibrils...
July 30, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28757278/distribution-and-chronotropic-effects-of-serotonin-in-the-zebrafish-heart
#11
Matthew R Stoyek, Michael G Jonz, Frank M Smith, Roger P Croll
Several lines of evidence suggest that serotonin (5-HT) has a regulatory role in cardiovascular function from embryogenesis through adulthood. However, the reported actions of 5-HT are often contradictory and include bradycardia or tachycardia, hypotension or hypertension, and vasodilation or vasoconstriction. Clarifying such cardiac effects requires further research and may benefit from utilizing a model simpler than the mammalian hearts traditionally used in these studies. In the present study, we describe the cardiac distribution and chronotropic responses of 5-HT in the zebrafish heart...
September 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28755687/response-to-ecg-july-2017
#12
Moisés Rodríguez-Mañero, Javier García-Seara, José Luis Martínez-Sande
No abstract text is available yet for this article.
August 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28751012/the-j-to-t-peak-interval-as-a-biomarker-in-drug-safety-studies-a-method-of-accuracy-assessment-applied-to-two-algorithms
#13
W Brian Chiu, Johan de Bie, David W Mortara
OBJECTIVES: To evaluate performance of J-to-T-peak (JTP) measurements of 12-lead ECGs, in a five-arm study using drugs with various levels of electrolyte channel block. METHODS: The novel evaluation method distinguishes between different aspects of measurement. "Random noise" is the variability among repeated measurements made without changing the conditions. "Context noise" is the variability of changes in context of the measurement, e.g. T-wave morphology, autonomic nervous system state...
July 12, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28721542/molecular-characterization-modeling-in-silico-analysis-of-equine-pituitary-gonadotropin-alpha-subunit-and-docking-interaction-studies-with-ganirelix
#14
Anuradha Bhardwaj, Varij Nayan, Parvati Sharma, Sanjay Kumar, Yash Pal, Jitender Singh
Equine pituitary gonadotropins (eLH, eFSH, eCG) are heterodimeric glycoprotein hormones with alpha (α) and beta (β) subunits. It is responsible for maintenance of pregnancy in mares during early gestation and fairly valuable for inducing superovulation in animals other than equines. The alpha subunit is common, while beta subunit is species-specific in all glycoprotein hormones. In the present investigation, molecular cloning and in silico characterization including homology modeling and molecular docking analysis of the equine chorionic gonadotropin (eCG) alpha subunit was carried out for gaining structural and functional insights into the eCG alpha subunit and its possible interaction with ganirelix, a gonadotropin-releasing hormone (GnRH) antagonist...
December 2016: In Silico Pharmacology
https://www.readbyqxmd.com/read/28711633/novel-measure-of-autonomic-remodeling-associated-with-sudden-cardiac-arrest-in-diabetes
#15
Yang Yang, Aapo L Aro, Sandeep G Nair, Reshmy Jayaraman, Kyndaron Reinier, Carmen Rusinaru, Audrey Uy-Evanado, Hirad Yarmohammadi, Jonathan Jui, Sumeet S Chugh
BACKGROUND: Diabetes is independently associated with an increased risk of sudden cardiac arrest (SCA), with a need to identify novel methods for risk stratification. Diabetic patients can develop autonomic dysfunction that has been associated with an increased risk of ventricular arrhythmogenesis and manifests as reduced heart rate variability (HRV). However, previously published studies have not accounted for resting heart rate (HR), important from both pathophysiological and prognosticating standpoints...
July 13, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28708228/clinical-and-subclinical-cardiac-late-effects-in-pediatric-hodgkin-s-lymphoma-survivors
#16
Carlo Materazzo, Maura Massimino, Elisabetta Schiavello, Marta Podda, Lorenza Gandola, Graziella Cefalo, Serena Catania, Cristina Meazza, Ivan Moschetti, Monica Terenziani
PURPOSE: Cardiac late effects are responsible for a significant burden of mortality and morbidity among pediatric Hodgkin's lymphoma (HL) survivors (HLS). The aim of our study was to assess clinical and subclinical cardiac sequelae in a cohort of childhood HLS treated in the 1980s with doxorubicin, bleomycin, vinblastine, and dacarbazine (the ABVD regimen) and limited-field radiotherapy (RT). METHODS: We retrospectively examined a series of HLS treated from 1979 to 1989...
July 8, 2017: Tumori
https://www.readbyqxmd.com/read/28701672/the-shortest-qrs-duration-of-an-electrocardiogram-might-be-an-optimal-electrocardiographic-predictor-for-response-to-cardiac-resynchronization-therapy
#17
Jan-Yow Chen, Kuo-Hung Lin, Kuan-Cheng Chang, Che-Yi Chou
QRS duration has been associated with the response to cardiac resynchronization therapy (CRT). However, the methods for defining QRS duration to predict the outcome of CRT have discrepancies in previous reports. The aim of this study was to determine an optimal measurement of QRS duration to predict the response to CRT.Sixty-one patients who received CRT were analyzed. All patients had class III-IV heart failure, left ventricular ejection fraction not more than 35%, and complete left bundle branch block. The shortest, longest, and average QRS durations from the 12 leads of each electrocardiogram (ECG) were measured...
August 3, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28701321/pituitary-adenylate-cyclase-activating-polypeptide-pacap-drives-cardiorespiratory-responses-to-heat-stress-in-neonatal-mice
#18
Karlene T Barrett, John Andrew Daubenspeck, Richard J A Wilson
The neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has emerged as a principal and rate-limiting regulator of physiological stress responses in adult rodents and has been implicated in SIDS (Sudden Infant Death Syndrome). Recent studies show that PACAP plays a role in neonatal cardiorespiratory responses to hypoxia, hypercapnia and hypothermia, but not hyperthermia, which is often associated with SIDS. Here we tested the hypothesis that, consistent with a role in SIDS, PACAP is involved in regulating the neonatal cardiorespiratory responses to severe heat...
July 12, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28697825/-screening-and-follow-up-for-congenital-heart-disease-in-children-aged-0-3-years-in-rural-areas-of-chongqing-china
#19
Lei Zhang, Mei-Yu An, Bing Zhu, Wan-Dong Shen, Shu-Jiang Tan, Xiao-Juan Ji, Jie Tian, Xiao-Yan Liu
OBJECTIVE: To examine the incidence of congenital heart disease (CHD) in children aged 0-3 years in the rural areas of Chongqing, and to determine the suitable "screening-diagnosis-follow-up" system and screening indicators for CHD in these areas. METHODS: Children aged 0-3 years from rural areas of the Fuling Disctrict of Chongqing were selected by cluster sampling. Using the "screening-diagnosis-evaluation system" employed at the levels of village/town, district/county, and province/city, the children were screened for seven indicators, i...
July 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28691853/assessment-of-cardiac-autonomic-tone-following-long-sudarshan-kriya-yoga-in-art-of-living-practitioners
#20
Lakshmi Bhaskar, Chhaya Kharya, K K Deepak, Vinod Kochupillai
OBJECTIVE: The breathing processes are known to modulate cardiac autonomic tone and improve psychological status. We investigated cardiac autonomic tone following long Sudarshan Kriya Yoga (SKY) using heart rate variability (HRV) and skin conductance level (SCL). METHODS: Thirty healthy volunteers (age 28.3 ± 8.4 years; 23 M: 7 F) participated in the study. Electrocardiogram (ECG) and SCL were recorded for 5 min each, before and after long SKY. Long SKY is a combination of pranayama and cyclic rhythmic breathing and is performed by following the guided audio instructions...
July 10, 2017: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
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