A complete heart block in a young male: a case report and review of literature of cardiac sarcoidosis.

PubMed

Patel, Brijesh; Shah, Mahek; Gelaye, Alehegn; Dusaj, Raman

2017-01-01

Cardiac sarcoidosis is one of the uncommon causes of heart failure. Generally, it presents in the form of varying clinical manifestations ranging from asymptomatic to fatal arrhythmias such as ventricular tachycardia and complete heart block. It is difficult to make a diagnosis strictly based on clinical grounds. However, in the setting of extracardiac sarcoidosis and patients presenting with advanced heart block or ventricular arrhythmia, direct cardiac involvement should be suspected. The definitive diagnosis of cardiac sarcoidosis can be made from endomyocardial biopsy, but it is falling out of favor due to patchy myocardial involvement, considerable procedure-related risks, and advancement in additional imaging modalities. Once cardiac sarcoidosis has been diagnosed, management of the disease remains challenging. Steroids are considered the mainstay of therapy, and implantable cardioverter defibrillator therapy can be considered in a selected group of patients at greater risk for malignant ventricular arrhythmias.

Atrioventricular block, ECG tracing (image)

MedlinePlus

... an abnormal rhythm (arrhythmia) called an atrioventricular (AV) block. P waves show that the top of the ... wave (and heart contraction), there is an atrioventricular block, and a very slow pulse (bradycardia).

Successful emergency cardiac pacing and permanent pacemaker insertion in a preterm 29-week gestation hydropic baby with congenital complete heart block.

PubMed

Beake, Matthew Jonathan; Bhole, Vinay; Johnston, Tracey; Rasiah, Shree Vishna

2015-02-01

A preterm 29-week gestation baby was delivered because of gross foetal hydrops secondary to congenital complete heart block. Despite a poor prognosis, she survived stabilisation and received emergency epicardial pacing followed by permanent pacemaker insertion on day 13, weighing 1.2 kg.

Treating Arrhythmias in Children

MedlinePlus

... by preventing the episodes from starting, decreasing the heart rate during the episode or shortening how long the ... disorders can be controlled with a pacemaker. Slow heart rates, such as heart block, are the most common ...

Mechanical signaling coordinates the embryonic heart

NASA Astrophysics Data System (ADS)

Chiou, Kevin; Rocks, Jason; Prosser, Benjamin; Discher, Dennis; Liu, Andrea

The heart is an active material which relies on robust signaling mechanisms between cells in order to produce well-timed, coordinated beats. Heart tissue is composed primarily of active heart muscle cells (cardiomyocytes) embedded in a passive extracellular matrix. During a heartbeat, cardiomyocyte contractions are coordinated across the heart to form a wavefront that propagates through the tissue to pump blood. In the adult heart, this contractile wave is coordinated via intercellular electrical signaling.Here we present theoretical and experimental evidence for mechanical coordination of embryonic heartbeats. We model cardiomyocytes as mechanically excitable Eshelby inclusions embedded in an overdamped elastic-fluid biphasic medium. For physiological parameters, this model replicates recent experimental measurements of the contractile wavefront which are not captured by electrical signaling models. We additionally challenge our model by pharmacologically blocking gap junctions, inhibiting electrical signaling between myocytes. We find that while adult hearts stop beating almost immediately after gap junctions are blocked, embryonic hearts continue beating even at significantly higher concentrations, providing strong support for a mechanical signaling mechanism.

The clinical spectrum of autoimmune congenital heart block

PubMed Central

Brito-Zerón, Pilar; Izmirly, Peter M.; Ramos-Casals, Manuel; Buyon, Jill P.; Khamashta, Munther A.

2017-01-01

Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder. PMID:25800217

[Fetal bradycardia: a retrospective study in 9 Spanish centers].

PubMed

Perin, F; Rodríguez Vázquez del Rey, M M; Deiros Bronte, L; Ferrer Menduiña, Q; Rueda Nuñez, F; Zabala Arguelles, J I; García de la Calzada, D; Teodoro Marin, S; Centeno Malfaz, F; Galindo Izquierdo, A

2014-11-01

The aim of this study is to review the current management and outcomes of fetal bradycardia in 9 Spanish centers. Retrospective multicenter study: analysis of all fetuses with bradycardia diagnosed between January 2008 and September 2010. Underlying mechanisms of fetal bradyarrhythmias were studied with echocardiography. A total of 37 cases were registered: 3 sinus bradycardia, 15 blocked atrial bigeminy, and 19 high grade atrioventricular blocks. Sinus bradycardia: 3 cases (100%) were associated with serious diseases. Blocked atrial bigeminy had an excellent outcome, except for one case with post-natal tachyarrhythmia. Of the atrioventricular blocks, 16% were related to congenital heart defects with isomerism, 63% related to the presence of maternal SSA/Ro antibodies, and 21% had unclear etiology. Overall mortality was 20% (37%, if terminations of pregnancy are taken into account). Risk factors for mortality were congenital heart disease, hydrops and/or ventricular dysfunction. Management strategies differed among centers. Steroids were administrated in 73% of immune-mediated atrioventricular blocks, including the only immune-mediated IInd grade block. More than half (58%) of atrioventricular blocks had a pacemaker implanted in a follow-up of 18 months. Sustained fetal bradycardia requires a comprehensive study in all cases, including those with sinus bradycardia. Blocked atrial bigeminy has a good prognosis, but tachyarrhythmias may develop. Heart block has significant mortality and morbidity rates, and its management is still highly controversial. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

[Successful outcome of a pregnancy with an extremely low fetal heart rate (34 bpm) due to isolated complete heart block--case report].

PubMed

Hamela-Olkowska, Anita; Dangel, Joanna; Miszczak-Knecht, Maria

2009-09-01

Isolated complete congenital heart block (CHB) in the majority of cases is associated with the presence of autoantibodies to SSA (Ro) and SSB (La) antigens in the maternal serum. The prognosis is less favorable in fetuses with a ventricular rate < 55bpm. We have reported a case of a fetus with an isolated non-autoimmune CHB with an extremely low ventricular rate (34bpm) in which the outcome was favorable. In the neonate the non-compaction of the myocardium was diagnosed.

[The effects of nicergoline on the heart rate in the normotensive or spontaneously hypertensive rat. Possible participation of central alpha-1 receptors].

PubMed

Huchet, A M; Schmitt, H

1986-01-01

The cardiovascular effects of nicergoline, a preferential alpha 1-adrenoceptor blocking drug, were studied in anaesthetized normotensive or spontaneously hypertensive (SH) rats. Nicergoline (300 micrograms/kg, i.v.) significantly reduced blood pressure and heart rate in control, bivagotomized or beta-blocked normotensive or SH rats. In bilaterally vagotomized and beta-blocked rats, nicergoline reduced mean blood pressure but did no longer modify heart rate. Thus, it is postulated that nicergoline could reduce the sympathetic tone and increase the vagal nerve activity, possibly by inhibiting central alpha 1-adrenoceptors. The nicergoline--induced bradycardia was greater in bivagotomized SHR than in normotensive ones. Intracerebroventricular injections of nicergoline (30 micrograms/kg) did not modify heart rate in normotensive control, bivagotomized or beta-blocked rats. On the contrary, nicergoline (30 micrograms/kg) injected into the cisterna magna induced a significant bradycardia in the three groups of normotensive rats. Blood pressure was reduced in the same way in all groups centrally treated by nicergoline. In conclusion, it seems that nicergoline reduces blood pressure by peripheral alpha-adrenoceptor blockade and modulates the autonomic nervous activity by inhibiting alpha 1-adrenoceptors mainly localized in the brainstem.

Magnetophysiologic and echocardiographic comparison of blocked atrial bigeminy and 2:1 atrioventricular block in the fetus.

PubMed

Wiggins, Delonia L; Strasburger, Janette F; Gotteiner, Nina L; Cuneo, Bettina; Wakai, Ronald T

2013-08-01

Blocked atrial bigeminy (BAB) and second-degree atrioventricular block with 2:1 conduction block (2:1 AVB) both present as ventricular bradycardia and can be difficult to distinguish by echocardiography. Since the prognosis and clinical management of these rhythms are different, an accurate diagnosis is essential. To identify magnetic and mechanical heart rate and rhythm parameters that could reliably distinguish BAB from 2:1 AVB. A retrospective study of ten BAB and seven 2:1 AVB subjects was performed, using fMCG and pulsed Doppler ultrasound. Distinguishing BAB from 2:1 AVB by using fMCG was relatively straightforward because in BAB the ectopic P wave (P') occurred early, resulting in a bigeminal (short-long) atrial rhythm. The normalized coupling interval of the ectopic beat (PP' of the blocked beat to PP of the conducted beat) was 0.29 ± 0.03. In contrast, the echocardiographic assessment of inflow-outflow gave a normalized mechanical coupling interval (AA'/AA) near 0.5, which made it difficult to distinguish BAB from 2:1 AVB. Heart rate distinguished most subjects with BAB from those with 2:1 AVB (82 ± 5.7 beats/min vs 69 ± 4.2 beats/min), but was not a completely reliable indicator. In most subjects, BAB alternated with sinus rhythm or other rhythms, resulting in complex heart rate and rhythm patterns. Fetal BAB and 2:1 AV block can be difficult to distinguish using echocardiography because in many fetuses with BAB the mechanical rhythm does not accurately reflect the magnetic rhythm. fMCG provides a more reliable means of making a differential diagnosis. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Biventricular non-compaction hypertrophic cardiomyopathy in association with congenital complete heart block and type I mitochondrial complex deficiency.

PubMed

Dhar, Ranjana; Reardon, William; McMahon, Colin J

2015-06-01

We report a baby girl with an antenatal diagnosis of biventricular non-compaction and complete heart block detected at 22 weeks' gestation. Postnatal echocardiography confirmed severe biventricular non-compaction hypertrophic cardiomyopathy, multiple muscular ventricular septal defects, and mild-moderate pulmonary valve stenosis. Skeletal muscle biopsy confirmed complex 1 mitochondrial respiratory chain deficiency. An epicardial VVI pacemaker was implanted on day 3 of life and revised at 7 years of age. She remains stable at 8 years of age following pacing and medical treatment with carvedilol, aspirin, co-enzyme Q10, and carnitine. This represents the first report of biventricular non-compaction hypertrophic phenotype in association with congenital complete heart block and complex 1 mitochondrial respiratory chain deficiency in a child.

[Present status and trend of heart fluid mechanics research based on medical image analysis].

PubMed

Gan, Jianhong; Yin, Lixue; Xie, Shenghua; Li, Wenhua; Lu, Jing; Luo, Anguo

2014-06-01

With introduction of current main methods for heart fluid mechanics researches, we studied the characteristics and weakness for three primary analysis methods based on magnetic resonance imaging, color Doppler ultrasound and grayscale ultrasound image, respectively. It is pointed out that particle image velocity (PIV), speckle tracking and block match have the same nature, and three algorithms all adopt block correlation. The further analysis shows that, with the development of information technology and sensor, the research for cardiac function and fluid mechanics will focus on energy transfer process of heart fluid, characteristics of Chamber wall related to blood fluid and Fluid-structure interaction in the future heart fluid mechanics fields.

Commonly Asked Questions about Children and Heart Disease

MedlinePlus

... heart is a pump with a built-in electrical system. Normally, electricity starts in the upper chamber and spreads to ... function. Heart block occurs when the spread of electricity from the upper chambers (atria) to the lower ...

Pectoral nerves (PECS) and intercostal nerve block for cardiac resynchronization therapy device implantation.

PubMed

Fujiwara, Atsushi; Komasawa, Nobuyasu; Minami, Toshiaki

2014-01-01

A 71-year-old man was scheduled to undergo cardiac resynchronization therapy device (CRTD) implantation. He was combined with severe chronic heart failure due to ischemic heart disease. NYHA class was 3 to 4 and electrocardiogram showed non-sustained ventricular. Ejection fraction was about 20% revealed by transthoracic echocardiogram. He was also on several anticoagulation medications. We planned to implant the device under the greater pectoral muscle. As general anesthesia was considered risky, monitored anesthesia care utilizing peripheral nerve block and slight sedation was scheduled. Pectoral nerves (PECS) block and intercostal block was performed under ultrasonography with ropivacaine. For sedation during the procedure, continuous infusion of dexmedetomidine without a loading dose was performed. The procedure lasted about 3 hours, but the patient showed no pain or restlessness. Combination of PECS block and intercostal block may provide effective analgesia for CRTD implantation.

Acquired heart block: a possible complication of patent ductus arteriosus in a preterm infant.

PubMed

Grasser, Monika; Döhlemann, Christoph; Mittal, Rashmi; Till, Holger; Dietz, Hans-Georg; Münch, Georg; Holzinger, Andreas

2008-01-01

A large patent ductus arteriosus (PDA) is a frequently encountered clinical problem in extremely low birth weight (ELBW) infants. It leads to an increased pulmonary blood flow and in a decreased or reversed diastolic flow in the systemic circulation, resulting in complications. Here we report a possible complication of PDA not previously published. On day 8 of life, a male ELBW infant (birth weight 650 g) born at a gestational age of 23 weeks and 3 days developed an atrioventricular block (AV block). The heart rate dropped from 168/min to 90/min, and the ECG showed a Wenckebach second-degree AV block and intraventricular conduction disturbances. Echocardiography demonstrated a PDA with a large left-to-right shunt and large left atrium and left ventricle with high contractility. Within several minutes after surgical closure of the PDA, the heart rate increased, and after 30 min the AV block had improved to a 1:1 conduction ratio. Echocardiography after 2 h revealed a significant decrease of the left ventricular and atrial dimensions. Within 12 h, the AV block completely reversed together with the intraventricular conduction disturbances. We suggest that PDA with a large left-to-right shunt and left ventricular volume overload may lead to an AV block in an ELBW infant. Surgical closure of the PDA may be indicated. (c) 2007 S. Karger AG, Basel.

EXTERIOR VIEW WITH HEART OF DIXIE MUSEUM'S HISTORIC LOCOMOTIVE IN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EXTERIOR VIEW WITH HEART OF DIXIE MUSEUM'S HISTORIC LOCOMOTIVE IN MUSEUM'S POWELL AVENUE YARD (BOTTOM) AND SOUTHERN RAILWAY BOXCAR ON ACTIVE TRACKAGE (ABOVE). - Heart of Dixie Railroad, Rolling Stock, 1800 Block Powell Avenue, Birmingham, Jefferson County, AL

Transcatheter Heart Valve Selection and Permanent Pacemaker Implantation in Patients With Pre-Existent Right Bundle Branch Block.

PubMed

van Gils, Lennart; Tchetche, Didier; Lhermusier, Thibault; Abawi, Masieh; Dumonteil, Nicolas; Rodriguez Olivares, Ramón; Molina-Martin de Nicolas, Javier; Stella, Pieter R; Carrié, Didier; De Jaegere, Peter P; Van Mieghem, Nicolas M

2017-03-03

Right bundle branch block is an established predictor for new conduction disturbances and need for a permanent pacemaker (PPM) after transcatheter aortic valve replacement. The aim of the study was to evaluate the absolute rates of transcatheter aortic valve replacement related PPM implantations in patients with pre-existent right bundle branch block and categorize for different transcatheter heart valves. We pooled data on 306 transcatheter aortic valve replacement patients from 4 high-volume centers in Europe and selected those with right bundle branch block at baseline without a previously implanted PPM. Logistic regression was used to evaluate whether PPM rate differed among transcatheter heart valves after adjustment for confounders. Mean age was 83±7 years and 63% were male. Median Society of Thoracic Surgeons score was 6.3 (interquartile range, 4.1-10.2). The following transcatheter valve designs were used: Medtronic CoreValve (n=130; Medtronic, Minneapolis, MN); Edwards Sapien XT (ES-XT; n=124) and Edwards Sapien 3 (ES-3; n=32; Edwards Lifesciences, Irvine, CA); and Boston Scientific Lotus (n=20; Boston Scientific Corporation, Marlborough, MA). Overall permanent pacemaker implantation rate post-transcatheter aortic valve replacement was 41%, and per valve design: 75% with Lotus, 46% with CoreValve, 32% with ES-XT, and 34% with ES-3. The indication for PPM implantation was total atrioventricular block in 98% of the cases. Lotus was associated with a higher PPM rate than all other valves. PPM rate did not differ between ES-XT and ES-3. Ventricular paced rhythm at 30-day and 1-year follow-up was present in 81% at 89%, respectively. Right bundle branch block at baseline is associated with a high incidence of PPM implantation for all transcatheter heart valves. PPM rate was highest for Lotus and lowest for ES-XT and ES-3. Pacemaker dependency remained high during follow-up. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Cardiogenic shock

MedlinePlus

... heart rhythm (bradycardia) or problem with the electrical system of the heart (heart block) Cardiogenic shock occurs when ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is ...

Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction.

PubMed

Sanna, M Germana; Vincent, Kevin P; Repetto, Emanuela; Nguyen, Nhan; Brown, Steven J; Abgaryan, Lusine; Riley, Sean W; Leaf, Nora B; Cahalan, Stuart M; Kiosses, William B; Kohno, Yasushi; Brown, Joan Heller; McCulloch, Andrew D; Rosen, Hugh; Gonzalez-Cabrera, Pedro J

2016-01-01

The molecular pharmacology of the G protein-coupled receptors for sphingosine 1-phosphate (S1P) provides important insight into established and new therapeutic targets. A new, potent bitopic S1P3 antagonist, SPM-354, with in vivo activity, has been used, together with S1P3-knockin and S1P3-knockout mice to define the spatial and functional properties of S1P3 in regulating cardiac conduction. We show that S1P3 is a key direct regulator of cardiac rhythm both in vivo and in isolated perfused hearts. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in vivo and S1P in isolated hearts induced a spectrum of cardiac effects, ranging from sinus bradycardia to complete heart block, as measured by a surface electrocardiogram in anesthetized mice and in volume-conducted Langendorff preparations. The agonist effects on complete heart block are absent in S1P3-knockout mice and are reversed in wild-type mice with SPM-354, as characterized and described here. Homologous knockin of S1P3-mCherry is fully functional pharmacologically and is strongly expressed by immunohistochemistry confocal microscopy in Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4 (HCN4)-positive atrioventricular node and His-Purkinje fibers, with relative less expression in the HCN4-positive sinoatrial node. In Langendorff studies, at constant pressure, SPM-354 restored sinus rhythm in S1P-induced complete heart block and fully reversed S1P-mediated bradycardia. S1P3 distribution and function in the mouse ventricular cardiac conduction system suggest a direct mechanism for heart block risk that should be further studied in humans. A richer understanding of receptor and ligand usage in the pacemaker cells of the cardiac system is likely to be useful in understanding ventricular conduction in health, disease, and pharmacology. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Chronic hypertension with subsequent congestive heart failure in a western lowland gorilla (Gorilla gorilla gorilla).

PubMed

Miller, C L; Schwartz, A M; Barnhart, J S; Bell, M D

1999-06-01

Chronic severe subclinical systemic hypertension was diagnosed in a 28-yr-old male western lowland gorilla (Gorilla gorilla gorilla). Thoracic radiography, electrocardiography, and echocardiography revealed an enlarged heart with a hypertrophied left ventricle, mitral regurgitation, and a persistent left bundle branch block. Enalapril, later combined with nifedipine, was of some value in reducing the hypertension, with partial reversal of cardiac enlargement and resolution of the bundle branch block. Two years after initiation of treatment, the gorilla developed lethargy and dyspnea. The diagnosis of heart failure was confirmed under anesthesia; the gorilla did not recover and was euthanized. Postmortem examination confirmed congestive heart failure with chronic, fibrosing cardiomyopathy similar to that in other gorillas.

Newborn infant with maternal anti-SSA antibody-induced complete heart block accompanying cardiomyopathy.

PubMed

Iida, Midori; Inamura, Noboru; Takeuchi, Makoto

2006-01-01

Newborn case of maternal anti-SSA antibody-induced congenital complete heart block (CCHB) accompanying cardiomyopathy is presented. Unexpectedly, she died of ventricular tachycardia, not bradycardia, 6 days after birth. Autopsy revealed left ventricular cardiomyopathy with endocardial fibroelastosis. Thus, when evaluating fetal cardiac performance in cases of maternal anti-SSA antibody-induced CCHB, it is necessary to pay attention to myocardial attributes such as endocardial hyperplasia.

Reversible chronic acquired complete atrioventricular block.

PubMed

Rakovec, P; Milcinski, G; Voga, G; Korsic, L

1982-01-01

The return of atrioventricular conduction is reported in a case after nearly four years of complete acquired heart block. After recovery from atrioventricular block, right bundle branch block persisted, but P-R interval and H-V interval were normal. Three months later a relapse of second degree infranodal atrioventricular block was noted. A short review of similar cases from the literature is given.

High-resolution echocardiography

NASA Technical Reports Server (NTRS)

Nathan, R.

1979-01-01

High resolution computer aided ultrasound system provides two-and three-dimensional images of beating heart from many angles. System provides means for determining whether small blood vessels around the heart are blocked or if heart wall is moving normally without interference of dead and noncontracting muscle tissue.

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management.

PubMed

Baruteau, Alban-Elouen; Pass, Robert H; Thambo, Jean-Benoit; Behaghel, Albin; Le Pennec, Solène; Perdreau, Elodie; Combes, Nicolas; Liberman, Leonardo; McLeod, Christopher J

2016-09-01

Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities. Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for biological pacing are promising research fields. In utero percutaneous pacing appears to be at high risk and needs further development before it can be adopted into routine clinical practice. Cardiac resynchronization therapy is of proven value in case of pacing-induced cardiomyopathy.

Effective Heart Disease Detection Based on Quantitative Computerized Traditional Chinese Medicine Using Representation Based Classifiers.

PubMed

Shu, Ting; Zhang, Bob; Tang, Yuan Yan

2017-01-01

At present, heart disease is the number one cause of death worldwide. Traditionally, heart disease is commonly detected using blood tests, electrocardiogram, cardiac computerized tomography scan, cardiac magnetic resonance imaging, and so on. However, these traditional diagnostic methods are time consuming and/or invasive. In this paper, we propose an effective noninvasive computerized method based on facial images to quantitatively detect heart disease. Specifically, facial key block color features are extracted from facial images and analyzed using the Probabilistic Collaborative Representation Based Classifier. The idea of facial key block color analysis is founded in Traditional Chinese Medicine. A new dataset consisting of 581 heart disease and 581 healthy samples was experimented by the proposed method. In order to optimize the Probabilistic Collaborative Representation Based Classifier, an analysis of its parameters was performed. According to the experimental results, the proposed method obtains the highest accuracy compared with other classifiers and is proven to be effective at heart disease detection.

His bundle electrography

MedlinePlus

... a part of the heart that carries the signals that control the time between heartbeats (contractions). ... through the center of the heart. If these signals are blocked, you will have problems with your ...

Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease. An electrophysiological-pathological correlation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, S.I.; Bharati, S.; Glass, J.

1981-04-01

A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis ofmore » the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.« less

Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease: an electrophysiological-pathological correlation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, S.I.; Bharati, S.; Glass, J.

1981-04-01

A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis ofmore » the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.« less

Fatal Lyme carditis and endodermal heterotopia of the atrioventricular node.

PubMed Central

Cary, N. R.; Fox, B.; Wright, D. J.; Cutler, S. J.; Shapiro, L. M.; Grace, A. A.

1990-01-01

A fatal case of Lyme carditis occurring in a Suffolk farmworker is reported. Post-mortem examination of the heart showed pericarditis, focal myocarditis and prominent endocardial and interstitial fibrosis. The additional finding of endodermal heterotopia ('mesothelioma') of the atrioventricular node raises the possibility that this could also be related to Lyme infection and account for the relatively frequent occurrence of atrioventricular block in this condition. Lyme disease should always be considered in a case of atrioventricular block, particularly in a young patient from a rural area. The heart block tends to improve and therefore only temporary pacing may be required. Images Figure 1 Figure 2 Figure 3 PMID:2349186

Ivabradine vs metoprolol in patients with acute inferior wall myocardial infarction-"Expanding arena for ivabradine".

PubMed

Priti, Kumari; Ranwa, Bhanwar L; Gokhroo, Rajendra K; Kishore, Kamal; Bisht, Devendra Singh; Gupta, Sajal

2017-08-01

Atrioventricular (AV) blocks are of concern with the use of beta blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart rate with a lesser risk of AV blocks. To compare ivabradine with metoprolol in acute inferior wall MI in terms of feasibility, tolerability, and efficacy. It was a prospective double-blind single-center randomized controlled study. Of 1032 patients with acute inferior wall MI, 468 eligible patients were randomized in 1:1 manner to ivabradine (group A) and metoprolol (group B). Intention to treat analysis of 426 patients (group A-232 and group B-232) was performed. The primary endpoint was 30-day incidence of major adverse cardiovascular events including death, reinfarction, complete heart block (CHB), and heart failure. Secondary endpoints included 30 days incidence of recurrent angina, readmission, first- or second-degree AV block, and tachyarrhythmias. Both the drugs decreased the mean heart rate to 62.22±2.95 (group A) vs 62.53±3.59 (group B) beats per minute (P=0.33). Ejection fraction improved in both the groups (5.15±1.93% in group A vs 5.52±2.18% in group B, P=0.065). The two groups did not differ significantly in their primary endpoints in terms of death (group A=1.72% vs group B=1.72%, OR=1.00, 95% CI=0.25-4.05, P=1.00), reinfarction (group A=0.86% vs group B=0.86%, OR=1.00, 95% CI=0.14-7.16, P=1.00), heart failure (group A=4.31% vs group B=2.59%, OR=1.70, 95% CI=0.61-4.75, P=0.31), or CHB (0% vs 2.59%, OR=0.07, 95% CI=0.00-1.34, P=0.08). There were no significant differences in the secondary endpoints of recurrent angina, readmission, and tachyarrhythmias except for more first- and second-degree AV blocks with metoprolol (12.93% vs 2.59%, OR=5.59, 95% CI=2.28-13.72, P=0.0002). Ivabradine is well tolerated and equally effective as metoprolol in acute inferior wall ST elevation myocardial infarction patients for lowering the heart rate with lesser risk of AV blocks. © 2017 John Wiley & Sons Ltd.

Proposal for a new definition of congenital complete atrioventricular block.

PubMed

Brucato, A; Jonzon, A; Friedman, D; Allan, L D; Vignati, G; Gasparini, M; Stein, J I; Montella, S; Michaelsson, M; Buyon, J

2003-01-01

The classic old definition of congenital heart block by Yater (1929) is still generally accepted: 'Heart block established in a young patient. There must be some evidence of the existence of the slow pulse at a fairly early age and absence of a history of any infection which might cause the condition after birth: notably diphtheria, rheumatic fever, chorea and congenital syphilis'. However, other definitions are used. We systematically reviewed 1825 cases from 38 separate studies. We conclude that complete AV blocks detected in utero in the absence of structural abnormalities differ from blocks detected later in life with respect to pathogenesis (they are generally associated with maternal anti-Ro/SSA antibodies), poorer childhood prognosis, increased risk of developing late-onset dilated cardiomyopathy, different maternal clinical features and increased risk of recurrence in future pregnancies. For these reasons we propose a new modern definition of congenital complete AV block which might be acceptable to cardiologists, rheumatologists, pediatricians and obstetricians: 'an AV block is defined as congenital if it is diagnosed in utero, at birth or within the neonatal period (0-27 days after birth)'.

Effect of PFDA on Cardiac Membrane Function.

DTIC Science & Technology

1983-03-01

NO. 3. RECIPIENT’S CATALOG NUMBER AFOS-TR - / .... 4. TITLE (and Subtitle) 5. TVPF nF REPORT & PERIOD COVERED EFFECT OF PFDA ON CARDIAC MEMBRANE...Continue on reverse side II necessary and Identify by block number) Heart, Thyroxine, Triiodothyronine, PFDA 0t C) 20, ABSTRACT (Continue on revereD...eide If neceesary and Identify by block number) LTJ "Yihe in vivo and in vitro heart rates of rats treated with 75 mg/kg PFDA was __j significantly

Anesthetic management of the neonate with congenital complete heart block: a 16-year review.

PubMed

Kussman, Barry D; Madril, Danielle R; Thiagarajan, Ravi R; Walsh, Edward P; Laussen, Peter C

2005-12-01

Anesthesia for patients with complete heart block can be associated with significant hemodynamic instability. The aim of this study is to review our anesthetic experience of neonates with congenital complete heart block (CCHB) who underwent placement of either a temporary epicardial pacing system or a permanent epicardial pacemaker. The anesthetic management of neonates with CCHB who underwent pacemaker placement at a single institution over a 16-year period was reviewed. Twenty-four neonates were identified, 17 with a structurally normal heart (NL) and seven with associated congenital heart defects (CHD). Median (range) gestational age was 36.9 (26-41) weeks, birth weight 2.9 (1.0-4.1) kg, and baseline heart rate 47 (38-80) b.min(-1). A temporary epicardial pacing system was placed in six patients (four CHD, two NL; P = 0.003) following institution of mechanical ventilation and inotropic support for a low cardiac output state, and a permanent epicardial pacemaker was placed in 18 patients. Atropine 0.02 mg.kg(-1) IV prior to induction (n = 5) increased heart rate less than 20%. Intraoperative hypotension was documented in nine neonates, five of seven with CHD and four of 17 with NL (P = 0.02). In four patients (44%) hypotension occurred despite concurrent inotropic support. Intraoperative cardiac arrest occurred in one neonate, necessitating institution of extracorporeal membrane oxygenation. Two patients (8.3%) died in hospital from complex CHD and complications of prematurity. Early institution of mechanical ventilation, inotropic support and pacing are necessary in the neonate with CCHB and poor hemodynamic function, particularly with coexisting CHD or prematurity.

Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart.

PubMed

Liu, G S; Richards, S C; Olsson, R A; Mullane, K; Walsh, R S; Downey, J M

1994-07-01

Agonists selective for the A1 adenosine receptor mimic the protective effect of ischaemic preconditioning against infarction in the rabbit heart. Unselective adenosine antagonists block this protection but, paradoxically, the A1 adenosine receptor selective antagonist 8-cyclopentyl- 1,3-dipropylxanthine (DPCPX) does not. The aim of this study was to test the hypothesis that the newly described A3 adenosine receptor, which has an agonist profile similar to the A1 receptor but is insensitive to DPCPX, might mediate preconditioning. Isolated rabbit hearts perfused with Krebs buffer experienced 30 min of regional ischaemia followed by 120 min of reperfusion. Infarct size was measured by tetrazolium staining. In control hearts infarction was 32.2(SEM 1.5)% of the risk zone. Preconditioning by 5 min ischaemia and 10 min reperfusion reduced infarct size to 8.8(2.3)%. Replacing the regional ischaemia with 5 min perfusion with 10 microM adenosine or 65 nM N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA), an adenosine A3 receptor agonist, was equally protective. The unselective antagonist 8-p-sulphophenyl theophylline at 100 microM abolished protection by preconditioning, adenosine, and APNEA, but 200 nM DPCPX did not block protection by any of the interventions. Likewise the potent but unselective A3 receptor antagonist 8-(4-carboxyethenylphenyl)-1,3-dipropylxanthine (BW A1433) completely blocked protection from ischaemic preconditioning. Because protection against infarction afforded by ischaemic preconditioning, adenosine, or the A3 receptor agonist APNEA could not be blocked by DPCPX and because the potent A3 receptor antagonist BW A1433 blocked protection from ischaemic preconditioning, these data indicate that the protection of preconditioning is not exclusively mediated by the adenosine A1 receptor in rabbit heart and could involve the A3 receptor.

Complications with the MICRA TPS Pacemaker System: Persistent Complete Heart Block and Late Capture Failure.

PubMed

Holm, Niels; Müller, Andreas; Zbinden, Rainer

2017-04-01

A Medtronic MICRA transcatheter pacing system (Medtronic, Minneapolis, MN, USA) was implanted in an 86-year-old patient with sick sinus syndrome and left bundle branch block after transfemoral aortic valve implantation. During implantation she developed a persistent complete heart block due to manipulation with the large-bore delivery catheter. Two weeks later, acute pacemaker dysfunction occurred due to massive increase of pacing threshold and impedance without obvious pacemaker dislocation or myocardial perforation. Recurrent capture failure was seen with pacing output set at 5 V/1.0 ms. Hence, microdislocation or fixation of the tines in the right ventricular trabeculae has to be assumed. © 2016 Wiley Periodicals, Inc.

Heart bypass surgery - series (image)

MedlinePlus

... or more coronary arteries are seriously blocked and blood supply to the heart muscle is insufficient. Several tests are done to identify the cause of the chest pain (angina), such as blood tests and x-ray studies (angiograms).

Absence of Rapid Propagation through the Purkinje Network as a Potential Cause of Line Block in the Human Heart with Left Bundle Branch Block.

PubMed

Okada, Jun-Ichi; Washio, Takumi; Nakagawa, Machiko; Watanabe, Masahiro; Kadooka, Yoshimasa; Kariya, Taro; Yamashita, Hiroshi; Yamada, Yoko; Momomura, Shin-Ichi; Nagai, Ryozo; Hisada, Toshiaki; Sugiura, Seiryo

2018-01-01

Background: Cardiac resynchronization therapy is an effective device therapy for heart failure patients with conduction block. However, a problem with this invasive technique is the nearly 30% of non-responders. A number of studies have reported a functional line of block of cardiac excitation propagation in responders. However, this can only be detected using non-contact endocardial mapping. Further, although the line of block is considered a sign of responders to therapy, the mechanism remains unclear. Methods: Herein, we created two patient-specific heart models with conduction block and simulated the propagation of excitation based on a cellmodel of electrophysiology. In one model with a relatively narrow QRS width (176 ms), we modeled the Purkinje network using a thin endocardial layer with rapid conduction. To reproduce a wider QRS complex (200 ms) in the second model, we eliminated the Purkinje network, and we simulated the endocardial mapping by solving the inverse problem according to the actual mapping system. Results: We successfully observed the line of block using non-contact mapping in the model without the rapid propagation of excitation through the Purkinje network, although the excitation in the wall propagated smoothly. This model of slow conduction also reproduced the characteristic properties of the line of block, including dense isochronal lines and fractionated local electrocardiograms. Further, simulation of ventricular pacing from the lateral wall shifted the location of the line of block. By contrast, in the model with the Purkinje network, propagation of excitation in the endocardial map faithfully followed the actual propagation in the wall, without showing the line of block. Finally, switching the mode of propagation between the two models completely reversed these findings. Conclusions: Our simulation data suggest that the absence of rapid propagation of excitation through the Purkinje network is the major cause of the functional line of block recorded by non-contact endocardial mapping. The line of block can be used to identify responders as these patients loose rapid propagation through the Purkinje network.

[Intermittent left bundle branch block - reversal to normal conduction during general anesthesia].

PubMed

Silva, Ana Maria Oliveira Correia da; Silva, Emília Alexandra Gaspar Lima da

Transient changes in intraoperative cardiac conduction are uncommon. Rare cases of the development or remission of complete left bundle branch block under general and locoregional anesthesia associated with myocardial ischemia, hypertension, tachycardia, and drugs have been reported. Complete left bundle branch block is an important clinical manifestation in some chronic hypertensive patients, which may also be a sign of coronary artery disease, aortic valve disease, or underlying cardiomyopathy. Although usually permanent, it can occur intermittently depending on heart rate (when heart rate exceeds a certain critical value). This is a case of complete left bundle branch block recorded in the preoperative period of urgent surgery that reverted to normal intraoperative conduction under general anesthesia after a decrease in heart rate. It resurfaced, intermittently and in a heart-rate-dependent manner, in the early postoperative period, eventually reverting to normal conduction in a sustained manner during semi-intensive unit monitoring. The test to identify markers of cardiac muscle necrosis was negative. Pain due to the emergency surgical condition and in the early postoperative period may have been the cause of the increase in heart rate up to the critical value, causing blockage. Although the development or remission of this blockade under anesthesia is uncommon, the anesthesiologist should be alert to the possibility of its occurrence. It may be benign; however, the correct diagnosis is very important. The electrocardiographic manifestations may mask or be confused with myocardial ischemia, factors that are especially important in a patient under general anesthesia unable to report the characteristic symptoms of ischemia. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Anesthetic efficacy and heart rate effects of the intraosseous injection of 1.5% etidocaine (1:200,000 epinephrine) after an inferior alveolar nerve block.

PubMed

Stabile, P; Reader, A; Gallatin, E; Beck, M; Weaver, J

2000-04-01

The purpose of this study was to determine the anesthetic efficacy and heart rate effects of an intraosseous (IO) injection of 1.5% etidocaine with 1:200,000 epinephrine after an inferior alveolar nerve block. In a repeated-measures designed study, 48 subjects randomly received 2 combinations of injections at 2 separate appointments. The combinations were an inferior alveolar nerve (IAN) block (with 3% mepivacaine) + IO injection with 1.8 mL of 1.5% etidocaine hydrochloride containing 1:200,000 epinephrine, and an IAN + mock IO injection. The first molar was blindly tested with a pulp tester at 2-minute cycles for 60 minutes after the injection. Anesthesia was considered successful when 2 consecutive 80 readings (no subject response) were obtained. Heart rate (pulse rate) was measured with a pulse oximeter. Lip numbness occurred in 100% of the subjects with both the techniques. For the first molar, anesthetic success for the IAN + mock IO and the IAN + IO etidocaine hydrochloride groups, respectively, were 81% and 100%. The differences were significant (P <.05) when the IAN + IO etidocaine hydrochloride technique was compared with the IAN + mock IO. A mean increase in heart rate of 32 beats/min occurred in 90% of the subjects with the IO injection of the etidocaine hydrochloride solution. In 89% of these subjects, the heart rate returned to within 5 beats of baseline values 4 minutes or less after solution deposition. The IO injection of 1.8 mL of 1.5% etidocaine hydrochloride with 1:200,000 epinephrine, when used to augment an inferior alveolar nerve block, significantly increased anesthetic success in the first molar. The majority of subjects receiving the IO injection of the etidocaine hydrochloride solution had a transient increase in heart rate.

Long-term bradycardia caused by atrioventricular block can remodel the canine heart to detect the histamine H1 blocker terfenadine-induced torsades de pointes arrhythmias.

PubMed

Takahara, Akira; Sugiyama, Atsushi; Ishida, Yuko; Satoh, Yoshioki; Wang, Kai; Nakamura, Yuji; Hashimoto, Keitaro

2006-03-01

Although a second-generation histamine H(1) blocker terfenadine induced torsades de pointes (TdP) arrhythmias in patients via the blockade of a rapid component of delayed rectifier K(+) current (I(Kr)), such action of terfenadine has not been detected in previous animal models. We analysed the potential of the canine persistent atrioventricular block heart, a new in vivo proarrhythmia model, to detect a torsadogenic effect of terfenadine of an oral dose of 3 or 30 mg kg(-1). The doses can provide therapeutic to supra-therapeutic plasma concentrations as an anti-histamine. In 2 weeks of bradycardiac heart model, there were no significant changes in any of the electrocardiogram parameters after the administration of both doses of terfenadine. In 4-6 weeks of bradycardiac heart model, the low dose of terfenadine hardly affected any of the electrocardiogram parameters except that it induced TdP in one out of six animals. The high dose significantly decreased the atrial rate and ventricular rate, prolonged the QT interval, and induced TdP in five out of six animals. Moreover, temporal variability of repolarization increased after the high-dose administration. These results suggest that long-term bradycardia caused by atrioventricular block can remodel the canine heart to detect terfenadine-induced TdP.

Mechanical dispersion is associated with poor outcome in heart failure with a severely depressed left ventricular function and bundle branch blocks.

PubMed

Stankovic, Ivan; Janicijevic, Aleksandra; Dimic, Aleksandra; Stefanovic, Milica; Vidakovic, Radosav; Putnikovic, Biljana; Neskovic, Aleksandar N

2018-03-01

Bundle branch blocks (BBB)-related mechanical dyssynchrony and dispersion may improve patient selection for device therapy, but their effect on the natural history of this patient population is unknown. A total of 155 patients with LVEF ≤ 35% and BBB, not treated with device therapy, were included. Mechanical dyssynchrony was defined as the presence of either septal flash or apical rocking. Contraction duration was assessed as time interval from the electrocardiographic R-(Q-)wave to peak longitudinal strain in each of 17 left ventricular segments. Mechanical dispersion was defined as either the standard deviation of all time intervals (dispersion SD ) or as the difference between the longest and shortest time intervals (dispersion delta ). Patients were followed for cardiac mortality during a median period of 33 months. Mechanical dyssynchrony was not associated with survival. More pronounced mechanical dispersion delta was found in patients with dyssynchrony than in those without. In the multivariate regression analysis, patients' functional class, diabetes mellitus and dispersion delta were independently associated with mortality. Mechanical dispersion, but not dyssynchrony, was independently associated with mortality and it may be useful for risk stratification of patients with heart failure (HF) and BBB. Key Messages Mechanical dispersion, measured by strain echocardiography, is associated with poor outcome in heart failure with a severely depressed left ventricular function and bundle branch blocks. Mechanical dispersion may be useful for risk stratification of patients with heart failure and bundle branch blocks.

Medical Tests and Procedures for Finding and Treating Heart and Blood Vessel Disease

MedlinePlus

... the narrowed or blocked blood vessel. Then the balloon is inflated, opening the narrowed artery. Awire mesh tube, called a stent, may be left in place to help keep the artery open. Angioplasty may be done during a heart attack. There are many medical tests and procedures to find and treat heart ...

Computerized analysis of the 12-lead electrocardiogram to identify epicardial ventricular tachycardia exit sites.

PubMed

Yokokawa, Miki; Jung, Dae Yon; Joseph, Kim K; Hero, Alfred O; Morady, Fred; Bogun, Frank

2014-11-01

Twelve-lead electrocardiogram (ECG) criteria for epicardial ventricular tachycardia (VT) origins have been described. In patients with structural heart disease, the ability to predict an epicardial origin based on QRS morphology is limited and has been investigated only for limited regions in the heart. The purpose of this study was to determine whether a computerized algorithm is able to accurately differentiate epicardial vs endocardial origins of ventricular arrhythmias. Endocardial and epicardial pace-mapping were performed in 43 patients at 3277 sites. The 12-lead ECGs were digitized and analyzed using a mixture of gaussian model (MoG) to assess whether the algorithm was able to identify an epicardial vs endocardial origin of the paced rhythm. The MoG computerized algorithm was compared to algorithms published in prior reports. The computerized algorithm correctly differentiated epicardial vs endocardial pacing sites for 80% of the sites compared to an accuracy of 42% to 66% of other described criteria. The accuracy was higher in patients without structural heart disease than in those with structural heart disease (94% vs 80%, P = .0004) and for right bundle branch block (82%) compared to left bundle branch block morphologies (79%, P = .001). Validation studies showed the accuracy for VT exit sites to be 84%. A computerized algorithm was able to accurately differentiate the majority of epicardial vs endocardial pace-mapping sites. The algorithm is not region specific and performed best in patients without structural heart disease and with VTs having a right bundle branch block morphology. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Fluid Dynamic Characterization of a Polymeric Heart Valve Prototype (Poli-Valve) tested under Continuous and Pulsatile Flow Conditions

PubMed Central

De Gaetano, Francesco; Serrani, Marta; Bagnoli, Paola; Brubert, Jacob; Stasiak, Joanna; Moggridge, Geoff D.; Costantino, Maria Laura

2016-01-01

Introduction Only mechanical and biological heart valve prostheses are currently commercially available. The former show longer durability but require anticoagulant therapy, the latter display better fluid dynamic behaviour but do not have adequate durability. New Polymeric Heart Valves (PHVs) could potentially combine the haemodynamic properties of biological valves with the durability of mechanical valves. This work presents a hydrodynamic evaluation of two groups of newly developed supra-annular tri-leaflet prosthetic heart valves made from styrenic block copolymers (SBC): Poli-Valves. Methods Two types of Poli-Valves made of SBC differing in polystyrene fraction content were tested under continuous and pulsatile flow conditions as prescribed by ISO 5840 Standard. An ad - hoc designed pulse duplicator allowed the valve prototypes to be tested at different flow rates and frequencies. Pressure and flow were recorded; pressure drops, effective orifice area (EOA), and regurgitant volume were computed to assess the valve’s behaviour. Results Both types Poli-Valves met the minimum requirements in terms of regurgitation and EOA as specified by ISO 5840 Standard. Results were compared with five mechanical heart valves (MHVs) and five tissue heart valves (THVs), currently available on the market. Conclusion Based on these results, polymeric heart valves based on styrenic block copolymers, as Poli-Valves are, can be considered as promising alternative for heart valve replacement in near future. PMID:26689146

Interaction between histamine and dichloroisoproterenol, hexamethonium, pempidine, and diphenhydramine, in normal and reserpine-treated heart preparations

PubMed Central

Mannaioni, P. F.

1960-01-01

Histamine stimulated the isolated auricles and heart of the guinea-pig. The effect was best seen in auricles which had been previously depressed by treatment with reserpine. Ganglionic blocking drugs (hexamethonium and pempidine), applied to auricles which had been previously treated with reserpine, abolished the diphasic effect of nicotine, but did not alter the response to histamine. Dichloroisoproterenol did not modify the stimulant action of histamine in isolated auricles, either before or after treatment with reserpine; nor did it alter the response of the isolated heart. Diphenhydramine reduced or blocked the stimulant action of histamine in auricles which had been previously treated with reserpine. The results support the hypothesis that histamine stimulates the myocardium by a direct action on specific receptors. PMID:13766225

Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block

PubMed Central

Hu, Yu-Feng; Dawkins, James Frederick; Cho, Hee Cheol; Marbán, Eduardo; Cingolani, Eugenio

2016-01-01

Somatic reprogramming by reexpression of the embryonic transcription factor T-box 18 (TBX18) converts cardiomyocytes into pacemaker cells. We hypothesized that this could be a viable therapeutic avenue for pacemaker-dependent patients afflicted with device-related complications, and therefore tested whether adenoviral TBX18 gene transfer could create biological pacemaker activity in vivo in a large-animal model of complete heart block. Biological pacemaker activity, originating from the intramyocardial injection site, was evident in TBX18-transduced animals starting at day 2 and persisted for the duration of the study (14 days) with minimal backup electronic pacemaker use. Relative to controls transduced with a reporter gene, TBX18-transduced animals exhibited enhanced autonomic responses and physiologically superior chronotropic support of physical activity. Induced sinoatrial node cells could be identified by their distinctive morphology at the site of injection in TBX18-transduced animals, but not in controls. No local or systemic safety concerns arose. Thus, minimally invasive TBX18 gene transfer creates physiologically relevant pacemaker activity in complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically relevant disease model. PMID:25031269

Mechanism of the cardiovascular activity of dibenzoxazepine in cats.

PubMed

Lundy, P M

1978-04-01

Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.

Machine Learning Algorithm Predicts Cardiac Resynchronization Therapy Outcomes: Lessons From the COMPANION Trial.

PubMed

Kalscheur, Matthew M; Kipp, Ryan T; Tattersall, Matthew C; Mei, Chaoqun; Buhr, Kevin A; DeMets, David L; Field, Michael E; Eckhardt, Lee L; Page, C David

2018-01-01

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in heart failure patients with reduced left ventricular function and intraventricular conduction delay. However, individual outcomes vary significantly. This study sought to use a machine learning algorithm to develop a model to predict outcomes after CRT. Models were developed with machine learning algorithms to predict all-cause mortality or heart failure hospitalization at 12 months post-CRT in the COMPANION trial (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure). The best performing model was developed with the random forest algorithm. The ability of this model to predict all-cause mortality or heart failure hospitalization and all-cause mortality alone was compared with discrimination obtained using a combination of bundle branch block morphology and QRS duration. In the 595 patients with CRT-defibrillator in the COMPANION trial, 105 deaths occurred (median follow-up, 15.7 months). The survival difference across subgroups differentiated by bundle branch block morphology and QRS duration did not reach significance ( P =0.08). The random forest model produced quartiles of patients with an 8-fold difference in survival between those with the highest and lowest predicted probability for events (hazard ratio, 7.96; P <0.0001). The model also discriminated the risk of the composite end point of all-cause mortality or heart failure hospitalization better than subgroups based on bundle branch block morphology and QRS duration. In the COMPANION trial, a machine learning algorithm produced a model that predicted clinical outcomes after CRT. Applied before device implant, this model may better differentiate outcomes over current clinical discriminators and improve shared decision-making with patients. © 2018 American Heart Association, Inc.

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

PubMed Central

Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

2015-01-01

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

Accelerated graft dysfunction in heart transplant patients with persistent atrioventricular conduction block.

PubMed

Lee, William; Tay, Andre; Walker, Bruce D; Kuchar, Dennis L; Hayward, Christopher S; Spratt, Phillip; Subbiah, Rajesh N

2016-12-01

Bradyarrhythmia following heart transplantation is common-∼7.5-24% of patients require permanent pacemaker (PPM) implantation. While overall mortality is similar to their non-paced counterparts, the effects of chronic right ventricular pacing (CRVP) in heart transplant patients have not been studied. We aim to examine the effects of CRVP on heart failure and mortality in heart transplant patients. Records of heart transplant recipients requiring PPM at St Vincent's Hospital, Sydney, Australia between January 1990 and January 2015 were examined. Patient's without a right ventricular (RV) pacing lead or a follow-up time of <1 year were excluded. Patients with pre-existing abnormal left ventricular function (<50%) were analysed separately. Patients were grouped by pacing dependence (100% pacing dependent vs. non-pacing dependent). The primary endpoint was clinical or echocardiographic heart failure (<35%) in the first 5 years post-PPM. Thirty-three of 709 heart transplant recipients were studied. Two patients had complete RV pacing dependence, and the remaining 31 patients had varying degrees of pacing requirement, with an underlying ventricular escape rhythm. The primary endpoint occurred significantly more in the pacing-dependent group; 2 (100%) compared with 2 (6%) of the non pacing dependent group (P < 0.0001 by log-rank analysis, HR = 24.58). Non-pacing-dependent patients had reversible causes for heart failure, unrelated to pacing. In comparison, there was no other cause of heart failure in the pacing-dependent group. Permanent atrioventricular block is rare in the heart transplant population. We have demonstrated CRVP as a potential cause of accelerated graft failure in pacing-dependent heart transplant patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Right bundle branch block as a risk factor for subsequent cardiac events.

DOT National Transportation Integrated Search

1990-08-01

The identification of risk factors for adverse cardiac events is valuable to the certification of airmen. This study examines the importance of right bundle branch block (RBBB) as a risk factor for myocardial infarction (MI), atherosclerotic heart di...

Vasodilators and α-adrenoceptor antagonists in hypertension and heart failure

PubMed Central

Taylor, S. H.

1981-01-01

1 The mechanism of the increase in arteriolar resistance in hypertension and heart failure is differently derived. In hypertension, venous compliance is normal and the concentric narrowing of the arteriolar resistance vessels is `anatomical'; it is not due to increased stimulation or enhanced sensitivity of the vascular smooth muscle. In heart failure narrowing of both the arteriolar resistance and venous capacitance vessels derives predominantly from increased sympathoadrenal stimulation of α1-adrenoceptors in the vascular smooth muscle. 2 Vasodilator drugs which relax vascular smooth muscle differ widely in their site of activity. None are entirely specific for arteries, arterioles or veins, but they may be grouped for therapeutic convenience into those predominantly acting on arterioles (for example hydralazine) and those acting on veins (for example nitrates). 3 Control of the resting blood pressure in stable essential hypertension appears to be equally well achieved with non-specific arteriolar dilators (for example hydralazine, minoxidil, calcium antagonists) as those with specific α1-adrenoceptor blocking properties (for example prazosin, indoramin). Pressure surges due to dynamic exercise and mental stress are little influenced by either category of drug. In contrast, α-adrenoceptor antagonists appear to be capable of partly suppressing increase in ambulatory pressure and the pressor responses to isometric exercise and cold, particularly in patients pre-treated with β-blocking drugs. 4 In acute heart failure, non-selective α-blocking drugs (for example phentolamine) produce an equal reduction in left ventricular filling pressure but greater increase in cardiac output than vasodilator drugs with a more balanced relaxing effect on arterioles and venules. 5 In chronic heart failure, the little information available indicates that non-selective arteriolar dilatation is probably associated with a greater increase in cardiac output lesser reduction in left ventricular filling pressure than with specific α1-adrenoceptor blocking drugs. Attenuation of the initial haemodynamic benefits during extended treatment is common to all vasodilators, including α-adrenoceptor antagonists. 6 α-Adrenoceptor antagonists have yet to be convincingly shown to be haemodynamically superior to drugs with less specific vasodilator activity in the treatment of hypertension and heart failure.

The role of the Na+/Ca2+ exchanger, INa and ICaL in the genesis of dofetilide-induced torsades de pointes in isolated, AV-blocked rabbit hearts

PubMed Central

Farkas, Attila S; Makra, Péter; Csík, Norbert; Orosz, Szabolcs; Shattock, Michael J; Fülöp, Ferenc; Forster, Tamás; Csanády, Miklós; Papp, Julius Gy; Varró, András; Farkas, András

2009-01-01

Background and purpose: The Na+/Ca2+ exchanger (NCX) may contribute to triggered activity and transmural dispersion of repolarization, which are substrates of torsades de pointes (TdP) type arrhythmias. This study examined the effects of selective inhibition of the NCX by SEA0400 on the occurrence of dofetilide-induced TdP. Experimental approach: Effects of SEA0400 (1 µmol·L−1) on dofetilide-induced TdP was studied in isolated, Langendorff-perfused, atrioventricular (AV)-blocked rabbit hearts. To verify the relevance of the model, lidocaine (30 µmol·L−1) and verapamil (750 nmol·L−1) were also tested against dofetilide-induced TdP. Key results: Acute AV block caused a chaotic idioventricular rhythm and strikingly increased beat-to-beat variability of the RR and QT intervals. SEA0400 exaggerated the dofetilide-induced increase in the heart rate-corrected QT interval (QTc) and did not reduce the incidence of dofetilide-induced TdP [100% in the SEA0400 + dofetilide group vs. 75% in the dofetilide (100 nmol·L−1) control]. In the second set of experiments, verapamil further increased the dofetilide-induced QTc prolongation and neither verapamil nor lidocaine reduced the dofetilide-induced increase in the beat-to-beat variability of the QT interval. However, lidocaine decreased and verapamil prevented the development of dofetilide-induced TdP as compared with the dofetilide control (TdP incidence: 13%, 0% and 88% respectively). Conclusions and implications: Na+/Ca2+ exchanger does not contribute to dofetilide-induced TdP, whereas Na+ and Ca2+ channel activity is involved in TdP genesis in isolated, AV-blocked rabbit hearts. Neither QTc prolongation nor an increase in the beat-to-beat variability of the QT interval is a sufficient prerequisite of TdP genesis in rabbit hearts. PMID:19222480

Analgesic effects of maxillary and inferior alveolar nerve blocks in cats undergoing dental extractions.

PubMed

Aguiar, Joana; Chebroux, Alexandre; Martinez-Taboada, Fernando; Leece, Elizabeth A

2015-02-01

The aim of this study was to evaluate the analgesic effects of maxillary and/or inferior alveolar nerve blocks with lidocaine and bupivacaine in cats undergoing dental extractions. Twenty-nine cats were enrolled. Using an adapted composite pain scale, cats were pain scored before the dental procedure and 30 mins, and 1, 2 and 4 h after isoflurane disconnection. Cats were sedated with buprenorphine (20 µg/kg), medetomidine (10 µg/kg) and acepromazine (20 µg/kg) intramuscularly. Anaesthesia was induced using alfaxalone (1-2 mg/kg) intravenously and maintained with isoflurane in oxygen. Each cat was randomly assigned to receive maxillary and/or inferior alveolar nerve blocks or no nerve blocks prior to dental extractions. Each nerve block was performed using lidocaine (0.25 mg/kg) and bupivacaine (0.25 mg/kg). Heart rate, systolic arterial blood pressure, respiratory rate, end tidal carbon dioxide and isoflurane vaporiser settings were recorded 5 mins before and after the dental extractions, and the difference calculated. Group mean differences (mean ± SD) for heart rate (-9.7 ± 10.6 vs 7.6 ± 9.5 beats/min [nerve block vs control group, respectively], P <0.0001), systolic arterial blood pressure (-10.33 ± 18.44 vs 5.21 ± 15.23 mmHg, P = 0.02) and vaporiser settings (-0.2 ± 0.2 vs 0.1 ± 0.4, P = 0.023) were significantly different between groups. The control group had higher postoperative pain scores (median [interquartile range]) at 2 h (3 [1.75-4.00] vs 1 [0-2], P = 0.008) and 4 h (4 [2-6] vs 2 [1-2], P = 0.006) after the dental extractions. Maxillary and inferior alveolar nerve blocks with lidocaine and bupivacaine administered prior to dental extractions resulted in a reduction in heart rate and blood pressure while allowing for a reduction in isoflurane. Cats receiving nerve blocks had lower postoperative pain scores than the group without nerve blocks. © ISFM and AAFP 2014.

Feasibility and safety of adenosine cardiovascular magnetic resonance in patients with MR conditional pacemaker systems at 1.5 Tesla.

PubMed

Klein-Wiele, Oliver; Garmer, Marietta; Urbien, Rhyan; Busch, Martin; Kara, Kaffer; Mateiescu, Serban; Grönemeyer, Dietrich; Schulte-Hermes, Michael; Garbrecht, Marc; Hailer, Birgit

2015-12-22

Cardiovascular Magnetic Resonance (CMR) with adenosine stress is a valuable diagnostic tool in coronary artery disease (CAD). However, despite the development of MR conditional pacemakers CMR is not yet established in clinical routine for pacemaker patients with known or suspected CAD. A possible reason is that adenosine stress perfusion for ischemia detection in CMR has not been studied in patients with cardiac conduction disease requiring pacemaker therapy. Other than under resting conditions it is unclear whether MR safe pacing modes (paused pacing or asynchronous mode) can be applied safely because the effect of adenosine on heart rate is not precisely known in this entity of patients. We investigate for the first time feasibility and safety of adenosine stress CMR in pacemaker patients in clinical routine and evaluate a pacing protocol that considers heart rate changes under adenosine. We retrospectively analyzed CMR scans of 24 consecutive patients with MR conditional pacemakers (mean age 72.1 ± 11.0 years) who underwent CMR in clinical routine for the evaluation of known or suspected CAD. MR protocol included cine imaging, adenosine stress perfusion and late gadolinium enhancement. Pacemaker indications were sinus node dysfunction (n = 18) and second or third degree AV block (n = 6). Under a pacing protocol intended to avoid competitive pacing on the one hand and bradycardia due to AV block on the other no arrhythmia occurred. Pacemaker stimulation was paused to prevent competitive pacing in sinus node dysfunction with resting heart rate >45 bpm. Sympatho-excitatory effect of adenosine led to a significant acceleration of heart rate by 12.3 ± 8.3 bpm (p < 0.001), no bradycardia occurred. On the contrary in AV block heart rate remained constant; asynchronous pacing above resting heart rate did not interfere with intrinsic rhythm. Adenosine stress CMR appears to be feasible and safe in patients with MR conditional pacemakers. Heart rate response to adenosine has to be considered for the choice of pacing modes during CMR.

Fluid dynamic characterization of a polymeric heart valve prototype (Poli-Valve) tested under continuous and pulsatile flow conditions.

PubMed

De Gaetano, Francesco; Serrani, Marta; Bagnoli, Paola; Brubert, Jacob; Stasiak, Joanna; Moggridge, Geoff D; Costantino, Maria Laura

2015-11-01

Only mechanical and biological heart valve prostheses are currently commercially available. The former show longer durability but require anticoagulant therapy; the latter display better fluid dynamic behavior but do not have adequate durability. New Polymeric Heart Valves (PHVs) could potentially combine the hemodynamic properties of biological valves with the durability of mechanical valves. This work presents a hydrodynamic evaluation of 2 groups of newly developed supra-annular, trileaflet prosthetic heart valves made from styrenic block copolymers (SBC): Poli-Valves. 2 types of Poli-Valves made of SBC and differing in polystyrene fraction content were tested under continuous and pulsatile flow conditions as prescribed by ISO 5840 Standard. A pulse duplicator designed ad hoc allowed the valve prototypes to be tested at different flow rates and frequencies. Pressure and flow were recorded; pressure drops, effective orifice area (EOA), and regurgitant volume were computed to assess the behavior of the valve. Both types of Poli-Valves met the minimum requirements in terms of regurgitation and EOA as specified by the ISO 5840 Standard. Results were compared with 5 mechanical heart valves (MHVs) and 5 tissue heart valves (THVs), currently available on the market. Based on these results, PHVs based on styrenic block copolymers, as are Poli-Valves, can be considered a promising alternative for heart valve replacement in the near future.

A Comparison of Efficacy of Segmental Epidural Block versus Spinal Anaesthesia for Percutaneous Nephrolithotomy.

PubMed

Nandanwar, Avinash S; Patil, Yogita; Wagaskar, Vinayak G; Baheti, Vidyasagar H; Tanwar, Harshwardhan V; Patwardhan, Sujata K

2015-08-01

Percutaneous nephrolithotomy (PCNL) is done under general anaesthesia in most of the centres. Associated complications and cost are higher for general anaesthesia than for regional anaesthesia. Present study is designed to compare the efficacy of epidural block versus spinal anaesthesia with regards to intraoperative mean arterial pressure, heart rate, postoperative pain intensity, analgesic requirement, Postoperative complications and patient satisfaction in patients undergoing PCNL. After taking Ethical Committee clearance, patients were randomly allocated into 2 groups using table of randomization (n= 40 each) Group E- Epidural block, Group S- Spinal block. Various parameters like intraoperative mean arterial pressure, heart rate, postoperative pain intensity, analgesic requirement, postoperative complications and patient satisfaction were studied in these groups. Quantitative data was analysed using unpaired t-test and qualitative data was analysed using chi-square test. Twenty four times in Epidural as compared to fifteen times in spinal anaesthesia two or more attempts required. Mean time (min) required to achieve the block of anaesthesia in group E and group S was 15.45±2.8 and 8.52±2.62 min respectively. Mean arterial pressure (MAP) at 5 min, 10 min and 15 min were significantly lower in spinal group as compared to epidural group. After 30 minutes, differences were not significant but still MAP was lower in spinal group. After 30 minutes difference in heart rate between two groups was statistically significant and higher rate recorded in spinal group till the end of 3 hours. Postoperative VAS score was significantly higher in spinal group and 4 hours onwards difference was highly significant. Postoperative Nausea Vomiting (PONV) Score was significantly higher in spinal group as compared to epidural group. For PCNL, segmental epidural block is better than spinal anaesthesia in terms of haemodynamic stability, postoperative analgesia, patient satisfaction and reduced incidence of PONV. Epidural anaesthesia is difficult to execute and takes longer time to act as compared to spinal block which limits its use.

Effects of HRV-Guided vs. Predetermined Block Training on Performance, HRV and Serum Hormones.

PubMed

Nuuttila, Olli-Pekka; Nikander, Aku; Polomoshnov, Dmitry; Laukkanen, Jari Antero; Häkkinen, Keijo

2017-11-01

The aim of this study was to compare heart rate variability -guided (HRVG) and predetermined (PD) block periodization of high intensity aerobic training (HIT). Endurance performance, neuromuscular performance, heart rate variability (HRV) and serum hormone concentrations were measured before, in the middle and after the 8-week training period in 24 endurance trained males. Both groups improved significantly maximal treadmill velocity (V max ) (p<0.001) and 3000 m running performance (HRVG; p<0.001 and PD; p=0.001). The relative changes in V max and countermovement jump were significantly greater in HRVG (p<0.05). Nocturnal heart rate decreased in both groups (p<0.01), but HRV (RMSSD, LF and TP) increased significantly only in HRVG (p<0.05). The significant increase in serum testosterone concentration was observed from mid to post in HRVG (p<0.05). Significant correlations were found between individual V max changes and absolute serum testosterone levels. Individual baseline level of HF correlated significantly with V max changes in PD. Block periodization of HIT seems to be an effective way to improve endurance and running performance in already endurance trained males. Based on training induced increases in endurance and neuromuscular performance combined with significant changes in HRV and serum testosterone levels observed in HRVG, individually HRV -guided block training may be more optimal compared to predetermined training. © Georg Thieme Verlag KG Stuttgart · New York.

Efficacy and Safety of a Lidocaine and Ropivacaine Mixture for Scalp Nerve Block and Local Infiltration Anesthesia in Patients Undergoing Awake Craniotomy.

PubMed

Chaki, Tomohiro; Sugino, Shigekazu; Janicki, Piotr K; Ishioka, Yoshiya; Hatakeyama, Yosuke; Hayase, Tomo; Kaneuchi-Yamashita, Miki; Kohri, Naonori; Yamakage, Michiaki

2016-01-01

Mixtures of various local anesthetics, such as lidocaine and ropivacaine, have been widely used. However, their efficacy and safety for scalp nerve blocks and local infiltration during awake craniotomy have not been fully elucidated. We prospectively investigated 53 patients who underwent awake craniotomy. Scalp block was performed for the blockade of the supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, greater occipital, and lesser occipital nerves with a mixture containing equal volumes of 2% lidocaine and 0.75% ropivacaine, including 5 μg/mL of epinephrine. Infiltration anesthesia was applied at the site of skin incision using the same mixture. The study outcomes included changes in heart rate and blood pressure after head pinning and skin incision, and incidence of severe pain on emergence from anesthesia. Total doses and plasma concentrations of lidocaine and ropivacaine were measured at different time points after performing the block. The heart rate and blood pressure after head pinning were marginally, but significantly, increased when compared with baseline values. There were no significant differences in heart rate and blood pressure before and after the skin incision. Nineteen percent of the patients (10/53) complained of incisional pain at emergence from anesthesia. The highest observed blood concentrations of lidocaine and ropivacaine were 1.9±0.9 and 1.1±0.4 μg/mL, respectively. No acute anesthetic toxicity symptom was observed. Scalp block with a mixture of lidocaine and ropivacaine seems to provide effective and safe anesthetic management in patients undergoing awake craniotomy.

Complete Atrioventricular Block Complicating Mitral Infective Endocarditis Caused by Streptococcus Agalactiae.

PubMed

Arai, Masaru; Nagashima, Koichi; Kato, Mahoto; Akutsu, Naotaka; Hayase, Misa; Ogura, Kanako; Iwasawa, Yukino; Aizawa, Yoshihiro; Saito, Yuki; Okumura, Yasuo; Nishimaki, Haruna; Masuda, Shinobu; Hirayama, Astushi

2016-09-08

BACKGROUND Infective endocarditis (IE) involving the mitral valve can but rarely lead to complete atrioventricular block (CAVB). CASE REPORT A 74-year-old man with a history of infective endocarditis caused by Streptococcus gordonii (S. gordonii) presented to our emergency room with fever and loss of appetite, which had lasted for 5 days. On admission, results of serologic tests pointed to severe infection. Electrocardiography showed normal sinus rhythm with first-degree atrioventricular block and incomplete right bundle branch block, and transthoracic echocardiography and transesophageal echocardiography revealed severe mitral regurgitation caused by posterior leaflet perforation and 2 vegetations (5 mm and 6 mm) on the tricuspid valve. The patient was initially treated with ceftriaxone and gentamycin because blood and cutaneous ulcer cultures yielded S. agalactiae. On hospital day 2, however, sudden CAVB requiring transvenous pacing occurred, and the patient's heart failure and infection worsened. Although an emergent surgery is strongly recommended, even in patients with uncontrolled heart failure or infection, surgery was not performed because of the Child-Pugh class B liver cirrhosis. Despite intensive therapy, the patient's condition further deteriorated, and he died on hospital day 16. On postmortem examination, a 2×1-cm vegetation was seen on the perforated posterior mitral leaflet, and the infection had extended to the interventricular septum. Histologic examination revealed extensive necrosis of the AV node. CONCLUSIONS This rare case of CAVB resulting from S. agalactiae IE points to the fact that in monitoring patients with IE involving the mitral valve, clinicians should be aware of the potential for perivalvular extension of the infection, which can lead to fatal heart block.

Hypotension and AV block after diesel exhaust exposure in heart failure-prone rats: role of gaseous and particulate components

EPA Science Inventory

Acute inhalations ofdiesel engine exhaust (DE) and fine particulate matter (PM2.5) have been demonstrated to provoke adverse cardiac events in humans with preexisting heart disease. Electrophysiologic dysfunction and autonomic imbalance are among the mechanisms widely held to und...

Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications

PubMed Central

Gay, Maresha S.; Li, Yong; Xiong, Fuxia; Lin, Thant; Zhang, Lubo

2015-01-01

The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1), 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA) blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner. PMID:25923220

Clinical and electrocardiographic presentations of transient trifascicular block in three cats.

PubMed

Oxford, Eva M; Giacomazzi, Flavia B; Moïse, N Sydney; Santilli, Roberto A

2018-06-01

This report describes transient trifascicular block in three cats presented with lethargy and inappetence, and elevated cardiac troponin I concentrations. The electrocardiogram (ECG) of cat 1 showed a sinus rhythm with pronounced first-degree atrioventricular (AV) block, right bundle branch block, and left anterior fascicular block. The ECG of cat 2 showed truncular left bundle branch block alternating with left anterior fascicular block coupled with prolonged PR intervals, second-degree heart block, and paroxysmal third-degree AV block. The ECG of cat 3 showed first-degree AV block with concomitant right bundle branch block. The diagnosis of trifascicular block was made when paroxysmal third-degree AV block was documented. All cats recovered with medical management within weeks. Each cat resumed a sinus rhythm. Elevated cardiac troponin I concentrations suggested myocarditis that improved. Copyright © 2018 Elsevier B.V. All rights reserved.

Naval Air Development Center Medical Standards for Research Subjects Exposed to Hazardous Aerospace Environments

DTIC Science & Technology

1991-02-01

evidence of isolated hypertrophy compatible with athletic training. c. Left or right bundle branch block. d. Wolff - Parkinson - White or other pre-excitation... syndrome . e. Second or third-degree heart block. (Atrio-ventricular dissociation post-stress is not necessarily disqualifying.) f. QT-prolongation (QTc

Transvenous demand Pacemaker Treatment for intermittent complete Heart Block in a Cat.

PubMed

Forterre, S; Nürnberg, J H; Forterre, F; Skrodzki, M; Lange, P E

2001-11-01

A 13-year-old male neutered domestic shorthaired cat had repeated syncopal episodes over a 6 month period, which had variable duration and continued to increase in frequency. Intermittent ventricular asystole, due to complete heart block, and hyperthyroidism were documented. As the syncopal episodes did not respond to a 4-week medical treatment and symptoms became severe, a transvenous ventricular demand pacemaker system (VVIM) was implanted via the external jugular vein. The unipolar lead was tunneled subcutaneously and connected with the generator in a preformed ventral abdominal muscle pocket. During follow up of 18-months there were no recurrences of the syncopal episodes.

Earlier Right Ventricular Pacing in Cardiac Resynchronization Therapy for a Patient with Right Axis Deviation.

PubMed

Hattori, Yusuke; Ishibashi, Kohei; Noda, Takashi; Okamura, Hideo; Kanzaki, Hideaki; Anzai, Toshihisa; Yasuda, Satoshi; Kusano, Kengo

2017-09-01

We describe the case of a 37-year-old woman who presented with complete right bundle branch block and right axis deviation. She was admitted to our hospital due to severe heart failure and was dependent on inotropic agents. Cardiac resynchronization therapy was initiated but did not improve her condition. After the optimization of the pacing timing, we performed earlier right ventricular pacing, which led to an improvement of her heart failure. Earlier right ventricular pacing should be considered in patients with complete right bundle branch block and right axis deviation when cardiac resynchronization therapy is not effective.

To beta block or not to beta block; that is the question.

PubMed

Ince, Can

2015-09-24

The fast-acting β-1 blocker esmolol has been the center of attention since the landmark article by Morrelli and colleagues suggesting that, in patients with sepsis, reducing heart rate by administering esmolol can result in a survival benefit. However, the use of esmolol for the treatment of sepsis and the underlying mechanism responsible for this benefit remain controversial. This commentary discusses the study by Jacquet-Lagrèze and colleagues, who in a pig model of sepsis tested the hypothesis that administration of esmolol to reduce heart rate may correct sepsis-induced sublingual and gut microcirculatory alterations which are known to be associated with adverse outcome.

Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I.

PubMed

Kruse, Martin; Schulze-Bahr, Eric; Corfield, Valerie; Beckmann, Alf; Stallmeyer, Birgit; Kurtbay, Güven; Ohmert, Iris; Schulze-Bahr, Ellen; Brink, Paul; Pongs, Olaf

2009-09-01

Progressive familial heart block type I (PFHBI) is a progressive cardiac bundle branch disease in the His-Purkinje system that exhibits autosomal-dominant inheritance. In 3 branches of a large South African Afrikaner pedigree with an autosomal-dominant form of PFHBI, we identified the mutation c.19G-->A in the transient receptor potential cation channel, subfamily M, member 4 gene (TRPM4) at chromosomal locus 19q13.3. This mutation predicted the amino acid substitution p.E7K in the TRPM4 amino terminus. TRPM4 encodes a Ca2+-activated nonselective cation (CAN) channel that belongs to the transient receptor potential melastatin ion channel family. Quantitative analysis of TRPM4 mRNA content in human cardiac tissue showed the highest expression level in Purkinje fibers. Cellular expression studies showed that the c.19G-->A missense mutation attenuated deSUMOylation of the TRPM4 channel. The resulting constitutive SUMOylation of the mutant TRPM4 channel impaired endocytosis and led to elevated TRPM4 channel density at the cell surface. Our data therefore revealed a gain-of-function mechanism underlying this type of familial heart block.

Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I

PubMed Central

Kruse, Martin; Schulze-Bahr, Eric; Corfield, Valerie; Beckmann, Alf; Stallmeyer, Birgit; Kurtbay, Güven; Ohmert, Iris; Schulze-Bahr, Ellen; Brink, Paul; Pongs, Olaf

2009-01-01

Progressive familial heart block type I (PFHBI) is a progressive cardiac bundle branch disease in the His-Purkinje system that exhibits autosomal-dominant inheritance. In 3 branches of a large South African Afrikaner pedigree with an autosomal-dominant form of PFHBI, we identified the mutation c.19G→A in the transient receptor potential cation channel, subfamily M, member 4 gene (TRPM4) at chromosomal locus 19q13.3. This mutation predicted the amino acid substitution p.E7K in the TRPM4 amino terminus. TRPM4 encodes a Ca2+-activated nonselective cation (CAN) channel that belongs to the transient receptor potential melastatin ion channel family. Quantitative analysis of TRPM4 mRNA content in human cardiac tissue showed the highest expression level in Purkinje fibers. Cellular expression studies showed that the c.19G→A missense mutation attenuated deSUMOylation of the TRPM4 channel. The resulting constitutive SUMOylation of the mutant TRPM4 channel impaired endocytosis and led to elevated TRPM4 channel density at the cell surface. Our data therefore revealed a gain-of-function mechanism underlying this type of familial heart block. PMID:19726882

Molecular analysis of the Na+ channel blocking actions of the novel class I anti-arrhythmic agent RSD 921

PubMed Central

Pugsley, Michael K; Goldin, Alan L

1999-01-01

RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xenopus laevis oocytes were examined using a two-electrode voltage clamp.RSD 921 produced similarly potent tonic block of all three wild-type channel isoforms, with EC50 values between 35 and 47 μM, whereas the EC50 for block of the IFMQ3 mutant channel was 110±5.5 μM.Block of Na+ channels by RSD 921 was concentration and use-dependent, with marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle, wild-type neuronal and IFMQ3 mutant channels.RSD 921 produced a minimal hyperpolarizing shift in the steady-state voltage-dependence of inactivation of all three wild-type channel isoforms.Open channel block of the IFMQ3 mutant channel was best fit with a first order blocking scheme with kon equal to 0.11±0.012×106 M−1 s−1 and koff equal to 12.5±2.5 s−1, resulting in KD of 117±31 μM. Recovery from open channel block occurred with a time constant of 14±2.7 s−1.These results suggest that RSD 921 preferentially interacts with the open state of the Na+ channel, and that the drug may produce potent local anaesthetic or anti-arrhythmic action under conditions of shortened action potentials, such as during anoxia or ischaemia. PMID:10369450

Molecular analysis of the Na+ channel blocking actions of the novel class I anti-arrhythmic agent RSD 921.

PubMed

Pugsley, M K; Goldin, A L

1999-05-01

RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xenopus laevis oocytes were examined using a two-electrode voltage clamp. RSD 921 produced similarly potent tonic block of all three wild-type channel isoforms, with EC50 values between 35 and 47 microM, whereas the EC50 for block of the IFMQ3 mutant channel was 110+5.5 microM. Block of Na+ channels by RSD 921 was concentration and use-dependent, with marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle, wild-type neuronal and IFMQ3 mutant channels. RSD 921 produced a minimal hyperpolarizing shift in the steady-state voltage-dependence of inactivation of all three wild-type channel isoforms. Open channel block of the IFMQ3 mutant channel was best fit with a first order blocking scheme with k(on) equal to 0.11+/-0.012x10(6) M(-1) s(-1) and k(off) equal to 12.5+/-2.5 s(-1), resulting in KD of 117+/-31 microM. Recovery from open channel block occurred with a time constant of 14+/-2.7 s(-1). These results suggest that RSD 921 preferentially interacts with the open state of the Na+ channel, and that the drug may produce potent local anaesthetic or anti-arrhythmic action under conditions of shortened action potentials, such as during anoxia or ischaemia.

Transport stress induces heart damage in newly hatched chicks via blocking the cytoprotective heat shock response and augmenting nitric oxide production.

PubMed

Sun, F; Zuo, Y-Z; Ge, J; Xia, J; Li, X-N; Lin, J; Zhang, C; Xu, H-L; Li, J-L

2018-04-20

Transport stress affects the animal's metabolism and psychological state. As a pro-survival pathway, the heat shock response (HSR) protects healthy cells from stressors. However, it is unclear whether the HSR plays a role in transport stress-induced heart damage. To evaluate the effects of transport stress on heart damage and HSR protection, newly hatched chicks were treated with transport stress for 2 h, 4 h and 8 h. Transport stress caused decreases in body weight and increases in serum creatine kinase (CK) activity, nitric oxide (NO) content in heart tissue, cardiac nitric oxide syntheses (NOS) activity and NOS isoforms transcription. The mRNA expression of heat shock factors (HSFs, including HSF1-3) and heat shock proteins (HSPs, including HSP25, HSP40, HSP47, HSP60, HSP70, HSP90 and HSP110) in the heart of 2 h transport-treated chicks was upregulated. After 8 h of transport stress in chicks, the transcription levels of the same HSPs and HSF2 were reduced in the heart. It was also found that the changes in the HSP60, HSP70 and HSP90 protein levels had similar tendencies. These results suggested that transport stress augmented NO generation through enhancing the activity of NOS and the transcription of NOS isoforms. Therefore, this study provides new evidence that transport stress induces heart damage in the newly hatched chicks by blocking the cytoprotective HSR and augmenting NO production.

Complete Atrioventricular Block Complicating Mitral Infective Endocarditis Caused by Streptococcus Agalactiae

PubMed Central

Arai, Masaru; Nagashima, Koichi; Kato, Mahoto; Akutsu, Naotaka; Hayase, Misa; Ogura, Kanako; Iwasawa, Yukino; Aizawa, Yoshihiro; Saito, Yuki; Okumura, Yasuo; Nishimaki, Haruna; Masuda, Shinobu; Hirayama, Atsushi

2016-01-01

Patient: Male, 74 Final Diagnosis: Infective endocarditis Symptoms: Apetite loss • fever Medication: — Clinical Procedure: Transesophageal echocardiography Specialty: Cardiology Objective: Rare co-existance of disease or pathology Background: Infective endocarditis (IE) involving the mitral valve can but rarely lead to complete atrioventricular block (CAVB). Case Report: A 74-year-old man with a history of infective endocarditis caused by Streptococcus gordonii (S. gordonii) presented to our emergency room with fever and loss of appetite, which had lasted for 5 days. On admission, results of serologic tests pointed to severe infection. Electrocardiography showed normal sinus rhythm with first-degree atrioventricular block and incomplete right bundle branch block, and transthoracic echocardiography and transesophageal echocardiography revealed severe mitral regurgitation caused by posterior leaflet perforation and 2 vegetations (5 mm and 6 mm) on the tricuspid valve. The patient was initially treated with ceftriaxone and gentamycin because blood and cutaneous ulcer cultures yielded S. agalactiae. On hospital day 2, however, sudden CAVB requiring transvenous pacing occurred, and the patient’s heart failure and infection worsened. Although an emergent surgery is strongly recommended, even in patients with uncontrolled heart failure or infection, surgery was not performed because of the Child-Pugh class B liver cirrhosis. Despite intensive therapy, the patient’s condition further deteriorated, and he died on hospital day 16. On postmortem examination, a 2×1-cm vegetation was seen on the perforated posterior mitral leaflet, and the infection had extended to the interventricular septum. Histologic examination revealed extensive necrosis of the AV node. Conclusions: This rare case of CAVB resulting from S. agalactiae IE points to the fact that in monitoring patients with IE involving the mitral valve, clinicians should be aware of the potential for perivalvular extension of the infection, which can lead to fatal heart block. PMID:27604147

Targeting Inflammation in Heart Failure with Histone Deacetylase Inhibitors

PubMed Central

McKinsey, Timothy A

2011-01-01

Cardiovascular insults such as myocardial infarction and chronic hypertension can trigger the heart to undergo a remodeling process characterized by myocyte hypertrophy, myocyte death and fibrosis, often resulting in impaired cardiac function and heart failure. Pathological cardiac remodeling is associated with inflammation, and therapeutic approaches targeting inflammatory cascades have shown promise in patients with heart failure. Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models, suggesting unforeseen potential for this class of compounds for the treatment of heart failure. In addition to their beneficial effects on myocardial cells, HDAC inhibitors have potent antiinflammatory actions. This review highlights the roles of HDACs in the heart and the potential for using HDAC inhibitors as broad-based immunomodulators for the treatment of human heart failure. PMID:21267510

Blood pressure response to combined general anaesthesia/interscalene brachial plexus block for outpatient shoulder arthroscopy.

PubMed

Janssen, Hauke; Stosch, Roland von; Pöschl, Rupert; Büttner, Benedikt; Bauer, Martin; Hinz, José Maria; Bergmann, Ingo

2014-01-01

Shoulder surgery is often performed in the beach-chair position, a position associated with arterial hypotension and subsequent risk of cerebral ischaemia. It can be performed under general anaesthesia or with an interscalene brachial plexus block, each of which has specific advantages but also specific negative effects on blood pressure control. It would be worthwhile to combine the advantages of the two, but the effects of the combination on the circulation are not well investigated. We studied blood pressure, heart rate, and incidence of adverse circulatory events in patients undergoing shoulder surgery in general anaesthesia with or without an interscalene block. Prospective, randomised, blinded study in outpatients (age 18 to 80 years) undergoing shoulder arthroscopy. General anaesthesia was with propofol/opioid, interscalene block with 40 ml 1% mepivacaine. Hypotension requiring treatment was defined as a mean arterial pressure <60 mmHg or a systolic pressure <80% of baseline; relevant bradycardia was a heart rate <50 bpm with a decrease in blood pressure. Forty-two patients had general anaesthesia alone, 41 had general anaesthesia plus interscalene block. The average systolic blood pressure under anaesthesia in the beach-chair position was 114 ± 7.3 vs. 116 ± 8.3 mmHg (p = 0.09; all comparisons General vs. General-Regional). The incidence of a mean arterial pressure under 60 mmHg or a decrease in systolic pressure of more than 20% from baseline was 64% vs. 76% (p = 0.45). The number of patients with a heart rate lower than 50 and a concomitant blood pressure decrease was 8 vs. 5 (p = 0.30). One can safely combine interscalene block with general anaesthesia for surgery in the beach-chair position in ASA I and II patients. DRKS00005295.

Central α- and β-adrenoceptors modifying arterial blood pressure and heart rate in conscious cats

PubMed Central

Day, M.D.; Roach, A.G.

1974-01-01

1 In conscious unrestrained cats noradrenaline, α-methylnoradrenaline and clonidine, infused into the lateral cerebral ventricles (i.c.v.) caused dose-related falls in blood pressure and heart rate; both effects were abolished after i.c.v. phentolamine. 2 In 12 out of 20 cats, i.c.v. isoprenaline and salbutamol when given caused dose-related pressor responses and tachycardias. These effects were abolished after i.c.v. β-adrenoceptor blocking drugs but were unaffected by α-adrenoceptor blocking agents. 3 In 5 out of 20 cats, i.c.v. isoprenaline regularly produced dose-related falls in blood pressure with associated tachycardias; both effects were abolished after i.c.v. β-adrenoceptor blocking agents. 4 Intracerebroventricular dopamine produced cardiovascular responses which were qualitatively similar to those produced by i.c.v. isoprenaline. 5 Intracerebroventricular adrenaline produced complex responses in untreated animals but typical α-effects were obtained after prior i.c.v. treatment with a β-adrenoceptor blocking agent and typical β-effects after i.c.v. pretreatment with an α-adrenoceptor blocking agent. 6 The cardiovascular changes produced by i.c.v. β-adrenoceptor agonists were abolished after systemic administration of hexamethonium or bethanidine. 7 The results are discussed in the light of the mode of action of β-adrenoceptor stimulants and β-adrenoceptor blocking agents in the treatment of hypertension. PMID:4451747

HeartSaver: a mobile cardiac monitoring system for auto-detection of atrial fibrillation, myocardial infarction, and atrio-ventricular block.

PubMed

Sankari, Ziad; Adeli, Hojjat

2011-04-01

A mobile medical device, dubbed HeartSaver, is developed for real-time monitoring of a patient's electrocardiogram (ECG) and automatic detection of several cardiac pathologies, including atrial fibrillation, myocardial infarction and atrio-ventricular block. HeartSaver is based on adroit integration of four different modern technologies: electronics, wireless communication, computer, and information technologies in the service of medicine. The physical device consists of four modules: sensor and ECG processing unit, a microcontroller, a link between the microcontroller and the cell phone, and mobile software associated with the system. HeartSaver includes automated cardiac pathology detection algorithms. These algorithms are simple enough to be implemented on a low-cost, limited-power microcontroller but powerful enough to detect the relevant cardiac pathologies. When an abnormality is detected, the microcontroller sends a signal to a cell phone. This operation triggers an application software on the cell phone that sends a text message transmitting information about patient's physiological condition and location promptly to a physician or a guardian. HeartSaver can be used by millions of cardiac patients with the potential to transform the cardiac diagnosis, care, and treatment and save thousands of lives. Copyright © 2011 Elsevier Ltd. All rights reserved.

Humoral regulation of heart rate during digestion in pythons (Python molurus and Python regius).

PubMed

Enok, Sanne; Simonsen, Lasse Stærdal; Pedersen, Signe Vesterskov; Wang, Tobias; Skovgaard, Nini

2012-05-15

Pythons exhibit a doubling of heart rate when metabolism increases several times during digestion. Pythons, therefore, represent a promising model organism to study autonomic cardiovascular regulation during the postprandial state, and previous studies show that the postprandial tachycardia is governed by a release of vagal tone as well as a pronounced stimulation from nonadrenergic, noncholinergic (NANC) factors. Here we show that infusion of plasma from digesting donor pythons elicit a marked tachycardia in fasting snakes, demonstrating that the NANC factor resides in the blood. Injections of the gastrin and cholecystokinin receptor antagonist proglumide had no effect on double-blocked heart rate or blood pressure. Histamine has been recognized as a NANC factor in the early postprandial period in pythons, but the mechanism of its release has not been identified. Mast cells represent the largest repository of histamine in vertebrates, and it has been speculated that mast cells release histamine during digestion. Treatment with the mast cell stabilizer cromolyn significantly reduced postprandial heart rate in pythons compared with an untreated group but did not affect double-blocked heart rate. While this study indicates that histamine induces postprandial tachycardia in pythons, its release during digestion is not stimulated by gastrin or cholecystokinin nor is its release from mast cells a stimulant of postprandial tachycardia.

Suppression of class I and II histone deacetylases blunts pressure-overload cardiac hypertrophy.

PubMed

Kong, Yongli; Tannous, Paul; Lu, Guangrong; Berenji, Kambeez; Rothermel, Beverly A; Olson, Eric N; Hill, Joseph A

2006-06-06

Recent work has demonstrated the importance of chromatin remodeling, especially histone acetylation, in the control of gene expression in the heart. In cell culture models of cardiac hypertrophy, pharmacological suppression of histone deacetylases (HDACs) can either blunt or amplify cell growth. Thus, HDAC inhibitors hold promise as potential therapeutic agents in hypertrophic heart disease. In the present investigation, we studied 2 broad-spectrum HDAC inhibitors in a physiologically relevant banding model of hypertrophy, observing dose-responsive suppression of ventricular growth that was well tolerated in terms of both clinical outcome and cardiac performance measures. In both short-term (3-week) and long-term (9-week) trials, cardiomyocyte growth was blocked by HDAC inhibition, with no evidence of cell death or apoptosis. Fibrotic change was diminished in hearts treated with HDAC inhibitors, and collagen synthesis in isolated cardiac fibroblasts was blocked. Preservation of systolic function in the setting of blunted hypertrophic growth was documented by echocardiography and by invasive pressure measurements. The hypertrophy-associated switch of adult and fetal isoforms of myosin heavy chain expression was attenuated, which likely contributed to the observed preservation of systolic function in HDAC inhibitor-treated hearts. Together, these data suggest that HDAC inhibition is a viable therapeutic strategy that holds promise in the treatment of load-induced heart disease.

Quality of Care Provided by Physician’s Extenders in Air Force Primary Medicine Clinics.

DTIC Science & Technology

1980-01-01

WITHOUT 214 ARRHYTHMIAS OR HEART BLOCK GASTROENTERITIS :634 HEART MURMUR [ 11 13. 15 MEASLES. MUMPS, CHICKEN POX 213. 215. 217 OTHER HEART DISEASES 01...mumps, chicken pox 8 11 7 16 Hepatitis or exposure to hepatitis 11 8 4 17 Infectious mononucleosis 1 15 2 *4 Gonorrhea (or exposure to gonorrhea) 17 28...Operation of the New Mexico Experimental Medical Care Review Organization," Medical Care 14 (Supplement 9), December 1976. Daniels, M., and S. A

A Comparison of Efficacy of Segmental Epidural Block versus Spinal Anaesthesia for Percutaneous Nephrolithotomy

PubMed Central

Nandanwar, Avinash S; Patil, Yogita; Baheti, Vidyasagar H.; Tanwar, Harshwardhan V.; Patwardhan, Sujata K.

2015-01-01

Introduction Percutaneous nephrolithotomy (PCNL) is done under general anaesthesia in most of the centres. Associated complications and cost are higher for general anaesthesia than for regional anaesthesia. Present study is designed to compare the efficacy of epidural block versus spinal anaesthesia with regards to intraoperative mean arterial pressure, heart rate, postoperative pain intensity, analgesic requirement, Postoperative complications and patient satisfaction in patients undergoing PCNL. Materials and Methods After taking Ethical Committee clearance, patients were randomly allocated into 2 groups using table of randomization (n= 40 each) Group E- Epidural block, Group S- Spinal block. Various parameters like intraoperative mean arterial pressure, heart rate, postoperative pain intensity, analgesic requirement, postoperative complications and patient satisfaction were studied in these groups. Statistical Analysis Quantitative data was analysed using unpaired t-test and qualitative data was analysed using chi-square test. Results Twenty four times in Epidural as compared to fifteen times in spinal anaesthesia two or more attempts required. Mean time (min) required to achieve the block of anaesthesia in group E and group S was 15.45±2.8 and 8.52±2.62 min respectively. Mean arterial pressure (MAP) at 5 min, 10 min and 15 min were significantly lower in spinal group as compared to epidural group. After 30 minutes, differences were not significant but still MAP was lower in spinal group. After 30 minutes difference in heart rate between two groups was statistically significant and higher rate recorded in spinal group till the end of 3 hours. Postoperative VAS score was significantly higher in spinal group and 4 hours onwards difference was highly significant. Postoperative Nausea Vomiting (PONV) Score was significantly higher in spinal group as compared to epidural group. Conclusion For PCNL, segmental epidural block is better than spinal anaesthesia in terms of haemodynamic stability, postoperative analgesia, patient satisfaction and reduced incidence of PONV. Epidural anaesthesia is difficult to execute and takes longer time to act as compared to spinal block which limits its use. PMID:26436021

[Effectiveness of Sacral Intervertebral Epidural Block for Umbilical Hernia Repair in Children].

PubMed

Nagamine, Norimitsu; Furuya, Atsushi; Suzuki, Sho; Kondo, Satoko; Kiuchi, Riko; Suzuki, Satomi; Nonaka, Akihiko

2015-02-01

Effectiveness of sacral intervertebral epidural block (S 2-3 block) for umbilical hernia repair has not been clarified. We investigate 24 children, undergoing umbilical hernia repair; mean age of 3 years (age range: 20-65 months). Under general anesthesia, epidural block was performed at S 2-3 interspace with 1 ml x kg(-1) ropivacaine (0.2%) at injecting rate of 1 ml x sec(-1) followed by 0.25 ml x kg(-1) normal saline. In all cases, neither systolic blood pressure nor heart rate increased > 15% from those just before the block. Postoperative analgesics were given in 6 patients (25%) rectally. Mean time between the block and the administration of analgesic was 10.5 hours. S 2-3 block can be effective for postoperative pain in umbilical hernia repair.

Lyme carditis with isolated left bundle branch block and myocarditis successfully treated with oral doxycycline.

PubMed

Cunha, Burke A; Elyasi, Maekal; Singh, Prince; Jimada, Ismail

2018-01-01

Lyme disease may present with a variety of cardiac manifestations ranging from first degree to third degree heart block. Cardiac involvement with Lyme disease may be asymptomatic, or symptomatic. Atrioventrical conduction abnormalities are the most common manifestation of Lyme carditis. Less common, are alternating right bundle branch block (RBBB) and left bundle branch block (LBBB). We present an interesting case of a young male whose main manifestation of Lyme carditis was isolated LBBB. He also had mild Lyme myocarditis. The patient was successfully treated with oral doxycycline, and his isolated LBBB and myocarditis rapidly resolved.

Atrioventricular and intraventricular block after transcatheter aortic valve implantation.

PubMed

Lee, Jane J; Goldschlager, Nora; Mahadevan, Vaikom S

2018-06-24

Aortic stenosis is the most common valvular heart disease in industrialized countries and the most common cause of left ventricular outflow tract (LVOT) obstruction. Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement for intermediate to high-risk surgical candidates with symptomatic severe aortic stenosis. Conduction system abnormalities, including atrioventricular (AV) and intraventricular (IV) block, are the most common complication of TAVR. In this review, we aim to explore the anatomical issues relevant to atrioventricular block, the relevant clinical and procedural aspects, and the management and long-term implications of AV and IV block.

NECA and bradykinin at reperfusion reduce infarction in rabbit hearts by signaling through PI3K, ERK, and NO.

PubMed

Yang, Xi-Ming; Krieg, Thomas; Cui, Lin; Downey, James M; Cohen, Michael V

2004-03-01

The adenosine A1/A2 adenosine agonist 5'-(N-ethylcarboxamido) adenosine (NECA) and bradykinin both limit infarction when administered at reperfusion in rabbits. This study compares the signal transduction pathways responsible for their anti-infarct effect. Receptor agonists were administered to isolated rabbit hearts starting 25 min after the onset of a 30-min period of ischemia and continued into the 2-h reperfusion period. Infarct size was measured. Both NECA and bradykinin decreased infarction from 31.5 +/- 2.4% of the risk zone in untreated hearts to 11.8 +/- 2.0% and 15.4 +/- 2.4%, respectively (P<0.05). Protection from both agents was blocked by PD98059, wortmannin, and Nomega-nitro-L-arginine methyl ester (L-NAME), thus demonstrating dependence on activation of extracellular regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) and stimulation of nitric oxide synthase (NOS). Both wortmannin and PD98059 prevented phosphorylation of ERK 1/2 in NECA-treated hearts, whereas only wortmannin and not PD98059 blocked Akt phosphorylation. These data suggest Akt is upstream of ERK 1/2. In addition, 8-(3-chlorostyryl) caffeine blocked NECA's protection indicating that A2 adenosine receptors trigger NECA's anti-infarct effect. Of note, both bradykinin and acetylcholine (ACh) administered before ischemia to trigger preconditioning's cardioprotection use PI3K and NOS in their signaling pathway. Curiously, however, ACh, unlike bradykinin, was not protective when administered at reperfusion. Hence, both NECA and bradykinin administered at reperfusion protect through a common signaling pathway that includes PI3K, NO, and ERK.

Mechanisms and management of the heart in Myotonic Dystrophy

PubMed Central

McNally, Elizabeth M.; Sparano, Dina

2015-01-01

Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy and is caused by expansion of short nucleotide repeats that, in turn, produce toxic RNA aggregates within cells. DM is multisystemic, and the heart is primary site of pathology. DM patients exhibit cardiac conduction disorders including atrial fibrillation, atrio-ventricular heart block and ventricular arrhythmias. DM patients are also at risk for cardiomyopathy and congestive heart failure. Myotonic dystrophy is also characterized by myotonia, muscle weakness, and profound fatigue. The management of these symptoms requires input from the cardiologist and a team approach to minimize the debilitating aspects of the disorder and optimize cardiac function. PMID:21642660

Laughter-induced left bundle branch block.

PubMed

Chow, Grant V; Desai, Dipan; Spragg, David D; Zakaria, Sammy

2012-10-01

We present the case of a patient with ischemic heart disease and intermittent left bundle branch block, reproducibly induced by laughter. Following treatment of ischemia with successful deployment of a drug-eluting stent, no further episodes of inducible LBBB were seen. Transient ischemia, exacerbated by elevated intrathoracic pressure during laughter, may have contributed to onset of this phenomenon. © 2012 Wiley Periodicals, Inc.

Cardiac resynchronization therapy with His bundle pacing as a method of treatment of chronic heart failure in patients with permanent atrial fibrillation and left bundle branch block.

PubMed

Boczar, Krzysztof; Sławuta, Agnieszka; Ząbek, Andrzej; Dębski, Maciej; Gajek, Jacek; Lelakowski, Jacek; Małecka, Barbara

CRT is a therapeutic option for patients with heart failure, sinus rhythm, prolonged QRS complex duration and reduced ejection fraction. We present a case of 71-year-old woman with dilated cardiomyopathy, NYHA functional class III and AF. We implanted CRT combined with direct His-bundle pacing. The indication for such a therapy was a left bundle branch block with a QRS complex of 178ms and a left ventricular EF of 15%, left ventricular end-diastolic diameter (LVEDD) of 75mm. After 8months of follow-up the LVEDD was 60mm with EF 35-40%. Copyright © 2017. Published by Elsevier Inc.

Comparison of the calculation QRS angle for bundle branch block detection

NASA Astrophysics Data System (ADS)

Goeirmanto, L.; Mengko, R.; Rajab, T. L.

2016-04-01

QRS angle represent condition of blood circulation in the heart. Normally QRS angle is between -30 until 90 degree. Left Axis Defiation (LAD) and Right Axis Defiation (RAD) are abnormality conditions that lead to Bundle Branch Block. QRS angle is calculated using common method from physicians and compared to mathematical method using difference amplitudos and difference areas. We analyzed the standard 12 lead electrocardiogram data from MITBIH physiobank database. All methods using lead I and lead avF produce similar QRS angle and right QRS axis quadrant. QRS angle from mathematical method using difference areas is close to common method from physician. Mathematical method using difference areas can be used as a trigger for detecting heart condition.

Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease.

PubMed

Priyamvada, P S; Morkhandikar, S; Srinivas, B H; Parameswaran, S

2015-01-01

Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig) light chains. In heavy chain amyloidosis (AH), deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL), the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda) AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

Maternal positioning affects fetal heart rate changes after epidural analgesia for labour.

PubMed

Preston, R; Crosby, E T; Kotarba, D; Dudas, H; Elliott, R D

1993-12-01

Adverse fetal heart rate (FHR) changes suggestive of fetal hypoxia are seen in patients with normal term pregnancies after initiation of epidural block for labour analgesia. It was our hypothesis that, in some parturients, these changes were a consequence of concealed aortocaval compression resulting in decreased uterine blood flow. We expected that the full lateral position compared with the wedged supine position would provide more effective prophylaxis against aortocaval compression. To test our hypothesis we studied the role of maternal positioning on FHR changes during onset of epidural analgesia for labour. Eighty-eight ASA Class I or II term parturients were randomized into two groups: those to be nursed in the wedged supine position and those to be nursed in the full lateral position during induction of an epidural block. External FHR monitoring was employed to assess the fetal response to initiation of labour epidural analgesia. Epidural catheters were sited with the parturients in the sitting position and the patients then assumed the study position. After a negative test dose, a standardized regimen of bupivacaine 0.25% was employed to provide labour analgesia. The quality and efficacy of the block were assessed using VAS pain scores, motor block scores and sensory levels. The results demonstrated that there was no difference in the quality of analgesia provided nor in the incidence of asymmetric blocks. There was no difference in the observed incidence of FHR changes occurring during the initiation of the epidural block.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse effects of permanent atrial fibrillation on heart failure in patients with preserved left ventricular function and chronic right apical pacing for complete heart block.

PubMed

Lampe, Brigitte; Hammerstingl, Christoph; Schwab, Jörg Otto; Mellert, Fritz; Stoffel-Wagner, Birgit; Grigull, Andreas; Fimmers, Rolf; Maisch, Bernhard; Nickenig, Georg; Lewalter, Thorsten; Yang, Alexander

2012-10-01

The impact of atrial fibrillation (AF) on heart failure (HF) was evaluated in patients with preserved left ventricular (LV) function and long-term right ventricular (RV) pacing for complete heart block. Clinical, echocardiographic, and laboratory parameters of HF were assessed in 35 patients with established AF who had undergone ablation of the atrioventricular node and pacemaker implantation (Group A) and 31 patients who received dual-chamber pacing for spontaneous complete heart block (Group B). During a follow-up period of 12.7 ± 7.5 years, New York Heart Association (NYHA) functional class increased from 1.3 ± 0.5 to 2.1 ± 0.6 (p < 0.0001) in Group A, and from 1.3 ± 0.4 to 1.6 ± 0.7 (p < 0.01) in Group B. Left ventricular ejection fraction (LVEF) decreased from 59.7 ± 5.1 to 53.0 ± 8.2 (p < 0.0001) in Group A, but remained stable (58.6 ± 4.2 vs. 56.9 ± 7.0 %, p = 0,21) in Group B. At the end of follow-up, markers of LV function were moderately depressed in Group A compared with those in Group B: NYHA class 2.1 ± 0.6 versus 1.6 ± 0.7, p = 0.001; LVEF 53.0 ± 8.2 versus 56.9 ± 7.0 %, p < 0.05; LV diastolic diameter 53.6 ± 5.8 mm versus 50.7 ± 4.9 mm, p < 0.05; N-terminal pro-brain natriuretic peptide (NT-proBNP) 1116.8 ± 883.9 versus 622.9 ± 1059.4 pg/ml, p < 0.05. Progression of paroxysmal AF to permanent AF during follow-up was common, while new onset of AF was rare. Permanent AF was an independent predictor of declining LVEF >10 %, increasing NYHA class ≥1, and NT-proBNP levels >1,000 pg/ml. Permanent AF was associated with adverse effects on LV function and symptoms of HF in patients with long-term RV pacing for complete heart block, and appears to play an important role in the development of HF in this specific patient cohort.

Early-onset Lyme carditis with concurrent disseminated erythema migrans.

PubMed

Patel, Kinjan P; Farjo, Peter D; Juskowich, Joy J; Hama Amin, Ali; Mills, James D

2017-01-01

Lyme disease is an infection that is estimated to affect over 300,000 people in the United States annually. Typically, it presents with erythema migrans (EM), an annular rash at the site of tick attachment, within 3 to 30 days of inoculation. Untreated patients may progress to early disseminated disease. A further complication, Lyme carditis is rare but may occur several weeks later. It commonly manifests as a variable atrioventricular (AV) conduction block, with a high-grade AV block occurring in only 1% of untreated patients. This case demonstrates an unusually early presentation of Lyme carditis with complete heart block. A 21-year-old male was transferred from an outside emergency department (ED) for possible pacemaker placement due to symptomatic third-degree AV block. Four days earlier the patient presented to the outside ED with fever, chills, and unrecognized EM on his right neck. He was discharged with antipyretics, but no antibiotic therapy. On the day of transfer, he returned with persistent fevers, EM now on his trunk and upper extremities, lightheadedness, and substernal chest pressure. An electrocardiogram revealed the third-degree AV block leading to transfer. Upon arrival, the patient was promptly diagnosed with Lyme carditis. Pacemaker implantation was deferred, and intravenous (IV) ceftriaxone was initiated. Within 48 hours his third-degree AV block improved to a first-degree block. By this time, his EM had also resolved. He was discharged with oral doxycycline and a 30-day event monitor, which ultimately showed persistent first-degree AV block. This case reinforces a unique presentation of Lyme carditis. Disseminated EM and Lyme carditis may present concurrently within 2 weeks of tick attachment. Early recognition and treatment is important for preventing progression to disseminated infection. Lyme-associated AV block will reverse within 48 to 72 hours of initiating IV antibiotic therapy and will not require pacemaker implantation. Lyme carditis should be considered in patients without heart disease who present with any degree of AV block.

Transcription factor ETV1 is essential for rapid conduction in the heart.

PubMed

Shekhar, Akshay; Lin, Xianming; Liu, Fang-Yu; Zhang, Jie; Mo, Huan; Bastarache, Lisa; Denny, Joshua C; Cox, Nancy J; Delmar, Mario; Roden, Dan M; Fishman, Glenn I; Park, David S

2016-12-01

Rapid impulse propagation in the heart is a defining property of pectinated atrial myocardium (PAM) and the ventricular conduction system (VCS) and is essential for maintaining normal cardiac rhythm and optimal cardiac output. Conduction defects in these tissues produce a disproportionate burden of arrhythmic disease and are major predictors of mortality in heart failure patients. Despite the clinical importance, little is known about the gene regulatory network that dictates the fast conduction phenotype. Here, we have used signal transduction and transcriptional profiling screens to identify a genetic pathway that converges on the NRG1-responsive transcription factor ETV1 as a critical regulator of fast conduction physiology for PAM and VCS cardiomyocytes. Etv1 was highly expressed in murine PAM and VCS cardiomyocytes, where it regulates expression of Nkx2-5, Gja5, and Scn5a, key cardiac genes required for rapid conduction. Mice deficient in Etv1 exhibited marked cardiac conduction defects coupled with developmental abnormalities of the VCS. Loss of Etv1 resulted in a complete disruption of the normal sodium current heterogeneity that exists between atrial, VCS, and ventricular myocytes. Lastly, a phenome-wide association study identified a link between ETV1 and bundle branch block and heart block in humans. Together, these results identify ETV1 as a critical factor in determining fast conduction physiology in the heart.

Transcription factor ETV1 is essential for rapid conduction in the heart

PubMed Central

Shekhar, Akshay; Lin, Xianming; Liu, Fang-Yu; Zhang, Jie; Mo, Huan; Bastarache, Lisa; Denny, Joshua C.; Cox, Nancy J.; Delmar, Mario; Roden, Dan M.; Fishman, Glenn I.; Park, David S.

2016-01-01

Rapid impulse propagation in the heart is a defining property of pectinated atrial myocardium (PAM) and the ventricular conduction system (VCS) and is essential for maintaining normal cardiac rhythm and optimal cardiac output. Conduction defects in these tissues produce a disproportionate burden of arrhythmic disease and are major predictors of mortality in heart failure patients. Despite the clinical importance, little is known about the gene regulatory network that dictates the fast conduction phenotype. Here, we have used signal transduction and transcriptional profiling screens to identify a genetic pathway that converges on the NRG1-responsive transcription factor ETV1 as a critical regulator of fast conduction physiology for PAM and VCS cardiomyocytes. Etv1 was highly expressed in murine PAM and VCS cardiomyocytes, where it regulates expression of Nkx2-5, Gja5, and Scn5a, key cardiac genes required for rapid conduction. Mice deficient in Etv1 exhibited marked cardiac conduction defects coupled with developmental abnormalities of the VCS. Loss of Etv1 resulted in a complete disruption of the normal sodium current heterogeneity that exists between atrial, VCS, and ventricular myocytes. Lastly, a phenome-wide association study identified a link between ETV1 and bundle branch block and heart block in humans. Together, these results identify ETV1 as a critical factor in determining fast conduction physiology in the heart. PMID:27775552

Suppression of Class I and II Histone Deacetylases Blunts Pressure-Overload Cardiac Hypertrophy

PubMed Central

Kong, Yongli; Tannous, Paul; Lu, Guangrong; Berenji, Kambeez; Rothermel, Beverly A.; Olson, Eric N.; Hill, Joseph A.

2014-01-01

Background Recent work has demonstrated the importance of chromatin remodeling, especially histone acetylation, in the control of gene expression in the heart. In cell culture models of cardiac hypertrophy, pharmacological suppression of histone deacetylases (HDACs) can either blunt or amplify cell growth. Thus, HDAC inhibitors hold promise as potential therapeutic agents in hypertrophic heart disease. Methods and Results In the present investigation, we studied 2 broad-spectrum HDAC inhibitors in a physiologically relevant banding model of hypertrophy, observing dose-responsive suppression of ventricular growth that was well tolerated in terms of both clinical outcome and cardiac performance measures. In both short-term (3-week) and long-term (9-week) trials, cardiomyocyte growth was blocked by HDAC inhibition, with no evidence of cell death or apoptosis. Fibrotic change was diminished in hearts treated with HDAC inhibitors, and collagen synthesis in isolated cardiac fibroblasts was blocked. Preservation of systolic function in the setting of blunted hypertrophic growth was documented by echocardiography and by invasive pressure measurements. The hypertrophy-associated switch of adult and fetal isoforms of myosin heavy chain expression was attenuated, which likely contributed to the observed preservation of systolic function in HDAC inhibitor–treated hearts. Conclusions Together, these data suggest that HDAC inhibition is a viable therapeutic strategy that holds promise in the treatment of load-induced heart disease. PMID:16735673

Change of Exhaled Acetone Concentration in a Diabetic Patient with Acute Decompensated Heart Failure.

PubMed

Yokokawa, Tetsuro; Ichijo, Yasuhiro; Houtsuki, Yu; Matsumoto, Yoshiyuki; Oikawa, Masayoshi; Yoshihisa, Akiomi; Sugimoto, Koichi; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-Ichi; Shimouchi, Akito; Takeishi, Yasuchika

2017-10-21

In heart failure patients, exhaled acetone concentration, a noninvasive biomarker, is increased according to heart failure severity. Moreover, exhaled acetone concentration is also known to be affected by diabetes mellitus. However, there have been no reports on exhaled acetone concentration in heart failure patients with diabetes mellitus. A 77-year old man was admitted to our hospital with acute decompensated heart failure and atrioventricular block. He had controlled diabetes mellitus under insulin treatment with hemoglobin A1c of 6.5%. He underwent treatment of diuretics and permanent pacemaker implantation. His condition improved and he was discharged at Day 12. Due to the heart failure improvement, his levels of exhaled acetone concentration decreased from 1.623 ppm at admission to 0.664 ppm at discharge. This is the first report to reveal a change of exhaled acetone concentration in a diabetic patient with acute decompensated heart failure.

Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicente, Jose; Johannesen, Lars; Hosseini, Meisam

Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Furthermore, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the "CiPA" initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans.

Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block

DOE PAGES

Vicente, Jose; Johannesen, Lars; Hosseini, Meisam; ...

2016-12-30

Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Furthermore, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the "CiPA" initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans.

Evaluation and management of bradycardia in neonates and children.

PubMed

Baruteau, Alban-Elouen; Perry, James C; Sanatani, Shubhayan; Horie, Minoru; Dubin, Anne M

2016-02-01

Heart rate is commonly used in pediatric early warning scores. Age-related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Bradycardia is defined as a heart rate below the lowest normal value for age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. As a result of several different etiologies, it may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited sinus node dysfunction or progressive cardiac conduction disorders. Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. The simplest aspect of severe bradycardia management is reflected in the Pediatric and Advanced Life Support (PALS) guidelines. Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current practice for evaluation and management of bradycardia in neonates and children. Bradycardia is defined as a heart rate below the lowest normal value for age. Age related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Bradycardia may occur in a structurally normal heart or in association with congenital heart disease. Genetic variants in multiple genes have been described. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. Early diagnosis and appropriate management are critical in order to prevent sudden death.

Presystolic tricuspid valve closure: an alternative mechanism of diastolic sound genesis.

PubMed

Lee, C H; Xiao, H B; Gibson, D G

1990-01-01

We describe a previously unrecognised cause of an added diastolic heart sound. The patient had first-degree heart block and diastolic tricuspid regurgitation, leading to presystolic closure of the tricuspid valve and the production of a loud diastolic sound. Unlike previously described mechanisms for diastolic sounds, this sound was generated by the sudden acceleration of retrograde AV flow in late diastole.

EXTERIOR VIEW WITH HISTORIC LOCOMOTIVES, COAL AND PASSENGER CARS INCLUDING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EXTERIOR VIEW WITH HISTORIC LOCOMOTIVES, COAL AND PASSENGER CARS INCLUDING THE WOODWARD IRON COMPANY NO. 38 LOCOMOTIVE AND TENDER LOCATED IN THE HEART OF DIXIE MUSEUM'S POWELL AVENUE YARD AND SOUTHERN RAILROAD BOXCARS ON ACTIVE TRACKS OF BIRMINGHAM'S RAILROAD RESERVATION. IN BACKGROUND AT RIGHT AND CENTER IS THE BIRMINGHAM CITY CENTER. - Heart of Dixie Railroad, Rolling Stock, 1800 Block Powell Avenue, Birmingham, Jefferson County, AL

Heat shock transcription factor 1 protects against pressure overload-induced cardiac fibrosis via Smad3.

PubMed

Zhou, Ning; Ye, Yong; Wang, Xingxu; Ma, Ben; Wu, Jian; Li, Lei; Wang, Lin; Wang, Dao Wen; Zou, Yunzeng

2017-04-01

Fibrotic cardiac muscle exhibits high stiffness and low compliance which are major risk factors of heart failure. Although heat shock transcription factor 1 (HSF1) was identified as an intrinsic cardioprotective factor, the role that HSF1 plays in cardiac fibrosis remains unclear. Our study aims to investigate the role of HSF1 in pressure overload-induced cardiac fibrosis and the underlying mechanism. HSF1 phosphorylation was significantly downregulated in transverse aortic constriction (TAC)-treated mouse hearts and mechanically stretched cardiac fibroblasts (cFBs). HSF1 transgenic (TG) mice, HSF1 deficient heterozygote (KO) mice, and their wild-type littermates were subjected to sham or TAC surgery for 4 weeks. HSF1 overexpression significantly attenuated pressure overload-induced cardiac fibrosis and dysfunction. Conversely, HSF1 KO mice showed deteriorated fibrotic response and cardiac dysfunction upon TAC. Moreover, we uncovered that overexpression of HSF1 protected against fibrotic response of cFBs to pressure overload. Mechanistically, we observed that the phosphorylation and the nuclear distribution of the Smad family member 3 (Smad3) were significantly decreased in HSF1-overexpressing mouse hearts, while being greatly increased in HSF1 KO mouse hearts upon TAC, compared to the control hearts, respectively. Similar alteration of Smad3 phosphorylation and nuclear distribution were found in isolated mouse cardiac fibroblasts and mechanically stretched cFBs. Constitutively active Smad3 blocked the anti-fibrotic effect of HSF1 in cFBs. Furthermore, we found a direct binding of phosphorylated HSF1 and Smad3, which can be suppressed by mechanical stress. In conclusion, the present study demonstrated for the first time that HSF1 acts as a novel negative regulator of cardiac fibrosis by blocking Smad3 activation. HSF1 activity is decreased in fibrotic hearts. HSF1 overexpression attenuates pressure overload-induced cardiac fibrosis and dysfunction. Deficiency of HSF1 deteriorates fibrotic response and cardiac dysfunction upon TAC. HSF1 inhibits phosphorylation and nuclear distribution of Smad3 via direct binding to Smad3. Active Smad3 blocks the anti-fibrotic effect of HSF1.

Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis, but negatively impacts cardiac function

PubMed Central

Ermolova, N.E.; Martinez, L.; Vetrone, S.A.; Jordan, M. C.; Roos, K. .P.; Sweeney, H.L.; Spencer, M.J.

2014-01-01

Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease caused by mutations in the gene encoding dystrophin (DYS). Tumor necrosis factor (TNF) has been implicated in the pathogenesis of DMD since short-term treatment of mdx mice with TNF blocking drugs proved beneficial; however, it is not clear whether long-term treatment will also improve long-term outcomes of fibrosis and cardiac health. In this investigation, short and long-term dosing studies were carried out using the TNF blocking drug Remicade and a variety of outcome measures were assessed. Here we show no demonstrable benefit to muscle strength or morphology with 10mg/kg or 20 mg/kg Remicade; however, 3mg/kg produced positive strength benefits. Remicade treatment correlated with reductions in myostatin mRNA in the heart, and concomitant reductions in cardiac and skeletal fibrosis. Surprisingly, although Remicade treated mdx hearts were less fibrotic, reductions in LV mass and ejection fraction were also observed, and these changes coincided with reductions in AKT phosphorylation on threonine 308. Thus, TNF blockade benefits mdx skeletal muscle strength and fibrosis, but negatively impacts AKT activation, leading to deleterious changes to dystrophic heart function. These studies uncover a previously unknown relationship between TNF blockade and alteration of muscle growth signaling pathways. PMID:24844454

Heart block

MedlinePlus

... a pacemaker. DO NOT go through the usual security station at an airport, courthouse, or other place that requires people to walk through a security screening. Tell the security personnel you have a ...

Cardiac Metabolism in Heart Failure - Implications beyond ATP production

PubMed Central

Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale

2013-01-01

The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714

Pulmonary Right Ventricular Resynchronization in Congenital Heart Disease: Acute Improvement in Right Ventricular Mechanics and Contraction Efficiency.

PubMed

Janoušek, Jan; Kovanda, Jan; Ložek, Miroslav; Tomek, Viktor; Vojtovič, Pavel; Gebauer, Roman; Kubuš, Peter; Krejčíř, Miroslav; Lumens, Joost; Delhaas, Tammo; Prinzen, Frits

2017-09-01

Electromechanical discoordination may contribute to long-term pulmonary right ventricular (RV) dysfunction in patients after surgery for congenital heart disease. We sought to evaluate changes in RV function after temporary RV cardiac resynchronization therapy. Twenty-five patients aged median 12.0 years after repair of tetralogy of Fallot and similar lesions were studied echocardiographically (n=23) and by cardiac catheterization (n=5) after primary repair (n=4) or after surgical RV revalvulation for significant pulmonary regurgitation (n=21). Temporary RV cardiac resynchronization therapy was applied in the presence of complete right bundle branch block by atrial-synchronized RV free wall pacing in complete fusion with spontaneous ventricular depolarization using temporary electrodes. The q-RV interval at the RV free wall pacing site (mean 77.2% of baseline QRS duration) confirmed pacing from a late activated RV area. RV cardiac resynchronization therapy carried significant decrease in QRS duration ( P <0.001) along with elimination of the right bundle branch block QRS morphology, increase in RV filling time ( P =0.002), pulmonary artery velocity time integral ( P =0.006), and RV maximum +dP/dt ( P <0.001), and decrease in RV index of myocardial performance ( P =0.006). RV mechanical synchrony improved: septal-to-lateral RV mechanical delay decreased ( P <0.001) and signs of RV dyssynchrony pattern were significantly abolished. RV systolic stretch fraction reflecting the ratio of myocardial stretching and contraction during systole diminished ( P =0.001). In patients with congenital heart disease and right bundle branch block, RV cardiac resynchronization therapy carried multiple positive effects on RV mechanics, synchrony, and contraction efficiency. © 2017 American Heart Association, Inc.

Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction, and repolarization.

PubMed

Sah, Rajan; Mesirca, Pietro; Mason, Xenos; Gibson, William; Bates-Withers, Christopher; Van den Boogert, Marjolein; Chaudhuri, Dipayan; Pu, William T; Mangoni, Matteo E; Clapham, David E

2013-07-09

Transient receptor potential (TRP) channels are a superfamily of broadly expressed ion channels with diverse physiological roles. TRPC1, TRPC3, and TRPC6 are believed to contribute to cardiac hypertrophy in mouse models. Human mutations in TRPM4 have been linked to progressive familial heart block. TRPM7 is a divalent-permeant channel and kinase of unknown function, recently implicated in the pathogenesis of atrial fibrillation; however, its function in ventricular myocardium remains unexplored. We generated multiple cardiac-targeted knockout mice to test the hypothesis that TRPM7 is required for normal ventricular function. Early cardiac Trpm7 deletion (before embryonic day 9; TnT/Isl1-Cre) results in congestive heart failure and death by embryonic day 11.5 as a result of hypoproliferation of the compact myocardium. Remarkably, Trpm7 deletion late in cardiogenesis (about embryonic day 13; αMHC-Cre) produces viable mice with normal adult ventricular size, function, and myocardial transcriptional profile. Trpm7 deletion at an intermediate time point results in 50% of mice developing cardiomyopathy associated with heart block, impaired repolarization, and ventricular arrhythmias. Microarray analysis reveals elevations in transcripts of hypertrophy/remodeling genes and reductions in genes important for suppressing hypertrophy (Hdac9) and for ventricular repolarization (Kcnd2) and conduction (Hcn4). These transcriptional changes are accompanied by action potential prolongation and reductions in transient outward current (Ito; Kcnd2). Similarly, the pacemaker current (If; Hcn4) is suppressed in atrioventricular nodal cells, accounting for the observed heart block. Trpm7 is dispensable in adult ventricular myocardium under basal conditions but is critical for myocardial proliferation during early cardiogenesis. Loss of Trpm7 at an intermediate developmental time point alters the myocardial transcriptional profile in adulthood, impairing ventricular function, conduction, and repolarization.

Near-Infrared Spectroscopy Enhances Intravascular Ultrasound Assessment of Vulnerable Coronary Plaque: A Combined Pathological and In Vivo Study.

PubMed

Puri, Rishi; Madder, Ryan D; Madden, Sean P; Sum, Stephen T; Wolski, Kathy; Muller, James E; Andrews, Jordan; King, Karilane L; Kataoka, Yu; Uno, Kiyoko; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; Virmani, Renu; Maehara, Akiko; Mintz, Gary S; Nicholls, Stephen J

2015-11-01

Pathological studies demonstrate the dual significance of plaque burden (PB) and lipid composition for mediating coronary plaque vulnerability. We evaluated relationships between intravascular ultrasound (IVUS)-derived PB and arterial remodeling with near-infrared spectroscopy (NIRS)-derived lipid content in ex vivo and in vivo human coronary arteries. Ex vivo coronary NIRS and IVUS imaging was performed through blood in 116 coronary arteries of 51 autopsied hearts, followed by 2-mm block sectioning (n=2070) and histological grading according to modified American Heart Association criteria. Lesions were defined as the most heavily diseased 2-mm block per imaged artery on IVUS. IVUS-derived PB and NIRS-derived lipid core burden index (LCBI) of each block and lesion were analyzed. Block-level analysis demonstrated significant trends of increasing PB and LCBI across more complex atheroma (Ptrend <0.001 for both LCBI and PB). Lesion-based analyses demonstrated the highest LCBI and remodeling index within coronary fibroatheroma (Ptrend <0.001 and 0.02 versus all plaque groups, respectively). Prediction models demonstrated similar abilities of PB, LCBI, and remodeling index for discriminating fibroatheroma (c indices: 0.675, 0.712, and 0.672, respectively). A combined PB+LCBI analysis significantly improved fibroatheroma detection accuracy (c index 0.77, P=0.028 versus PB; net-reclassification index 43%, P=0.003), whereas further adding remodeling index did not (c index 0.80, P=0.27 versus PB+LCBI). In vivo comparisons of 43 age- and sex-matched patients (to the autopsy cohort) undergoing combined NIRS-IVUS coronary imaging yielded similar associations to those demonstrated ex vivo. Adding NIRS to conventional IVUS-derived PB imaging significantly improves the ability to detect more active, potentially vulnerable coronary atheroma. © 2015 American Heart Association, Inc.

[Correlation between succinate-dependent Ca2+ accumulation and transamination in the heart and the liver mitochondria of experimental animals].

PubMed

Saakian, I R; Saakian, G G

2006-01-01

Glutamate (GLU) and alpha-ketoglutarate (KGL), the substrates involved in transamination, have reciprocal effects on succinate-dependent respiration, NADH reduction, as well as on the accumulation and stable retention of Ca2+ in heart and liver mitochondria and homogenates from experimental animals. The succinate-dependent Ca2+ accumulation was shown to be highly sensitive to changes of the concentration ratios of GLU and KGL within the range 1:10 mM. GLU activated this process by transamination of oxalacetate (OAA) to aspartate. The predomination of KGL blocked the activating effect of GLU. The predomination of GLU eliminated the block produced by KGL or phosphoenolpyruvate (sources of OAA and GTP) but did not eliminate the Ca2+ accumulation-suppressing effect of aminoacetate, inhibitor of transaminases.

[Arrhythmias and heart blocks in flying personnel with mitral valve prolapses].

PubMed

Zakharov, V P; Karlov, V N; Bondareva, S V; Vlasov, V D

1999-01-01

Investigated were 76 pilots with ECG-verified mitral valve prolapses (MVP) of the 1st and 2nd degree (w/o profound regurgitation). There were various heart blocks and ECG repolarization changes in 35 cases. Comparison of results of the cardiovascular functional investigations of flyers with MVP displayed non-specific cardiac rhythm and conductance disturbances that were registered more often during ECG-monitoring or test loading. According to the data of this study, bicycle and treadmill ergometry revealed "pseudoischemic" shifts in ECG. Literary indications of a significant loss in human endurance of physical loads due to MVP combined with the strain-induced arrhythmia received the experimental confirmation. Probably, arrhythmias in flyers with diagnosed MVP are predominantly associated with electric instability of the myocardium against the autonomous dysfunction with prevailing adrenergic effects.

The use of α- or β-blockers to ameliorate the chronic stress of captivity in the house sparrow (Passer domesticus).

PubMed

Fischer, Clare Parker; Romero, L Michael

2016-01-01

When wild animals are brought into captivity for the first time, they frequently develop chronic stress symptoms. Animals can develop glucocorticoid dysregulation or changes in the sympathetic nervous system over the course of the first week in captivity. By blocking the action of epinephrine and norepinephrine using α- or β-blockers, we hoped to reduce the degree of chronic stress symptoms exhibited by newly captured house sparrows. We measured corticosterone, heart rate and heart rate variability in 24 house sparrows ( Passer domesticus ) over the first week of captivity. The birds were treated with saline, propranolol (a β-blocker) or phentolamine (an α-blocker) for the first 3 days of captivity. We also compared newly captured animals with animals that had been held in captivity for 1 month. During the first week of captivity, baseline corticosterone increased, but that increase was blocked by propranolol. Heart rate was not different between the treatment groups, but it was higher during the first week than after 1 month in captivity. Sympathetic nervous system activity (as measured by heart rate variability) decreased over the first week of captivity, but was not affected by treatment. β-Blockers, but not α-blockers, might help to improve some symptoms of chronic stress in newly captured animals.

Actions of derivatives of lysergic acid on the heart of venus mercenaria

PubMed Central

Wright, Anne McCoy; Moorhead, Merilyn; Welsh, J. H.

1962-01-01

5-Hydroxytryptamine and a number of (+)-lysergic acid derivatives have been tested on the heart of Venus mercenaria. One group of derivatives was found to increase the amplitude and frequency of heart beat in a manner much like 5-hydroxytryptamine. It included the monoethylamide, diethylamide, propanolamide (ergometrine), butanolamide (methylergometrine) and certain peptide derivatives of lysergic acid without substituents in positions 1 or 2. Of these, lysergic acid diethylamide was the most active. Given sufficient time (up to 4 hr), as little as 10 ml. of 10-16 M lysergic acid diethylamide produced a maximum increase in amplitude and frequency in about one-half of the 80 hearts on which it was tested. Its action was very slowly reversed by washing, as was true of all lysergic acid derivatives. A second group of lysergic acid derivatives, substituted in positions 1 or 2, had weak excitor action, if any, and specific 5-hydroxytryptamine blocking action. This group consisted of 1-methyl-, 1-acetyl-, and 2-bromo-lysergic acid diethylamide and 1-methyllysergic acid butanolamide (methysergide). Of these, the last showed least signs of excitor action, usually none up to 10-4 M, and it blocked 5-hydroxytryptamine in a molar ratio of about one to one. PMID:14008412

Blocked Urethral Valves

MedlinePlus

... Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... and Urinary Tract Glands & Growth Head Neck & Nervous System Heart Infections Learning Disabilities Obesity Orthopedic Prevention Sexually ...

Atrial myxoma

MedlinePlus

... Pieces of the tumor can move to the brain, eye, or limbs. If the tumor grows inside the heart, it can block blood flow. This may require emergency ... myxoma References Lenihan DJ, Yusuf SW. Tumors ...

Myocardial NF-κB activation is essential for zebrafish heart regeneration

PubMed Central

Karra, Ravi; Knecht, Anne K.; Kikuchi, Kazu; Poss, Kenneth D.

2015-01-01

Heart regeneration offers a novel therapeutic strategy for heart failure. Unlike mammals, lower vertebrates such as zebrafish mount a strong regenerative response following cardiac injury. Heart regeneration in zebrafish occurs by cardiomyocyte proliferation and reactivation of a cardiac developmental program, as evidenced by induction of gata4 regulatory sequences in regenerating cardiomyocytes. Although many of the cellular determinants of heart regeneration have been elucidated, how injury triggers a regenerative program through dedifferentiation and epicardial activation is a critical outstanding question. Here, we show that NF-κB signaling is induced in cardiomyocytes following injury. Myocardial inhibition of NF-κB activity blocks heart regeneration with pleiotropic effects, decreasing both cardiomyocyte proliferation and epicardial responses. Activation of gata4 regulatory sequences is also prevented by NF-κB signaling antagonism, suggesting an underlying defect in cardiomyocyte dedifferentiation. Our results implicate NF-κB signaling as a key node between cardiac injury and tissue regeneration. PMID:26472034

Myocardial NF-κB activation is essential for zebrafish heart regeneration.

PubMed

Karra, Ravi; Knecht, Anne K; Kikuchi, Kazu; Poss, Kenneth D

2015-10-27

Heart regeneration offers a novel therapeutic strategy for heart failure. Unlike mammals, lower vertebrates such as zebrafish mount a strong regenerative response following cardiac injury. Heart regeneration in zebrafish occurs by cardiomyocyte proliferation and reactivation of a cardiac developmental program, as evidenced by induction of gata4 regulatory sequences in regenerating cardiomyocytes. Although many of the cellular determinants of heart regeneration have been elucidated, how injury triggers a regenerative program through dedifferentiation and epicardial activation is a critical outstanding question. Here, we show that NF-κB signaling is induced in cardiomyocytes following injury. Myocardial inhibition of NF-κB activity blocks heart regeneration with pleiotropic effects, decreasing both cardiomyocyte proliferation and epicardial responses. Activation of gata4 regulatory sequences is also prevented by NF-κB signaling antagonism, suggesting an underlying defect in cardiomyocyte dedifferentiation. Our results implicate NF-κB signaling as a key node between cardiac injury and tissue regeneration.

Dysfunction of an On-X Heart Valve by Pannus.

PubMed

Abad, Cipriano; Urso, Stefano; Gomez, Elsa; De la Vega, Maria

2016-09-01

A 68-year-old woman with a history of previous double-valve replacement with On-X mechanical heart valves presented with clinical, echocardiographic and cardiac catheterization signs of obstruction of the On-X tricuspid heart valve prosthesis. The patient was successfully reoperated, but at surgery the valve was seen to be invaded by an abnormal overgrowth of pannus that blocked one of the leaflets. A small amount of non-obstructive fresh thrombus was also observed. The valve was successfully replaced with a biological heart valve prosthesis. The patient was discharged home, and is doing well four months after the operation, when echocardiography demonstrated normal function in the tricuspid valve. The present case represents the first ever report of pannus formation and subsequent dysfunction in an On-X heart valve, and also the first case of tricuspid valve malfunction and obstruction using this type of heart valve substitute.

DDD pacemaker for severe heart failure-alternate to CRT.

PubMed

Krishnamani, N C

Patients with severe systolic Heart Failure continue to have poor quality of life and increased mortality in spite of optimal medical management. Cardiac Resynchronization Therapy [CRT] is promising modality in patients with systolic heart failure and electrocardiographic [ECG] evidence of left bundle branch block [LBBB]. Cost issues continue to elude many deserving cases of this therapy in our society. Relatively cost effective Dual chamber pacing [DDD] with right atrial and isolated left ventricular pacing [RA-LV] can be a good alternative. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Carvedilol inhibits cADPR- and IP3-induced Ca2+ release.

PubMed

Morgan, Anthony J; Bampali, Konstantina; Ruas, Margarida; Factor, Cailley; Back, Thomas G; Chen, S R Wayne; Galione, Antony

2016-06-01

Spontaneous Ca 2+ waves, also termed store-overload-induced Ca 2+ release (SOICR), in cardiac cells can trigger ventricular arrhythmias especially in failing hearts. SOICR occurs when RyRs are activated by an increase in sarcoplasmic reticulum (SR) luminal Ca 2+ . Carvedilol is one of the most effective drugs for preventing arrhythmias in patients with heart failure. Furthermore, carvedilol analogues with minimal β-blocking activity also block SOICR showing that SOICR-inhibiting activity is distinct from that for β-block. We show here that carvedilol is a potent inhibitor of cADPR-induced Ca 2+ release in sea urchin egg homogenate. In addition, the carvedilol analog VK-II-86 with minimal β-blocking activity also suppresses cADPR-induced Ca 2+ release. Carvedilol appeared to be a non-competitive antagonist of cADPR and could also suppress Ca 2+ release by caffeine. These results are consistent with cADPR releasing Ca 2+ in sea urchin eggs by sensitizing RyRs to Ca 2+ involving a luminal Ca 2+ activation mechanism. In addition to action on the RyR, we also observed inhibition of inositol 1,4,5-trisphosphate (IP 3 )-induced Ca 2+ release by carvedilol suggesting a common mechanism between these evolutionarily related and conserved Ca 2+ release channels.

Effects of nicergoline on the cardiovascular system of dogs and rats.

PubMed

Huchet, A M; Mouillé, P; Chelly, J; Lucet, B; Doursout, M F; Lechat, P; Schmitt, H

1981-01-01

In pentobarbitalized closed-chest dogs, nicergoline (10--100 microgram/kg, i.v.) reduced blood pressure, heart rate, and splanchnic nerve activity. Intracisternal administration of nicergoline (3 microgram/kg) only reduced splanchnic nerve activity. In open-chest dogs, nicergoline reduced blood pressure, cardiac output, and total peripheral resistance but did not change heart rate. In pithed rats treated with a beta-adrenoceptor-blocking agent, nicergoline reduced the pressor responses to noradrenaline and adrenaline. Nicergoline slightly attenuated the pressor responses of dogs to noradrenaline and tyramine and, in addition, reversed the hypertension induced by adrenaline and dimethylphenylpiperazinium. Nicergoline (100 microgram/kg) increased the tachycardia induced in dogs by stimulation of the right cardiovascular nerve and prevented the inhibitory effect of clonidine on this response. However, nicergoline only partially antagonized the effect of clonidine once it was fully established. Nicergoline did not antagonize the hypotensive and bradycardic effects of clonidine when they were established. Nicergoline did not affect the vagally mediated bradycardia evoked by carotid nerve stimulation in beta-adrenoceptor-blocked dogs. The compound did not change blood pressure in Cl spinal cord transected dogs. In conclusion, nicergoline appears to decrease blood pressure by blocking alpha-adrenoceptors and, at least at some doses, by a central inhibition of the sympathetic tone. Nicergoline appears to be a preferential alpha 1-adrenoceptor-blocking agent.

Dual-chamber pacemakers for treating symptomatic bradycardia due to sick sinus syndrome without atrioventricular block: a systematic review and economic evaluation.

PubMed

Edwards, Steven J; Karner, Charlotta; Trevor, Nicola; Wakefield, Victoria; Salih, Fatima

2015-08-01

Bradycardia [resting heart rate below 60 beats per minute (b.p.m.)] can be caused by conditions affecting the natural pacemakers of the heart, such as sick sinus syndrome (SSS) and atrioventricular (AV) blocks. People suffering from bradycardia may present with palpitations, exercise intolerance and fainting. The only effective treatment for patients suffering from symptomatic bradycardia is implantation of a permanent pacemaker. To appraise the clinical effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber atrial pacemakers for treating symptomatic bradycardia in people with SSS and no evidence of AV block. All databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) were searched from inception to June 2014. A systematic review of the clinical and economic literature was carried out in accordance with the general principles published by the Centre for Reviews and Dissemination. Randomised controlled trials (RCTs) evaluating dual-chamber and single-chamber atrial pacemakers and economic evaluations were included. Pairwise meta-analysis was carried out. A de novo economic model was developed. Of 493 references, six RCTs were included in the review. The results were predominantly influenced by the largest trial DANPACE. Dual-chamber pacing was associated with a statistically significant reduction in reoperation [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.36 to 0.63] compared with single-chamber atrial pacing. The difference is primarily because of the development of AV block requiring upgrade to a dual-chamber device. The risk of paroxysmal atrial fibrillation was also reduced with dual-chamber pacing compared with single-chamber atrial pacing (OR 0.75, 95% CI 0.59 to 0.96). No statistically significant difference was found between the pacing modes for mortality, heart failure, stroke, chronic atrial fibrillation or quality of life. However, the risk of developing heart failure may vary with age and device. The de novo economic model shows that dual-chamber pacemakers are more expensive and more effective than single-chamber atrial devices, resulting in a base-case incremental cost-effectiveness ratio (ICER) of £6506. The ICER remains below £20,000 in probabilistic sensitivity analysis, structural sensitivity analysis and most scenario analyses and one-way sensitivity analyses. The risk of heart failure may have an impact on the decision to use dual-chamber or single-chamber atrial pacemakers. Results from an analysis based on age (> 75 years or ≤ 75 years) and risk of heart failure indicate that dual-chamber pacemakers dominate single-chamber atrial pacemakers (i.e. are less expensive and more effective) in older patients, whereas dual-chamber pacemakers are dominated by (i.e. more expensive and less effective) single-chamber atrial pacemakers in younger patients. However, these results are based on a subgroup analysis and should be treated with caution. In patients with SSS without evidence of impaired AV conduction, dual-chamber pacemakers appear to be cost-effective compared with single-chamber atrial pacemakers. The risk of developing a complete AV block and the lack of tools to identify patients at high risk of developing the condition argue for the implantation of a dual-chamber pacemaker programmed to minimise unnecessary ventricular pacing. However, considerations have to be made around the risk of developing heart failure, which may depend on age and device. This study is registered as PROSPERO CRD42013006708. The National Institute for Health Research Health Technology Assessment programme.

Management of Arrhythmias in Heart Failure

PubMed Central

Masarone, Daniele; Limongelli, Giuseppe; Rubino, Marta; Valente, Fabio; Vastarella, Rossella; Ammendola, Ernesto; Gravino, Rita; Verrengia, Marina; Salerno, Gemma; Pacileo, Giuseppe

2017-01-01

Heart failure patients are predisposed to develop arrhythmias. Supraventricular arrhythmias can exacerbate the heart failure symptoms by decreasing the effective cardiac output and their control require pharmacological, electrical, or catheter-based intervention. In the setting of atrial flutter or atrial fibrillation, anticoagulation becomes paramount to prevent systemic or cerebral embolism. Patients with heart failure are also prone to develop ventricular arrhythmias that can present a challenge to the managing clinician. The management strategy depends on the type of arrhythmia, the underlying structural heart disease, the severity of heart failure, and the range from optimization of heart failure therapy to catheter ablation. Patients with heart failure, irrespective of ejection fraction are at high risk for developing sudden cardiac death, however risk stratification is a clinical challenge and requires a multiparametric evaluation for identification of patients who should undergo implantation of a cardioverter defibrillator. Finally, patients with heart failure can also develop symptomatic bradycardia, caused by sinus node dysfunction or atrio-ventricular block. The treatment of bradycardia in these patients with pacing is usually straightforward but needs some specific issue. PMID:29367535

A bio-inspired microstructure induced by slow injection moulding of cylindrical block copolymers.

PubMed

Stasiak, Joanna; Brubert, Jacob; Serrani, Marta; Nair, Sukumaran; de Gaetano, Francesco; Costantino, Maria Laura; Moggridge, Geoff D

2014-08-28

It is well known that block copolymers with cylindrical morphology show alignment with shear, resulting in anisotropic mechanical properties. Here we show that well-ordered bi-directional orientation can be achieved in such materials by slow injection moulding. This results in a microstructure, and anisotropic mechanical properties, similar to many natural tissues, making this method attractive for engineering prosthetic fibrous tissues. An application of particular interest to us is prosthetic polymeric heart valve leaflets, mimicking the shape, microstructure and hence performance of the native valve. Anisotropic layers have been observed for cylinder-forming block copolymers centrally injected into thin circular discs. The skin layers exhibit orientation parallel to the flow direction, whilst the core layer shows perpendicularly oriented domains; the balance of skin to core layers can be controlled by processing parameters such as temperature and injection rate. Heart valve leaflets with a similar layered structure have been prepared by injection moulding. Numerical modelling demonstrates that such complex orientation can be explained and predicted by the balance of shear and extensional flow.

Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

PubMed

Pillai, Indulekha C L; Li, Shen; Romay, Milagros; Lam, Larry; Lu, Yan; Huang, Jie; Dillard, Nathaniel; Zemanova, Marketa; Rubbi, Liudmilla; Wang, Yibin; Lee, Jason; Xia, Ming; Liang, Owen; Xie, Ya-Hong; Pellegrini, Matteo; Lusis, Aldons J; Deb, Arjun

2017-02-02

Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development. Copyright © 2017 Elsevier Inc. All rights reserved.

The heart of the matter: from guided microtools to 3-D printing and precision genome editing, promising research could lead to new advances in pediatric cardiology.

PubMed

Chandler, David L

2015-01-01

The smooth, powerful muscles of a newborn baby?s heart are pulsing normally, squeezing in and letting go rhythmically as a 3-mm-wide catheter-like tube snakes its way through, entering via an artery and being guided slowly by a surgeon. When it reaches its target?a protruding knot of malformed muscle tissue within a ventricle that has been partly blocking the valve?the tip of the precisely controlled tube whirs into action, with tiny scissor-like rotating blades gently grinding up the excess tissue as those pieces are sucked back into the device, leaving no floating particles that could lead to a blockage elsewhere. The defect is fully removed, and the heart?s function is restored to normal, leaving the child with the prospect of a normal life. The whole minimally invasive process takes place inside a beating heart and would otherwise have required open-heart surgery, with the heart stopped for a cardiopulmonary bypass.

Influence of Competitive-Anxiety on Heart Rate Variability in Swimmers.

PubMed

Fortes, Leonardo S; da Costa, Bruna D V; Paes, Pedro P; do Nascimento Júnior, José R A; Fiorese, Lenamar; Ferreira, Maria E C

2017-12-01

The aim of this study was to analyze the relationship between competitive anxiety and heart rate variability (HRV) in swimming athletes. A total of 66 volunteers (41 male and 27 female) who swam the 400-m freestyle in the Brazilian Swimming Championships participated. Thirty minutes before the 400-m freestyle event, the athletes answered the Competitive Anxiety Inventory (CSAI-2R) questionnaire, then underwent anthropometric (body weight, height, and skinfold thickness) and HRV measurements. Then, at a second meeting, held 3 h after the 400-m freestyle event, the athletes returned to the evaluation room for HRV measurement (Polar ® RS800cx, Kempele, Finland). Multiple linear regression was used to evaluate the relationship between competitive anxiety and HRV. The multiple linear regression was performed in three blocks (block 1: cognitive anxiety, block 2: somatic anxiety, and block 3: self-confidence), adopting the forward model. The results indicated a significant association between cognitive anxiety (p = 0.001) and HRV. An increased magnitude of the association was observed when somatic anxiety was inserted in the model (p = 0.001). In contrast, self-confidence showed, which was inserted in block 3, no relationship with HRV (p = 0.27). It was concluded that cognitive and somatic anxieties were associated with the HRV of swimmers. Athletes with a high magnitude of cognitive and/or somatic anxiety demonstrated more significant autonomic nervous system disturbance. Practically, psychological interventions are needed to improve anxiety states that are specific to perform well, and to improve HRV.

Extraction of SelectSecure leads compared to conventional pacing leads in patients with congenital heart disease and congenital atrioventricular block.

PubMed

Shepherd, Emma; Stuart, Graham; Martin, Rob; Walsh, Mark A

2015-06-01

SelectSecure™ pacing leads (Medtronic Inc) are increasingly being used in pediatric patients and adults with structural congenital heart disease. The 4Fr lead is ideal for patients who may require lifelong pacing and can be advantageous for patients with complex anatomy. The purpose of this study was to compare the extraction of SelectSecure leads with conventional (stylette-driven) pacing leads in patients with structural congenital heart disease and congenital atrioventricular block. The data on lead extractions from pediatric and adult congenital heart disease (ACHD) patients from August 2004 to July 2014 at Bristol Royal Hospital for Children and the Bristol Heart Institute were reviewed. Multivariable regression analysis was used to determine whether conventional pacing leads were associated with a more difficult extraction process. A total of 57 patients underwent pacemaker lead extractions (22 SelectSecure, 35 conventional). No deaths occurred. Mean age at the time of extraction was 17.6 ± 10.5 years, mean weight was 47 ± 18 kg, and mean lead age was 5.6 ± 2.6 years (range 1-11 years). Complex extraction (partial extraction/femoral extraction) was more common in patients with conventional pacing leads at univariate (P < .01) and multivariate (P = .04) levels. Lead age was also a significant predictor of complex extraction (P < .01). SelectSecure leads can be successfully extracted using techniques that are used for conventional pacing leads. They are less likely to be partially extracted and are less likely to require extraction using a femoral approach compared with conventional pacing leads. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Redistribution of blood within the body is important for thermoregulation in an ectothermic vertebrate (Crocodylus porosus).

PubMed

Seebacher, Frank; Franklin, Craig E

2007-11-01

Changes in blood flow are a principal mechanism of thermoregulation in vertebrates. Changes in heart rate will alter blood flow, although multiple demands for limited cardiac output may compromise effective thermoregulation. We tested the hypothesis that regional differences in blood flow during heating and cooling can occur independently from changes in heart rate. We measured heart rate and blood pressure concurrently with blood flow in the crocodile, Crocodylus porosus. We measured changes in blood flow by laser Doppler flowmetry, and by injecting coloured microspheres. All measurements were made under different heat loads, with and without blocking cholinergic and beta-adrenergic receptors (autonomic blockade). Heart rates were significantly faster during heating than cooling in the control animals, but not when autonomic receptors were blocked. There were no significant differences in blood flow distribution between the control and autonomic blockade treatments. In both treatments, blood flow was directed to the dorsal skin and muscle and away from the tail and duodenum during heating. When the heat source was switched off, there was a redistribution of blood from the dorsal surface to the duodenum. Blood flow to the leg skin and muscle, and to the liver did not change significantly with thermal state. Blood pressure was significantly higher during the autonomic blockade than during the control. Thermal time constants of heating and cooling were unaffected by the blockade of autonomic receptors. We concluded that animals partially compensated for a lack of differential heart rates during heating and cooling by redistributing blood within the body, and by increasing blood pressure to increase flow. Hence, measures of heart rate alone are insufficient to assess physiological thermoregulation in reptiles.

Re-entry using anatomically determined isthmuses: a curable ventricular tachycardia in repaired congenital heart disease.

PubMed

Kapel, Gijsbert F L; Reichlin, Tobias; Wijnmaalen, Adrianus P; Piers, Sebastiaan R D; Holman, Eduard R; Tedrow, Usha B; Schalij, Martin J; Stevenson, William G; Zeppenfeld, Katja

2015-02-01

Ventricular tachycardia (VT) is an important cause of late morbidity and mortality in repaired congenital heart disease. The substrate often includes anatomic isthmuses that can be transected by radiofrequency catheter ablation similar to isthmus block for atrial flutter. This study evaluates the long-term efficacy of isthmus block for treatment of re-entry VT in adults with repaired congenital heart disease. Thirty-four patients (49±13 years; 74% male) with repaired congenital heart disease who underwent radiofrequency catheter ablation of VT in 2 centers were included. Twenty-two (65%) had a preserved left and right ventricular function. Patients were inducible for 1 (interquartile range, 1-2) VT, median cycle length: 295 ms (interquartile range, 242-346). Ablation aimed to transect anatomic isthmuses containing VT re-entry circuit isthmuses. Procedural success was defined as noninducibility of any VT and transection of the anatomic isthmus and was achieved in 25 (74%) patients. During long-term follow-up (46±29 months), all patients with procedural success (18/25 with internal cardiac defibrillators) were free of VT recurrence but 7 of 18 experienced internal cardiac defibrillator-related complications. One patient with procedural success and depressed cardiac function received an internal cardiac defibrillator shock for ventricular fibrillation. None of the 18 patients (12/18 with internal cardiac defibrillators) with complete success and preserved cardiac function experienced any ventricular arrhythmia. In contrast, VT recurred in 4 of 9 patients without procedural success. Four patients died from nonarrhythmic causes. In patients with repaired congenital heart disease with preserved ventricular function and isthmus-dependent re-entry, VT isthmus ablation can be curative. © 2014 American Heart Association, Inc.

Palonosetron Injection

MedlinePlus

... works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting. ... beat or heart rhythm dizziness or lightheadedness fainting fast, slow or ... the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting ...

Dolasetron Injection

MedlinePlus

... works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting. ... beat or heart rhythm dizziness lightheadedness, or fainting fast, slow or ... the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting ...

3D Heart: a new visual training method for electrocardiographic analysis.

PubMed

Olson, Charles W; Lange, David; Chan, Jack-Kang; Olson, Kim E; Albano, Alfred; Wagner, Galen S; Selvester, Ronald H S

2007-01-01

This new training method is based on developing a sound understanding of the sequence in which electrical excitation spreads through both the normal and the infarcted myocardium. The student is made aware of the cardiac electrical performance through a series of 3-dimensional pictures during the excitation process. The electrocardiogram 3D Heart 3-dimensional program contains a variety of different activation simulations. Currently, this program enables the user to view the activation simulation for all of the following pathology examples: normal activation; large, medium, and small anterior myocardial infarction (MI); large, medium, and small posterolateral MI; large, medium, and small inferior MI. Simulations relating to other cardiac abnormalities, such as bundle branch block and left ventricular hypertrophy fasicular block, are being developed as part of a National Institute of Health (NIH) Phase 1 Small Business Innovation Research (SBIR) program.

GDF15 is a heart-derived hormone that regulates body growth.

PubMed

Wang, Ting; Liu, Jian; McDonald, Caitlin; Lupino, Katherine; Zhai, Xiandun; Wilkins, Benjamin J; Hakonarson, Hakon; Pei, Liming

2017-08-01

The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well-established clinical observation that children with heart diseases often develop FTT. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

FPGA Implementation of Heart Rate Monitoring System.

PubMed

Panigrahy, D; Rakshit, M; Sahu, P K

2016-03-01

This paper describes a field programmable gate array (FPGA) implementation of a system that calculates the heart rate from Electrocardiogram (ECG) signal. After heart rate calculation, tachycardia, bradycardia or normal heart rate can easily be detected. ECG is a diagnosis tool routinely used to access the electrical activities and muscular function of the heart. Heart rate is calculated by detecting the R peaks from the ECG signal. To provide a portable and the continuous heart rate monitoring system for patients using ECG, needs a dedicated hardware. FPGA provides easy testability, allows faster implementation and verification option for implementing a new design. We have proposed a five-stage based methodology by using basic VHDL blocks like addition, multiplication and data conversion (real to the fixed point and vice-versa). Our proposed heart rate calculation (R-peak detection) method has been validated, using 48 first channel ECG records of the MIT-BIH arrhythmia database. It shows an accuracy of 99.84%, the sensitivity of 99.94% and the positive predictive value of 99.89%. Our proposed method outperforms other well-known methods in case of pathological ECG signals and successfully implemented in FPGA.

Amoco unit acquires two blocks covering 2. 7 million acres in Poland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-10-12

This paper reports that an Amoco Production Co. unit has signed the first agreement by a western company for conventional petroleum exploration rights in Poland. The agreement between Amoco Poland Ltd. and Poland's Ministry of Environmental Protection, Natural Resources, and Forestry calls for Amoco to make an initial $20 million investment to conduct seismic surveys and drill wildcats on two blocks. Block A is a 1,695,750 acre spread southwest of Warsaw in the heart of the Polish trough. Block B covers about 979,000 acres southeast of Lublin on the Polish-Ukrainian border. The state has an option to acquire as muchmore » as 30% interest in future hydrocarbon development.« less

Aquaporin-1 shifts the critical transmural pressure to compress the aortic intima and change transmural flow: theory and implications.

PubMed

Joshi, Shripad; Jan, Kung-Ming; Rumschitzki, David S

2015-12-01

Transmural-pressure (ΔP)-driven plasma advection carries macromolecules into the vessel wall, the earliest prelesion atherosclerotic event. The wall's hydraulic conductivity, LP, the water flux-to-ΔP ratio, is high at low pressures, rapidly decreases, and remains flat to high pressures (Baldwin AL, Wilson LM. Am J Physiol Heart Circ Physiol 264: H26-H32, 1993; Nguyen T, Toussaint, Xue JD, Raval Y, Cancel CB, Russell LM, Shou S, Sedes Y, Sun O, Yakobov Y, Tarbell JM, Jan KM, Rumschitzki DS. Am J Physiol Heart Circ Physiol 308: H1051-H1064, 2015; Tedgui A, Lever MJ. Am J Physiol Heart Circ Physiol. 247: H784-H791, 1984. Shou Y, Jan KM, Rumschitzki DS. Am J Physiol Heart Circ Physiol 291: H2758-H2771, 2006) due to pressure-induced subendothelial intima (SI) compression that causes endothelial cells to partially block internal elastic laminar fenestrae. Nguyen et al. showed that rat and bovine aortic endothelial cells express the membrane protein aquaporin-1 (AQP1) and transmural water transport is both transcellular and paracellular. They found that LP lowering by AQP1 blocking was perplexingly ΔP dependent. We hypothesize that AQP1 blocking lowers average SI pressure; therefore, a lower ΔP achieves the critical force/area on the endothelium to partially block fenestrae. To test this hypothesis, we improve the approximate model of Huang et al. (Huang Y, Rumschitzki D, Chien S, Weinbaum SS. Am J Physiol Heart Circ Physiol 272: H2023-H2039, 1997) and extend it by including transcellular AQP1 water flow. Results confirm the observation by Nguyen et al.: wall LP and water transport decrease with AQP1 disabling. The model predicts 1) low-pressure LP experiments correctly; 2) AQP1s contribute 30-40% to both the phenomenological endothelial + SI and intrinsic endothelial LP; 3) the force on the endothelium for partial SI decompression with functioning AQP1s at 60 mmHg equals that on the endothelium at ∼43 mmHg with inactive AQP1s; and 4) increasing endothelial AQP1 expression increases wall LP and shifts the ΔP regime where LP drops to significantly higher ΔP than in Huang et al. Thus AQP1 upregulation (elevated wall LP) might dilute and slow low-density lipoprotein binding to SI extracellular matrix, which may be beneficial for early atherogenesis. Copyright © 2015 the American Physiological Society.

Genetics Home Reference: progressive familial heart block

MedlinePlus

... Le Marec H, Roden DM, Mochizuki N, Schott JJ, Delmar M. A connexin40 mutation associated with a ... P, Mansourati J, Victor J, Nguyen JM, Schott JJ, Boisseau P, Escande D, Le Marec H. Progressive ...

Treating Heart Failure with Preserved Ejection Fraction: A Challenge for Clinicians.

PubMed

Howard, Patricia A

2015-06-01

Despite a decline in many forms of cardiovascular disease, heart failure (HF) continues to increase. Heart failure with preserved ejection fraction (HFpEF) is common, especially among persons with multiple comorbidities. HFpEF presents many challenges for clinicians due to the incomplete understanding of the underlying mechanisms and lack of consensus on the most effective strategies for treatment. Angiotensin and beta receptor-blocking drugs, which form the cornerstone for the treatment of systolic HF, have failed to show similar benefits in patients with impaired diastolic function. This article provides an overview of drug therapy for HFpEF, including newer agents now under investigation.

The use of α- or β-blockers to ameliorate the chronic stress of captivity in the house sparrow (Passer domesticus)

PubMed Central

Fischer, Clare Parker; Romero, L. Michael

2016-01-01

When wild animals are brought into captivity for the first time, they frequently develop chronic stress symptoms. Animals can develop glucocorticoid dysregulation or changes in the sympathetic nervous system over the course of the first week in captivity. By blocking the action of epinephrine and norepinephrine using α- or β-blockers, we hoped to reduce the degree of chronic stress symptoms exhibited by newly captured house sparrows. We measured corticosterone, heart rate and heart rate variability in 24 house sparrows (Passer domesticus) over the first week of captivity. The birds were treated with saline, propranolol (a β-blocker) or phentolamine (an α-blocker) for the first 3 days of captivity. We also compared newly captured animals with animals that had been held in captivity for 1 month. During the first week of captivity, baseline corticosterone increased, but that increase was blocked by propranolol. Heart rate was not different between the treatment groups, but it was higher during the first week than after 1 month in captivity. Sympathetic nervous system activity (as measured by heart rate variability) decreased over the first week of captivity, but was not affected by treatment. β-Blockers, but not α-blockers, might help to improve some symptoms of chronic stress in newly captured animals. PMID:27752321

Consecutive pharmacological activation of PKA and PKC mimics the potent cardioprotection of temperature preconditioning

PubMed Central

Khaliulin, Igor; Parker, Joanna E.; Halestrap, Andrew P.

2010-01-01

Aims Temperature preconditioning (TP) provides very powerful protection against ischaemia/reperfusion. Understanding the signalling pathways involved may enable the development of effective pharmacological cardioprotection. We investigated the interrelationship between activation of protein kinase A (PKA) and protein kinase C (PKC) in the signalling mechanisms of TP and developed a potent pharmacological intervention based on this mechanism. Methods and results Isolated rat hearts were subjected to TP, 30 min global ischaemia, and 60 min reperfusion. Other control and TP hearts were perfused with either sotalol (β-adrenergic blocker) or H-89 (PKA inhibitor). Some hearts were pre-treated with either isoproterenol (β-adrenergic agonist) or adenosine (PKC activator) that were given alone, simultaneously, or sequentially. Pre-treatment with isoproterenol, adenosine, and the consecutive isoproterenol/adenosine treatment was also combined with the PKC inhibitor chelerythrine. Cardioprotection was evaluated by haemodynamic function recovery, lactate dehydrogenase release, measurement of mitochondrial permeability transition pore opening, and protein carbonylation during reperfusion. Cyclic AMP and PKA activity were increased in TP hearts. H-89 and sotalol blocked the cardioprotective effect of TP and TP-induced PKC activation. Isoproterenol, adenosine, and the consecutive treatment increased PKC activity during pre-ischaemia. Isoproterenol significantly reduced myocardial glycogen content. Isoproterenol and adenosine, alone or simultaneously, protected hearts but the consecutive treatment gave the highest protection. Cardioprotective effects of adenosine were completely blocked by chelerythrine but those of the consecutive treatment only attenuated. Conclusion The signal transduction pathway of TP involves PKA activation that precedes PKC activation. Pharmacologically induced consecutive PKA/PKC activation mimics TP and induces extremely potent cardioprotection. PMID:20558443

Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.

PubMed

Makki, Nader; Dollery, Jenn; Jones, Danielle; Crestanello, Juan; Lilly, Scott

Permanent pacemaker (PPM) placement occurs in 5-20% of patients after transcatheter aortic valve replacement (TAVR). Although predictors of pacemaker implantation have been established, features that predispose patients to pacemaker utilization on follow up have not been widely reported. We performed a retrospective review of patients undergoing commercial TAVR between 2011 and 2016. We collated patients that underwent in-hospital PPM implantation and had a follow up of at least 3months. Data abstraction was performed for electrophysiological studies (EPS), pacemaker indication, timing, and device interrogation for pacemaker dependency on follow up. A total of 24 patients received in-hospital PPM post-TAVR (14% of total cohort), and mean follow up was 22months. Indications for PPM included resting complete heart block (CHB; 15/24, 63%), left bundle branch block and abnormal electrophysiological study (EPS; 7/24, 29%), alternating bundle branch block (1/24, 4%) and tachy-brady syndrome (1/24, 4%). Pacemaker dependency (underlying ventricular asystole, complete heart block, or >50% pacing) occurred in 8/24 patients (33%) during follow-up, 7 of whom had resting CHB, and one with CHB invoked during EPS. Pacemaker dependency after TAVR is common among those that exhibited CHB, but not among those with a prolonged HV delay during EPS. Although preliminary, these observations are relevant to management of rhythm disturbances after TAVR, and may inform the practice of EPS-based PPM implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Electrical Heart Defibrillation with Ion Channel Blockers

NASA Astrophysics Data System (ADS)

Feeney, Erin; Clark, Courtney; Puwal, Steffan

Heart disease is the leading cause of mortality in the United States. Rotary electrical waves within heart muscle underlie electrical disorders of the heart termed fibrillation; their propagation and breakup leads to a complex distribution of electrical activation of the tissue (and of the ensuing mechanical contraction that comes from electrical activation). Successful heart defibrillation has, thus far, been limited to delivering large electrical shocks to activate the entire heart and reset its electrical activity. In theory, defibrillation of a system this nonlinear should be possible with small electrical perturbations (stimulations). A successful algorithm for such a low-energy defibrillator continues to elude researchers. We propose to examine in silica whether low-energy electrical stimulations can be combined with antiarrhythmic, ion channel-blocking drugs to achieve a higher rate of defibrillation and whether the antiarrhythmic drugs should be delivered before or after electrical stimulation has commenced. Progress toward a more successful, low-energy defibrillator will greatly minimize the adverse effects noted in defibrillation and will assist in the development of pediatric defibrillators.

Effect of fluorocarbons on acetylcholinesterase activity and some counter measures

NASA Technical Reports Server (NTRS)

Young, W.; Parker, J. A.

1975-01-01

An isolated vagal sympathetic heart system has been successfully used for the study of the effect of fluorocarbons (FCs) on cardiac performance and in situ enzyme activity. Dichlorodifluoromethane sensitizes this preparation to sympathetic stimulation and to exogenous epinephrine challenge. Partial and complete A-V block and even cardiac arrest have been induced by epinephrine challenge in the FC sensitized heart. Potassium chloride alone restores the rhythmicity but not the normal contractility of the heart in such a situation. Addition of glucose will, however, completely restore the normal function of the heart which is sensitized by dichlorodifluoromethane. The ED 50 values of acetylcholinesterase activity which are used as a measure of relative effectiveness of fluorocarbons are compared with the maximum permissible concentration. Kinetic studies indicate that all the fluorocarbons tested so far are noncompetitive.

Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest.

PubMed

Li, Duan; Mabrouk, Omar S; Liu, Tiecheng; Tian, Fangyun; Xu, Gang; Rengifo, Santiago; Choi, Sarah J; Mathur, Abhay; Crooks, Charles P; Kennedy, Robert T; Wang, Michael M; Ghanbari, Hamid; Borjigin, Jimo

2015-04-21

The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain-heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain's autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain.

Dystrophic heart failure blocked by membrane sealant poloxamer

NASA Astrophysics Data System (ADS)

Yasuda, Soichiro; Townsend, Dewayne; Michele, Daniel E.; Favre, Elizabeth G.; Day, Sharlene M.; Metzger, Joseph M.

2005-08-01

Dystrophin deficiency causes Duchenne muscular dystrophy (DMD) in humans, an inherited and progressive disease of striated muscle deterioration that frequently involves pronounced cardiomyopathy. Heart failure is the second leading cause of fatalities in DMD. Progress towards defining the molecular basis of disease in DMD has mostly come from studies on skeletal muscle, with comparatively little attention directed to cardiac muscle. The pathophysiological mechanisms involved in cardiac myocytes may differ significantly from skeletal myofibres; this is underscored by the presence of significant cardiac disease in patients with truncated or reduced levels of dystrophin but without skeletal muscle disease. Here we show that intact, isolated dystrophin-deficient cardiac myocytes have reduced compliance and increased susceptibility to stretch-mediated calcium overload, leading to cell contracture and death, and that application of the membrane sealant poloxamer 188 corrects these defects in vitro. In vivo administration of poloxamer 188 to dystrophic mice instantly improved ventricular geometry and blocked the development of acute cardiac failure during a dobutamine-mediated stress protocol. Once issues relating to optimal dosing and long-term effects of poloxamer 188 in humans have been resolved, chemical-based membrane sealants could represent a new therapeutic approach for preventing or reversing the progression of cardiomyopathy and heart failure in muscular dystrophy.

Discovery of novel small molecule inhibitors of cardiac hypertrophy using high throughput, high content imaging

PubMed Central

Reid, Brian G.; Stratton, Matthew S.; Bowers, Samantha; Cavasin, Maria A.; Demos-Davies, Kimberley M.; Susano, Isidro; McKinsey, Timothy A.

2016-01-01

Chronic cardiac hypertrophy is maladaptive and contributes to the pathogenesis of heart failure. The objective of this study was to identify small molecule inhibitors of pathological cardiomyocyte hypertrophy. High content screening was performed with primary neonatal rat ventricular myocytes (NRVMs) cultured on 96-well plates and treated with a library of 3241 distinct small molecules. Non-toxic hit compounds that blocked hypertrophy in response to phenylephrine (PE) and phorbol myristate acetate (PMA) were identified based on their ability to reduce cell size and inhibit expression of atrial natriuretic factor (ANF), which is a biomarker of pathological cardiac hypertrophy. Many of the hit compounds are existing drugs that have not previously been evaluated for benefit in the setting of cardiovascular disease. One such compound, the anti-malarial drug artesunate, blocked left ventricular hypertrophy (LVH) and improved cardiac function in adult mice subjected to transverse aortic constriction (TAC). These findings demonstrate that phenotypic screening with primary cardiomyocytes can be used to discover anti-hypertrophic lead compounds for heart failure drug discovery. Using annotated libraries of compounds with known selectivity profiles, this screening methodology also facilitates chemical biological dissection of signaling networks that control pathological growth of the heart. PMID:27130278

A novel design of combining the angiotensin converting enzyme (ACE) inhibitor captopril with the angiotensin receptor blocker (ARB) losartan using homo coupling via PEG diacid linker.

PubMed

Hashemzadeh, Mehrnoosh; Park, Shery; Ju, Hee; Movahed, Mohammad R

2013-12-01

Cardiovascular disease is the leading cause of death in American adults. Furthermore, the incidence of congestive heart failure is on the rise as a major cause of hospitalization and mortality in this population. Angiotensin Converting Enzyme (ACE) inhibitors prevent the production of angiotensin II, which has been shown to reduce mortality in patients with congestive heart failure. Angiotensin II receptor blockers (ARB) were developed as a direct inhibitor of angiotensin II. ARBs have been shown to be effective in the treatment of patients with systolic heart failure but do not cause chronic coughing which is a common side effect of ACE inhibitors. In theory, a compound that has the combined effect of an ACE inhibitor and an ARB should be more effective in treating heart failure patients than either agents alone. Therefore, the purpose of this manuscript is to design and discuss the benefits of a new molecule, which combines captopril, an ACE inhibitor, with losartan, an ARB. In this experiment Captopril and Losartan were modified and synthesized separately and combined by homo or mono coupling. This was achieved by taking advantage of PEG (Polyethylene glycol) as a linker. It is expected that this molecule will have the combined modes of action of both ACEs and ARBs. Benefits from combination therapy include; increased efficacy, reduced adverse effects, convenience, compliance, and prolonged duration. Consequently, this combined molecule is expected to block the production of angiotensin II more efficiently and effectively. Although captopril and losartan work in the same system by blocking the effect of angiotensin II they have different action sites and mechanisms some patents are also discussed. Losartan blocks the AT1 receptor which is expressed on the cell surface, while captopril inhibits ACE, preventing production of angiotensin II, which is present in both the plasma and on the cell surface, especially on endothelial and smooth muscle cells.

Endocannabinoids protect the rat isolated heart against ischaemia

PubMed Central

Lépicier, Philippe; Bouchard, Jean-François; Lagneux, Caroline; Lamontagne, Daniel

2003-01-01

The purpose of this study was to determine whether endocannabinoids can protect the heart against ischaemia and reperfusion. Rat isolated hearts were exposed to low-flow ischaemia (0.5–0.6 ml min−1) and reperfusion. Functional recovery as well as CK and LDH overflow into the coronary effluent were monitored. Infarct size was determined at the end of the experiments. Phosphorylation levels of p38, ERK1/2, and JNK/SAPK kinases were measured by Western blots. None of the untreated hearts recovered from ischaemia during the reperfusion period. Perfusion with either 300 nM palmitoylethanolamide (PEA) or 300 nM 2-arachidonoylglycerol (2-AG), but not anandamide (up to 1 μM), 15 min before and throughout the ischaemic period, improved myocardial recovery and decreased the levels of coronary CK and LDH. PEA and 2-AG also reduced infarct size. The CB2-receptor antagonist, SR144528, blocked completely the cardioprotective effect of both PEA and 2-AG, whereas the CB1-receptor antagonist, SR141716A, blocked partially the effect of 2-AG only. In contrast, both ACEA and JWH015, two selective agonists for CB1- and CB2- receptors, respectively, reduced infarct size at a concentration of 50 nM. PEA enhanced the phosphorylation level of p38 MAP kinase during ischaemia. PEA perfusion doubled the baseline phosphorylation level of ERK1/2, and enhanced its increase upon reperfusion. The cardioprotective effect of PEA was completely blocked by the p38 MAP kinase inhibitor, SB203580, and significantly reduced by the ERK1/2 inhibitor, PD98059, and the PKC inhibitor, chelerythrine. In conclusion, endocannabinoids exert a strong cardioprotective effect in a rat model of ischaemia–reperfusion that is mediated mainly through CB2-receptors, and involves p38, ERK1/2, as well as PKC activation. PMID:12813004

Lyme Carditis Buried Beneath ST-Segment Elevations

PubMed Central

Umpierrez De Reguero, Adrian

2017-01-01

Lyme disease is caused by the spirochete Borrelia burgdorferi and is carried to human hosts by infected ticks. There are nearly 30,000 cases of Lyme disease reported to the CDC each year, with 3-4% of those cases reporting Lyme carditis. The most common manifestation of Lyme carditis is partial heart block following bacterial-induced inflammation of the conducting nodes. Here we report a 45-year-old gentleman that presented to the hospital with intense nonradiating chest pressure and tightness. Lab studies were remarkable for elevated troponins. EKG demonstrated normal sinus rhythm with mild ST elevations. Three weeks prior to hospital presentation, patient had gone hunting near Madison. One week prior to admission, he noticed an erythematous lesion on his right shoulder. Because of his constellation of history, arthralgias, and carditis, he was started on ceftriaxone to treat probable Lyme disease. This case illustrates the importance of thorough history taking and extensive physical examination when assessing a case of possible acute myocardial infarction. Because Lyme carditis is reversible, recognition of this syndrome in young patients, whether in the form of AV block, myocarditis, or acute myocardial ischemia, is critical to the initiation of appropriate antibiotics in order to prevent permanent heart block, or even death. PMID:28713599

Selectivity of beta-adrenergic stimulating and blocking agents.

PubMed

Löfdahl, C G; Svedmyr, N

1984-01-01

Studies have been performed to answer two questions: whether there are subgroups of beta 2-receptors separating effects in bronchial and skeletal muscle and whether beta 1-receptors in asthmatic airways mediate bronchoconstriction. Asthmatic patients have been studied in randomised cross-over trials. Effects on FEV1, heart rate and skeletal muscle tremor have been monitored. In some experimental studies, two new compounds, D2343 and QH-25, have shown a selectivity for beta 2-receptors in bronchial muscle compared to skeletal muscle. Studies in asthmatics did not confirm this. Thus, the beta 2-receptors in the two organs appear to be identical. The clinical effect of beta 1-receptors in the the airways was studied by giving selective beta 1-receptor blocking agents. It was shown that pafenolol , a beta-blocker more beta 1-selective than metoprolol, had less effect on FEV1 than metoprolol given in equipotent beta 1-blocking doses. Beta 1-receptor stimulation with a new selective beta 1-stimulating agent, prenalterol, did not give bronchodilation in doses which gave a significant increase of heart rate. Thus, beta 1-receptors do not contribute to bronchodilation in asthmatic patients.

No histologic evidence of foetal cardiotoxicity following exposure to maternal hydroxychloroquine.

PubMed

Friedman, Deborah; Lovig, Leif; Halushka, Marc; Clancy, Robert M; Izmirly, Peter M; Buyon, Jill P

2017-01-01

It is currently recommended that hydroxychloroquine (HCQ) be maintained during pregnancy in patients with systemic lupus erythematosus. Recent data suggest that this Toll-like receptor inhibitor may also reduce the recurrence rate of anti-SSA/Ro associated congenital heart block (CHB). This case report describes a unique situation in which a CHB-afflicted, HCQ-exposed pregnancy was electively terminated. The heart did not reveal any characteristic features of cardiotoxicity, providing further evidence supporting the safety of foetal exposure to HCQ.

In Vitro Cardiovascular Effects of Dihydroartemisin-Piperaquine Combination Compared with Other Antimalarials

PubMed Central

Crumb, William; Pace, Silvia; Ubben, David; Wible, Barb; Yan, Gan-Xin; Funck-Brentano, Christian

2012-01-01

The in vitro cardiac properties of dihydroartemisinin (DHA) plus piperaquine phosphate (PQP) were compared with those of other antimalarial compounds. Results with antimalarial drugs, chosen on the basis of their free therapeutic maximum concentration in plasma (Cmax), were expressed as the fold of that particular effect with respect to their Cmax. The following tests were used at 37°C: hERG (human ether-à-go-go-related gene) blockade and trafficking, rabbit heart ventricular preparations, and sodium and slow potassium ion current interference (INa and IKs, respectively). Chloroquine, halofantrine, mefloquine, and lumefantrine were tested in the hERG studies, but only chloroquine, dofetilide, lumefantrine, and the combination of artemether-lumefantrine were used in the rabbit heart ventricular preparations, hERG trafficking studies, and INa and IKs analyses. A proper reference was used in each test. In hERG studies, the high 50% inhibitory concentration (IC50) of halofantrine, which was lower than its Cmax, was confirmed. All the other compounds blocked hERG, with IC50s ranging from 3- to 30-fold their Cmaxs. In hERG trafficking studies, the facilitative effects of chloroquine at about 30-fold its Cmax were confirmed and DHA blocked it at a concentration about 300-fold its Cmax. In rabbit heart ventricular preparations, dofetilide, used as a positive control, revealed a high risk of torsades de pointes, whereas chloroquine showed a medium risk. Neither DHA-PQP nor artemether-lumefantrine displayed an in vitro signal for a significant proarrhythmic risk. Only chloroquine blocked the INa ion current and did so at about 30-fold its Cmax. No effect on IKs was detected. In conclusion, despite significant hERG blockade, DHA-PQP and artemether-lumefantrine do not appear to induce potential torsadogenic effects in vitro, affect hERG trafficking, or block sodium and slow potassium ion currents. PMID:22391528

[The effect of hypothyroidism on cardiac function in dogs].

PubMed

Stephan, I; Nolte, I; Hoppen, H O

2003-06-01

The thyroid hormones have direct and indirect effects on the heart. So it is possible that depression of left ventricular function is associated with hypothyroidism. This publication describes cardiac findings (auscultation, electrocardiography, echocardiography) in ten hypothyroid dogs. Low heart rates, reduced R-amplitudes and bradycardic arrhythmias (first and second-degree AV block) were found on the electrocardiogram before treatment. On the echocardiograms most of the dogs showed reduced contractillity and reduced left ventricular wall thickness. Seven dogs were reexamined after levothyroxine supplementation. Effects of treatment were increased heart rates and R-amplitudes as well as disappearance of the bradycardic arrhythmias in electrocardiographic examination. The echocardiographic examination showed increased contractility and increased left ventricular wall thickness.

Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest

PubMed Central

Li, Duan; Mabrouk, Omar S.; Liu, Tiecheng; Tian, Fangyun; Xu, Gang; Rengifo, Santiago; Choi, Sarah J.; Mathur, Abhay; Crooks, Charles P.; Kennedy, Robert T.; Wang, Michael M.; Ghanbari, Hamid; Borjigin, Jimo

2015-01-01

The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain–heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain’s autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain. PMID:25848007

Pericardial constriction after cardiac transplantation.

PubMed

Bansal, Ramesh; Perez, Leandro; Razzouk, Anees; Wang, Nan; Bailey, Leonard

2010-03-01

In this study we present a series of 5 cases that developed constrictive pericarditis after orthotopic heart transplantation. All 5 patients had pericardial effusion of non-infectious etiology in the early post-transplant period. They subsequently presented with heart failure unresponsive to standard medical management. The diagnosis was made by comprehensive echo-Doppler studies. Findings were confirmed at surgical inspection and complete pericardiectomy led to improvement in hemodynamics in 4 patients. One patient had relief from constriction but died of non-cardiac complications. One patient with constriction has been re-listed for transplantation due to intermittent heart block and associated cardiac allograft vasculopathy. Early diagnosis of pericardial constriction after orthotopic heart transplantation requires a high index of clinical suspicion and optimal use of Doppler echocardiography. Early diagnosis and timely surgical pericardiectomy may correct this condition entirely and result in satisfactory long-term results.

Bradycardia in a Pediatric Heart Transplant Recipient: Is It the Sugammadex?

PubMed

King, Adele; Naguib, Aymen; Tobias, Joseph D

2017-01-01

Sugammadex is a novel pharmacologic agent that is used to selectively reverse the effects of the neuromuscular blocking agents rocuronium and vecuronium. Various advantages have been reported when comparing its reversal of neuromuscular blockade to that achieved with acetylcholinesterase inhibitors (neostigmine). In heart transplant recipients, bradycardia may occur following the administration of acetylcholinesterase inhibitors, due to the denervation of the heart. Theoretically, the combination of rocuronium and sugammadex could be advantageous in this clinical scenario to avoid the potential bradycardia resulting from neostigmine administration. We present a 10-year-old male who developed profound bradycardia immediately following the administration of intravenous sugammadex. The options for reversal of neuromuscular blockade in heart transplant recipients is discussed, previous reports of bradycardia following sugammadex are presented, and the role of sugammadex in the bradycardia in our patient is reviewed.

Carvedilol case history: the discovery and development of the first β-blocker for the treatment of congestive heart failure.

PubMed

Ruffolo, Robert R; Feuerstein, Giora Z

2006-06-01

Carvedilol is a multiple action drug that blocks β1-, β2- and α1- adrenoceptors, and has potent antioxidant properties. Carvedilol is the first drug of its kind to be approved for the treatment of congestive heart failure, and is now the standard of care for this devastating disease. The discovery and development of carvedilol encountered an adverse regulatory climate, skepticism by the cardiology community and hesitance by the company, and in the early 1990s, the fate of the drug was uncertain. Nonetheless, in the largest heart failure study conducted up until that point, carvedilol produced marked reductions in morbidity and mortality, and has given new hope to patients afflicted with congestive heart failure. The story behind carvedilol contains important observations and lessons for scientists, regulators and physicians.

Congenital heart defect causing mutation in Nkx2.5 displays in vivo functional deficit.

PubMed

Zakariyah, Abeer F; Rajgara, Rashida F; Veinot, John P; Skerjanc, Ilona S; Burgon, Patrick G

2017-04-01

The Nkx2.5 gene encodes a transcription factor that plays a critical role in heart development. In humans, heterozygous mutations in NKX2.5 result in congenital heart defects (CHDs). However, the molecular mechanisms by which these mutations cause the disease remain unknown. NKX2.5-R142C is a mutation that was reported to be associated with atrial septal defect (ASD) and atrioventricular (AV) block in 13-patients from one family. The R142C mutation is located within both the DNA-binding domain and the nuclear localization sequence of NKX2.5 protein. The pathogenesis of CHDs in humans with R142C point mutation is not well understood. To examine the functional deficit associated with this mutation in vivo, we generated and characterized a knock-in mouse that harbours the human mutation R142C. Systematic structural and functional examination of the embryonic, newborn, and adult mice revealed that the homozygous embryos Nkx2.5 R141C/R141C are developmentally arrested around E10.5 with delayed heart morphogenesis and downregulation of Nkx2.5 target genes, Anf, Mlc2v, Actc1 and Cx40. Histological examination of Nkx2.5 R141C/+ newborn hearts showed that 36% displayed ASD, with at least 80% 0f adult heterozygotes displaying a septal defect. Moreover, heterozygous Nkx2.5 R141C/+ newborn mice have downregulation of ion channel genes with 11/12 adult mice manifesting a prolonged PR interval that is indicative of 1st degree AV block. Collectively, the present study demonstrates that mice with the R141C point mutation in the Nkx2.5 allele phenocopies humans with the NKX2.5 R142C point mutation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanistic insight into prolonged electromechanical delay in dyssynchronous heart failure: a computational study

PubMed Central

Constantino, Jason; Hu, Yuxuan; Lardo, Albert C.

2013-01-01

In addition to the left bundle branch block type of electrical activation, there are further remodeling aspects associated with dyssynchronous heart failure (HF) that affect the electromechanical behavior of the heart. Among the most important are altered ventricular structure (both geometry and fiber/sheet orientation), abnormal Ca2+ handling, slowed conduction, and reduced wall stiffness. In dyssynchronous HF, the electromechanical delay (EMD), the time interval between local myocyte depolarization and myofiber shortening onset, is prolonged. However, the contributions of the four major HF remodeling aspects in extending EMD in the dyssynchronous failing heart remain unknown. The goal of this study was to determine the individual and combined contributions of HF-induced remodeling aspects to EMD prolongation. We used MRI-based models of dyssynchronous nonfailing and HF canine electromechanics and constructed additional models in which varying combinations of the four remodeling aspects were represented. A left bundle branch block electrical activation sequence was simulated in all models. The simulation results revealed that deranged Ca2+ handling is the primary culprit in extending EMD in dyssynchronous HF, with the other aspects of remodeling contributing insignificantly. Mechanistically, we found that abnormal Ca2+ handling in dyssynchronous HF slows myofiber shortening velocity at the early-activated septum and depresses both myofiber shortening and stretch rate at the late-activated lateral wall. These changes in myofiber dynamics delay the onset of myofiber shortening, thus giving rise to prolonged EMD in dyssynchronous HF. PMID:23934857

Identifying the Evolutionary Building Blocks of the Cardiac Conduction System

PubMed Central

Jensen, Bjarke; Boukens, Bastiaan J. D.; Postma, Alex V.; Gunst, Quinn D.; van den Hoff, Maurice J. B.; Moorman, Antoon F. M.; Wang, Tobias; Christoffels, Vincent M.

2012-01-01

The endothermic state of mammals and birds requires high heart rates to accommodate the high rates of oxygen consumption. These high heart rates are driven by very similar conduction systems consisting of an atrioventricular node that slows the electrical impulse and a His-Purkinje system that efficiently activates the ventricular chambers. While ectothermic vertebrates have similar contraction patterns, they do not possess anatomical evidence for a conduction system. This lack amongst extant ectotherms is surprising because mammals and birds evolved independently from reptile-like ancestors. Using conserved genetic markers, we found that the conduction system design of lizard (Anolis carolinensis and A. sagrei), frog (Xenopus laevis) and zebrafish (Danio rerio) adults is strikingly similar to that of embryos of mammals (mouse Mus musculus, and man) and chicken (Gallus gallus). Thus, in ectothermic adults, the slow conducting atrioventricular canal muscle is present, no fibrous insulating plane is formed, and the spongy ventricle serves the dual purpose of conduction and contraction. Optical mapping showed base-to-apex activation of the ventricles of the ectothermic animals, similar to the activation pattern of mammalian and avian embryonic ventricles and to the His-Purkinje systems of the formed hearts. Mammalian and avian ventricles uniquely develop thick compact walls and septum and, hence, form a discrete ventricular conduction system from the embryonic spongy ventricle. Our study uncovers the evolutionary building plan of heart and indicates that the building blocks of the conduction system of adult ectothermic vertebrates and embryos of endotherms are similar. PMID:22984480

A novel mechanism of bradycardia and the character of acetylcholine in the heart.

PubMed

Młynarska, M S; Garlicki, M; Jakobczak, M M; Skowron-Cendrzak, A

2006-01-01

At first the aim of our study was to observe the simultaneous responses of two hearts after intraarterial (into a. femoralis) adrenaline administration, in the rat with its own heart and a transplanted one--hence non-innervated. After these, some next experiments were performed: in some rats the His bundle of the heterotopically transplanted heart was damaged before transplantation. In all experiments the heart rate was observed on ECG and simultaneously, the arterial blood pressure was recorded from femoral artery in Vetbutal-anaesthetized rats. 1) both the heterotopically transplanted, non-innervated heart and the animal's own heart reacted to adrenaline administeration by producing bradycardia, 2) the heterotopically transplanted heart with the damaged His bundle--hence with a ventricular block reacted to adrenaline administration by raising the heart rate, whereas at the same time and in the same animal its own heart reacted by producing bradycardia. 1) the cause of bradycardia after adrenaline administration does not lie in the reflex from the arcus aortae, since we observed bradycardia after adrenaline administration also in the transplanted, non-innervated heart; therefore the baroreceptor reflex is not the cause of bradycardia after adrenaline administration; 2) bradycardia after adrenaline occurs in both the proper heart and the transplanted, non-innervated one, as a result of an interaction between two cholinergic centres which must be situated above and below the point of the His bundle interruption. The role of acetylcholine in the heart results from the interaction between these two centres.

Stroke - secondary to cardiogenic embolism

MedlinePlus Videos and Cool Tools

A blood clot, or embolus, can form and break-off from the heart. The clot travels through the bloodstream where it can lodge in an artery of the brain, blocking the flow of oxygen-rich blood. The lack of oxygen results in damage, destruction, ...

Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

PubMed

Clancy, Robert M; Markham, Androo J; Jackson, Tanisha; Rasmussen, Sara E; Blumenberg, Miroslav; Buyon, Jill P

2017-09-01

The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical S -adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor 3 (RAPGEF3), tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, and dual specificity phosphatase 1, were downregulated. Agnostic Database for Annotation, Visualization and Integrated Discovery analysis revealed a significant increase in inflammatory genes, including complement C3A receptor 1 (C3AR1), F2R-like thrombin/trypsin receptor 3, and neutrophil cytosolic factor 2. In addition, stimulated fibroblasts expressed high levels of phospho-MADS box transcription enhancer factor 2 [a substrate of MAPK5 (ERK5)], which was inhibited by BIX-02189, a specific inhibitor of ERK5. Translation to human disease leveraged an unprecedented opportunity to interrogate the transcriptome of fibroblasts freshly isolated and cell sorted without stimulation from a fetal heart with CHB and a matched healthy heart. Consistent with the in vitro data, five IFN response genes were among the top 10 most highly expressed transcripts in CHB fibroblasts. In addition, the expression of matrix-related genes reflected fibrosis. These data support the novel finding that cardiac injury in CHB may occur secondary to abnormal remodeling due in part to upregulation of type 1 IFN response genes. NEW & NOTEWORTHY Congenital heart block is a rare disease of the fetal heart associated with maternal anti-Ro autoantibodies which can result in death and for survivors, lifelong pacing. This study provides in vivo and in vitro transcriptome-support that injury may be mediated by an effect of Type I Interferon on fetal fibroblasts. Copyright © 2017 the American Physiological Society.

Prevalence of Chagas heart disease in a region endemic for Trypanosoma cruzi: evidence from a central Bolivian community.

PubMed

Yager, Jessica E; Lozano Beltran, Daniel F; Torrico, Faustino; Gilman, Robert H; Bern, Caryn

2015-09-01

Though the incidence of new Trypanosoma cruzi infections has decreased significantly in endemic regions in the Americas, medical professionals continue to encounter a high burden of resulting Chagas disease among infected adults. The current prevalence of Chagas heart disease in a community setting is not known; nor is it known how recent insecticide vector control measures may have impacted the progression of cardiac disease in an infected population. We sought to determine the current prevalence of T. cruzi infection and associated Chagas heart disease in a Bolivian community endemic for T. cruzi. Nested within a community serosurvey in rural and periurban communities in central Bolivia, we performed a cross-sectional cardiac substudy to evaluate adults for historical, clinical, and electrocardiographic evidence of cardiac disease. All adults between the ages of 20 and 60 years old with T. cruzi infection and those with a clinical history, physical exam, or electrocardiogram consistent with cardiac abnormalities were also scheduled for echocardiography. Of the 604 cardiac substudy participants with definitive serology results, 183 were seropositive for infection with T. cruzi (30.3%). Participants who were seropositive for T. cruzi infection were more likely to have conduction system defects (1.6% vs. 0% for complete right bundle branch block and 10.4% vs. 1.9% for any bundle branch block; p = 0.008 and p < 0.001, respectively). However, there was no statistically significant difference in the prevalence of bradycardia among seropositive versus seronegative participants. Echocardiogram findings were not consistent with a high burden of Chagas cardiomyopathy: valvulopathies were the most common abnormality, and few participants were found to have low ejection fraction or left ventricular dilatation. No participants had significant heart failure. Though almost one-third of adults in the community were seropositive for T. cruzi infection, few had evidence of Chagas heart disease. Copyright © 2015 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

Effect of block weight on work demands and physical workload during masonry work.

PubMed

Van Der Molen, H F; Kuijer, P P F M; Hopmans, P P W; Houweling, A G; Faber, G S; Hoozemans, M J M; Frings-Dresen, M H W

2008-03-01

The effect of block weight on work demands and physical workload was determined for masons who laid sandstone building blocks over the course of a full work day. Three groups of five sandstone block masons participated. Each group worked with a different block weight: 11 kg, 14 kg or 16 kg. Productivity and durations of tasks and activities were assessed through real time observations at the work site. Energetic workload was also assessed through monitoring the heart rate and oxygen consumption at the work site. Spinal load of the low back was estimated by calculating the cumulated elastic energy stored in the lumbar spine using durations of activities and previous data on corresponding compression forces. Block weight had no effect on productivity, duration or frequency of tasks and activities, energetic workload or cumulative spinal load. Working with any of the block weights exceeded exposure guidelines for work demands and physical workload. This implies that, regardless of block weight in the range of 11 to 16 kg, mechanical lifting equipment or devices to adjust work height should be implemented to substantially lower the risk of low back injuries.

Skin aging parameters: A window to heart block.

PubMed

Roshdy, Hisham Samir; Soliman, Mohammad Hassan; El-Dosouky, Ibtesam Ibrahim; Ghonemy, Soheir

2018-01-01

Skin acts as a mirror to the internal state of the body. We tried to find the relation between skin aging parameters and the incidence of degenerative AV block. This study included 97 patients divided into 2 groups; group D comprised 49 patients with advanced-degree AV block, and group C comprised the 48 matched control group. All were subjected to full history taking, thorough clinical examination, calculation of intrinsic skin aging score, and resting 12-lead surface electrocardiography (ECG). ECG for all patients assessed left ventricular end-systolic diameter, left ventricular end-diastolic diameter, ejection fraction, left atrium (LA) diameter, aortic root diameter, mitral annular calcification, aortic sclerosis. Coronary angiography was also performed when indicated for patients in group D. Patients in group D had a higher percentages of uneven pigmentation, fine skin wrinkles, lax appearance, seborrheic keratosis, total score > 7 (38 [77.55%] vs 10 [20.83%]), mitral annular calcification score of 33 (67.34%) vs 5 (10.41%), aortic sclerosis score of 21 (42.85%) vs 4 (8.33%), and mean LA diameter of 39.98 ± 5.52 vs 36.21 ± 3 mm (P < 0.001). Total score > 6 is the best cutoff value to predict advanced-degree heart block with 89.79% sensitivity and 64.58% specificity. Seborrheic keratosis was the strongest independent predictor. Any population with a total intrinsic skin aging score of >6 is at high risk for developing advanced-degree AV block and should undergo periodic ECG follow-up for early detection of any conduction disturbance in the early asymptomatic stages to minimize sudden cardiac death. © 2017 Wiley Periodicals, Inc.

[Pre- and post-orthotopic heart transplantation electrocardiogram characteristics of 998 patients].

PubMed

Guan, H Q; Chen, Z J; Zhou, Y; Liu, J; Sun, W X; Yuan, J; Liao, Y H; Dong, N G; Liu, J P; Feng, K G; Zhang, Q; Zhao, X; Qian, C; Hu, F

2017-04-24

Objective: To analyze pre- and post-operation electrocardiograms (ECGs) features of patients underwent orthotopic heart transplantation (OHT), and provide evidences for identifying and analyzing post OHT ECGs. Methods: Nine hundreds and ninty-eight pre- and post- OHT standard 12-leads ECGs from 110 consecutive patients, who underwent OHT in our hospital from May 2008 to May 2014, were analyzed. Results: The mean heart rate(HR)was (86.9±16.4) beats per minute before OHT, and (100.0±0.4) beats per minute after OHT. P wave's amplitude, duration, amplitude multiplied by duration of donor heart in lead Ⅱ were (0.124±0.069)mV, (111.1±17.2)ms, (14.34±9.51)mV·ms before OHT; (0.054±0.037)mV, (86.9±27.0)ms, (5.02±4.03)mV·ms at 1 month after OHT; (0.073±0.049)mV, (93.9±17.5) ms, (7.00±4.81)mV·ms at 6 years after OHT. ECGs rotation occurred in 83.64%(92/110) patients after OHT, and prevalence of clockwise rotation was 76.36%(84/110). Sinus tachycardia was evidenced in 99.09%(109/110) patients after OHT, and incomplete right bundle branch block was present in 60.91%(67/110) patients after OHT. Pseudo complete atrioventricular block mostly occurred at 2 days after OHT. Prevalence of double sinus rhythm was 27.95%(263/941) post OHT, 40% of them occurred between the 1st and the 2nd month post OHT; the atrial rate of recipient hearts was (104.0±10.2) beats per minucte between the 3rd and the 6th month post OHT, and was (95.3±4.2) beats per minucte between the 4th year and the 5th year. P wave's amplitude, duration, amplitude multiplied by duration of recipient heart in lead Ⅱ were (0.066±0.055) mV, (52.8±34.7) ms, (4.67±4.95) mV·ms at 1 month after OHT, (0.043±0.040)mV, (44.4±40.5) ms , (3.11±3.61) mV·ms between the 1st year and 2nd year after OHT. The absolute value of P-wave(originating from the donor heart) terminal force in chest leads increased in 48.99%(461/941) patients post OHT, the P-wave terminal force of V(1) , V(2) and V(3) were -0.044(-0.066, -0.028), -0.060(-0.087, -0.038), -0.035(-0.056, 0) mm·s. Notched P wave in chest leads was presented in 10.31%(97/941) patients post OHT. PR segment depression in chest leads occurred in 60.24%(100/166) patients between the 3rd month and the 6th month, the incidence of PR segment depression in V(1) , V(2) and V(3) was 21.04%(198/941), 37.41%(352/941) and 28.69%(270/941), respectively. Conclusions: OHT is related to significantly changed ECGs. The mean HR increased significantly after OHT, then decreased gradually after half a year to one year, but it was still higher than preoperative mean HR after five or six years; the P waves of donor heart were usually inconspicuous or small in first month after OHT, and they became bigger after 2 months, and their duration and amplitude then became relatively steady afterwards. ECGs rotation, especially the clockwise rotation, was common post OHT. A variety of arrhythmias originating from the donor heart including sinus tachycardia and incomplete right bundle branch block could be found. Pseudo complete atrioventricular block could also be found in the early phase after OHT. With the extension of time, the incidence of double sinus rhythm reduced gradually. The atrial rate and P wave of recipient heart presented with a tendency to become lower. The absolute value of P-waves(originating from the donor heart) terminal force in chest leads (mainly V(1), V(2) and V(3)) increased, notched P waves in chest leads (mainly V(1), V(2)) and PR segments depression in chest leads (mainly V(2), V(3) and V(4)) also belong to typical post OHT ECGs features.

The cardiac effects of carbon nanotubes in rat.

PubMed

Hosseinpour, Mina; Azimirad, Vahid; Alimohammadi, Maryam; Shahabi, Parviz; Sadighi, Mina; Ghamkhari Nejad, Ghazaleh

2016-01-01

Carbon nanotubes (CNTs) are novel candidates in nanotechnology with a variety of increasing applications in medicine and biology. Therefore the investigation of nanomaterials' biocompatibility can be an important topic. The aim of present study was to investigate the CNTs impact on cardiac heart rate among rats. Electrocardiogram (ECG) signals were recorded before and after injection of CNTs on a group with six rats. The heart rate variability (HRV) analysis was used for signals analysis. The rhythm-to-rhythm (RR) intervals in HRV method were computed and features of signals in time and frequency domains were extracted before and after injection. RESULTS of the HRV analysis showed that CNTs increased the heart rate but generally these nanomaterials did not cause serious problem in autonomic nervous system (ANS) normal activities. Injection of CNTs in rats resulted in increase of heart rate. The reason of phenomenon is that multiwall CNTs may block potassium channels. The suppressed and inhibited IK and potassium channels lead to increase of heart rate.

Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allison, Patrick; Huang, Tianfang; Broka, Derrick

2013-10-01

Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGFβ family of ligands and receptors is essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronarymore » smooth muscle cells. In this in vitro study, 18 hour exposure to 1.34 μM arsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 μM arsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease in vimentin positive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGFβ2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity. - Highlights: • Arsenic blocks TGFβ2 induced expression of EMT genes. • Arsenic blocks TGFβ2 triggered Smad2/3 phosphorylation and nuclear translocation. • Arsenic blocks epicardial cell differentiation into cardiac mesenchyme. • Arsenic does not block TGFβ2 induced smooth muscle cell differentiation.« less

Cardiac tissue geometry as a determinant of unidirectional conduction block: assessment of microscopic excitation spread by optical mapping in patterned cell cultures and in a computer model.

PubMed

Fast, V G; Kléber, A G

1995-05-01

Unidirectional conduction block (UCB) and reentry may occur as a consequence of an abrupt tissue expansion and a related change in the electrical load. The aim of this study was to evaluate critical dimensions of the tissue necessary for establishing UCB in heart cell culture. Neonatal rat heart cell cultures with cell strands of variable width emerging into a large cell area were grown using a technique of patterned cell growth. Action potential upstrokes were measured using a voltage sensitive dye (RH-237) and a linear array of 10 photodiodes with a 15 microns resolution. A mathematical model was used to relate action potential wave shapes to underlying ionic currents. UCB (block of a single impulse in anterograde direction - from a strand to a large area - and conduction in the retrograde direction) occurred in narrow cell strands with a width of 15(SD 4) microns (1-2 cells in width, n = 7) and there was no conduction block in strands with a width of 31(8) microns (n = 9, P < 0.001) or larger. The analysis of action potential waveshapes indicated that conduction block was either due to geometrical expansion alone (n = 5) or to additional local depression of conduction (n = 2). In wide strands, action potential upstrokes during anterograde conduction were characterised by multiple rising phases. Mathematical modelling showed that two rising phases were caused by electronic current flow, whereas local ionic current did not coincide with the rising portions of the upstrokes. (1) High resolution optical mapping shows multiphasic action potential upstrokes at the region of abrupt expansion. At the site of the maximum decrement in conduction, these peaks were largely determined by the electrotonus and not by the local ionic current. (2) Unidirectional conduction block occurred in strands with a width of 15(4) microns (1-2 cells).

Right bundle branch block without overt heart disease predicts higher risk of pacemaker implantation: the study of atomic-bomb survivors.

PubMed

Kusumoto, Saburo; Kawano, Hiroaki; Makita, Naomasa; Ichimaru, Shinichiro; Kaku, Takashi; Haruta, Daisuke; Hida, Ayumi; Sera, Nobuko; Imaizumi, Misa; Nakashima, Eiji; Maemura, Koji; Akahoshi, Masazumi

2014-06-01

We investigated the clinical course of complete right bundle branch block (RBBB) or RBBB with axis deviation (AD) in terms of subsequent pacemaker implantation for high-degree atrioventricular (AV) block or sick sinus syndrome (SSS). Among the 16,170 atomic-bomb survivors in our biennial health examination between July 1967 and December 2010, we detected 520 newly-acquired RBBB subjects with no organic heart disease, and selected 1038 age- (at RBBB diagnosis) and sex-matched subjects without RBBB to serve as comparison subjects. Multivariate Cox regression analysis was used to estimate the hazard ratios (HRs) for the risk of pacemaker implantation due to all causes, AV block or SSS between RBBB and comparison subjects and between RBBB subjects with and without AD. The risk of pacemaker implantation for RBBB was 4.79 (95% confidence interval [CI] 1.89-12.58; P=0.001), 3.77 (95% CI, 1.09-13.07; P=0.036), and 6.28 (95% CI, 1.24-31.73, P=0.026) when implantation was for all causes, AV block and SSS, respectively. RBBB subjects with AD had a higher risk for all-cause pacemaker implantation than subjects without AD (HR, 3.03; 95% CI, 1.00-9.13, P=0.049). RBBB subjects with AD were younger than subjects without AD at the time of RBBB diagnosis (59.4±7.6 vs 74.4±3.1 years old, P=0.019), and their progression from diagnosis to pacemaker implantation took longer (15.1±6.6 vs 6.4±3.0 years, P=0.032). RBBB, especially with AD, progresses to AV block and SSS that requires pacemaker implantation; the mechanisms by which the conduction defect progresses differ among patients with and without AD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evolving regulatory paradigm for proarrhythmic risk assessment for new drugs.

PubMed

Vicente, Jose; Stockbridge, Norman; Strauss, David G

Fourteen drugs were removed from the market worldwide because their potential to cause torsade de pointes (torsade), a potentially fatal ventricular arrhythmia. The observation that most drugs that cause torsade block the potassium channel encoded by the human ether-à-go-go related gene (hERG) and prolong the heart rate corrected QT interval (QTc) on the ECG, led to a focus on screening new drugs for their potential to block the hERG potassium channel and prolong QTc. This has been a successful strategy keeping torsadogenic drugs off the market, but has resulted in drugs being dropped from development, sometimes inappropriately. This is because not all drugs that block the hERG potassium channel and prolong QTc cause torsade, sometimes because they block other channels. The regulatory paradigm is evolving to improve proarrhythmic risk prediction. ECG studies can now use exposure-response modeling for assessing the effect of a drug on the QTc in small sample size first-in-human studies. Furthermore, the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a new in vitro paradigm for cardiac safety evaluation of new drugs that provides a more accurate and comprehensive mechanistic-based assessment of proarrhythmic potential. Under CiPA, the prediction of proarrhythmic potential will come from in vitro ion channel assessments coupled with an in silico model of the human ventricular myocyte. The preclinical assessment will be checked with an assessment of human phase 1 ECG data to determine if there are unexpected ion channel effects in humans compared to preclinical ion channel data. While there is ongoing validation work, the heart rate corrected J-T peak interval is likely to be assessed under CiPA to detect inward current block in presence of hERG potassium channel block. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of a PExSim for modeling a POLVAD artificial heart and the human circulatory system with left ventricle assistance

NASA Astrophysics Data System (ADS)

Siewnicka, Alicja; Fajdek, Bartlomiej; Janiszowski, Krzysztof

2010-01-01

This paper presents a model of the human circulatory system with the possible addition of a parallel assist device, which was developed for the purpose of artificial heart monitoring. Information about an identification experiment of an extracorporeal ventricle assist device POLVAD is included. The modelling methods applied and the corresponding functional blocks in a PExSim package are presented. The results of the simulation for physiological conditions, left ventricle failure and pathological conditions with parallel assistance are included.

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Crataegus extract blocks potassium currents in guinea pig ventricular cardiac myocytes.

PubMed

Müller, A; Linke, W; Klaus, W

1999-05-01

Crataegus extract is used in cardiology for the treatment of mild to moderate heart failure (NYHA II) in Germany. However, little is known about the electrophysiological actions of Crataegus extract in the heart. Recently, it was shown that Crataegus extract prolongs the refractory period in isolated perfused hearts and increases action potential duration in guinea pig papillary muscle. It was the aim of this study to find out the mechanism of the increase in action potential duration caused by Crataegus extract. Using the patch-clamp technique, we measured the effects of Crataegus extract (10 mg/l; flavonoid content: 2.25%, total procyanidin content: 11.3 +/- 0.4%) on the inward rectifier and the delayed rectifier potassium current in isolated guinea pig ventricular myocytes. To get some insight into the mechanism underlying the positive inotropic effect of Crataegus extract, we also looked for effects on the L-type calcium current. Crataegus extract slightly blocked both the delayed and the inward rectifier potassium current. The inhibition amounted to 25% and about 15%, respectively. This amount of inhibition of these repolarising currents is sufficient to explain the prolongation of action potential duration caused by Crataegus extract. To our surprise we could not detect any influence of Crataegus extract on the L-type calcium current. In summary, our results show that Crataegus extract blocks repolarising potassium currents in ventricular myocytes. This effect is similar to the action of class III antiarrhythmic drugs and might be the basis of the antiarrhythmic effects described for Crataegus extract. Our measurements of the L-type calcium current indicate that Crataegus extract's positive inotropic effect is not caused by phosphodiesterase inhibition or a beta-sympathomimetic effect.

The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics

PubMed Central

Formgren, H.

1976-01-01

1 The effect of metoprolol, a new β1-adrenoceptor blocking agent, was compared to practolol in the treatment of hypertension in seventeen asthmatics during concurrent optimum bronchodilator therapy with a selective β2-adrenoceptor-stimulant. 2 The two β-adrenoceptor antagonists were given at two dose levels, practolol (200 mg and 400 mg) daily, and metoprolol (100 mg and 200 mg) daily, in a twice-daily dosage schedule, at 12 h intervals, for 17 days. The comparison was made double-blind and a crossover design was used. The drugs were given in randomized order. The study started with a run-in placebo period and there was a washout period on placebo between the treatment periods. Spirometry, blood pressures and heart rates were recorded in a standardized manner. 3 At the lower dose levels no influence on FEV1 was noted, and no difference was found between the two active drugs. At the higher dose level FEV1 was reduced by both β-adrenoceptor-blocking drugs. Four out of twelve patients given the higher dose experienced exacerbation of their asthma. The heart rate fell with both drugs and at both dose levels. During the placebo period a marked increase of heart rate was noted. The blood pressure fell at both dose levels compared to placebo, no difference being recorded between the two drugs. 4 Metoprolol and practolol are equally effective β1-adrenoceptor blocking drugs. In this study it was found that metoprolol could be used in asthmatics who had indications for β-adrenoceptor blockade, provided that the total daily dose did not exceed 100 mg. Optimal bronchodilator treatment with a bronchoselective β-adrenoceptor agonist is an absolute prerequisite in order to avoid the risk of aggravation of asthma. PMID:22216522

Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease.

PubMed

Passos, Lívia Silva Araújo; Villani, Fernanda Nobre Amaral; Magalhães, Luísa Mourão Dias; Gollob, Kenneth J; Antonelli, Lis Ribeiro do Vale; Nunes, Maria Carmo Pereira; Dutra, Walderez Ornelas

2016-09-15

The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double-negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi-specific DN T cells. We observed that parasite stimulation significantly increased the expression of CD1a, CD1b, CD1c, and CD1d by CD14(+) cells from patients with Chagas disease. Importantly, among the analyzed molecules, only CD1d expression showed an association with the activation of DN T cells, as well as with worse ventricular function in patients with Chagas disease. Blocking of CD1d-mediated antigen presentation led to a clear reduction of DN T-cell activation and a decrease in the expression of interferon γ (IFN-γ) by DN T cells. Thus, our results showed that antigen presentation via CD1d is associated with activation of DN T cells in Chagas disease and that CD1d blocking leads to downregulation of IFN-γ by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Small heterodimer partner blocks cardiac hypertrophy by interfering with GATA6 signaling.

PubMed

Nam, Yoon Seok; Kim, Yoojung; Joung, Hosouk; Kwon, Duk-Hwa; Choe, Nakwon; Min, Hyun-Ki; Kim, Yong Sook; Kim, Hyung-Seok; Kim, Don-Kyu; Cho, Young Kuk; Kim, Yong-Hoon; Nam, Kwang-Il; Choi, Hyoung Chul; Park, Dong Ho; Suk, Kyoungho; Lee, In-Kyu; Ahn, Youngkeun; Lee, Chul-Ho; Choi, Hueng-Sik; Eom, Gwang Hyeon; Kook, Hyun

2014-08-15

Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA-binding domain. Through interactions with other transcription factors, SHP regulates diverse biological events, including glucose metabolism in liver. However, the role of SHP in adult heart diseases has not yet been demonstrated. We aimed to investigate the role of SHP in adult heart in association with cardiac hypertrophy. The roles of SHP in cardiac hypertrophy were tested in primary cultured cardiomyocytes and in animal models. SHP-null mice showed a hypertrophic phenotype. Hypertrophic stresses repressed the expression of SHP, whereas forced expression of SHP blocked the development of hypertrophy in cardiomyocytes. SHP reduced the protein amount of Gata6 and, by direct physical interaction with Gata6, interfered with the binding of Gata6 to GATA-binding elements in the promoter regions of natriuretic peptide precursor type A. Metformin, an antidiabetic agent, induced SHP and suppressed cardiac hypertrophy. The metformin-induced antihypertrophic effect was attenuated either by SHP small interfering RNA in cardiomyocytes or in SHP-null mice. These results establish SHP as a novel antihypertrophic regulator that acts by interfering with GATA6 signaling. SHP may participate in the metformin-induced antihypertrophic response. © 2014 American Heart Association, Inc.

The role of 17-beta estradiol in ischemic preconditioning protection of the heart.

PubMed

Babiker, Fawzi A; Hoteit, Lamia J; Joseph, Shaji; Mustafa, Abu Salim; Juggi, Jasbir S

2012-09-01

The protective effects of 17-beta estradiol (E2) on cardiac tissue during ischemia/reperfusion (I/R) injury have not yet been fully elucidated. To assess the protective effects of short- and long-term E2 treatments on cardiac tissue exposed to I/R, and to assess the effects of these treatments in combination with ischemic preconditioning (IPC) on cardiac protection from I/R injury. SPRAGUE DAWLEY RATS WERE ASSIGNED TO THE FOLLOWING TREATMENT PROTOCOLS: control (no preconditioning); IPC (isolated hearts were subjected to two cycles of 5 min global ischemia followed by 10 min of reperfusion); E2 preconditioning (E2PC; isolated hearts were subjected to E2 pharmacological perfusion for 15 min); short-term in vivo E2 pretreatment for 3 h; long-term in vivo E2 pretreatment or withdrawal (ovariectomy followed by a six-week treatment with E2 or a placebo); combined IPC and E2PC; combined IPC and short- or long-term E2 pretreatments or withdrawal. All hearts were isolated and stabilized for at least 30 min before being subjected to 40 min of global ischemia followed by 30 min of reperfusion; left ventricular function and vascular hemodynamics were then assessed. IPC, E2PC and short-term E2 pretreatment led to the recovery of left ventricle function and vascular hemodynamics. Long-term E2 and placebo treatments did not result in any protection compared with untreated controls. The combination of E2PC or short-term E2 treatments with IPC did not block the IPC protection or result in any additional protection to the heart. Long-term E2 treatment blocked IPC protection; however, placebo treatment did not. Short-term treatment with E2 protected the heart against I/R injury through a pathway involving the regulation of tumour necrosis factor-alpha. The combination of short-term E2 treatment with IPC did not provide additional protection to the heart. Short-term E2 treatment may be a suitable alternative for classical estrogen replacement therapy.

A vector-free ECG interpretation with P, QRS & T waves as unbalanced transitions between stable configurations of the heart electric field during P-R, S-T & T-P segments

PubMed Central

2014-01-01

Since cell membranes are weak sources of electrostatic fields, this ECG interpretation relies on the analogy between cells and electrets. It is here assumed that cell-bound electric fields unite, reach the body surface and the surrounding space and form the thoracic electric field that consists from two concentric structures: the thoracic wall and the heart. If ECG leads measure differences in electric potentials between skin electrodes, they give scalar values that define position of the electric field center along each lead. Repolarised heart muscle acts as a stable positive electric source, while depolarized heart muscle produces much weaker negative electric field. During T-P, P-R and S-T segments electric field is stable, only subtle changes are detectable by skin electrodes. Diastolic electric field forms after ventricular depolarization (T-P segments in the ECG recording). Telediastolic electric field forms after the atria have been depolarized (P-Q segments in the ECG recording). Systolic electric field forms after the ventricular depolarization (S-T segments in the ECG recording). The three ECG waves (P, QRS and T) can then be described as unbalanced transitions of the heart electric field from one stable configuration to the next and in that process the electric field center is temporarily displaced. In the initial phase of QRS, the rapidly diminishing septal electric field makes measured potentials dependent only on positive charges of the corresponding parts of the left and the right heart that lie within the lead axes. If more positive charges are near the "DOWN" electrode than near the "UP" electrode, a Q wave will be seen, otherwise an R wave is expected. Repolarization of the ventricular muscle is dampened by the early septal muscle repolarization that reduces deflection of T waves. Since the "UP" electrode of most leads is near the usually larger left ventricle muscle, T waves are in these leads positive, although of smaller amplitude and longer duration than the QRS wave in the same lead. The proposed interpretation is applied to bundle branch blocks, fascicular (hemi-) blocks and changes during heart muscle ischemia. PMID:24506945

Drug insight: If inhibitors as specific heart-rate-reducing agents.

PubMed

Borer, Jeffrey S

2004-12-01

Heart rate is determined primarily by spontaneously repeating net inward current carried by sodium ions and potassium ions through hyperpolarization-activated cyclic-nucleotide-gated channels. Within the heart, these channels are found most abundantly in sinoatrial cardiomyocytes. The channels open in response to membrane hyperpolarization, modulated by local cAMP concentrations. They permit activation of the I(f) current, which can be blocked specifically by molecules characterized by linked benzazepinone and benzocyclobutane rings, and which are devoid of effects on cardiac conduction, inotropy or peripheral vascular tone. The resulting heart-rate reduction has been effective in angina prevention in clinical trials involving 4,000 patients, using the prototype I(f) inhibitor, ivabradine. No serious adverse events have been attributed to the treatment; the most prominent side-effect is dose-related, always reversible and often transient visual symptoms that seldom result in voluntary drug discontinuation.

Chloroquine-induced cardiomyopathy: a reversible cause of heart failure.

PubMed

Yogasundaram, Haran; Hung, Whitney; Paterson, Ian D; Sergi, Consolato; Oudit, Gavin Y

2018-06-01

Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-rheumatic medications frequently used in the treatment of connective tissue disorders. We present the case of a 45-year-old woman with CQ-induced cardiomyopathy leading to severe heart failure. Electrocardiographic abnormalities included bifascicular block, while structural disease consisted of severe biventricular and biatrial hypertrophy. Appropriate diagnosis via endomyocardial biopsy led to cessation of CQ and subsequent dramatic improvement in symptoms and structural heart disease. Cardiac toxicity is an under-recognized adverse effect of CQ/HCQ leading to cardiomyopathy with concentric hypertrophy and conduction abnormalities, with the potential for significant morbidity and mortality. Predisposing factors for CQ/HCQ-induced cardiomyopathy have been proposed. CQ/HCQ cardiomyopathy is a phenocopy of Fabry disease, and α-galactosidase A polymorphism may account for some heterogeneity of disease presentation. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Novel technique for airless connection of artificial heart to vascular conduits.

PubMed

Karimov, Jamshid H; Gao, Shengqiang; Dessoffy, Raymond; Sunagawa, Gengo; Sinkewich, Martin; Grady, Patrick; Sale, Shiva; Moazami, Nader; Fukamachi, Kiyotaka

2017-12-01

Successful implantation of a total artificial heart relies on multiple standardized procedures, primarily the resection of the native heart, and exacting preparation of the atrial and vascular conduits for pump implant and activation. Achieving secure pump connections to inflow/outflow conduits is critical to a successful outcome. During the connection process, however, air may be introduced into the circulation, traveling to the brain and multiple organs. Such air emboli block blood flow to these areas and are detrimental to long-term survival. A correctly managed pump-to-conduit connection prevents air from collecting in the pump and conduits. To further optimize pump-connection techniques, we have developed a novel connecting sleeve that enables airless connection of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) to the conduits. In this brief report, we describe the connecting sleeve design and our initial results from two acute in vivo implantations using a scaled-down version of the CFTAH.

Comparison of the effect of pindolol and propranolol on heart rate after acute and chronic administration.

PubMed Central

Finch, M B; O'Connor, P C; Harron, D W; Shanks, R G

1983-01-01

1 The present study compared the effects in healthy volunteers of the acute and chronic administration of placebo, pindolol and propranolol to see if the partial agonist activity of pindolol was reduced by the beta-adrenoceptor blocking activity of pindolol on chronic administration. 2 Five subjects received in random order for 8 days placebo, propranolol 160 mg and pindolol 10 mg; on days 1 and 8 treatments were given twice at 0 and 2 h. Heart rate in supine position and at end of exercise was recorded before dosing and at 2 and 4 h post-dosing on days 1 and 8. 3 Propranolol and pindolol reduced exercise heart rate to the same extent on days 1 and 8. 4 Propranolol reduced supine heart rate more than pindolol on days 1 and 8 but the difference was only significant on day 8. PMID:6849778

Class I HDACs Regulate Angiotensin II-Dependent Cardiac Fibrosis via Fibroblasts and Circulating Fibrocytes

PubMed Central

Williams, Sarah M.; Golden-Mason, Lucy; Ferguson, Bradley S.; Douglas, Katherine B.; Cavasin, Maria A.; Demos-Davies, Kim; Yeager, Michael E.; Stenmark, Kurt R.; McKinsey, Timothy A.

2014-01-01

Fibrosis, which is defined as excessive accumulation of fibrous connective tissue, contributes to the pathogenesis of numerous diseases involving diverse organ systems. Cardiac fibrosis predisposes individuals to myocardial ischemia, arrhythmias and sudden death, and is commonly associated with diastolic dysfunction. Histone deacetylase (HDAC) inhibitors block cardiac fibrosis in pre-clinical models of heart failure. However, which HDAC isoforms govern cardiac fibrosis, and the mechanisms by which they do so, remains unclear. Here, we show that selective inhibition of class I HDACs potently suppresses angiotensin II (Ang II)-mediated cardiac fibrosis by targeting two key effector cell populations, cardiac fibroblasts and bone marrow-derived fibrocytes. Class I HDAC inhibition blocks cardiac fibroblast cell cycle progression through derepression of the genes encoding the cyclin-dependent kinase (CDK) inhibitors, p15 and p57. In contrast, class I HDAC inhibitors block agonist-dependent differentiation of fibrocytes through a mechanism involving repression of ERK1/2 signaling. These findings define novel roles for class I HDACs in the control of pathological cardiac fibrosis. Furthermore, since fibrocytes have been implicated in the pathogenesis of a variety of human diseases, including heart, lung and kidney failure, our results suggest broad utility for isoform-selective HDAC inhibitors as anti-fibrotic agents that function, in part, by targeting these circulating mesenchymal cells. PMID:24374140

Dual developmental role of transcriptional regulator Ets1 in Xenopus cardiac neural crest vs. heart mesoderm

PubMed Central

Nie, Shuyi; Bronner, Marianne E.

2015-01-01

Aims Ets1 is an important transcription factor that is expressed in both the cardiac neural crest (NC) and heart mesoderm of vertebrate embryos. Moreover, Ets1 deletion in humans results in congenital heart abnormalities. To clarify the functional contributions of Ets1 in cardiac NC vs. heart mesoderm, we performed tissue-targeted loss-of-function analysis to compare the relative roles of Ets1 in these two tissues during heart formation using Xenopus embryos as a model system. Methods and results We confirmed by in situ hybridization analysis that Ets1 is expressed in NC and heart mesoderm during embryogenesis. Using a translation-blocking antisense morpholino to knockdown Ets1 protein selectively in the NC, we observed defects in NC delamination from the neural tube, collective cell migration, as well as segregation of NC streams in the cranial and cardiac regions. Many cardiac NC cells failed to reach their destination in the heart, resulting in defective aortic arch artery formation. A different set of defects was noted when Ets1 knockdown was targeted to heart mesoderm. The formation of the primitive heart tube was dramatically delayed and the endocardial tissue appeared depleted. As a result, the conformation of the heart was severely disrupted. In addition, the outflow tract septum was missing, and trabeculae formation in the ventricle was abolished. Conclusion Our study shows that Ets1 is required in both the cardiac NC and heart mesoderm, albeit for different aspects of heart formation. Our results reinforce the suggestion that proper interaction between these tissues is critical for normal heart development. PMID:25691536

Cold bupivacaine versus magnesium sulfate added to room temperature bupivacaine in sonar-guided femoral and sciatic nerve block in arthroscopic anterior cruciate ligament reconstruction surgery.

PubMed

Alzeftawy, Ashraf Elsayed; El-Daba, Ahmad Ali

2016-01-01

Cooling of local anesthetic potentiates its action and increases its duration. Magnesium sulfate (MgSo 4 ) added to local anesthetic prolongs the duration of anesthesia and postoperative analgesia with minimal side effects. The aim of this prospective, randomized, double-blind study was to compare the effect of cold to 4°C bupivacaine 0.5% and Mg added to normal temperature (20-25°C) bupivacaine 0.5% during sonar-guided combined femoral and sciatic nerve blocks on the onset of sensory and motor block, intraoperative anesthesia, duration of sensory and motor block, and postoperative analgesia in arthroscopic anterior cruciate ligament (ACL) reconstruction surgery. A total of 90 American Society of Anesthesiologists classes I and II patients who were scheduled to undergo elective ACL reconstruction were enrolled in the study. The patients were randomly allocated to 3 equal groups to receive sonar-guided femoral and sciatic nerve blocks. In Group I, 17 ml of room temperature (20-25°C) 0.5% bupivacaine and 3 ml of room temperature saline were injected for each nerve block whereas in Group II, 17 ml of cold (4°C) 0.5% bupivacaine and 3 ml of cold saline were injected for each nerve block. In Group III, 17 ml of room temperature 0.5% bupivacaine and 3 ml of MgSo 4 5% were injected for each nerve block. The onset of sensory and motor block was evaluated every 3 min for 30 min. Surgery was started after complete sensory and motor block were achieved. Intraoperatively, the patients were evaluated for heart rate and mean arterial pressure, rescue analgesic and sedative requirements plus patient and surgeon satisfaction. Postoperatively, hemodynamics, duration of analgesia, resolution of motor block, time to first analgesic, total analgesic consumption, and the incidence of side effects were recorded. There was no statistically significant difference in demographic data, mean arterial pressure, heart rate, and duration of surgery. Onset of both sensory and motor block was significantly shorter in both Groups II and III compared to Group I. Intraoperative anesthetic quality was comparable between groups with good patient and surgeon satisfaction. The time to first analgesia was significantly longer in Groups II and III compared to Group I with nonsignificant difference between each other. Moreover, the total opioid consumption was significantly lower in Groups II and III and duration of analgesia and motor block were significantly longer in Groups II and III compared to Group I. There was no difference in the incidence of side effects. The use of cold 0.5% bupivacaine or the addition of Mg to normal temperature 0.5% bupivacaine prolongs the sensory and motor block duration without increasing side effects and enhances the quality of intra- and post-operative analgesia with better patient satisfaction in sonar-guided femoral and sciatic nerve block for arthroscopic ACL reconstruction surgery.

Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording.

PubMed

Dietrichson, P; Espen, E

1981-08-01

Two different beta-adrenoreceptor antagonists, atenolol and timolol, were separately compared with a placebo in the suppression of essential tremor. In two-week single-blind placebo-controlled studies with cross-over, timolol (5 mg twice daily) and atenolol (100 mg once daily) produced an equal reduction in sitting heart rate and sitting blood pressure. Timolol was effective in reducing tremor while atenolol failed to reduce tremor amplitude. These results indicate that essential tremor can be reduced but not blocked, by the adrenergic blocker timolol with both beta 1 and beta 2 blocking properties; but not by the relatively selective beta 1 blocking drug atenolol. Possibly, the tremor reduction is medicated by a peripheral effect on beta 2 adrenoreceptors.

A case of advanced second-degree atrioventricular block in a ferret secondary to lymphoma

PubMed Central

Menicagli, F.; Lanza, A.; Sbrocca, F.; Baldi, A.; Spugnini, E.P.

2016-01-01

A female ferret was referred as an emergency for severe respiratory distress symptoms. At presentation, the patient was listlessness, dyspnoeic, and hyper-responsive. The clinical examination evidenced dyspnea with cyanosis, altered cardiac rhythm, and hepatomegaly. Electrocardiography showed an advanced second-degree atrioventricular (AV) block. The liver aspirate was diagnostic for lymphoma. The patient did not respond to supportive therapy and rapidly died. Post-mortem exams confirmed the presence of lymphoma with hepatic involvement. Moreover, a pericardial lymphocytic infiltration and a widespread myocardial nodular localization of lymphoma were evidenced as well. This condition was probably the cause of the cardiac arrhythmia. To the best of our knowledge, ours is the first report of cardiac lymphoma causing heart block in ferrets. PMID:27200273

A comparison of retrobulbar block, sub-Tenon block, and topical anesthesia during cataract surgery.

PubMed

Ryu, Jung-Hee; Kim, Minsuk; Bahk, Jae-Hyon; Do, Sang-Hwan; Cheong, Il-Young; Kim, Yong-Chul

2009-01-01

This randomized, double-blinded, prospective study was performed to compare the intraoperative hemodynamic variables and the patient-reported outcomes, such as intra- and postoperative analgesia and patient satisfaction, of retrobulbar block, sub-Tenon block, and topical anesthesia during cataract surgery under monitored anesthesia care. Eighty-one patients, ASA physical status I-III, undergoing elective cataract surgery under monitored anesthesia care, aged between 43 and 78 years, were randomly assigned to three groups: retrobulbar block (group R), sub-Tenon block (group S), or topical anesthesia (group T). Three minutes after the start of monitored anesthesia care with lidocaine-propofol-remifentanil mixture, an ophthalmologist performed regional anesthesia. Intraoperative hemodynamics, pain score, and patients' satisfaction with the anesthetic experiences were recorded by a study-blinded anesthesiologist. Mean arterial pressure and heart rate in group R were significantly higher than those in groups S and T during and just after the regional block (p<0.05). Group R required smaller dosage of patient controlled sedation and fewer supplemental bolus doses than groups S and T (p<0.05). On the other hand, group S showed the highest satisfaction scores among the three groups (p<0.05). Sub-Tenon block seems to be better than retrobulbar block and topical anesthesia in patient satisfaction though adequate analgesia was achieved after retrobulbar block during cataract surgery under monitored anesthesia care.

Parturition in horses is dominated by parasympathetic activity of the autonomous nervous system.

PubMed

Nagel, Christina; Erber, Regina; Ille, Natascha; von Lewinski, Mareike; Aurich, Jörg; Möstl, Erich; Aurich, Christine

2014-07-01

External and internal stressors prolong parturition in different species. At parturition, sympathoadrenal activation should be avoided because an increased sympathetic tone may cause uterine atonia via β2-receptors. We hypothesized that at physiological parturition, horses are under parasympathetic dominance, and stress-response mechanisms are not activated during delivery of the foal. To evaluate stress responses, heart rate, heart rate variability, catecholamines, and cortisol were analyzed in mares (n = 17) throughout foaling. Heart rate decreased from 2 hours before (51 ± 1 beats/minute) to 2 hours after delivery (41 ± 2 beats/minute; P < 0.05). Heart rate variability variables, standard deviation of the beat-to-beat interval, and root mean square of successive beat-to-beat differences, changed over time (P < 0.05) with the highest values within 15 minutes after delivery. The number of mares with atrioventricular blocks and the number of atrioventricular blocks per mare increased over time (P < 0.01) and were significantly elevated from 15 minutes before to 45 minutes after birth of the foal. Salivary cortisol concentrations increased to a maximum at 30 minutes after delivery (25.0 ± 3.4 ng/mL; P < 0.01). Plasma epinephrine and norepinephrine concentrations showed significant fluctuations from rupture of the allantochorion to expulsion of the fetal membranes (P < 0.01) but were not markedly elevated at any time. In conclusion, mares give birth under high parasympathetic tone. Cortisol release during and after foaling is most likely part of the endocrine pathways regulating parturition and not a labor-associated stress response. Copyright © 2014 Elsevier Inc. All rights reserved.

Nurse-led titration of angiotensin converting enzyme inhibitors, beta-adrenergic blocking agents, and angiotensin receptor blockers for people with heart failure with reduced ejection fraction.

PubMed

Driscoll, Andrea; Currey, Judy; Tonkin, Andrew; Krum, Henry

2015-12-21

Heart failure is associated with high mortality and hospital readmissions. Beta-adrenergic blocking agents, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) can improve survival and reduce hospital readmissions and are recommended as first-line therapy in the treatment of heart failure. Evidence has also shown that there is a dose-dependent relationship of these medications with patient outcomes. Despite this evidence, primary care physicians are reluctant to up-titrate these medications. New strategies aimed at facilitating this up-titration are warranted. Nurse-led titration (NLT) is one such strategy. To assess the effects of NLT of beta-adrenergic blocking agents, ACEIs, and ARBs in patients with heart failure with reduced ejection fraction (HFrEF) in terms of safety and patient outcomes. We searched the Cochrane Central Register of Controlled Trials in the Cochrane Library (CENTRAL Issue 11 of 12, 19/12/2014), MEDLINE OVID (1946 to November week 3 2014), and EMBASE Classic and EMBASE OVID (1947 to 2014 week 50). We also searched reference lists of relevant primary studies, systematic reviews, clinical trial registries, and unpublished theses sources. We used no language restrictions. Randomised controlled trials (RCTs) comparing NLT of beta-adrenergic blocking agents, ACEIs, and/or ARBs comparing the optimisation of these medications by a nurse to optimisation by another health professional in patients with HFrEF. Two review authors (AD & JC) independently assessed studies for eligibility and risk of bias. We contacted primary authors if we required additional information. We examined quality of evidence using the GRADE rating tool for RCTs. We analysed extracted data by risk ratio (RR) with 95% confidence interval (CI) for dichotomous data to measure effect sizes of intervention group compared with usual-care group. Meta-analyses used the fixed-effect Mantel-Haenszel method. We assessed heterogeneity between studies by Chi(2) and I(2). We included seven studies (1684 participants) in the review. One study enrolled participants from a residential care facility, and the other six studies from primary care and outpatient clinics. All-cause hospital admission data was available in four studies (556 participants). Participants in the NLT group experienced a lower rate of all-cause hospital admissions (RR 0.80, 95% CI 0.72 to 0.88, high-quality evidence) and fewer hospital admissions related to heart failure (RR 0.51, 95% CI 0.36 to 0.72, moderate-quality evidence) compared to the usual-care group. Six studies (902 participants) examined all-cause mortality. All-cause mortality was also lower in the NLT group (RR 0.66, 95% CI 0.48 to 0.92, moderate-quality evidence) compared to usual care. Approximately 27 deaths could be avoided for every 1000 people receiving NLT of beta-adrenergic blocking agents, ACEIs, and ARBs. Only three studies (370 participants) reported outcomes on all-cause and heart failure-related event-free survival. Participants in the NLT group were more likely to remain event free compared to participants in the usual-care group (RR 0.60, 95% CI 0.46 to 0.77, moderate-quality evidence). Five studies (966 participants) reported on the number of participants reaching target dose of beta-adrenergic blocking agents. This was also higher in the NLT group compared to usual care (RR 1.99, 95% CI 1.61 to 2.47, low-quality evidence). However, there was a substantial degree of heterogeneity in this pooled analysis. We rated the risk of bias in these studies as high mainly due to a lack of clarity regarding incomplete outcome data, lack of reporting on adverse events associated with the intervention, and the inability to blind participants and personnel. Participants in the NLT group reached maximal dose of beta-adrenergic blocking agents in half the time compared with participants in usual care. Two studies reported on adverse events; one of these studies stated there were no adverse events, and the other study found one adverse event but did not specify the type or severity of the adverse event. Participants in the NLT group experienced fewer hospital admissions for any cause and an increase in survival and number of participants reaching target dose within a shorter time period. However, the quality of evidence regarding the proportion of participants reaching target dose was low and should be interpreted with caution. We found high-quality evidence supporting NLT as one strategy that may improve the optimisation of beta-adrenergic blocking agents resulting in a reduction in hospital admissions. Despite evidence of a dose-dependent relationship of beta-adrenergic blocking agents, ACEIs, and ARBs with improving outcomes in patients with HFrEF, the translation of this evidence into clinical practice is poor. NLT is one strategy that facilitates the implementation of this evidence into practice.

Heart Block

MedlinePlus

... to begin a new heartbeat 60 to 100 times a minute. From the SA node, the signal travels through the right and left atria. This causes ... AV node. This slowing allows the ventricles enough time to finish filling with ... leaves the AV node and travels along a pathway called the bundle of His. ...

[Intervention among patients with right bundle branch block and left anterior hemiblock. Operatory risk (author's transl)].

PubMed

Coriat, P; Harari, A; Tarot, J P; Ducardonnet, A; Viars, P

1981-01-01

In order to assess the risk of advanced heart block during anesthesia in patients with right bundle branch block and left anterior hemiblock, 35 consecutive patients were monitored throughout the pre-, intra- and postoperative period. As conventional ECG monitoring may only detect advanced atrioventricular block, patients were monitored according to the Holter method which can easily detect even minor changes of atrioventricular conduction namely slight increased PR interval or dropped P wave. All patients were asymptomatic, in normal sinus rhythm without second degree AV block. Surgical procedures were performed under general anesthesia (n = 15) and epidural anesthesia using lidocaine (n = 20). No episode of second or third degree atrioventricular block occurred. The only modifications observed were rare and transient increase of PR, occurring during surgical procedures in 5 patients, always associated with a sinus bradycardia. They immediately regressed at the termination of the sinus bradycardia either spontaneously or following atropine injection, strongly suggesting the responsability of increased vagal tone. Thus general or epidural anesthesia did not compromise infranodal conduction in any of the observed patients. These data indicate that anesthesia can be safely used without prophylactic preoperative insertion of pacemakers in patients with asymptomatic chronic right bundle branch block and left anterior hemi-block.

In-hospital outcome in patients with ST elevation myocardial infarction and right bundle branch block. A sub-study from RENASICA II, a national multicenter registry.

PubMed

Juárez-Herrera, Ursulo; Jerjes Sánchez, Carlos; González-Pacheco, Héctor; Martínez-Sánchez, Carlos

2010-01-01

Compare in-hospital outcome in patients with ST-elevation myocardial infarction with right versus left bundle branch block. RENASICA II, a national Mexican registry enrolled 8098 patients with final diagnosis of acute coronary syndrome secondary to ischemic heart disease. In 4555 STEMI patients, 545 had bundle branch block, 318 (58.3%) with right and 225 patients with left (41.6%). Both groups were compared in terms of in-hospital outcome through major cardiovascular adverse events; (cardiovascular death, recurrent ischemia and reinfarction). Multivariable analysis was performed to identify in-hospital mortality risk among right and left bundle branch block patients. There were not statistical differences in both groups regarding baseline characteristics, time of ischemia, myocardial infarction location, ventricular dysfunction and reperfusion strategies. In-hospital outcome in bundle branch block group was characterized by a high incidence of major cardiovascular adverse events with a trend to higher mortality in patients with right bundle branch block (OR 1.70, CI 1.19 - 2.42, p < 0.003), compared to left bundle branch block patients. In this sub-study right bundle branch block accompanying ST-elevation myocardial infarction of any location at emergency room presentation was an independent predictor of high in-hospital mortality.

New-Onset Left Bundle Branch Block Induced by Transcutaneous Aortic Valve Implantation.

PubMed

Massoullié, Grégoire; Bordachar, Pierre; Ellenbogen, Kenneth A; Souteyrand, Géraud; Jean, Frédéric; Combaret, Nicolas; Vorilhon, Charles; Clerfond, Guillaume; Farhat, Mehdi; Ritter, Philippe; Citron, Bernard; Lusson, Jean-R; Motreff, Pascal; Ploux, Sylvain; Eschalier, Romain

2016-03-01

New-onset left bundle branch block (LBBB) is a specific concern of transcutaneous aortic valve implantation (TAVI) given its estimated incidence ranging from 5% to 65%. This high rate of occurrence is dependent on the type of device used (size and shape), implantation methods, and patient co-morbidities. The appearance of an LBBB after TAVI reflects a very proximal lesion of the left bundle branch as it exits the bundle of His. At times transient, its persistence can lead to permanent pacemaker implantation in 15% to 20% of cases, most often for high-degree atrioventricular block. The management of LBBB after TAVI is currently not defined by international societies resulting in individual centers developing their own management strategy. The potential consequences of LBBB are dysrhythmias (atrioventricular block, syncope, and sudden death) and functional (heart failure) complications. Prompt postprocedural recognition and management (permanent pacemaker implantation) of patients prevents the occurrence of potential complications and may constitute the preferred approach in this frail and elderly population despite additional costs and complications of cardiac pacing. Moreover, the expansion of future indications for TAVI necessitates better identification of the predictive factors for the development of LBBB. Indeed, long-term right ventricular pacing may potentially increase the risk of developing heart failure in this population. In conclusion, it is thus imperative to not only develop new aortic prostheses with a less-deleterious impact on the conduction system but also to prescribe appropriate pacing modes in this frail population. Copyright © 2016 Elsevier Inc. All rights reserved.

Alpha-1-Adrenergic Receptors in Heart Failure: The Adaptive Arm of the Cardiac Response to Chronic Catecholamine Stimulation

PubMed Central

Jensen, Brian C.; O'Connell, Timothy D.; Simpson, Paul C.

2013-01-01

Alpha-1-adrenergic receptors are G-protein coupled receptors (GPCRs) activated by catecholamines. The alpha-1A and alpha-1B subtypes are expressed in mouse and human myocardium, whereas the alpha-1D protein is found only in coronary arteries. There are far fewer alpha-1-ARs than beta-ARs in the non-failing heart, but their abundance is maintained or increased in the setting of heart failure, which is characterized by pronounced chronic elevation of catecholamines and b□eta-AR dysfunction. Decades of evidence from gain- and loss-of-function studies in isolated cardiac myocytes and numerous animal models demonstrate important adaptive functions for cardiac alpha-1-ARs, to include physiological hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Clinical trial data indicate that blocking alpha-1-ARs is associated with incident heart failure in patients with hypertension. Collectively, these findings suggest that alpha-1-AR activation might mitigate the well-recognized toxic effects of beta-ARs in the hyperadrenergic setting of chronic heart failure. Thus, exogenous cardioselective activation of alpha-1-ARs might represent a novel and viable approach to the treatment of heart failure. PMID:24145181

Sudden cardiac arrest as a rare presentation of myxedema coma: case report.

PubMed

Salhan, Divya; Sapkota, Deepak; Verma, Prakash; Kandel, Saroj; Abdulfattah, Omar; Lixon, Antony; Zwenge, Deribe; Schmidt, Frances

2017-01-01

Myxedema coma is a decompensated hypothyroidism which occurs due to long-standing, undiagnosed, or untreated hypothyroidism. Untreated hypothyroidism is known to affect almost all organs including the heart. It is associated with a decrease in cardiac output, stroke volume due to decreased myocardial contractility, and an increase in systemic vascular resistance. It can cause cardiac arrhythmias and the most commonly seen conduction abnormalities are sinus bradycardia, heart block, ventricular tachycardia, and torsade de pointes. The authors report a case of an elderly man who presented with sudden cardiac arrest and myxedema coma and who was successfully revived.

Acute pericarditis with cardiac tamponade induced by pacemaker implantation.

PubMed

Shingaki, Masami; Kobayashi, Yutaka; Suzuki, Haruo

2015-11-01

An 87-year-old woman was diagnosed with third-degree atrioventricular block and underwent pacemaker implantation. On postoperative day 12, she experienced cardiac tamponade that was suspected on computed tomography to be caused by lead perforation; therefore, we performed open-heart surgery. However, we could not identify a perforation site on the heart, and drained a 400-mL exudative pericardial effusion. Subsequently, we diagnosed the pericardial effusion as due to pericarditis induced by pacemaker implantation. It is sometimes difficult to distinguish pericarditis from pacemaker lead perforation, so both should be included in the differential diagnosis. © The Author(s) 2014.

The natural history of congenitally corrected transposition of the great arteries.

PubMed

Huhta, James

2011-01-01

The natural history of congenitally corrected transposition of the great arteries is of clinical/surgical importance once the fetus is born without heart block or signs of heart failure. Without significant tricuspid valve malformation, associated defects such as ventricular septal defect and left ventricular outflow obstruction can be repaired surgically. The mortality and long-term outcome appear to be linked strongly with the severity of tricuspid valve regurgitation. Some patients with an intact ventricular septum and no right ventricular dysfunction will live long lives without detection, and some women will successfully complete pregnancy.

Hemodynamic Improvement in Cardiac Resynchronization Does Not Require Improvement in Left Ventricular Rotation Mechanics

PubMed Central

Ashikaga, Hiroshi; Leclercq, Christophe; Wang, Jiangxia; Kass, David A.; McVeigh, Elliot R.

2010-01-01

Background Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics. Methods and Results In dogs with left bundle branch block and pacing-induced heart failure (n=7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity. Conclusions CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT. PMID:20478988

Generation of strip-format fibrin-based engineered heart tissue (EHT).

PubMed

Schaaf, Sebastian; Eder, Alexandra; Vollert, Ingra; Stöhr, Andrea; Hansen, Arne; Eschenhagen, Thomas

2014-01-01

This protocol describes a method for casting fibrin-based engineered heart tissue (EHT) in standard 24-well culture dishes. In principle, a hydrogel tissue engineering method requires cardiomyocytes, a liquid matrix that forms a gel, a casting mold, and a device that keeps the developing tissue in place. This protocol refers to neonatal rat heart cells as the cell source; the matrix of choice is fibrin, and the tissues are generated in rectangular agarose-casting molds (12 × 3 × 3 mm) prepared in standard 24-well cell culture dishes, in which a pair of flexible silicone posts is suspended from above. A master mix of freshly isolated cells, medium, fibrinogen, and thrombin is pipetted into the casting mold and, over a period of 2 h, polymerizes and forms a fibrin cell block around two silicone posts. Silicone racks holding four pairs of silicone posts each are used to transfer the fresh fibrin cell blocks into new 24-well dishes with culture medium. Without further handling, the cells start to remodel the fibrin gel, form contacts with each other, elongate, and condense the gel to approximately ¼ of the initial volume. Spontaneous and rhythmic contractions start after 1 week. EHTs are viable and relatively stable for several weeks in this format and can be subjected to repeated measurements of contractile function and final morphological and molecular analyses.

Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording.

PubMed Central

Dietrichson, P; Espen, E

1981-01-01

Two different beta-adrenoreceptor antagonists, atenolol and timolol, were separately compared with a placebo in the suppression of essential tremor. In two-week single-blind placebo-controlled studies with cross-over, timolol (5 mg twice daily) and atenolol (100 mg once daily) produced an equal reduction in sitting heart rate and sitting blood pressure. Timolol was effective in reducing tremor while atenolol failed to reduce tremor amplitude. These results indicate that essential tremor can be reduced but not blocked, by the adrenergic blocker timolol with both beta 1 and beta 2 blocking properties; but not by the relatively selective beta 1 blocking drug atenolol. Possibly, the tremor reduction is medicated by a peripheral effect on beta 2 adrenoreceptors. Images PMID:7028921

Platelet P2Y₁₂ blockers confer direct postconditioning-like protection in reperfused rabbit hearts.

PubMed

Yang, Xi-Ming; Liu, Yanping; Cui, Lin; Yang, Xiulan; Liu, Yongge; Tandon, Narendra; Kambayashi, Junichi; Downey, James M; Cohen, Michael V

2013-05-01

Blockade of platelet activation during primary percutaneous intervention for acute myocardial infarction is standard care to minimize stent thrombosis. To determine whether antiplatelet agents offer any direct cardioprotective effect, we tested whether they could modify infarction in a rabbit model of ischemia/reperfusion caused by reversible ligation of a coronary artery. The P2Y₁₂ (adenosine diphosphate) receptor blocker cangrelor administered shortly before reperfusion in rabbits undergoing 30-minute regional ischemia/3-hour reperfusion reduced infarction from 38% of ischemic zone in control hearts to only 19%. Protection was dose dependent and correlated with the degree of inhibition of platelet aggregation. Protection was comparable to that seen with ischemic postconditioning (IPOC). Cangrelor protection, but not its inhibition of platelet aggregation, was abolished by the same signaling inhibitors that block protection from IPOC suggesting protection resulted from protective signaling rather than anticoagulation. As with IPOC, protection was lost when cangrelor administration was delayed until 10 minutes after reperfusion and no added protection was seen when cangrelor and IPOC were combined. These findings suggest both IPOC and cangrelor may protect by the same mechanism. No protection was seen when cangrelor was used in crystalloid-perfused isolated hearts indicating some component in whole blood is required for protection. Clopidogrel had a very slow onset of action requiring 2 days of treatment before platelets were inhibited, and only then the hearts were protected. Signaling inhibitors given just prior to reperfusion blocked clopidogrel's protection. Neither aspirin nor heparin was protective. Clopidogrel and cangrelor protected rabbit hearts against infarction. The mechanism appears to involve signal transduction during reperfusion rather than inhibition of intravascular coagulation. We hypothesize that both drugs protect by activating IPOC's protective signaling to prevent reperfusion injury. If true, patients receiving P2Y₁₂ inhibitors before percutaneous intervention may already be postconditioned thus explaining failure of recent clinical trials of postconditioning drugs.

The noble gas xenon induces pharmacological preconditioning in the rat heart in vivo via induction of PKC-ɛ and p38 MAPK

PubMed Central

Weber, Nina C; Toma, Octavian; Wolter, Jessica I; Obal, Detlef; Müllenheim, Jost; Preckel, Benedikt; Schlack, Wolfgang

2004-01-01

Xenon is an anesthetic with minimal hemodynamic side effects, making it an ideal agent for cardiocompromised patients. We investigated if xenon induces pharmacological preconditioning (PC) of the rat heart and elucidated the underlying molecular mechanisms. For infarct size measurements, anesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Rats received either the anesthetic gas xenon, the volatile anesthetic isoflurane or as positive control ischemic preconditioning (IPC) during three 5-min periods before 25-min ischemia. Control animals remained untreated for 45 min. To investigate the involvement of protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK), rats were pretreated with the PKC inhibitor calphostin C (0.1 mg kg−1) or the p38 MAPK inhibitor SB203580 (1 mg kg−1). Additional hearts were excised for Western blot and immunohistochemistry. Infarct size was reduced from 50.9±16.7% in controls to 28.1±10.3% in xenon, 28.6±9.9% in isoflurane and to 28.5±5.4% in IPC hearts. Both, calphostin C and SB203580, abolished the observed cardioprotection after xenon and isoflurane administration but not after IPC. Immunofluorescence staining and Western blot assay revealed an increased phosphorylation and translocation of PKC-ɛ in xenon treated hearts. This effect could be blocked by calphostin C but not by SB203580. Moreover, the phosphorylation of p38 MAPK was induced by xenon and this effect was blocked by calphostin C. In summary, we demonstrate that xenon induces cardioprotection by PC and that activation of PKC-ɛ and its downstream target p38 MAPK are central molecular mechanisms involved. Thus, the results of the present study may contribute to elucidate the beneficial cardioprotective effects of this anesthetic gas. PMID:15644876

Dexmedetomidine prolongs the effect of bupivacaine in supraclavicular brachial plexus block

PubMed Central

Agarwal, Sandhya; Aggarwal, Ritu; Gupta, Praveen

2014-01-01

Background: We compared the effects of adding dexmedetomidine to a 30 ml solution of 0.325% bupivacaine in supraclavicular brachial plexus block. Onset and duration of sensory and motor block along with the duration of analgesia were the primary endpoints. Materials and Methods: Fifty patients posted for upper limb surgeries were enrolled for a prospective, randomized, double-blind, placebo-controlled trial. Patients were divided into two groups, the control group S and the study group SD. In group S (n = 25), 30 ml of 0.325% bupivacaine + 1 ml normal saline; and in group SD (n = 25), 30 ml of 0.325% bupivacaine + 1 ml (100 μg) dexmedetomidine were given for supraclavicular brachial plexus block using the peripheral nerve stimulator. Onset and duration of sensory and motor blocks were assessed along with the duration of analgesia, sedation, and adverse effects, if any. Hemodynamic parameters, like heart rate (HR), systolic arterial blood pressure (SBP), and diastolic arterial blood pressure (DBP) were also monitored. Results: Demographic data and surgical characteristics were comparable in both the groups. The onset times for sensory and motor blocks were significantly shorter in SD than S group (P < 0.001), while the duration of blocks was significantly longer (P < 0.001) in SD group. Except for the initial recordings (at 0, 5, 10, and 15 min), heart rate levels in group SD were significantly lower (P < 0.001). SBP and DBP levels in SD group at 15, 30, 45, 60, 90 and 120 min were significantly lower than in S group (P < 0.001). In fact, when the percentage changes in HR/SBP/DBP were compared from 0-5/0-10/0-15/0-30/0-45/0-60/0-90/0-120 min in SD with S group, they came out to be highly significant (P < 0.001) in group SD. The duration of analgesia (DOA) was significantly longer in SD group than S group (P < 0.001). Except that, bradycardia was observed in one patient in the group SD, no other adverse effects were observed in either of the groups. Conclusion: Dexmedetomidine added as an adjuvant to bupivacaine for supraclavicular brachial plexus block significantly shortens the onset time and prolongs the duration of sensory and motor blocks and duration of analgesia. Patients in group SD were adequately sedated (modified Ramsay Sedation Score, RSS = 2/6 or 3/6) with no adverse effects except bradycardia in one patient of group SD. PMID:24574591

The activity state of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues.

PubMed Central

Wagenmakers, A J; Schepens, J T; Veldhuizen, J A; Veerkamp, J H

1984-01-01

An assay is described to define the proportion of the branched-chain 2-oxo acid dehydrogenase complex that is present in the active state in rat tissues. Activities are measured in homogenates in two ways: actual activities, present in tissues, by blocking both the kinase and phosphatase of the enzyme complex during homogenization, preincubation, and incubation with 1-14C-labelled branched-chain 2-oxo acid, and total activities by blocking only the kinase during the 5 min preincubation (necessary for activation). The kinase is blocked by 5 mM-ADP and absence of Mg2+ and the phosphatase by the simultaneous presence of 50 mM-NaF. About 6% of the enzyme is active in skeletal muscle of fed rats, 7% in heart, 20% in diaphragm, 47% in kidney, 60% in brain and 98% in liver. An entirely different assay, which measures activities in crude tissue extracts before and after treatment with a broad-specificity protein phosphatase, gave similar results for heart, liver and kidney. Advantages of our assay with homogenates are the presence of intact mitochondria, the simplicity, the short duration and the high sensitivity. The actual activities measured indicate that the degradation of branched-chain 2-oxo acids predominantly occurs in liver and kidney and is limited in skeletal muscle in the fed state. PMID:6430280

The activity state of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues.

PubMed

Wagenmakers, A J; Schepens, J T; Veldhuizen, J A; Veerkamp, J H

1984-05-15

An assay is described to define the proportion of the branched-chain 2-oxo acid dehydrogenase complex that is present in the active state in rat tissues. Activities are measured in homogenates in two ways: actual activities, present in tissues, by blocking both the kinase and phosphatase of the enzyme complex during homogenization, preincubation, and incubation with 1-14C-labelled branched-chain 2-oxo acid, and total activities by blocking only the kinase during the 5 min preincubation (necessary for activation). The kinase is blocked by 5 mM-ADP and absence of Mg2+ and the phosphatase by the simultaneous presence of 50 mM-NaF. About 6% of the enzyme is active in skeletal muscle of fed rats, 7% in heart, 20% in diaphragm, 47% in kidney, 60% in brain and 98% in liver. An entirely different assay, which measures activities in crude tissue extracts before and after treatment with a broad-specificity protein phosphatase, gave similar results for heart, liver and kidney. Advantages of our assay with homogenates are the presence of intact mitochondria, the simplicity, the short duration and the high sensitivity. The actual activities measured indicate that the degradation of branched-chain 2-oxo acids predominantly occurs in liver and kidney and is limited in skeletal muscle in the fed state.

Adenosine triphosphate-sensitive potassium channel blocking agent ameliorates, but the opening agent aggravates, ischemia/reperfusion-induced injury. Heart function studies in nonfibrillating isolated hearts.

PubMed

Tosaki, A; Hellegouarch, A

1994-02-01

This study was conducted to elucidate the role of the adenosine triphosphate (ATP)-sensitive potassium channel blocking agent glibenclamide and the opener cromakalim in the mechanism of reperfusion-induced injury. Recently, ATP-sensitive potassium channel openers have been proposed to reduce ischemia/reperfusion-induced injury, including arrhythmias and heart function. Thus, one might hypothesize that pharmacologic agents that enhance the loss of potassium ions in the myocardium through ATP-sensitive potassium channels would be arrhythmogenic, and agents that interfere with tissue potassium ion loss would be antiarrhythmic. Isolated "working" guinea pig hearts and phosphorus-31 nuclear magnetic resonance spectroscopy were used to study the recovery of myocardial function and phosphorus compounds after 30, 40 and 50 min of normothermic global ischemia followed by reperfusion in untreated control and glibenclamide- and cromakalim-treated groups. After 30 min of ischemia, 1, 3, 10 and 30 mumol/liter of glibenclamide dose-dependently reduced the incidence of reperfusion-induced ventricular fibrillation (total) from its control value of 92% to 75%, 33% (p < 0.05), 33% (p < 0.05) and 42% (p < 0.05), respectively. The incidence of ventricular tachycardia followed the same pattern. A reduction of arrhythmias was also observed after 40 and 50 min of ischemia followed by reperfusion in the glibenclamide-treated hearts. Cromakalim, at the same concentrations, did not reduce the incidence of reperfusion-induced arrhythmias. During reperfusion, glibenclamide (3 and 10 mumol/liter) improved the recovery of coronary blood flow, aortic flow, myocardial contractility and tissue ATP and creatine phosphate content, but cromakalim failed to ameliorate the recovery of postischemic myocardium compared with that in the drug-free control hearts. The preservation of myocardial potassium ions and phosphorus compounds by glibenclamide can improve the recovery of postischemic function, but the use of ATP-sensitive potassium channel openers as antihypertensive or antiarrhythmic agents may be of particular concern in those postinfarction patients who are known to be at high risk for sudden cardiac death.

Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001.

PubMed

Louis, A; Cleland, J G; Crabbe, S; Ford, S; Thackray, S; Houghton, T; Clark, A

2001-06-01

This is a synopsis of presentations made at the American College of Cardiology (ACC) in 2001 summarising recent research developments relating to heart failure. Clinical studies of particular interest to physicians with an interest in heart failure and its prevention are reviewed. The COPERNICUS trial lends further support to the use of the beta-blocker, carvedilol, in severe heart failure and the CAPRICORN trial to its use in patients with post-infarction left ventricular systolic dysfunction. The MIRACLE study reinforces the evidence from three smaller trials that cardiac resynchronisation therapy is an effective treatment for the relief of symptoms in patients with severe heart failure and cardiac dyssynchrony. The STAF trial casts further doubt on the wisdom of cardioversion as a routine strategy for the management of chronic atrial fibrillation. The RITZ-2 trial suggests that an intravenous, non-selective endothelin antagonist is effective in improving haemodynamics and symptoms and possibly in reducing morbidity in severe heart failure. Observational studies in heart failure suggest that a moderate excess of body fat and elevated blood cholesterol may be desirable in patients with heart failure, challenging the current non-evidenced-based vogue for cholesterol lowering therapy in heart failure. The RENAISSANCE and RECOVER outcome studies of etanercept, a tumour necrosis factor (TNF) receptor analogue that blocks the effect of TNF, were stopped because of lack of evidence of benefit shortly after the ACC.

Pulmonary Microwave Ablation Near the Heart: Antenna Positioning Can Mitigate Cardiac Complications in a Porcine Model

PubMed Central

Nocerino, Elisabetta; Mason, Peter J.; Schwahn, Denise J.; Hetzel, Scott; Turnquist, Alyssa M.; Lee, Fred T.; Brace, Christopher L.

2017-01-01

Purpose To determine how close to the heart pulmonary microwave ablation can be performed without causing cardiac tissue injury or significant arrhythmia. Materials and Methods The study was performed with approval from the institutional animal care and use committee. Computed tomographic fluoroscopically guided microwave ablation of the lung was performed in 12 swine. Antennas were randomized to either parallel (180° ± 20°) or perpendicular (90° ± 20°) orientation relative to the heart surface and to distances of 0–10 mm from the heart. Ablations were performed at 65 W for 5 minutes or until a significant arrhythmia (asystole, heart block, bradycardia, supraventricular or ventricular tachycardia) developed. Heart tissue was evaluated with vital staining and histologic examination. Data were analyzed with mixed effects logistic regression, receiver operating characteristic curves, and the Fisher exact test. Results Thirty-four pulmonary microwave ablations were performed with the antenna a median distance of 4 mm from the heart in both perpendicular (n = 17) and parallel (n = 17) orientation. Significant arrhythmias developed during six (18%) ablations. Cardiac tissue injury occurred with 17 ablations (50%). Risk of arrhythmia and tissue injury decreased with increasing antenna distance from the heart with both antenna orientations. No cardiac complication occurred with a distance of greater than or equal to 4.4 mm from the heart. The ablation zone extended to the pleural surface adjacent to the heart in 71% of parallel and 17% of perpendicular ablations performed 5–10 mm from the heart. Conclusion Microwave lung ablations performed more than or equal to 5 mm from the heart were associated with a low risk of cardiac complications. © RSNA, 2016 PMID:27732159

Molecular mechanism of emotional stress-induced and catecholamine-induced heart attack.

PubMed

Ueyama, Takashi; Senba, Emiko; Kasamatsu, Ken; Hano, Takuzo; Yamamoto, Katsuhiro; Nishio, Ichiro; Tsuruo, Yoshihiro; Yoshida, Ken-ichi

2003-01-01

Emotional or physical stress triggers 'tako-tsubo' cardiomyopathy or 'transient left ventricular apical ballooning', but the pathogenesis is unclear. In response to the immobilization stress of rats, a useful model of emotional stress, rapid activation of p44/p42 mitogen-activated protein kinase was observed in the heart, followed by a transient upregulation of immediate early genes in the smooth muscle cells of coronary arteries, the endothelial cells and the myocardium. Heat shock protein 70 was induced in the aortic and coronary arterial smooth muscle cells and in the myocardium. Natriuretic peptide genes were also upregulated in the myocardium. Sequential gene expression can be considered as an adaptive response to emotional stress. Blocking of both alpha-adrenoceptors and beta-adrenoceptors eliminated the upregulation of immediate early genes induced by stress, while alpha-agonists and beta-agonists upregulated immediate early genes in the perfused heart. Activation of alpha-adrenoceptors and beta-adrenoceptors is the primary trigger of emotional stress-induced molecular changes in the heart.

Identification of the protein responsible for pyruvate transport into rat liver and heart mitochondria by specific labelling with [3H]N-phenylmaleimide.

PubMed

Thomas, A P; Halestrap, A P

1981-05-15

1. N-Phenylmaleimide irreversibly inhibits pyruvate transport into rat heart and liver mitochondria to a much greater extent than does N-ethylmaleimide, iodoacetate or bromopyruvate. alpha-Cyanocinnamate protects the pyruvate transporter from attack by this thiol-blocking reagent. 2. In both heart and liver mitochondria alpha-cyanocinnamate diminishes labelling by [3H]N-phenylmaleimide of a membrane protein of subunit mol.wt. 15000 on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 3. Exposure of mitochondrial to unlabelled N-phenylmaleimide in the presence of alpha-cyanocinnamate, followed by removal of alpha-cyanocinnamate and exposure to [3H]N-phenylmaleimide, produced specific labelling of the same protein. 4. Both labelling and kinetic experiments with inhibitors gave values for the approximate amount of carrier present in liver and heart mitochondria of 100 and 450 pmol/mg of mitochondrial protein respectively. 5. The turnover numbers for net pyruvate transport and pyruvate exchange at 0 degrees C were 6 and 200 min-1 respectively.

Software development for the analysis of heartbeat sounds with LabVIEW in diagnosis of cardiovascular disease.

PubMed

Topal, Taner; Polat, Hüseyin; Güler, Inan

2008-10-01

In this paper, a time-frequency spectral analysis software (Heart Sound Analyzer) for the computer-aided analysis of cardiac sounds has been developed with LabVIEW. Software modules reveal important information for cardiovascular disorders, it can also assist to general physicians to come up with more accurate and reliable diagnosis at early stages. Heart sound analyzer (HSA) software can overcome the deficiency of expert doctors and help them in rural as well as urban clinics and hospitals. HSA has two main blocks: data acquisition and preprocessing, time-frequency spectral analyses. The heart sounds are first acquired using a modified stethoscope which has an electret microphone in it. Then, the signals are analysed using the time-frequency/scale spectral analysis techniques such as STFT, Wigner-Ville distribution and wavelet transforms. HSA modules have been tested with real heart sounds from 35 volunteers and proved to be quite efficient and robust while dealing with a large variety of pathological conditions.

Alpha1-adrenergic blockers: current usage considerations.

PubMed

Sica, Domenic A

2005-12-01

Alpha1-adrenergic-blocking drugs are effective in reducing blood pressure and do so in a fashion comparable to most other antihypertensive drug classes. These compounds are most effective in patients in the upright position, reducing systolic and diastolic pressures by 8%-10%. Alpha1-adrenergic-blocking drugs incrementally reduce blood pressure when combined with most drug classes and are the only antihypertensive drug class to improve plasma lipid profiles. Alpha1-adrenergic-blocking drugs are also accepted as important elements of the treatment plan for symptomatic benign prostatic hypertrophy. Dose escalation of an alpha1-adrenergic-blocking drug can trigger renal Na+ retention, and the ensuing volume expansion can attenuate its blood pressure-lowering effect. Orthostatic hypotension can occur with these compounds, particularly when a patient is volume-contracted. Dizziness, headache, and drowsiness are common side effects with alpha1-adrenergic blockers. A modest decline in the use of doxazosin and other alpha1-adrenergic-blocking drugs has occurred coincident to the early termination of the doxazosin treatment arm in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Twelve-lead electrocardiography in the young: physiologic and pathologic abnormalities.

PubMed

Kobza, Richard; Cuculi, Florim; Abächerli, Roger; Toggweiler, Stefan; Suter, Yves; Frey, Franz; Schmid, Johann Jakob; Erne, Paul

2012-12-01

BACKGROUND/ OBJECTIVE: The purpose of the present study was to analyze the prevalence of physiologic and pathologic ECG abnormalities in a cohort of young conscripts that represents the whole young generation of today. ECGs of all Swiss citizens who underwent conscription for the army during a 29-month period were analyzed manually. ECGs of 43,401 conscripts (mean age 19.2 ± 1.1 years) were analyzed; 158 conscripts were female. Incomplete right bundle branch block was found in 5870 (13.5%) and left anterior fascicular block in 360 (0.83%). First-degree AV block was present in 329 (0.8%) and Mobitz type I (Wenckebach) second-degree AV block in 3 (0.01%). Early repolarization was observed in 1035 (2.4%), T-wave inversion in 39 (0.09%), and minor T-wave changes in 182 (0.42%). Brugada-like abnormalities were observed in 6 (0.01%). None of the conscripts had atrial fibrillation or flutter. ECG abnormalities can be found in a relatively large proportion of young individuals. Incomplete right bundle branch block, left fascicular block, and first-degree AV block are the most frequent findings. No conscript presented with atrial fibrillation or flutter. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Side effects and complications of intraosseous anesthesia and conventional oral anesthesia

PubMed Central

Peñarrocha-Oltra, David; Ata-Ali, Javier; Oltra-Moscardó, María J.; Peñarrocha, Miguel

2012-01-01

Objective: To analyze the side effects and complications following intraosseous anesthesia (IA), comparing them with those of the conventional oral anesthesia techniques. Material and method: A simple-blind, prospective clinical study was carried out. Each patient underwent two anesthetic techniques: conventional (local infiltration and locoregional anesthetic block) and intraosseous, for respective dental operations. In order to allow comparison of IA versus conventional anesthesia, the two operations were similar and affected the same two teeth in opposite quadrants. Heart rate was recorded in all cases before injection of the anesthetic solution and again 30 seconds after injection. The complications observed after anesthetic administration were recorded. Results: A total of 200 oral anesthetic procedures were carried out in 100 patients. Both IA and conventional anesthesia resulted in a significant increase in heart rate, though the increase was greater with the latter technique. Incidents were infrequent with either anesthetic technique, with no significant differences between them. Regarding the complications, there were significant differences in pain at the injection site, with more intense pain in the case of IA (x2=3.532, p=0.030, Φ2=0.02), while the limitation of oral aperture was more pronounced with conventional anesthesia (x2=5.128, p<0.05, Φ2=0.014). Post-anesthetic biting showed no significant differences (x2=4.082, p=0.121, Φ2=0.009). Conclusions: Both anesthetic techniques significantly increased heart rate, and IA caused comparatively more pain at the injection site, while limited oral aperture was more frequent with conventional anesthesia. Post-anesthetic biting showed no significant differences between the two techniques. Key words:Intraosseous anesthesia, oral anesthesia, mandibular block, heart rate, adrenalin, complications. PMID:22143716

Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction

PubMed Central

Raasch, Walter; Schäfer, Ulrich; Qadri, Fatimunnisa; Dominiak, Peter

2002-01-01

Since agmatine has been identified as a clonidine displacing substance (CDS), the aim of this study was to investigate whether agmatine can mimic CDS-induced cardiovascular reactions in organ bath experiments, pithed spontaneously hypertensive rats (SHR) and anaesthetized SHR.Intravenously-administered agmatine significantly reduced the blood pressure and heart rate of anaesthetized SHR at doses higher than 1 and 3 mg kg−1, respectively. These effects are probably mediated via central mechanisms, since there was an approximate 8 fold rightward shift of the dose-response curve in the pithed SHR (indicating a weakened cardiovascular effect). Moreover, in organ bath experiments, agmatine failed to alter the contractility of intact or endothelium-denuded aortal rings. When agmatine was administered i.c.v. to anaesthetized SHR, blood pressure was increased without any alteration of heart rate, whereas blood pressure was unchanged and heart rate was increased after injection into the 4th brain ventricle. This suggests that haemodynamic reaction patterns after central application are related to distinct influences on central cardiovascular mechanisms.Agmatine reduces noradrenaline release in pithed SHR while α2-adrenoceptors are irreversibly blocked with phenoxybenzamine, but not while I1-binding sites are selectively blocked with AGN192403. This suggests that agmatine may modulate noradrenaline release in the same way that clonidine does, i.e. via imidazoline binding sites; this involves a reduction in sympathetic tone which in turn reduces blood pressure and heart rate.Finally, CDS-like cardiovascular activity appears not to be due to agmatine, since (i) blood pressure in anaesthetized SHR is decreased by agmatine and clonidine, and (ii) agmatine did not antagonize the blood pressure reaction to clonidine in pithed or anaesthetized SHR. PMID:11834614

Geranylgeranylacetone blocks doxorubicin-induced cardiac toxicity and reduces cancer cell growth and invasion through RHO pathway inhibition.

PubMed

Sysa-Shah, Polina; Xu, Yi; Guo, Xin; Pin, Scott; Bedja, Djahida; Bartock, Rachel; Tsao, Allison; Hsieh, Angela; Wolin, Michael S; Moens, An; Raman, Venu; Orita, Hajime; Gabrielson, Kathleen L

2014-07-01

Doxorubicin is a widely used chemotherapy for solid tumors and hematologic malignancies, but its use is limited due to cardiotoxicity. Geranylgeranylacetone (GGA), an antiulcer agent used in Japan for 30 years, has no significant adverse effects, and unexpectedly reduces ovarian cancer progression in mice. Because GGA reduces oxidative stress in brain and heart, we hypothesized that GGA would prevent oxidative stress of doxorubicin cardiac toxicity and improve doxorubicin's chemotherapeutic effects. Nude mice implanted with MDA-MB-231 breast cancer cells were studied after chronic treatment with doxorubicin, doxorubicin/GGA, GGA, or saline. Transthoracic echocardiography was used to monitor systolic heart function and xenografts evaluated. Mice were euthanized and cardiac tissue evaluated for reactive oxygen species generation, TUNEL assay, and RHO/ROCK pathway analysis. Tumor metastases were evaluated in lung sections. In vitro studies using Boyden chambers were performed to evaluate GGA effects on RHO pathway activator lysophosphatidic acid (LPA)-induced motility and invasion. We found that GGA reduced doxorubicin cardiac toxicity, preserved cardiac function, prevented TUNEL-positive cardiac cell death, and reduced doxorubicin-induced oxidant production in a nitric oxide synthase-dependent and independent manner. GGA also reduced heart doxorubicin-induced ROCK1 cleavage. Remarkably, in xenograft-implanted mice, combined GGA/doxorubicin treatment decreased tumor growth more effectively than doxorubicin treatment alone. As evidence of antitumor effect, GGA inhibited LPA-induced motility and invasion by MDA-MB-231 cells. These anti-invasive effects of GGA were suppressed by geranylgeraniol suggesting GGA inhibits RHO pathway through blocking geranylation. Thus, GGA protects the heart from doxorubicin chemotherapy-induced injury and improves anticancer efficacy of doxorubicin in breast cancer. ©2014 American Association for Cancer Research.

Oxytocin treatment does not change cardiovascular parameters, hematology and plasma electrolytes in parturient horse mares.

PubMed

Nagel, Christina; Trenk, Lisa; Wulf, Manuela; Ille, Natascha; Aurich, Jörg; Aurich, Christine

2017-03-15

In mares, foaling is associated with changes in hematology, plasma electrolytes, blood pressure and heart rate and it has been hypothesized that these are induced by oxytocin. To test this hypothesis, mares (n = 8-14/group) were treated with oxytocin (OT; 20 I.U.) or saline (CON) at 1 h (test A) and 12 h after foaling (test B) and during first postpartum diestrus (test C). Heart rate, heart rate variability (HRV), atrioventricular blocks, salivary cortisol concentration, blood pressure, plasma electrolytes and blood count were determined. Heart rate decreased from test A to C (P < 0.001) but at no time differed between groups. The HRV, blood pressure and occurrence of atrioventricular blocks did not change in response to oxytocin. Cortisol concentration decreased from test A to C (P < 0.001). Oxytocin induced a cortisol release in test B (time x treatment P < 0.001, time x test P < 0.001). Plasma sodium and chloride concentrations decreased from test A to C (P < 0.001) but did not differ between groups. In test A, potassium concentration increased in CON but not OT mares (time P < 0.01, time x test P < 0.01, time x treatment P < 0.05). Polymorphnuclear cell (PMN) numbers in blood decreased from test A to C (P < 0.001) while lymphocytes increased (P < 0.05). At no time PMN and lymphocytes differed between groups. Oxytocin treatment had no effect on skin temperature. In conclusion, except for a limited effect on cortisol release, oxytocin was without effect and the hypothesis of oxytocin-induced alterations in cardiac parameters, plasma electrolytes and hematology of foaling mares was not verified. Copyright © 2016 Elsevier Inc. All rights reserved.

Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

PubMed

Shizukuda, Yukitaka; Tripodi, Dorothy J; Zalos, Gloria; Bolan, Charles D; Yau, Yu-Ying; Leitman, Susan F; Waclawiw, Myron A; Rosing, Douglas R

2012-03-15

It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p < 0.05, using the Kruskal-Wallis test). No examples of heart block, other than first-degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation. Published by Elsevier Inc.

Cardiac basal metabolism: energetic cost of calcium withdrawal in the adult rat heart.

PubMed

Bonazzola, P; Takara, D

2010-07-01

Cardiac basal metabolism upon extracellular calcium removal and its relationship with intracellular sodium and calcium homeostasis was evaluated. A mechano-calorimetric technique was used that allowed the simultaneous and continuous measurement of both heat rate and resting pressure in arterially perfused quiescent adult rat hearts. Using pharmacological tools, the possible underlying mechanisms related to sodium and calcium movements were investigated. Resting heat rate (expressed in mW g(-1)(dry wt)) increased upon calcium withdrawal (+4.4 +/- 0.2). This response was: (1) unaffected by the presence of tetrodotoxin (+4.3 +/- 0.6), (2) fully blocked by both, the decrease in extracellular sodium concentration and the increase in extracellular magnesium concentration, (3) partially blocked by the presence of either nifedipine (+2.8 +/- 0.4), KB-R7943 (KBR; +2.5 +/- 0.2), clonazepam (CLO; +3.1 +/- 0.3) or EGTA (+1.9 +/- 0.3). The steady heat rate under Ca(2+)-free conditions was partially reduced by the addition of Ru360 (-1.1 +/- 0.2) but not CLO in the presence of EGTA, KBR or Ru360. Energy expenditure for resting state maintenance upon calcium withdrawal depends on the intracellular rise in both sodium and calcium. Our data are consistent with a mitochondrial Ca(2+) cycling, not detectable under normal calcium diastolic levels. The experimental condition here analysed, partially simulates findings reported under certain pathological situations including heart failure in which mildly increased levels of both diastolic sodium and calcium have also been found. Therefore, under such pathological conditions, hearts should distract chemical energy to fuel processes associated with sodium and calcium handling, making more expensive the maintenance of their functions.

Oxidative Stress by Monoamine Oxidase-A Impairs Transcription Factor EB Activation and Autophagosome Clearance, Leading to Cardiomyocyte Necrosis and Heart Failure.

PubMed

Santin, Yohan; Sicard, Pierre; Vigneron, François; Guilbeau-Frugier, Céline; Dutaur, Marianne; Lairez, Olivier; Couderc, Bettina; Manni, Diego; Korolchuk, Viktor I; Lezoualc'h, Frank; Parini, Angelo; Mialet-Perez, Jeanne

2016-07-01

In heart failure (HF), mitochondrial quality control and autophagy are progressively impaired, but the role of oxidative stress in this process and its underlying mechanism remain to be defined. By degrading norepinephrine and serotonin, the mitochondrial enzyme, monoamine oxidase-A (MAO-A), is a potent source of reactive oxygen species (ROS) in the heart and its activation leads to the persistence of mitochondrial damage. In this study, we analyzed the consequences of ROS generation by MAO-A on the autophagy-lysosome pathway in the heart. Cardiomyocyte-driven expression of MAO-A in mice led to mitochondrial fission and translocation of Drp1 and Parkin in the mitochondrial compartment. Ventricles from MAO-A transgenic mice displayed accumulation of LC3-positive autophagosomes, together with p62 and ubiquitylated proteins, indicating impairment of autophagy. In vitro adenoviral delivery of MAO-A in cardiomyocytes and the consequent generation of ROS blocked autophagic flux with accumulation of LC3II, p62, and ubiquitylated proteins, leading to mitochondrial fission and cell necrosis. In addition, MAO-A activation induced accumulation of lysosomal proteins, cathepsin D and Lamp1, reduced lysosomal acidification, and blocked the nuclear translocation of transcription factor-EB (TFEB), a master regulator of autophagy and lysosome biogenesis. Most interestingly, overexpression of TFEB attenuated autophagosome buildup, mitochondrial fission, cardiomyocyte death, and HF associated with MAO-A activation. This study unravels a new link between MAO-dependent H2O2 production and lysosomal dysfunction. Altogether, our findings demonstrate that the MAO-A/H2O2 axis has a negative impact on the elimination and recycling of mitochondria through the autophagy-lysosome pathway, which participates in cardiomyocyte death and HF. Antioxid. Redox Signal. 25, 10-27.

The Prevalence of Chagas Heart Disease in a Central Bolivian Community Endemic for Trypanosoma Cruzi

PubMed Central

Yager, Jessica E.; Lozano Beltran, Daniel F.; Torrico, Faustino; Gilman, Robert H.; Bern, Caryn

2015-01-01

Background Though the incidence of new Trypanosoma cruzi infections has decreased significantly in endemic regions in the Americas, medical professionals continue to encounter a high burden of resulting Chagas disease among infected adults. The current prevalence of Chagas heart disease in a community setting is not known; nor is it known how recent insecticide vector control measures may have impacted the progression of cardiac disease in an infected population. Objectives and Methods Nested within a community serosurvey in rural and periurban communities in central Bolivia, we performed a cross-sectional cardiac substudy to evaluate adults for historical, clinical, and electrocardiographic evidence of cardiac disease. All adults between the ages of 20 and 60 years old with T. cruzi infection and those with a clinical history, physical exam, or ECG consistent with cardiac abnormalities were also scheduled for echocardiography. Results and conclusions Of the 604 cardiac substudy participants with definitive serology results, 183 were seropositive for infection with T. cruzi (30.3%). Participants who were seropositive for T. cruzi infection were more likely to have conduction system defects (1.6% versus 0 for complete right bundle branch block and 10.4% versus 1.9% for any bundle branch block; p=0.008 and p<0.001, respectively). However, there was no statistically significant difference in the prevalence of bradycardia among seropositive versus seronegative participants. Echocardiogram findings were not consistent with a high burden of Chagas cardiomyopathy: valvulopathies were the most common abnormality, and few participants were found to have low ejection fraction or left ventricular dilatation. No participants had significant heart failure. Though almost one third of adults in the community were seropositive for T. cruzi infection, few had evidence of Chagas heart disease. PMID:26407509

Influence of Competitive-Anxiety on Heart Rate Variability in Swimmers

PubMed Central

Fortes, Leonardo S.; da Costa, Bruna D. V.; Paes, Pedro P.; do Nascimento Júnior, José R.A.; Fiorese, Lenamar; Ferreira, Maria E.C.

2017-01-01

The aim of this study was to analyze the relationship between competitive anxiety and heart rate variability (HRV) in swimming athletes. A total of 66 volunteers (41 male and 27 female) who swam the 400-m freestyle in the Brazilian Swimming Championships participated. Thirty minutes before the 400-m freestyle event, the athletes answered the Competitive Anxiety Inventory (CSAI-2R) questionnaire, then underwent anthropometric (body weight, height, and skinfold thickness) and HRV measurements. Then, at a second meeting, held 3 h after the 400-m freestyle event, the athletes returned to the evaluation room for HRV measurement (Polar® RS800cx, Kempele, Finland). Multiple linear regression was used to evaluate the relationship between competitive anxiety and HRV. The multiple linear regression was performed in three blocks (block 1: cognitive anxiety, block 2: somatic anxiety, and block 3: self-confidence), adopting the forward model. The results indicated a significant association between cognitive anxiety (p = 0.001) and HRV. An increased magnitude of the association was observed when somatic anxiety was inserted in the model (p = 0.001). In contrast, self-confidence showed, which was inserted in block 3, no relationship with HRV (p = 0.27). It was concluded that cognitive and somatic anxieties were associated with the HRV of swimmers. Athletes with a high magnitude of cognitive and/or somatic anxiety demonstrated more significant autonomic nervous system disturbance. Practically, psychological interventions are needed to improve anxiety states that are specific to perform well, and to improve HRV. Key points The level of competitive-anxiety can predict HRV’s response after competition in young swimming athletes. Young swimming athletes who demonstrate higher competitive-anxiety, may present high autonomic nervous system disorder, which can be evaluated by HRV. Coaches are encouraged to periodically evaluate the competitive-anxiety of young swimming athletes. PMID:29238249

Evaluation of an Acute RNAi-Mediated Therapeutic for Visual Dysfunction Associated with Traumatic Brain Injury

DTIC Science & Technology

2013-10-01

requiring pacemaker  Refusal of consent - Claustrophobia  Spinal Cord Injury  Unstable due to tracheal stenosis and lobar collapse  2 patients had...be stopped.  Heart Block necessitating pacemaker  Unstable from a respiratory point of view due to previous Left lower lobectomy, right upper

Native Valve Endocarditis due to Ralstonia pickettii: A Case Report and Literature Review.

PubMed

Orme, Joseph; Rivera-Bonilla, Tomas; Loli, Akil; Blattman, Negin N

2015-01-01

Ralstonia pickettii is a rare pathogen and even more rare in healthy individuals. Here we report a case of R. pickettii bacteremia leading to aortic valve abscess and complete heart block. To our knowledge this is the first case report of Ralstonia species causing infective endocarditis with perivalvular abscess.

A Versatile and Inexpensive Enzyme Purification Experiment for Undergraduate Biochemistry Labs.

ERIC Educational Resources Information Center

Farrell, Shawn O.; Choo, Darryl

1989-01-01

Develops an experiment that could be done in two- to three-hour blocks and does not rely on cold room procedures for most of the purification. Describes the materials, methods, and results of the purification of bovine heart lactate dehydrogenase using ammonium sulfate fractionation, dialysis, and separation using affinity chromatography and…

Articaine for supplemental intraosseous anesthesia in patients with irreversible pulpitis.

PubMed

Bigby, Jason; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel

2006-11-01

The purpose of this study was to determine the anesthetic efficacy and heart rate effect of 4% articaine with 1:100,000 epinephrine for supplemental intraosseous injection in mandibular posterior teeth diagnosed with irreversible pulpitis. Thirty-seven emergency patients, diagnosed with irreversible pulpitis of a mandibular posterior tooth, received an inferior alveolar nerve block and had moderate-to-severe pain upon endodontic access. The Stabident system was used to administer 1.8 ml of 4% articaine with 1:100,000 epinephrine. Success of the intraosseous injection was defined as none or mild pain upon endodontic access or initial instrumentation. The results demonstrated that anesthetic success was obtained in 86% (32 of 37) of the patients. Maximum mean heart rate was increased 32 beats/minute during the intraosseous injection. We can conclude that when the inferior alveolar nerve block fails to provide profound pulpal anesthesia, the intraosseous injection of 4% articaine with 1:100,000 epinephrine would be successful 86% of the time in achieving pulpal anesthesia in mandibular posterior teeth of patients presenting with irreversible pulpitis.

Improving the performance of AlGaN-based deep-ultraviolet light-emitting diodes using electron blocking layer with a heart-shaped graded Al composition

NASA Astrophysics Data System (ADS)

Kwon, M. R.; Park, T. H.; Lee, T. H.; Lee, B. R.; Kim, T. G.

2018-04-01

We propose a design for highly efficient AlGaN-based deep-ultraviolet light-emitting diodes (DUV LEDs) using a heart-shaped graded Al composition electron-blocking layer (EBL). This novel structure reduced downward band bending at the interface between the last quantum barrier and the EBL and flattened the electrostatic field in the interlayer between the barriers of the multi-quantum barrier EBL. Consequently, electron leakage was significantly suppressed and hole injection efficiency was found to have improved. The parameter values of simulation were extracted from the experimental data of the reference DUV LEDs. Using the SimuLED, we compared the electrical and optical properties of three structures with different Al compositions in the active region and the EBL. The internal quantum efficiency of the proposed structure was shown to exceed those of the reference DUV LEDs by a factor of 1.9. Additionally, the output power at 20 mA was found to increase by a factor of 2.1.

A Proliferative Burst During Preadolescence Establishes the Final Cardiomyocyte Number

PubMed Central

Naqvi, Nawazish; Li, Ming; Calvert, John W.; Tejada, Thor; Lambert, Jonathan P.; Wu, Jianxin; Kesteven, Scott H.; Holman, Sara R.; Matsuda, Torahiro; Lovelock, Joshua D.; Howard, Wesley W.; Iismaa, Siiri E.; Chan, Andrea Y.; Crawford, Brian H.; Wagner, Mary B.; Martin, David I. K.; Lefer, David J.; Graham, Robert M.; Husain, Ahsan

2014-01-01

SUMMARY It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here we show thata thyroid hormone surge activates the IGF-1/IGF1-R/Akt pathway on postnatal day-15andinitiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day15 is intermediate between that observed at postnatal day-2 and -21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases. PMID:24813607

Plasma-derived exosomes contribute to inflammation via the TLR9-NF-κB pathway in chronic heart failure patients.

PubMed

Ye, Wei; Tang, Xiaojun; Yang, Zhengquan; Liu, Chu; Zhang, Xin; Jin, Jing; Lyu, Jianxin

2017-07-01

Exosomes are small vesicles that contain proteins, DNA and RNA, and play an important role in inflammation; however, the underlying mechanism remains unclear. In the present study, we found increased plasma-derived exosomes in chronic heart failure patients compared with healthy controls. Further, our data demonstrated that plasma-derived exosomes carried mtDNA, and triggered an inflammatory response via the TLR9-NF-κB pathway, as well, the inflammatory effect was closely related to exosomal mtDNA copy number. However, the effect could be blocked by chloroquine (CQ), a TLR9 inhibitor. These findings reveal a new mechanism of exosome-induced inflammation, and provide a new perspective for intervention and treatment of inflammation-related diseases, such as chronic heart failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Positive Inotropic Effect of Pyruvate Involves an Increase in Myofilament Calcium Sensitivity

PubMed Central

Torres, Carlos A. A.; Varian, Kenneth D.; Canan, Cynthia H.; Davis, Jonathan P.; Janssen, Paul M. L.

2013-01-01

Pyruvate is a metabolic fuel that is a potent inotropic agent. Despite its unique inotropic and antioxidant properties, the molecular mechanism of its inotropic mechanism is still largely unknown. To examine the inotropic effect of pyruvate in parallel with intracellular calcium handling under near physiological conditions, we measured pH, myofilament calcium sensitivity, developed force, and calcium transients in ultra thin rabbit heart trabeculae at 37 °C loaded iontophoretically with the calcium indicator bis-fura-2. By contrasting conditions of control versus sarcoplasmic reticulum block (with either cyclopiazonic acid and ryanodine or with thapsigargin) we were able to characterize and isolate the effects of pyruvate on sarcoplasmic reticulum calcium handling and developed force. A potassium contracture technique was subsequently utilized to assess the force-calcium relationship and thus the myofilament calcium sensitivity. Pyruvate consistently increased developed force whether or not the sarcoplasmic reticulum was blocked (16.8±3.5 to 24.5±5.1 vs. 6.9±2.6 to 12.5±4.4 mN/mm2, non-blocked vs. blocked sarcoplasmic reticulum respectively, p<0.001, n = 9). Furthermore, the sensitizing effect of pyruvate on the myofilaments was demonstrated by potassium contractures (EC50 at baseline versus 20 minutes of pyruvate infusion (peak force development) was 701±94 vs. 445±65 nM, p<0.01, n = 6). This study is the first to demonstrate that a leftward shift in myofilament calcium sensitivity is an important mediator of the inotropic effect of pyruvate. This finding can have important implications for future development of therapeutic strategies in the management of heart failure. PMID:23691074

The role of Na-Ca exchange current in the cardiac action potential.

PubMed

Janvier, N C; Boyett, M R

1996-07-01

Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

Catheter ablation as a treatment of atrioventricular block.

PubMed

Tuohy, Stephen; Saliba, Walid; Pai, Manjunath; Tchou, Patrick

2018-01-01

Symptomatic second-degree atrioventricular (AV) block is typically treated by implantation of a pacemaker. An otherwise healthy AV conduction system can nevertheless develop AV block due to interference from junctional extrasystoles. When present with a high burden, these can produce debilitating symptoms from AV block despite an underlying normal AV node and His-Purkinje system properties. The purpose of this study was to describe a catheter ablation approach for alleviating symptomatic AV block due to a ventricular nodal pathway interfering with AV conduction. Common clinical monitoring techniques such as Holter and event recorders were used. Standard electrophysiological study techniques using multipolar recording and ablation catheters were utilized during procedures. A 55-year-old woman presented with highly symptomatic, high-burden second-degree AV block due to concealed and manifest junctional premature beats. Electrophysiological characteristics indicated interference of AV conduction due to a concealed ventricular nodal pathway as the cause of the AV block. The patient's AV nodal and His-Purkinje system conduction characteristics were otherwise normal. Radiofrequency catheter ablation of the pathway was successful in restoring normal AV conduction and eliminating her clinical symptoms. Pathways inserting into the AV junction can interfere with AV conduction. When present at a high burden, this type of AV block can be highly symptomatic. Catheter ablation techniques can be used to alleviate this type of AV block and restore normal AV conduction. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Nonsurgical reduction of the interventricular septum in patients with hypertrophic cardiomyopathy.

PubMed

Shamim, Waqar; Yousufuddin, Mohammed; Wang, Duolao; Henein, Michael; Seggewiss, Hubert; Flather, Marcus; Coats, Andrew J S; Sigwart, Ulrich

2002-10-24

In patients with hypertrophic cardiomyopathy and obstruction of the left ventricular outflow tract, nonsurgical reduction of the septum is a treatment option when medical therapy has failed. We investigated the long-term effects of nonsurgical reduction of the septum on functional capacity and electrocardiographic and echocardiographic characteristics. Sixty-four consecutive patients with hypertrophic cardiomyopathy and a mean (+/-SD) age of 48.5+/-17.2 years underwent nonsurgical reduction of the septum by injection of ethanol into the septal perforator branch of the left anterior descending coronary artery. These patients were assessed by exercise testing, electrocardiography, and resting and dobutamine (stress-induced) echocardiography after a mean period of 3.0+/-1.3 years. At follow-up, patients had significant improvements in New York Heart Association class, peak oxygen consumption (from 18.4+/-5.8 to 30.0+/-4.4 ml per kilogram of body weight per minute, P<0.001), and left ventricular outflow tract gradients (resting gradient, from 64+/-36 to 16+/-15 mm Hg; P<0.001; stress-induced gradient, from 132+/-34 to 45+/-19 mm Hg; P<0.001). Procedure-related complications included right bundle-branch block in all patients, complete heart block in 31 patients (48 percent), and significant increases in QRS and corrected QT intervals. Seventeen patients (27 percent) required permanent pacing. R-wave amplitude was significantly decreased (from 32+/-8 to 17+/-7 mV, P<0.001). The dimensions of the left ventricular cavity increased, and the interventricular septal thickness was reduced. Nonsurgical septal reduction leads to sustained improvements in both subjective and objective measures of exercise capacity in association with a persistent reduction in resting and stress-induced left ventricular outflow tract gradients. It is also associated with a high incidence of procedure-related complete heart block, however, often requiring permanent pacing. Copyright 2002 Massachusetts Medical Society

A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

NASA Astrophysics Data System (ADS)

Javed, Faizan; Venkatachalam, P. A.; H, Ahmad Fadzil M.

2006-04-01

In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition & Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions.

Macrophages and cardiac fibroblasts are the main producers of eotaxins and regulate eosinophil trafficking to the heart

PubMed Central

Diny, Nicola L.; Hou, Xuezhou; Barin, Jobert G.; Chen, Guobao; Talor, Monica V.; Schaub, Julie; Russell, Stuart D.; Klingel, Karin; Rose, Noel R.; Čiháková, Daniela

2016-01-01

Cardiac manifestations are a major cause of morbidity and mortality in patients with eosinophil-associated diseases. Eosinophils are thought to play a pathogenic role in myocarditis. We investigated the pathways that recruit eosinophils to the heart using a model of eosinophilic myocarditis, in which experimental autoimmune myocarditis (EAM) is induced in IFNγ−/−IL-17A−/− mice. Two conditions are necessary for efficient eosinophil trafficking to the heart: high eotaxin (CCL11, CCL24) expression in the heart and expression of the eotaxin receptor CCR3 by eosinophils. We identified cardiac fibroblasts as the source of CCL11 in the heart interstitium. CCL24 is produced by F4/80+ macrophages localized at inflammatory foci in the heart. Expression of CCL11 and CCL24 is controlled by Th2 cytokines, IL-4 and IL-13. To determine the relevance of this pathway in humans, we analyzed endomyocardial biopsy samples from myocarditis patients. Expression of CCL11 and CCL26 was significantly increased in eosinophilic myocarditis compared to chronic lymphocytic myocarditis and positively correlated with the number of eosinophils. Thus, eosinophil trafficking to the heart is dependent on the eotaxin-CCR3 pathway in a mouse model of EAM and associated with cardiac eotaxin expression in patients with eosinophilic myocarditis. Blocking this pathway may prevent eosinophil-mediated cardiac damage. PMID:27621211

[Estimation of the atrioventricular time interval by pulse Doppler in the normal fetal heart].

PubMed

Hamela-Olkowska, Anita; Dangel, Joanna

2009-08-01

To assess normative values of the fetal atrioventricular (AV) time interval by pulse-wave Doppler methods on 5-chamber view. Fetal echocardiography exams were performed using Acuson Sequoia 512 in 140 singleton fetuses at 18 to 40 weeks of gestation with sinus rhythm and normal cardiac and extracardiac anatomy. Pulsed Doppler derived AV intervals were measured from left ventricular inflow/outflow view using transabdominal convex 3.5-6 MHz probe. The values of AV time interval ranged from 100 to 150 ms (mean 123 +/- 11.2). The AV interval was negatively correlated with the heart rhythm (p<0.001). Fetal heart rate decreased as gestation progressed (p<0.001). Thus, the AV intervals increased with the age of gestation (p=0.007). However, in the same subgroup of the fetal heart rate there was no relation between AV intervals and gestational age. Therefore, the AV intervals showed only the heart rate dependence. The 95th percentiles of AV intervals according to FHR ranged from 135 to 148 ms. 1. The AV interval duration was negatively correlated with the heart rhythm. 2. Measurement of AV time interval is easy to perform and has a good reproducibility. It may be used for the fetal heart block screening in anti-Ro and anti-La positive pregnancies. 3. Normative values established in the study may help obstetricians in assessing fetal abnormalities of the AV conduction.

Spotlight on valsartan-sacubitril fixed-dose combination for heart failure: the evidence to date.

PubMed

Vilela-Martin, José Fernando

2016-01-01

Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

Spotlight on valsartan–sacubitril fixed-dose combination for heart failure: the evidence to date

PubMed Central

Vilela-Martin, José Fernando

2016-01-01

Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin–angiotensin–aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease. PMID:27274196

A Percutaneously Implantable Fetal Pacemaker

PubMed Central

Zhou, Li; Vest, Adriana N.; Chmait, Ramen H.; Bar-Cohen, Yaniv; Pruetz, Jay; Silka, Michael; Zheng, Kaihui; Peck, Ray; Loeb, Gerald E.

2015-01-01

A miniaturized, self-contained pacemaker that could be implanted with a minimally invasive technique would dramatically improve the survival rate for fetuses that develop hydrops fetalis as a result of congenital heart block. We are currently validating a device that we developed to address this bradyarrhythmia. Preclinical studies in a fetal sheep model are underway to demonstrate that the device can be implanted via a minimally invasive approach, can mechanically withstand the harsh bodily environment, can induce effective contractions of the heart muscle with an adequate safety factor, and can successfully operate for the required device lifetime of three months using the previously-developed closed loop transcutaneous recharging system. PMID:25570982

Blocking Mimicry Makes True and False Smiles Look the Same

PubMed Central

Rychlowska, Magdalena; Cañadas, Elena; Wood, Adrienne; Krumhuber, Eva G.; Fischer, Agneta; Niedenthal, Paula M.

2014-01-01

Recent research suggests that facial mimicry underlies accurate interpretation of subtle facial expressions. In three experiments, we manipulated mimicry and tested its role in judgments of the genuineness of true and false smiles. Experiment 1 used facial EMG to show that a new mouthguard technique for blocking mimicry modifies both the amount and the time course of facial reactions. In Experiments 2 and 3, participants rated true and false smiles either while wearing mouthguards or when allowed to freely mimic the smiles with or without additional distraction, namely holding a squeeze ball or wearing a finger-cuff heart rate monitor. Results showed that blocking mimicry compromised the decoding of true and false smiles such that they were judged as equally genuine. Together the experiments highlight the role of facial mimicry in judging subtle meanings of facial expressions. PMID:24670316

[Sudden cardiac death due to sarcoidosis. Case report].

PubMed

Sejben, István; Som, Zoltán; Cserni, Gábor

2017-07-01

Sarcoidosis is a systemic granulomatous disease of unknown aetiology, which is characterized by bilateral hilar lymphadenopathy and pulmonary disease. Clinically detected cardiac involvement occurs in 5% of sarcoid patients, although cardiac manifestations are discovered in 25% of the cases at autopsy. Sarcoid heart disease frequently causes atrioventricular block. The authors present the case of a 44-year-old man with bradycardia. On admission, second degree Mobitz II, then third degree atrioventricular block was diagnosed. Coronarography showed normal coronary arteries. 2.5 years following artificial Biotronik Entovis DR type pacemaker implantation, sudden cardiac death occurred. Autopsy revealed sarcoidosis with cardiac, pulmonary, splenic, renal and lymph node involvement. In case of young or middle-aged patients with atrioventricular block, it is best to search for other causes if the most common coronary origin can be excluded. Orv Hetil. 2017; 158(27): 1067-1070.

Protective Effect of Antenatal Antioxidant on Nicotine-Induced Heart Ischemia-Sensitive Phenotype in Rat Offspring.

PubMed

Xiao, DaLiao; Wang, Lei; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Zhang, Lubo

2016-01-01

Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS) in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC) in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε) protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3β (GSK3β) protein expression, it significantly increased the phosphorylation of GSK3β at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3β. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.

Electrophysiological effects of the aqueous extract of Averrhoa carambola L. leaves on the guinea pig heart.

PubMed

Vasconcelos, C M L; Araújo, M S; Conde-Garcia, E A

2006-07-01

This work aims to describe some electrophysiological changes promoted by the aqueous extract (AEx) from Averrhoa carambola leaves in guinea pig heart. The experiments were carried out on isolated heart or on right atrium-ventricle preparations. In 6 hearts, the extract induced many kinds of atrioventricular blocks (1st, 2nd, and 3rd degrees); increased the QT interval from 229+/-23 to 264+/-19 ms; increased the QRS complex duration from 27+/-3.1 to 59+/-11 ms, and depressed the cardiac rate from 136+/-17 to 89+/-14b pm. Furthermore, it decreased the conduction velocity of atrial impulse (17+/-3%); reduced the intraventricular pressure (86+/-6%), and increased the conduction time between the right atrium and the His bundle (27+/-6.5%). The conduction time from the His bundle to the right ventricle was not altered. Atropine sulfate did not change either the electrocardiographic parameters or the intraventricular pressure effects promoted by the A. carambola AEx. Based on these results, the popular use of such extracts should be avoided because it can promote electrical and mechanical changes in the normal heart.

PDK4 Inhibits Cardiac Pyruvate Oxidation in Late Pregnancy.

PubMed

Liu, Laura X; Rowe, Glenn C; Yang, Steven; Li, Jian; Damilano, Federico; Chan, Mun Chun; Lu, Wenyun; Jang, Cholsoon; Wada, Shogo; Morley, Michael; Hesse, Michael; Fleischmann, Bernd K; Rabinowitz, Joshua D; Das, Saumya; Rosenzweig, Anthony; Arany, Zoltan

2017-12-08

Pregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations, are not well understood. To determine the mechanisms underlying cardiac substrate use during pregnancy. We use here 13 C glucose, 13 C lactate, and 13 C fatty acid tracing analyses to show that hearts in late pregnant mice increase fatty acid uptake and oxidation into the tricarboxylic acid cycle, while reducing glucose and lactate oxidation. Mitochondrial quantity, morphology, and function do not seem altered. Insulin signaling seems intact, and the abundance and localization of the major fatty acid and glucose transporters, CD36 (cluster of differentiation 36) and GLUT4 (glucose transporter type 4), are also unchanged. Rather, we find that the pregnancy hormone progesterone induces PDK4 (pyruvate dehydrogenase kinase 4) in cardiomyocytes and that elevated PDK4 levels in late pregnancy lead to inhibition of PDH (pyruvate dehydrogenase) and pyruvate flux into the tricarboxylic acid cycle. Blocking PDK4 reverses the metabolic changes seen in hearts in late pregnancy. Taken together, these data indicate that the hormonal environment of late pregnancy promotes metabolic remodeling in the heart at the level of PDH, rather than at the level of insulin signaling. © 2017 American Heart Association, Inc.

Case studies on the effect of exercise and hot water submersion on intracardiac temperature and the performance of a pacemaker which varies pacing rate based on temperature.

PubMed

Fearnot, N E; Kitoh, O; Fujita, T; Okamura, H; Smith, H J; Calderini, M

1989-05-01

The effectiveness of using blood temperature change as an indicator to automatically vary heart rate physiologically was evaluated in 3 patients implanted with Model Sensor Kelvin 500 (Cook Pacemaker Corporation, Leechburg, PA, USA) pacemakers. Each patient performed two block-randomized treadmill exercise tests: one while programmed for temperature-based, rate-modulated pacing and the other while programmed without rate modulation. In 1 pacemaker patient and 4 volunteers, heart rates were recorded during exposure to a hot water bath. Blood temperature measured at 10 sec intervals and pacing rate measured at 1 min intervals were telemetered to a diagnostic programmer and data collector for storage and transfer to a computer. Observation comments and ECG-derived heart rates were manually recorded. The temperature-based pacemaker was shown to respond promptly not only to physical exertion but also to emotionally caused stress and submersion in a hot bath. These events cause increased heart rate in the normal heart. Using a suitable algorithm to process the measurement of blood temperature, it was possible to produce appropriate pacing rates in paced patients.

Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys.

PubMed

Schindler, Charles W; Graczyk, Zofi; Gilman, Joanne P; Negus, S Stevens; Bergman, Jack; Mello, Nancy K; Goldberg, Steven R

2007-12-08

As kappa agonists have been proposed as treatments for cocaine abuse, the cardiovascular effects of the kappa opioid receptor agonists ethylketocyclazocine (EKC) and enadoline were investigated in conscious squirrel monkeys. Both EKC and enadoline increased heart rate with little effect on blood pressure. This effect appeared to be specific for kappa receptors as the mu opioid agonist morphine did not mimic the effects of the kappa agonists. The opioid antagonist naltrexone, at a dose of 1.0 mg/kg, blocked the effect of EKC. An action at both central and peripheral receptors may be responsible for the heart rate increase following kappa agonist treatment. The ganglionic blocker chlorisondamine partially antagonized the effect of EKC on heart rate, suggesting central involvement, while the peripherally-acting agonist ICI 204,448 ((+/-)-1-[2,3- (Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) also increased heart rate, supporting a peripheral site of action. When given in combination with cocaine, EKC produced effects that were sub-additive, suggesting that the kappa agonists may be used safely as cocaine abuse treatments.

Buccal infiltration versus inferior alveolar nerve block in mandibular 2nd premolars with irreversible pulpitis.

PubMed

Yilmaz, K; Tunga, U; Ozyurek, T

2018-04-01

The purpose of this study is to compare the success rates of inferior alveolar nerve block (IANB) and buccal infiltration anesthesia of mandibular second premolar with irreversible pulpitis and to evaluate the level of patient discomfort with these methods. Forty patients, who had irreversible pulpitis in the mandibular 2 nd premolar teeth, were included in the study. Patients were randomly distributed in two groups. In one group IANB, in the other group buccal infiltration anesthesia were performed. The efficacy of these two different anesthesia techniques on the related teeth was investigated with the Heft-Parker visual analog scale. In addition, with a pulse oximetry device, the changes in the patients' heart rates were compared between the groups. The obtained data were evaluated statistically. Both anesthesia techniques reduced the pain significantly in patients before the administration (P < 0.05), but there was no significant difference among the groups regarding the pain control and success rates of anesthesia (P > 0.05). Both of the anesthesia techniques increased the heart rate (P < 0.05). The increase in the heart rate of the patients was significantly higher in the buccal infiltration anesthesia group than the other anesthesia group (P < 0.05). Within the limitation of this in vivo study, there was no difference between the efficacies of the buccal infiltration anesthesia and IANB anesthesia in the mandibular 2 nd premolar teeth with irreversible pulpitis. Buccal infiltration anesthesia caused more discomfort in the patients compared with the IANB during the administration.

Cardiac myocyte diversity and a fibroblast network in the junctional region of the zebrafish heart revealed by transmission and serial block-face scanning electron microscopy.

PubMed

Lafontant, Pascal J; Behzad, Ali R; Brown, Evelyn; Landry, Paul; Hu, Norman; Burns, Alan R

2013-01-01

The zebrafish has emerged as an important model of heart development and regeneration. While the structural characteristics of the developing and adult zebrafish ventricle have been previously studied, little attention has been paid to the nature of the interface between the compact and spongy myocardium. Here we describe how these two distinct layers are structurally and functionally integrated. We demonstrate by transmission electron microscopy that this interface is complex and composed primarily of a junctional region occupied by collagen, as well as a population of fibroblasts that form a highly complex network. We also describe a continuum of uniquely flattened transitional cardiac myocytes that form a circumferential plate upon which the radially-oriented luminal trabeculae are anchored. In addition, we have uncovered within the transitional ring a subpopulation of markedly electron dense cardiac myocytes. At discrete intervals the transitional cardiac myocytes form contact bridges across the junctional space that are stabilized through localized desmosomes and fascia adherentes junctions with adjacent compact cardiac myocytes. Finally using serial block-face scanning electron microscopy, segmentation and volume reconstruction, we confirm the three-dimensional nature of the junctional region as well as the presence of the sheet-like fibroblast network. These ultrastructural studies demonstrate the previously unrecognized complexity with which the compact and spongy layers are structurally integrated, and provide a new basis for understanding development and regeneration in the zebrafish heart.

Minimally Invasive Epicardial Pacemaker Implantation in Neonates with Congenital Heart Block.

PubMed

Costa, Roberto; Silva, Katia Regina da; Martinelli Filho, Martino; Carrillo, Roger

2017-10-01

Few studies have characterized the surgical outcomes following epicardial pacemaker implantation in neonates with congenital complete atrioventricular block (CCAVB). This study sought to assess the long-term outcomes of a minimally invasive epicardial approach using a subxiphoid access for pacemaker implantation in neonates. Between July 2002 and February 2015, 16 consecutive neonates underwent epicardial pacemaker implantation due to CCAVB. Among these, 12 (75.0%) had congenital heart defects associated with CCAVB. The patients had a mean age of 4.7 ± 5.3 days and nine (56.3%) were female. Bipolar steroid-eluting epicardial leads were implanted in all patients through a minimally invasive subxiphoid approach and fixed on the diaphragmatic ventricular surface. The pulse generator was placed in an epigastric submuscular position. All procedures were successful, with no perioperative complications or early deaths. Mean operating time was 90.2 ± 16.8 minutes. None of the patients displayed pacing or sensing dysfunction, and all parameters remained stable throughout the follow-up period of 4.1 ± 3.9 years. Three children underwent pulse generator replacement due to normal battery depletion at 4.0, 7.2, and 9.0 years of age without the need of ventricular lead replacement. There were two deaths at 12 and 325 days after pacemaker implantation due to bleeding from thrombolytic use and progressive refractory heart failure, respectively. Epicardial pacemaker implantation through a subxiphoid approach in neonates with CCAVB is technically feasible and associated with excellent surgical outcomes and pacing lead longevity.

Analysis of Morphological Characteristics and Origins of Idiopathic Premature Ventricular Contractions Under a 12-Lead Electrocardiogram in Children with Structurally Normal Hearts.

PubMed

Jiang, Jianbin; He, Yuee; Qiu, Huixian; Zhang, Yuanhai; Chu, Maoping; Li, Yuechun; Chen, Qi

2017-10-21

Up to 40% of healthy children have premature ventricular complexes or contractions (PVCs) detected with 24-hour Holter monitoring. We aimed to investigate the morphological characteristics and origins of idiopathic PVCs under a 12-lead electrocardiogram in children with structurally normal hearts. All asymptomatic monomorphic PVC patients with structurally normal hearts under 18 years of age were included in this retrospective study. Characteristics of PVCs in lead V 1 under a 12-lead electrocardiogram were classified as left bundle branch block (PVC-LBBB) or right bundle branch block (PVC-RBBB). According to limb leads, PVC-LBBB or PVC-RBBB was divided into: PVCs-LBBB type I; PVCs-LBBB type II; PVCs-RBBB type I; PVCs-RBBB type II; and PVCs-RBBB type III. Out of 178 PVC patients, 94 cases of PVCs-LBBB (PVCs-LBBB type I = 60; PVCs-LBBB type II = 34) and 84 cases of PVCs-RBBB (PVCs-RBBB type I = 3; PVCs-RBBB type II = 55; PVCs-RBBB type III = 26) were identified. The frequency of PVCs-LBBB type I increased with age and the frequency of PVCs-RBBB type II and III decreased with age. Among the children monitor tested, from 1 years old to 18 years old, PVCs originating from the left or right ventricular outflow tract gradually increased with age, while PVCs originating from the branch sources decreased with age.

A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure.

PubMed

Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

2016-10-01

Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease.

A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure

PubMed Central

Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

2016-01-01

Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease. PMID:27703506

Native Valve Endocarditis due to Ralstonia pickettii: A Case Report and Literature Review

PubMed Central

Orme, Joseph; Rivera-Bonilla, Tomas; Loli, Akil; Blattman, Negin N.

2015-01-01

Ralstonia pickettii is a rare pathogen and even more rare in healthy individuals. Here we report a case of R. pickettii bacteremia leading to aortic valve abscess and complete heart block. To our knowledge this is the first case report of Ralstonia species causing infective endocarditis with perivalvular abscess. PMID:25648998

Role of the urokinase plasminogen activator receptor in mediating impaired efferocytosis of anti-SSA/Ro-bound apoptotic cardiocytes: Implications in the pathogenesis of congenital heart block.

PubMed

Briassouli, Paraskevi; Komissarova, Elena V; Clancy, Robert M; Buyon, Jill P

2010-08-06

Binding of maternal anti-Ro/La antibodies to cognate antigen expressed on apoptotic cardiocytes decreases clearance by healthy cardiocytes, which may contribute to the development of autoimmune associated congenital heart block and fatal cardiomyopathy. Given recent evidence implicating the urokinase plasminogen activator receptor (uPAR) as a "don't eat me" signal during efferocytosis, experiments addressed whether surface bound anti-Ro antibodies inhibit apoptotic cell removal via an effect on the expression/function of the urokinase-type plasminogen activator protease uPA/uPAR system. As assessed by flow cytometry and confocal microscopy, uPAR colocalizes and interacts with Ro60 on the surface of apoptotic human fetal cardiocytes. Blocking of uPAR enhances phagocytosis of apoptotic cardiocytes by healthy cardiocytes and reverses the anti-Ro60-dependent impaired clearance of apoptotic cardiocytes. Binding of anti-Ro60 antibodies to apoptotic cardiocytes results in increased uPAR expression, as well as enhanced uPA activity. The binding of anti-Ro60 did not alter other surface molecules involved in cell recognition (calreticulin, CD31, or CD47). These data suggest that increased uPAR expression and uPA activity induced by anti-Ro60 binding to the apoptotic fetal cardiocyte provide a molecular basis by which these antibodies inhibit efferocytosis and ultimately lead to scar of the fetal conduction system and working myocardium.

Aldosterone increases cardiac vagal tone via G protein-coupled oestrogen receptor activation

PubMed Central

Brailoiu, G Cristina; Benamar, Khalid; Arterburn, Jeffrey B; Gao, Erhe; Rabinowitz, Joseph E; Koch, Walter J; Brailoiu, Eugen

2013-01-01

In addition to acting on mineralocorticoid receptors, aldosterone has been recently shown to activate the G protein-coupled oestrogen receptor (GPER) in vascular cells. In light of the newly identified role for GPER in vagal cardiac control, we examined whether or not aldosterone activates GPER in rat nucleus ambiguus. Aldosterone produced a dose-dependent increase in cytosolic Ca2+ concentration in retrogradely labelled cardiac vagal neurons of nucleus ambiguus; the response was abolished by pretreatment with the GPER antagonist G-36, but was not affected by the mineralocorticoid receptor antagonists, spironolactone and eplerenone. In Ca2+-free saline, the response to aldosterone was insensitive to blockade of the Ca2+ release from lysosomes, while it was reduced by blocking the Ca2+ release via ryanodine receptors and abolished by blocking the IP3 receptors. Aldosterone induced Ca2+ influx via P/Q-type Ca2+ channels, but not via L-type and N-type Ca2+ channels. Aldosterone induced depolarization of cardiac vagal neurons of nucleus ambiguus that was sensitive to antagonism of GPER but not of mineralocorticoid receptor. in vivo studies, using telemetric measurement of heart rate, indicate that microinjection of aldosterone into the nucleus ambiguus produced a dose-dependent bradycardia in conscious, freely moving rats. Aldosterone-induced bradycardia was blocked by the GPER antagonist, but not by the mineralocorticoid receptor antagonists. In summary, we report for the first time that aldosterone decreases heart rate by activating GPER in cardiac vagal neurons of nucleus ambiguus. PMID:23878371

Myotonic Dystrophy Initially Presenting as Tachycardiomyopathy Successful Catheter Ablation of Atrial Flutter

PubMed Central

Asbach, S.; Gutleben, K. J.; Dahlem, P.; Brachmann, J.; Nölker, G.

2010-01-01

Myotonic dystrophy is a genetic muscular disease that is frequently associated with cardiac arrhythmias. Bradyarrhythmias, such as sinus bradycardia and atrioventricular block, are more common than tachyarrhythmias. Rarely, previously undiagnosed patients with myotonic dystrophy initially present with a tachyarrhythmia. We describe the case of a 14-year-old boy, who was admitted to the hospital with clinical signs and symptoms of decompensated heart failure and severely reduced left ventricular function. Electrocardiography showed common-type atrial flutter with 2 : 1 conduction resulting in a heart rate of 160 bpm. Initiation of medical therapy for heart failure as well as electrical cardioversion led to a marked clinical improvement. Catheter ablation of atrial flutter was performed to prevent future cardiac decompensations and to prevent development of tachymyopathy. Left ventricular function normalized during followup. Genetic analysis confirmed the clinical suspicion of myotonic dystrophy as known in other family members in this case. PMID:20871860

Analysis of Blood Flow in a Partially Blocked Bifurcated Blood Vessel

NASA Astrophysics Data System (ADS)

Abdul-Razzak, Hayder; Elkassabgi, Yousri; Punati, Pavan K.; Nasser, Naseer

2009-09-01

Coronary artery disease is a major cause of death in the United States. It is the narrowing of the lumens of the coronary blood vessel by a gradual build-up of fatty material, atheroma, which leads to the heart muscle not receiving enough blood. This my ocardial ischemia can cause angina, a heart attack, heart failure as well as sudden cardiac death [9]. In this project a solid model of bifurcated blood vessel with an asymmetric stenosis is developed using GAMBIT and imported into FLUENT for analysis. In FLUENT, pressure and velocity distributions in the blood vessel are studied under different conditions, where the size and position of the blockage in the blood vessel are varied. The location and size of the blockage in the blood vessel are correlated with the pressures and velocities distributions. Results show that such correlation may be used to predict the size and location of the blockage.

Appropriate and inappropriate use of dronedarone in 2013.

PubMed

Naccarelli, Gerald V

2013-08-01

Dronedarone is a multichannel blocking antiarrhythmic agent that has been shown to prevent atrial fibrillation/flutter (AF/AFl) recurrences in several multi-center trials. In the ANDROMEDA trial, dronedarone treatment increased mortality and cardiovascular hospitalizations patients with decompensated heart failure. In the ATHENA trial, dronedarone was used in elderly high risk patients with paroxysmal or persistent AF/AFl, excluding those with advanced heart failure, cardiovascular hospitalizations were significantly reduced. Dronedarone increased mortality and cardiovascular hospitalizations in a different patient group with permanent AF/AFl. Although organic toxicity from the drug is very rare, post-marketing data has reported rare hepatic toxicity associated with dronedarone use. Current guidelines position dronedarone as a front-line antiarrhythmic in many patients with AF/Fl. However, dronedarone should not be used in patients with advanced heart failure or in permanent AF. Clinical trial results have helped us define appropriate and inappropriate candidates for dronedarone.

Electromagnetic induction and radiation-induced abnormality of wave propagation in excitable media

NASA Astrophysics Data System (ADS)

Ma, Jun; Wu, Fuqiang; Hayat, Tasawar; Zhou, Ping; Tang, Jun

2017-11-01

Continuous wave emitting from sinus node of the heart plays an important role in wave propagating among cardiac tissue, while the heart beating can be terminated when the target wave is broken into turbulent states by electromagnetic radiation. In this investigation, local periodical forcing is applied on the media to induce continuous target wave in the improved cardiac model, which the effect of electromagnetic induction is considered by using magnetic flux, then external electromagnetic radiation is imposed on the media. It is found that target wave propagation can be blocked to stand in a local area and the excitability of media is suppressed to approach quiescent but homogeneous state when electromagnetic radiation is imposed on the media. The sampled time series for membrane potentials decrease to quiescent state due to the electromagnetic radiation. It could accounts for the mechanism of abnormality in heart failure exposed to continuous electromagnetic field.

Role of the activation gate in determining the extracellular potassium dependency of block of HERG by trapped drugs.

PubMed

Pareja, Kristeen; Chu, Elaine; Dodyk, Katrina; Richter, Kristofer; Miller, Alan

2013-01-01

Drug induced long QT syndrome (diLQTS) results primarily from block of the cardiac potassium channel HERG (human-ether-a-go-go related gene). In some cases long QT syndrome can result in the lethal arrhythmia torsade de pointes, an arrhythmia characterized by a rapid heart rate and severely compromised cardiac output. Many patients requiring medication present with serum potassium abnormalities due to a variety of conditions including gastrointestinal dysfunction, renal and endocrine disorders, diuretic use, and aging. Extracellular potassium influences HERG channel inactivation and can alter block of HERG by some drugs. However, block of HERG by a number of drugs is not sensitive to extracellular potassium. In this study, we show that block of WT HERG by bepridil and terfenadine, two drugs previously shown to be trapped inside the HERG channel after the channel closes, is insensitive to extracellular potassium over the range of 0 mM to 20 mM. We also show that bepridil block of the HERG mutant D540K, a mutant channel that is unable to trap drugs, is dependent on extracellular potassium, correlates with the permeant ion, and is independent of HERG inactivation. These results suggest that the lack of extracellular potassium dependency of block of HERG by some drugs may in part be related to the ability of these drugs to be trapped inside the channel after the channel closes.

Increased prevalence of third-degree atrioventricular block in patients with type II diabetes mellitus.

PubMed

Movahed, Mohammad-Reza; Hashemzadeh, Mehrtash; Jamal, M Mazen

2005-10-01

Diabetes mellitus (DM) is a major risk for cardiovascular disease and mortality. There is some evidence that third-degree atrioventricular (AV) block occurs more commonly in patients with DM. In this study, we evaluated any possible association between DM and third-degree AV block using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in a very large inpatient database. We used patient treatment files containing discharge diagnoses using ICD-9 codes of inpatient treatment from all Veterans Health Administration hospitals. The cohort was stratified using the ICD-9-CM code for DM (n = 293,124), a control group with hypertension but no DM (n = 552,623), and the ICD-9 code for third-degree AV block (426.0) and smoking (305.1, V15.82). We performed multivariate analysis adjusting for coronary artery disease, congestive heart failure, smoking, and hyperlipidemia. Continuous and binary variables were analyzed using chi2 and Fisher exact tests. Third-degree AV block diagnosis was present in 3,240 of DM patients (1.1%) vs 3,367 patients (0.6%) in the control group. Using multivariate analysis, DM remained strongly associated with third-degree AV block (odds ratio, 3.1; 95% confidential interval, 3.0 to 3.3; p < 0.0001). Third-degree AV block occurs significantly more in patients with DM. This finding may, in part, explain the high cardiovascular mortality in DM patients.

[A case of severe bradycardia and AV block during administration of propofol].

PubMed

Takase, Hajime; Kudoh, Akira; Takazawa, Tomoko

2003-09-01

A 69-yr-old man underwent emergency laparotomy. He was in endotoxic shock. Preoperative evaluation including a full blood count, chest X-ray and ECG were normal. Body temperature was 37.4 degrees C. Preoperative arterial pressure was 140/80 mmHg and heart rate 65 bpm. Anesthesia was induced with ketamine 100 mg, propofol 20 mg, fentanyl 50 micrograms and vecuronium 4 mg and maintained with propofol 4 mg.kg-1.hr-1 and fentanyl. Soon after opening the abdominal peritoneum, severe bradycardia (< 20 bpm) occurred, but it was effectively treated by ephedrine 16 mg. After that, surgery was performed uneventfully. In the intensive care unit (ICU), the patient developed four episodes of severe atrioventricular (AV) block after stimulation of the trachea by suction drainage under sedation with propofol, although there was no AV block during sedation with ketamine and propofol. After stopping propofol, the AV block was no longer observed. He was discharged from the ICU on the 12th postoperative day. Postoperative Holter ECG and echocardiography showed no abnormalities. It is likely that stimulation of the trachea triggered vagovagal reflex and propofol prolonged AV conduction, causing the AV block.

Effect of Transversus Abdominis Plane Block on Cost of Laparoscopic Cholecystectomy Anesthesia

PubMed Central

Kokulu, Serdar; Bakı, Elif Doğan; Kaçar, Emre; Bal, Ahmet; Şenay, Hasan; Üstün, Kübra Demir; Yılmaz, Sezgin; Ela, Yüksel; Sıvacı, Remziye Gül

2014-01-01

Background Use of transversus abdominis plane (TAP) block for postoperative analgesia is continuously increasing. However, few studies have investigated intraoperative effects of TAP block. We aimed to study the effects of TAP block in terms of cost-effectiveness and consumption of inhalation agents. Material/Methods Forty patients undergoing laparoscopic cholecystectomy were enrolled in this study. Patients were randomly divided into 2 groups: Group 1 (n=20) patients received TAP block and Group 2 (n=20) patients did not receive TAP block. Standard anesthesia induction was used in all patients. For the maintenance of anesthesia, fractional inspired oxygen (FIO2) of 50% in air with desflurane was used with a fresh gas flow of 4 L/min. All patients were monitored with electrocardiography and for peripheral oxygen saturation (SpO2), end-tidal carbon dioxide (ET), heart rate (HR), noninvasive mean blood pressure (MBP), and bispectral index (BIS). Bilateral TAP blocks were performed under ultrasound guidance to Group 1 patients. The BIS value was maintained at between 40 and 50 during the surgery. The Dion formula was used to calculate consumption of desflurane for each patient. Results There was no difference between the groups with respect to demographic characteristics of the patients. Duration of anesthesia, surgery time, and dosage of fentanyl were similar in the 2 groups. However, the cost and consumption of desflurane was significantly lower in Group 1. Conclusions Total anesthesia consumption was lower and the cost-effectiveness of anesthesia was better in TAP block patients with general anesthesia than in non-TAP block patients undergoing laparoscopic cholecystectomy. PMID:25534331

Ivabradine prolongs phase 3 of cardiac repolarization and blocks the hERG1 (KCNH2) current over a concentration-range overlapping with that required to block HCN4.

PubMed

Lees-Miller, James P; Guo, Jiqing; Wang, Yibo; Perissinotti, Laura L; Noskov, Sergei Y; Duff, Henry J

2015-08-01

In Europe, ivabradine has recently been approved to treat patients with angina who have intolerance to beta blockers and/or heart failure. Ivabradine is considered to act specifically on the sinoatrial node by inhibiting the If current (the funny current) to slow automaticity. However, in vitro studies show that ivabradine prolongs phase 3 repolarization in ventricular tissue. No episodes of Torsades de Pointes have been reported in randomized clinical studies. The objective of this study is to assess whether ivabradine blocked the hERG1 current. In the present study we discovered that ivabradine prolongs action potential and blocks the hERG current over a range of concentrations overlapping with those required to block HCN4. Ivabradine produced tonic, rather than use-dependent block. The mutation Y652A significantly suppressed pharmacologic block of hERG by ivabradine. Disruption of C-type inactivation also suppressed block of hERG1 by ivabradine. Molecular docking and molecular dynamics simulations indicate that ivabradine may access the inner cavity of the hERG1 via a lipophilic route and has a well-defined binding site in the closed state of the channel. Structural organization of the binding pockets for ivabradine is discussed. Ivabradine blocks hERG and prolongs action potential duration. Our study is potentially important because it indicates the need for active post marketing surveillance of ivabradine. Importantly, proarrhythmia of a number of other drugs has only been discovered during post marketing surveillance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of transversus abdominis plane block on cost of laparoscopic cholecystectomy anesthesia.

PubMed

Kokulu, Serdar; Bakı, Elif Doğan; Kaçar, Emre; Bal, Ahmet; Şenay, Hasan; Üstün, Kübra Demir; Yılmaz, Sezgin; Ela, Yüksel; Sıvacı, Remziye Gül

2014-12-23

Use of transversus abdominis plane (TAP) block for postoperative analgesia is continuously increasing. However, few studies have investigated intraoperative effects of TAP block. We aimed to study the effects of TAP block in terms of cost-effectiveness and consumption of inhalation agents. Forty patients undergoing laparoscopic cholecystectomy were enrolled in this study. Patients were randomly divided into 2 groups: Group 1 (n=20) patients received TAP block and Group 2 (n=20) patients did not receive TAP block. Standard anesthesia induction was used in all patients. For the maintenance of anesthesia, fractional inspired oxygen (FIO2) of 50% in air with desflurane was used with a fresh gas flow of 4 L/min. All patients were monitored with electrocardiography and for peripheral oxygen saturation (SpO2), end-tidal carbon dioxide (ET), heart rate (HR), noninvasive mean blood pressure (MBP), and bispectral index (BIS). Bilateral TAP blocks were performed under ultrasound guidance to Group 1 patients. The BIS value was maintained at between 40 and 50 during the surgery. The Dion formula was used to calculate consumption of desflurane for each patient. There was no difference between the groups with respect to demographic characteristics of the patients. Duration of anesthesia, surgery time, and dosage of fentanyl were similar in the 2 groups. However, the cost and consumption of desflurane was significantly lower in Group 1. Total anesthesia consumption was lower and the cost-effectiveness of anesthesia was better in TAP block patients with general anesthesia than in non-TAP block patients undergoing laparoscopic cholecystectomy.

Optically Remote Noncontact Heart Rates Sensing Technique

NASA Astrophysics Data System (ADS)

Thongkongoum, W.; Boonduang, S.; Limsuwan, P.

2017-09-01

Heart rate monitoring via optically remote noncontact technique was reported in this research. A green laser (5 mW, 532±10 nm) was projected onto the left carotid artery. The reflected laser light on the screen carried the deviation of the interference patterns. The interference patterns were recorded by the digital camera. The recorded videos of the interference patterns were frame by frame analysed by 2 standard digital image processing (DIP) techniques, block matching (BM) and optical flow (OF) techniques. The region of interest (ROI) pixels within the interference patterns were analysed for periodically changes of the interference patterns due to the heart pumping action. Both results of BM and OF techniques were compared with the reference medical heart rate monitoring device by which a contact measurement using pulse transit technique. The results obtained from BM technique was 74.67 bpm (beats per minute) and OF technique was 75.95 bpm. Those results when compared with the reference value of 75.43±1 bpm, the errors were found to be 1.01% and 0.69%, respectively.

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

PubMed

Duncker, D; Veltmann, C

2018-05-09

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

Manifestations of Lyme carditis.

PubMed

Kostić, Tomislav; Momčilović, Stefan; Perišić, Zoran D; Apostolović, Svetlana R; Cvetković, Jovana; Jovanović, Andriana; Barać, Aleksandra; Šalinger-Martinović, Sonja; Tasić-Otašević, Suzana

2017-04-01

The first data of Lyme carditis, a relatively rare manifestation of Lyme disease, were published in eighties of the last century. Clinical manifestations include syncope, light-headedness, fainting, shortness of breath, palpitations, and/or chest pain. Atrioventricular (AV) electrical block of varying severity presents the most common conduction disorder in Lyme carditis. Although is usually mild, AV block can fluctuates rapidly and progress from a prolonged P-R interval to a His-Purkinje block within minutes to hours and days. Rarely, Lyme disease may be the cause of endocarditis, while some studies and reports, based on serological and/or molecular investigations, have suggested possible influence of Borrelia burgdorferi on degenerative cardiac valvular disease. Myocarditis, pericarditis, pancarditis, dilated cardiomyopathy, and heart failure have also been described as possible manifestations of Lyme carditis. The clinical course of Lyme carditis is generally mild, short term, and in most cases, completely reversible after adequate antibiotic treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons.

PubMed

Fortuna, Vitor; Pardanaud, Luc; Brunet, Isabelle; Ola, Roxana; Ristori, Emma; Santoro, Massimo M; Nicoli, Stefania; Eichmann, Anne

2015-06-23

The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pacemaker Use Following Heart Transplantation

PubMed Central

Mallidi, Hari R.; Bates, Michael

2017-01-01

Background: The incidence of permanent pacemaker implantation after orthotopic heart transplantation has been reported to be 2%-24%. Transplanted hearts usually exhibit sinus rhythm in the operating room following reperfusion, and most patients do not exhibit significant arrhythmias during the postoperative period. However, among the patients who do exhibit abnormalities, pacemakers may be implanted for early sinus node dysfunction but are rarely used after 6 months. Permanent pacing is often required for atrioventricular block. A different cohort of transplant patients presents later with bradycardia requiring pacemaker implantation, reported to occur in approximately 1.5% of patients. The objectives of this study were to investigate the indications for pacemaker implantation, compare the need for pacemakers following bicaval vs biatrial anastomosis, and examine the long-term outcomes of heart transplant patients who received pacemakers. Methods: For this retrospective, case-cohort, single-institution study, patients were identified from clinical research and administrative transplant databases. Information was supplemented with review of the medical records. Standard statistical techniques were used, with chi-square testing for categorical variables and the 2-tailed t test for continuous variables. Survival was compared with the use of log-rank methods. Results: Between January 1968 and February 2008, 1,450 heart transplants were performed at Stanford University. Eighty-four patients (5.8%) were identified as having had a pacemaker implanted. Of these patients, 65.5% (55) had the device implanted within 30 days of transplantation, and 34.5% (29) had late implantation. The mean survival of patients who had an early pacemaker implant was 6.4 years compared to 7.7 years for those with a late pacemaker implant (P<0.05). Sinus node dysfunction and heart block were the most common indications for pacemaker implantation. Starting in 1997, a bicaval technique was used for implantation. The incidence of pacemaker implantation by technique was 2.0% for bicaval and 9.1% for biatrial (P=0.001). Significantly more rejection episodes occurred in the pacemaker group (2.67 ± 2.18) compared with the no-pacemaker group (2.01 ± 2.05) (P<0.05). Conclusion: Our results show a decreased pacemaker need after bicaval anastomosis and that more patients who needed a pacemaker after transplantation had a pretransplant diagnosis of ischemic cardiomyopathy. In our cohort, the need for a permanent pacemaker was also associated with older donor grafts and an increase in the number of treated rejection episodes. PMID:28331443

Safety of an i.v. β-adrenergic blockade protocol for heart rate optimization before coronary CT angiography.

PubMed

Kassamali, Rahil H; Kim, Daniel H; Patel, Hiten; Raichura, Nitin; Hoey, Edward T D; Hodson, James; Hussain, Shahid

2014-10-01

The purpose of this study was to assess the safety of heart rate optimization by use of β-adrenergic blockade solely by the i.v. route before coronary CT angiography. The records of 679 patients undergoing CT coronary angiography after receiving i.v. β-adrenergic blockade were retrospectively analyzed. Health screening was completed before scanning, and heart rate was optimized by administration of i.v. metoprolol titrated to a maximum of 70 mg to achieve a heart rate less than 65 beats/min. The median i.v. dose was 20 mg (range, 5-70 mg). The 679 patients analyzed had a total of 10 complications (1.47%). Major complications, defined as not resolving with observation and analgesia alone, occurred in only three patients (0.44%). These complications included a second-degree atrioventricular block. A total of 299 patients (44.0%) needed more than 20 mg of i.v. metoprolol to achieve target heart rate. Only three patients needed the maximum i.v. dose of 70 mg metoprolol. Target heart rate was reached successfully in 666 patients (98.1%) with doses of less than 70 mg. This study did not show a statistically significant association between increasing complication frequency and increasing dose. This study showed that high doses of i.v. metoprolol can be used effectively and with a low rate of major complications to control heart rate before coronary CT angiography in correctly screened patients.

Design and Rationale of the Cognitive Intervention to Improve Memory in Heart Failure Patients Study.

PubMed

Pressler, Susan J; Giordani, Bruno; Titler, Marita; Gradus-Pizlo, Irmina; Smith, Dean; Dorsey, Susan G; Gao, Sujuan; Jung, Miyeon

Memory loss is an independent predictor of mortality among heart failure patients. Twenty-three percent to 50% of heart failure patients have comorbid memory loss, but few interventions are available to treat the memory loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate efficacy of computerized cognitive training intervention using BrainHQ to improve primary outcomes of memory and serum brain-derived neurotrophic factor levels and secondary outcomes of working memory, instrumental activities of daily living, and health-related quality of life among heart failure patients; (2) evaluate incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms and genomic moderators of BrainHQ effect. A sample of 264 heart failure patients within 4 equal-sized blocks (normal/low baseline cognitive function and gender) will be randomly assigned to (1) BrainHQ, (2) active control computer-based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week, 40-hour program individualized to each patient's performance. Data collection will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive statistics, mixed model analyses, and cost-utility analysis using intent-to-treat approach will be computed. This research will provide new knowledge about the efficacy of BrainHQ to improve memory and increase serum brain-derived neurotrophic factor levels in heart failure. If efficacious, the intervention will provide a new therapeutic approach that is easy to disseminate to treat a serious comorbid condition of heart failure.

Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice

PubMed Central

Morikawa, Yuka; Zhang, Min; Heallen, Todd; Leach, John; Tao, Ge; Xiao, Yang; Bai, Yan; Li, Wei; Willerson, James T.; Martin, James F.

2015-01-01

The mammalian heart regenerates poorly, and damage commonly leads to heart failure. Hippo signaling is an evolutionarily conserved kinase cascade that regulates organ size during development and prevents adult mammalian cardiomyocyte regeneration by inhibiting the transcriptional coactivator Yap, which also responds to mechanical signaling in cultured cells to promote cell proliferation. To identify Yap target genes that are activated during cardiomyocyte renewal and regeneration, we performed Yap chromatin immunoprecipitation sequencing (ChIP-Seq) and mRNA expression profiling in Hippo signaling-deficient mouse hearts. We found that Yap directly regulated genes encoding cell cycle progression proteins, as well as genes encoding proteins that promote F-actin polymerization and that link the actin cytoskeleton to the extracellular matrix. Included in the latter group were components of the dystrophin glycoprotein complex (DGC), a large molecular complex that, when defective, results in muscular dystrophy in humans. Cardiomyocytes near scar tissue of injured Hippo signaling-deficient mouse hearts showed cellular protrusions suggestive of cytoskeletal remodeling. The hearts of mdx mutant mice, which lack functional dystrophin and are a model for muscular dystrophy, showed impaired regeneration and cytoskeleton remodeling, but normal cardiomyocyte proliferation after injury. Our data showed that, in addition to genes encoding cell cycle progression proteins, Yap regulated genes that enhance cytoskeletal remodeling Thus, blocking the Hippo pathway input to Yap may tip the balance so that Yap responds to the mechanical changes associated with heart injury to promote repair. PMID:25943351

Tailor-made heart simulation predicts the effect of cardiac resynchronization therapy in a canine model of heart failure.

PubMed

Panthee, Nirmal; Okada, Jun-ichi; Washio, Takumi; Mochizuki, Youhei; Suzuki, Ryohei; Koyama, Hidekazu; Ono, Minoru; Hisada, Toshiaki; Sugiura, Seiryo

2016-07-01

Despite extensive studies on clinical indices for the selection of patient candidates for cardiac resynchronization therapy (CRT), approximately 30% of selected patients do not respond to this therapy. Herein, we examined whether CRT simulations based on individualized realistic three-dimensional heart models can predict the therapeutic effect of CRT in a canine model of heart failure with left bundle branch block. In four canine models of failing heart with dyssynchrony, individualized three-dimensional heart models reproducing the electromechanical activity of each animal were created based on the computer tomographic images. CRT simulations were performed for 25 patterns of three ventricular pacing lead positions. Lead positions producing the best and the worst therapeutic effects were selected in each model. The validity of predictions was tested in acute experiments in which hearts were paced from the sites identified by simulations. We found significant correlations between the experimentally observed improvement in ejection fraction (EF) and the predicted improvements in ejection fraction (P<0.01) or the maximum value of the derivative of left ventricular pressure (P<0.01). The optimal lead positions produced better outcomes compared with the worst positioning in all dogs studied, although there were significant variations in responses. Variations in ventricular wall thickness among the dogs may have contributed to these responses. Thus CRT simulations using the individualized three-dimensional heart models can predict acute hemodynamic improvement, and help determine the optimal positions of the pacing lead. Copyright © 2016 Elsevier B.V. All rights reserved.

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.

PubMed

Stennard, Fiona A; Costa, Mauro W; Lai, Donna; Biben, Christine; Furtado, Milena B; Solloway, Mark J; McCulley, David J; Leimena, Christiana; Preis, Jost I; Dunwoodie, Sally L; Elliott, David E; Prall, Owen W J; Black, Brian L; Fatkin, Diane; Harvey, Richard P

2005-05-01

The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program, defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical, repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20, underlie both congenital heart disease and adult cardiomyopathies.

The zebrafish as a novel animal model to study the molecular mechanisms of mechano-electrical feedback in the heart

PubMed Central

Werdich, Andreas A; Brzezinski, Anna; Jeyaraj, Darwin; Ficker, Eckhard; Wan, Xiaoping; McDermott, Brian M; Sabeh, M Khaled; MacRae, Calum A; Rosenbaum, David S

2013-01-01

Altered mechanical loading of the heart leads to hypertrophy, decompensated heart failure and fatal arrhythmias. However, the molecular mechanisms that link mechanical and electrical dysfunction remain poorly understood. Growing evidence suggest that ventricular electrical remodeling (VER) is a process that can be induced by altered mechanical stress, creating persistent electrophysiological changes that predispose the heart to life-threatening arrhythmias. While VER is clearly a physiological property of the human heart, as evidenced by “T wave memory”, it is also thought to occur in a variety of pathological states associated with altered ventricular activation such as bundle branch block, myocardial infarction, and cardiac pacing. Animal models that are currently being used for investigating stretch-induced VER have significant limitations. The zebrafish has recently emerged as an attractive animal model for studying cardiovascular disease and could overcome some of these limitations. Owing to its extensively sequenced genome, high conservation of gene function, and the comprehensive genetic resources that are available in this model, the zebrafish may provide new insights into the molecular mechanisms that drive detrimental electrical remodeling in response to stretch. Here, we have established a zebrafish model to study mechano-electrical feedback in the heart, which combines efficient genetic manipulation with high-precision stretch and high-resolution electrophysiology. In this model, only ninety minutes of ventricular stretch caused VER and recapitulated key features of VER found previously in the mammalian heart. Our data suggest that the zebrafish model is a powerful platform for investigating the molecular mechanisms underlying mechano-electrical feedback and VER in the heart. PMID:22835662

STUDIES WITH THE ELECTROCARDIOGRAPH ON THE ACTION OF THE VAGUS NERVE ON THE HUMAN HEART

PubMed Central

Robinson, G. Canby; Draper, George

1911-01-01

In hearts showing auricular fibrillation mechanical stimulation of the right vagus nerve causes, as a rule, marked slowing or stoppage of ventricular rhythm, without producing any appreciable effect in the electrocardiographic record of the auricular fibrillation. The ventricular pauses are apparently due to the blocking of stimuli from the auricles. The force of ventricular systole is distinctly weakened for several beats after vagus stimulation, and ectopic ventricular systoles have been seen in several instances, apparently the result of the vagus action. There may, in some cases, be lowered excitability of the ventricles, while no constant change is seen in the size of the electrical complexes representing ventricular systole. PMID:19867466

Diastolic mitral and tricuspid regurgitation by Doppler echocardiography in patients with atrioventricular block: new insight into the mechanism of atrioventricular valve closure.

PubMed

Schnittger, I; Appleton, C P; Hatle, L K; Popp, R L

1988-01-01

The purpose of this study was to prospectively determine the incidence of diastolic mitral and tricuspid regurgitation in atrioventricular (AV) block using Doppler echocardiography. The temporal relation between mitral and tricuspid diastolic insufficiency and the diastolic murmur recorded in patients with complete heart block was also investigated. Twenty-two consecutive patients with AV block (referred to the Echo-Doppler laboratory for routine clinical studies), aged 18 to 87 years, were enrolled in the study. Eleven patients had third degree AV block and a ventricular-inhibited (VVI) pacemaker, two patients had second degree AV block, seven patients had first degree AV block, one patient had blocked premature atrial complexes and one patient had atrial flutter with 4:1 AV block. Diastolic mitral regurgitation was detected in 20 patients, and diastolic tricuspid regurgitation in 21. A mid-diastolic murmur was detected in all patients except in the three youngest. The murmur occurred before diastolic regurgitation and coincided with peak forward flow through the AV valve after atrial contraction. M-mode mitral valve echocardiograms obtained in nine patients demonstrated near closure of some portions of the mitral valve after atrial contraction. Effective closure of the valve, however, did not occur unless ventricular systole supervened. In conclusion, diastolic mitral and tricuspid regurgitation are almost universally present in patients with AV block and are associated with a diastolic murmur. The murmur coincides with forward AV valve flow. Diastolic regurgitation is silent. Effective AV valve closure is not established until ventricular systole occurs, as demonstrated by M-mode echocardiographic recording of the mitral valve.

A Comparative Summary on Antioxidant-like Actions of Timolol with Other Antioxidants in Diabetic Cardiomyopathy.

PubMed

Turan, Belma

2016-01-01

Cellular signaling associated with cardiac β-adrenergic receptors (β-AR) is composed of coupled mechanism among β 1-/β2-AR and Gs proteins with contribution of constitutive β3-AR coupling to Gi proteins. However, down-regulation of β-ARs in the heart under pathological conditions is mediated with a signaling G proteins-included mechanism. Additionally, there are serious conflicting data on this field in literature yet. Although some of these conflictions are generally related with either experimental protocols for different approaches or different animal models. To treat cardiovascular disorders, generally, various types of β-blockers are used while their action mechanisms are not fully known yet. Furthermore, although β-blockers are generally used to block the activated β-ARs, they can be used to scavenge free radicals under oxidative stress. Studies, in whole-system, organ or cellular levels, showed that some β-blockers, including timolol, have protective-actions against increased oxidative stress in diseased heart via ROSscavenging. Additionally, it has been mentioned that some β-blockers nicely prevented the development of heart failure in both experimental and clinical studies by restoring sarcoplasmic reticulum (SR) Ca(2+) release channels, RyR2. Since diabetic cardiomyopathy is recognized due to its diminished responsiveness to β1-AR agonist stimulation in the heart with an up-regulation of β 3-AR, inducing a strong negative inotropic effect on left ventricular function, it has been shown that treatment of streptozotocin-diabetic rats with timolol provided a marked cardio-protection. Importantly, it has been also documented that timolol treatment-dependent cardio-protection in diabetic rats includes basically prevention of RyR2- hyperphosphorylation, which, in turn, block Ca(2+)-leakage from SR via scavenging oxidative agents to control redox-state of cardiomyocytes. This action of timolol in diabetic heart is very similar to other known antioxidants, such as N-acetylcysteine or selenium compounds. In this review article, antioxidant-like action of timolol in diabetic cardiomyopathy was summarized in way of comparison with the benefits obtained with other antioxidants in the similar animal model.

Effect of a telemonitoring-facilitated collaboration between general practitioner and heart failure clinic on mortality and rehospitalization rates in severe heart failure: the TEMA-HF 1 (TElemonitoring in the MAnagement of Heart Failure) study.

PubMed

Dendale, Paul; De Keulenaer, Gilles; Troisfontaines, Pierre; Weytjens, Caroline; Mullens, Wilfried; Elegeert, Ivan; Ector, Bavo; Houbrechts, Marita; Willekens, Koen; Hansen, Dominique

2012-03-01

Chronic heart failure (CHF) patients are frequently rehospitalized within 6 months after an episode of fluid retention. Rehospitalizations are preventable, but this requires an extensive organization of the healthcare system. In this study, we tested whether intensive follow-up of patients through a telemonitoring-facilitated collaboration between general practitioners (GPs) and a heart failure clinic could reduce mortality and rehospitalization rate. One hunderd and sixty CHF patients [mean age 76 ± 10 years, 104 males, mean left ventricular ejection fraction (LVEF) 35 ± 15%] were block randomized by sealed envelopes and assigned to 6 months of intense follow-up facilitated by telemonitoring (TM) or usual care (UC). The TM group measured body weight, blood pressure, and heart rate on a daily basis with electronic devices that transferred the data automatically to an online database. Email alerts were sent to the GP and heart failure clinic to intervene when pre-defined limits were exceeded. All-cause mortality was significantly lower in the TM group as compared with the UC group (5% vs. 17.5%, P = 0.01). The total number of follow-up days lost to hospitalization, dialysis, or death was significantly lower in the TM group as compared with the UC group (13 vs. 30 days, P = 0.02). The number of hospitalizations for heart failure per patient showed a trend (0.24 vs. 0.42 hospitalizations/patient, P = 0.06) in favour of TM. Telemonitoring-facilitated collaboration between GPs and a heart failure clinic reduces mortality and number of days lost to hospitalization, death, or dialysis in CHF patients. These findings need confirmation in a large trial.

Pharmacoresistant Cav 2·3 (E-type/R-type) voltage-gated calcium channels influence heart rate dynamics and may contribute to cardiac impulse conduction.

PubMed

Galetin, Thomas; Tevoufouet, Etienne E; Sandmeyer, Jakob; Matthes, Jan; Nguemo, Filomain; Hescheler, Jürgen; Weiergräber, Marco; Schneider, Toni

2013-07-01

Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contraction coupling. Whereas L-type (Cav 1·2, Cav 1·3) and T-type (Cav 3·1, Cav 3·2) channels are widely accepted for their functional relevance in the heart, the role of Cav 2·3 Ca(2+) channels expressing R-type currents remains to be elucidated. We have investigated heart rate dynamics in control and Cav 2·3-deficient mice using implantable electrocardiogram radiotelemetry and pharmacological injection experiments. Autonomic block revealed that the intrinsic heart rate does not differ between both genotypes. Systemic administration of isoproterenol resulted in a significant reduction in interbeat interval in both genotypes. It remained unaffected after administering propranolol in Cav 2·3(-|-) mice. Heart rate from isolated hearts as well as atrioventricular conduction for both genotypes differed significantly. Additionally, we identified and analysed the developmental expression of two splice variants, i.e. Cav 2·3c and Cav 2·3e. Using patch clamp technology, R-type currents could be detected in isolated prenatal cardiomyocytes and be related to R-type Ca(2+) channels. Our results indicate that on the systemic level, the pharmacologically inducible heart rate range and heart rate reserve are impaired in Cav 2·3 (-|-) mice. In addition, experiments on Langendorff perfused hearts elucidate differences in basic properties between both genotypes. Thus, Cav 2·3 does not only contribute to the cardiac autonomous nervous system but also to intrinsic rhythm propagation. Copyright © 2012 John Wiley & Sons, Ltd.

High-frequency autonomic modulation: a new model for analysis of autonomic cardiac control.

PubMed

Champéroux, Pascal; Fesler, Pierre; Judé, Sebastien; Richard, Serge; Le Guennec, Jean-Yves; Thireau, Jérôme

2018-05-03

Increase in high-frequency beat-to-beat heart rate oscillations by torsadogenic hERG blockers appears to be associated with signs of parasympathetic and sympathetic co-activation which cannot be assessed directly using classic methods of heart rate variability analysis. The present work aimed to find a translational model that would allow this particular state of the autonomic control of heart rate to be assessed. High-frequency heart rate and heart period oscillations were analysed within discrete 10 s intervals in a cohort of 200 healthy human subjects. Results were compared to data collected in non-human primates and beagle dogs during pharmacological challenges and torsadogenic hERG blockers exposure, in 127 genotyped LQT1 patients on/off β-blocker treatment and in subgroups of smoking and non-smoking subjects. Three states of autonomic modulation, S1 (parasympathetic predominance) to S3 (reciprocal parasympathetic withdrawal/sympathetic activation), were differentiated to build a new model of heart rate variability referred to as high-frequency autonomic modulation. The S2 state corresponded to a specific state during which both parasympathetic and sympathetic systems were coexisting or co-activated. S2 oscillations were proportionally increased by torsadogenic hERG-blocking drugs, whereas smoking caused an increase in S3 oscillations. The combined analysis of the magnitude of high-frequency heart rate and high-frequency heart period oscillations allows a refined assessment of heart rate autonomic modulation applicable to long-term ECG recordings and offers new approaches to assessment of the risk of sudden death both in terms of underlying mechanisms and sensitivity. © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Cascade and parallel combination (CPC) of adaptive filters for estimating heart rate during intensive physical exercise from photoplethysmographic signal

PubMed Central

Islam, Mohammad Tariqul; Tanvir Ahmed, Sk.; Zabir, Ishmam; Shahnaz, Celia

2018-01-01

Photoplethysmographic (PPG) signal is getting popularity for monitoring heart rate in wearable devices because of simplicity of construction and low cost of the sensor. The task becomes very difficult due to the presence of various motion artefacts. In this study, an algorithm based on cascade and parallel combination (CPC) of adaptive filters is proposed in order to reduce the effect of motion artefacts. First, preliminary noise reduction is performed by averaging two channel PPG signals. Next in order to reduce the effect of motion artefacts, a cascaded filter structure consisting of three cascaded adaptive filter blocks is developed where three-channel accelerometer signals are used as references to motion artefacts. To further reduce the affect of noise, a scheme based on convex combination of two such cascaded adaptive noise cancelers is introduced, where two widely used adaptive filters namely recursive least squares and least mean squares filters are employed. Heart rates are estimated from the noise reduced PPG signal in spectral domain. Finally, an efficient heart rate tracking algorithm is designed based on the nature of the heart rate variability. The performance of the proposed CPC method is tested on a widely used public database. It is found that the proposed method offers very low estimation error and a smooth heart rate tracking with simple algorithmic approach. PMID:29515812

Effects of Family-Center Empowerment Model on the Lifestyle of Heart Failure Patients: A Randomized Controlled Clinical Trial

PubMed Central

Rakhshan, Mahnaz; Kordshooli, Khadijeh Rahimi; Ghadakpoor, Soraya

2015-01-01

Background: Cardiovascular diseases are the most prevalent disorders in developed countries and heart failure is the major one among them. This disease is caused by numerous factors and one of the most considerable risk factors is unhealthy lifestyle. So the aim of this research was to study the effect of family-center empowerment model on the lifestyle of heart failure patients. Methods: This is a randomized controlled clinical trial on 70 heart failure patients referring to Hazrate Fatemeh heart clinic in Shiraz. After convenience sampling the patients were divided into two control and intervention groups using block randomization Method. The intervention based on family-center empowerment model was performed during 5 sessions. Research tools are lifestyle and demographic information questionnaires. Results: Both intervention and control groups were similar regarding their demographic information (P>0.001). Before the intervention on lifestyle, all measures of the two groups were equal (P>0.001) but after the intervention; statistically significant differences were reported in all dimensions of lifestyle, the total lifestyle score in the intervention group was 70.09±16.38 and in the control group -6.03±16.36 (P<0.001). Conclusion: Performing the family-center empowerment model for heart failure patients is practically possible, leading to improvement or refinement of their and their families’ lifestyle. Trial Registration Number: IRCT 2014072018468N3 PMID:26448952

Indirect blood pressure and heart rate measured quickly without observer bias using a semi-automatic machine (auto-manometer)--response to isometric exercise in normal healthy males and its modification by beta-adrenoceptor blockade.

PubMed Central

Nyberg, G

1977-01-01

1 In a double-blind crossover study, six volunteers performed sustained handgrip at 50% of maximal voluntary contraction before and 90 min following oral administration of 0.25 and 100 mg metoprolol tartrate, a beta1 selective adrenoceptor blocking agent. Blood pressure and heart rate were measured with the Auto-Manometer, an electronic semi-automatic device based on the principles of the London School of Hygiene and Tropical Medicine sphygmomanometer. It eliminates observer and digital bias completely, and also records heart rate at the same time as blood pressure is recorded. 2 Resting heart rate fell 15% after 25 mg, 21% after 100 mg and was unchanged after placebo. Systolic blood pressure fell 6% on both doses and was unchanged on placebo. Diastolic pressure did not change with any of the doses. 3 At 1 min of handgrip, heart rate was significantly lower after 25 and 100 mg than before drug or after placebo. There was no difference between the blood pressure levels attained before or after any of the dose levels. The rise of heart rate tended to be somewhat dampened after 100 mg only. The rise in blood pressure was unchanged after any dose compared with before. Images Figure 1 PMID:901695

Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion.

PubMed

Mackins, Christina J; Kano, Seiichiro; Seyedi, Nahid; Schäfer, Ulrich; Reid, Alicia C; Machida, Takuji; Silver, Randi B; Levi, Roberto

2006-04-01

Having identified renin in cardiac mast cells, we assessed whether its release leads to cardiac dysfunction. In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity. This activity was blocked by the selective renin inhibitor BILA2157, indicating that renin was responsible for Ang I formation. Local generation of cardiac Ang II from mast cell-derived renin also elicited norepinephrine release from isolated sympathetic nerve terminals. This action was mediated by Ang II-type 1 (AT1) receptors. In 2 models of ischemia/reperfusion using Langendorff-perfused guinea pig and mouse hearts, a significant coronary spillover of renin and norepinephrine was observed. In both models, this was accompanied by ventricular fibrillation. Mast cell stabilization with cromolyn or lodoxamide markedly reduced active renin overflow and attenuated both norepinephrine release and arrhythmias. Similar cardioprotection was observed in guinea pig hearts treated with BILA2157 or the AT1 receptor antagonist EXP3174. Renin overflow and arrhythmias in ischemia/reperfusion were much less prominent in hearts of mast cell-deficient mice than in control hearts. Thus, mast cell-derived renin is pivotal for activating a cardiac renin-angiotensin system leading to excessive norepinephrine release in ischemia/reperfusion. Mast cell-derived renin may be a useful therapeutic target for hyperadrenergic dysfunctions, such as arrhythmias, sudden cardiac death, myocardial ischemia, and congestive heart failure.

Puerarin blocks the signaling transmission mediated by P2X3 in SG and DRG to relieve myocardial ischemic damage.

PubMed

Liu, Shuangmei; Zhang, Chunping; Shi, Qingming; Li, Guilin; Song, Miaomiao; Gao, Yun; Xu, Changshui; Xu, Hong; Fan, Bo; Yu, Shicheng; Zheng, Chaoran; Zhu, Qicheng; Wu, Bing; Peng, Lichao; Xiong, Huangui; Wu, Qin; Liang, Shangdong

2014-02-01

P2X₃ receptors in stellate ganglia (SG) and cervical dorsal root ganglia (DRG) neurons are involved in sympathoexcitatory reflex induced by myocardial ischemic damage. Puerarin, a major active ingredient extracted from the traditional Chinese plant medicine Ge-gen, has been widely used in treatment of myocardial and cerebral ischemia. The present study is aimed to observe the effects of puerarin on the signaling transmission mediated by P2X₃ receptor in SG and DRG after myocardial ischemic damage. Our results showed that systolic blood pressure and heart rate increased, and the expression levels of P2X₃ mRNA and protein in SG and DRG were up-regulated after myocardial ischemic damage. Puerarin reduced systolic blood pressure and heart rate, relieved pain and decreased up-regulated expression of P2X₃ mRNA and protein in SG and DRG after myocardial ischemia. Puerarin inhibited the up-regulated ATP-activated currents in DRG neurons after myocardial ischemia. Thus, puerarin can relieve myocardial ischemic damage through blocking the P2X₃ signaling transmission and then depressed the aggravated sympathoexcitatory reflex. Copyright © 2014 Elsevier Inc. All rights reserved.

BET Acetyl-Lysine Binding Proteins Control Pathological Cardiac Hypertrophy

PubMed Central

Spiltoir, Jessica I.; Stratton, Matthew S.; Cavasin, Maria A.; Demos-Davies, Kim; Reid, Brian G.; Qi, Jun; Bradner, James E.; McKinsey, Timothy A.

2014-01-01

Cardiac hypertrophy is an independent predictor of adverse outcomes in patients with heart failure, and thus represents an attractive target for novel therapeutic intervention. JQ1, a small molecule inhibitor of bromodomain and extraterminal (BET) acetyl-lysine reader proteins, was identified in a high throughput screen designed to discover novel small molecule regulators of cardiomyocyte hypertrophy. JQ1 dose-dependently blocked agonist-dependent hypertrophy of cultured neonatal rat ventricular myocytes (NRVMs) and reversed the prototypical gene program associated with pathological cardiac hypertrophy. JQ1 also blocked left ventricular hypertrophy (LVH) and improved cardiac function in adult mice subjected to transverse aortic constriction (TAC). The BET family consists of BRD2, BRD3, BRD4 and BRDT. BRD4 protein expression was increased during cardiac hypertrophy, and hypertrophic stimuli promoted recruitment of BRD4 to the transcriptional start site (TSS) of the gene encoding atrial natriuretic factor (ANF). Binding of BRD4 to the ANF TSS was associated with increased phosphorylation of local RNA polymerase II. These findings define a novel function for BET proteins as signal-responsive regulators of cardiac hypertrophy, and suggest that small molecule inhibitors of these epigenetic reader proteins have potential as therapeutics for heart failure. PMID:23939492

Arrhythmogenic Right Ventricular Cardiomyopathy with Multiple Thrombi and Ventricular Tachycardia of Atypical Left Branch Bundle Block Morphology.

PubMed

Gong, Shenzhen; Wei, Xin; Liu, Guyue; Wu, Feng; Chen, Xiaoping

2018-04-06

A 61-year-old male patient was admitted to our hospital with recurrent palpitations and syncope. Electrocardiography, echocardiography, and contrast-enhanced computed tomography were performed. The patient was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) complicated by multiple thrombi, and ventricular tachycardia (VT) without typical left bundle branch block (LBBB) morphology. This case suggests that VT is not always the sole contributor to syncope and death in patients with ARVC, and pulmonary embolism should be considered. Furthermore, VT with typical LBBB morphology is not an absolute necessity as a major criterion for the diagnosis of ARVC when the right heart is extremely enlarged.

Comparing the Effect of Topical Anesthesia and Retrobulbar Block With Intravenous Sedation on Hemodynamic Changes and Satisfaction in Patients Undergoing Cataract Surgery (Phaco Method)

PubMed Central

Haddadi, Soudabeh; Marzban, Shideh; Fazeli, Baharak; Heidarzadeh, Abtin; Parvizi, Arman; Naderinabi, Bahram; Panjtan Panah, Mohamad Reza

2015-01-01

Background: Cataract is one of the most common surgical procedures in the elderly. In most cases, the elderly have cardiac ischemia or chronic coronary diseases, which would lead to more ischemic events during general anesthesia. Therefore, surgeons and anesthetists prefer regional aesthesia to the general one owing to its more advantages and less complications. Objectives: Therefore, this study aimed to compare topical method and retrobulbar block for pain intensity, patient’s satisfaction, hemodynamic changes and intra and postoperative complications. Patients and Methods: In a single-blinded clinical trial, 114 patients scheduled for cataract surgery, aged 50 to 90 years with ASA physical status of I-III, were randomly assigned to two groups under monitored anesthesia care as topical anesthesia and retrobulbar block. After the injection of intravenous sedation, which was the combination of midazolam 0.5-1 mg with fentanyl 0.5-1 µ/kg, patients received retro bulbar block or topical anesthesia. During the operation, heart rate, systolic and diastolic blood pressure, mean arterial blood pressure and arterial saturation of O2were measured every five minutes. In addition, pain (VAS) and satisfaction (ISAS) scores were recorded every 15 minutes, then at recovery and one hour after the ending of operation in the ward. Findings were statistically analyzed using SPSS 16. Results: In this study, no significant association was found between age, gender, education and physical condition of patients in both topical and retro bulbar block groups. Comparison of pain based on VAS, satisfaction based on ISAS score and MAP in the studied periods had no significant differences between the two groups of patients undergoing cataract surgery. However, significant differences were found between the two groups (P = 0.045, 0.02, 0.042 and P < 0.05) regarding heart rate, systolic and diastolic blood pressure and arterial oxygen saturation percentage after 20-30 minutes of the operation. Conclusions: Both methods, topical and retro bulbar block had similar impression in cataract surgery regarding analgesia and patient satisfaction. However, in non-complicated cataract surgeries with short duration, topical anesthesia may be the preferable method, because of non-invasiveness, appropriate analgesia, patient satisfaction and hemodynamic stability. PMID:25918686

Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy.

PubMed

Stockburger, Martin; de Teresa, Eduardo; Lamas, Gervasio; Desaga, Martin; Koenig, Carsten; Habedank, Dirk; Cobo, Erik; Navarro, Xavier; Wiegand, Uwe

2014-01-01

Previous studies showed unfavourable effects of right ventricular (RV) pacing. Ventricular pacing (VP), however, is required in many patients with atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV) remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced heart failure. The pre-specified PREVENT-HF German Substudy examined exercise capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). Patients with expected VP ≥80% were randomized to RV or BIV pacing. Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP. Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19), and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min, confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14 mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2 persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90). Our study suggests that BIV pacing produces better exercise capacity over 1 year compared with RV pacing in patients without advanced heart failure and AV block. In contrast, we observed no significant changes of NT-proBNP. Larger trials will allow appraising the clinical usefulness of BIV pacing in AV block. ClinicalTrials.gov Identifier: NCT00170326.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yagi, Yukihiro; Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567; Nakamura, Yuji

Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) ormore » siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct I{sub Kr} inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P{sub 1,3,4,5} and S1P{sub 1,5} receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P{sub 1} in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not observed by siponimod. • I{sub Kr} inhibition may play a key role in the fingolimod-induced QT prolongation.« less

The contribution of gastric digestion and ingestion of amino acids on the postprandial rise in oxygen consumption, heart rate and growth of visceral organs in pythons.

PubMed

Enok, Sanne; Simonsen, Lasse Stærdal; Wang, Tobias

2013-05-01

To investigate the contribution of gastric and intestinal processes to the postprandial rise in metabolism in pythons (Python regius), we measured oxygen consumption after ligation of the pyloric sphincter to prevent the chyme from entering the intestine. Pyloric blockade reduced the postprandial rise in metabolism during the first 18h after ingestion of mice amounting to 18% of the snake's body mass by 60%. In another series of the experiments, we showed that infusion of amino acids directly into the stomach or the intestine elicited similar metabolic responses. This indicates a lower gastric contribution to the SDA response than previously reported. To include an assessment of the gastric contribution to the postprandial cardiovascular response, we also measured blood and heart rate. While heart rate increased during digestion in snakes with pyloric blockade, there was no rise in the double-blocked heart rates compared to fasting controls. Thus, the non-adrenergic-non-cholinergic factor that stimulates heart rate during digestion does not stem from the stomach. Finally, there was no growth of the visceral organs in response to digestion when chyme was prevented from reaching the intestine. Copyright © 2013 Elsevier Inc. All rights reserved.

Great Institutions in Cardiothoracic Surgery: The University of Minnesota.

PubMed

Huddleston, Stephen J; Shumway, Sara

2016-01-01

With the loyal support of the chair of Surgery, Dr. Owen H. Wangensteen, the University of Minnesota cardiac surgery program led the way at the dawn of cardiac surgery when Dr F. John Lewis performed the first open heart surgery in the world using hypothermia while repairing an atrial septal defect on September 2, 1952. Soon after, Dr C. Walt Lillehei performed the first repair of a ventriculoseptal defect in the world using cross-circulation on March 26, 1954. Collaborating with Dr Richard DeWall in 1955, they developed the DeWall-Lillehei bubble oxygentor which was used at the University of Minnesota and many other centers worldwide for years to come, making open heart surgery safe and tractable. Dr Vincent Gott, a resident working in the laboratory of Lillehei, developed a method to treat complete heart block using ventricular pacing with a Grass physiological stimulator, and this led to a collaboration with Earl Bakken, founder of the Medtronic Corporation, to develop a temporary pacemaker. The program was fertile ground for many notable trainees, including Dr Norman Shumway, the "Father of Heart Transplant", and Dr Christiaan Barnard who performed the first heart transplant in the world. The collegial and forward thinking nature of the cardiac surgery program continues in the current training program today. Copyright © 2016 Elsevier Inc. All rights reserved.

[Post-surgical morbidity in paediatric patients undergoing surgery for congenital heart disease in the UMAE of Yucatan, Mexico].

PubMed

Castillo-Espínola, Addy; Velázquez-Ibarra, Ana; Zetina-Solórzano, Aurea; Bolado-García, Patricia; Gamboa-López, Gonzalo

To describe the clinical course of paediatric patients undergoing surgery for congenital heart disease in UMAE of Yucatan. Descriptive review was performed on the records of paediatric patients undergoing surgery for congenital heart disease from 1 November 2011 to 30 November 2013. The most frequent heart diseases were persistent ductus arteriosus (37.6%) and transposition of the great vessels. The median intensive care stay was 3 days. Mortality was 11.76%, with septic shock (44.4%) in most cases. The most frequent complications were sepsis (5.9%), low cardiac output syndrome (4.7%), cardiac arrest, and AV block and ventricular tachycardia (2.4% each). There was a moderate positive correlation between surgical complications and survival or death. The number of surgical patients is lower compared to reference centres for cardiovascular surgery. There is a marked tendency to perform corrective and palliative surgeries in specific disease in patients with added risk or 'bad' cardiac anatomy that prevent full correction at the first attempt. Prospective epidemiological and clinical studies should be conducted to understand the behaviour of congenital heart diseases treated in the region. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Neuregulin-1β promotes glucose uptake via PI3K/Akt in neonatal rat cardiomyocytes.

PubMed

Pentassuglia, Laura; Heim, Philippe; Lebboukh, Sonia; Morandi, Christian; Xu, Lifen; Brink, Marijke

2016-05-01

Nrg1β is critically involved in cardiac development and also maintains function of the adult heart. Studies conducted in animal models showed that it improves cardiac performance under a range of pathological conditions, which led to its introduction in clinical trials to treat heart failure. Recent work also implicated Nrg1β in the regenerative potential of neonatal and adult hearts. The molecular mechanisms whereby Nrg1β acts in cardiac cells are still poorly understood. In the present study, we analyzed the effects of Nrg1β on glucose uptake in neonatal rat ventricular myocytes and investigated to what extent mTOR/Akt signaling pathways are implicated. We show that Nrg1β enhances glucose uptake in cardiomyocytes as efficiently as IGF-I and insulin. Nrg1β causes phosphorylation of ErbB2 and ErbB4 and rapidly induces the phosphorylation of FAK (Tyr(861)), Akt (Thr(308) and Ser(473)), and its effector AS160 (Thr(642)). Knockdown of ErbB2 or ErbB4 reduces Akt phosphorylation and blocks the glucose uptake. The Akt inhibitor VIII and the PI3K inhibitors LY-294002 and Byl-719 abolish Nrg1β-induced phosphorylation and glucose uptake. Finally, specific mTORC2 inactivation after knockdown of rictor blocks the Nrg1β-induced increases in Akt-p-Ser(473) but does not modify AS160-p-Thr(642) or the glucose uptake responses to Nrg1β. In conclusion, our study demonstrates that Nrg1β enhances glucose uptake in cardiomyocytes via ErbB2/ErbB4 heterodimers, PI3Kα, and Akt. Furthermore, although Nrg1β activates mTORC2, the resulting Akt-Ser(473) phosphorylation is not essential for glucose uptake induction. These new insights into pathways whereby Nrg1β regulates glucose uptake in cardiomyocytes may contribute to the understanding of its regenerative capacity and protective function in heart failure. Copyright © 2016 the American Physiological Society.

Parallel effects of β-adrenoceptor blockade on cardiac function and fatty acid oxidation in the diabetic heart: Confronting the maze

PubMed Central

Sharma, Vijay; McNeill, John H

2011-01-01

Diabetic cardiomyopathy is a disease process in which diabetes produces a direct and continuous myocardial insult even in the absence of ischemic, hypertensive or valvular disease. The β-blocking agents bisoprolol, carvedilol and metoprolol have been shown in large-scale randomized controlled trials to reduce heart failure mortality. In this review, we summarize the results of our studies investigating the effects of β-blocking agents on cardiac function and metabolism in diabetic heart failure, and the complex inter-related mechanisms involved. Metoprolol inhibits fatty acid oxidation at the mitochondrial level but does not prevent lipotoxicity; its beneficial effects are more likely to be due to pro-survival effects of chronic treatment. These studies have expanded our understanding of the range of effects produced by β-adrenergic blockade and show how interconnected the signaling pathways of function and metabolism are in the heart. Although our initial hypothesis that inhibition of fatty acid oxidation would be a key mechanism of action was disproved, unexpected results led us to some intriguing regulatory mechanisms of cardiac metabolism. The first was upstream stimulatory factor-2-mediated repression of transcriptional master regulator PGC-1α, most likely occurring as a consequence of the improved function; it is unclear whether this effect is unique to β-blockers, although repression of carnitine palmitoyltransferase (CPT)-1 has not been reported with other drugs which improve function. The second was the identification of a range of covalent modifications which can regulate CPT-1 directly, mediated by a signalome at the level of the mitochondria. We also identified an important interaction between β-adrenergic signaling and caveolins, which may be a key mechanism of action of β-adrenergic blockade. Our experience with this labyrinthine signaling web illustrates that initial hypotheses and anticipated directions do not have to be right in order to open up meaningful directions or reveal new information. PMID:21949571

Parallel effects of β-adrenoceptor blockade on cardiac function and fatty acid oxidation in the diabetic heart: Confronting the maze.

PubMed

Sharma, Vijay; McNeill, John H

2011-09-26

Diabetic cardiomyopathy is a disease process in which diabetes produces a direct and continuous myocardial insult even in the absence of ischemic, hypertensive or valvular disease. The β-blocking agents bisoprolol, carvedilol and metoprolol have been shown in large-scale randomized controlled trials to reduce heart failure mortality. In this review, we summarize the results of our studies investigating the effects of β-blocking agents on cardiac function and metabolism in diabetic heart failure, and the complex inter-related mechanisms involved. Metoprolol inhibits fatty acid oxidation at the mitochondrial level but does not prevent lipotoxicity; its beneficial effects are more likely to be due to pro-survival effects of chronic treatment. These studies have expanded our understanding of the range of effects produced by β-adrenergic blockade and show how interconnected the signaling pathways of function and metabolism are in the heart. Although our initial hypothesis that inhibition of fatty acid oxidation would be a key mechanism of action was disproved, unexpected results led us to some intriguing regulatory mechanisms of cardiac metabolism. The first was upstream stimulatory factor-2-mediated repression of transcriptional master regulator PGC-1α, most likely occurring as a consequence of the improved function; it is unclear whether this effect is unique to β-blockers, although repression of carnitine palmitoyltransferase (CPT)-1 has not been reported with other drugs which improve function. The second was the identification of a range of covalent modifications which can regulate CPT-1 directly, mediated by a signalome at the level of the mitochondria. We also identified an important interaction between β-adrenergic signaling and caveolins, which may be a key mechanism of action of β-adrenergic blockade. Our experience with this labyrinthine signaling web illustrates that initial hypotheses and anticipated directions do not have to be right in order to open up meaningful directions or reveal new information.

Myocardial dysfunction and norepinephrine release in the isolated rat heart injured by electrolysis-induced oxygen free radicals.

PubMed

Chahine, R; Chen, X; Yamaguchi, N; de Champlain, J; Nadeau, R

1991-03-01

In the present investigation, we used electrolysis as a source of oxygen free radicals to test their possible role in norepinephrine release, as well as in the mechanism of cellular injury, cardiac dysfunction and arrhythmias. In the isolated rat heart perfused under constant pressure, according to the Langendorff technique, electrolysis of the Krebs-Henseleit solution (10 mA d.c. current for 1 min) produced myocardial irreversible dysfunction within 5 min. Fifteen minutes after electrolysis, significant falls in the left ventricular pressure (from 87.5 +/- 6.8 to 33.7 +/- 5.2 mmHg), dP/dt max (from 1230 +/- 90 to 375 +/- 59 mmHg/s), heart rate (from 287 +/- 18 to 119 +/- 13.5 beats/min) and coronary flow (from 14.8 +/- 9 to 3.4 +/- 1.7 ml/min) were observed, along with an increase in left ventricular end diastolic pressure from 10 to 50 +/- 3.5 mmHg (n = 8, P less than 0.01). AV conduction block and/or sinus bradycardia were noted in all preparations. An increase in norepinephrine washout from 298.5 +/- 84 at baseline to 610 +/- 110 pg/min/g 5 min after electrolysis was measured (n = 8, P less than 0.05) and a 44.8 +/- 9.2% and 35 +/- 7.5% reduction, respectively in right and left ventricular tissue norepinephrine content was also found at 30 min (n = 5, P less than 0.05). Pretreatment of the hearts 10 min before electrolysis and throughout the experimental period by superoxide dismutase (SOD; 100 U/ml), catalase (150 U/ml), a combination of SOD + catalase or mannitol (50 mM) partially blocked the deleterious effect of free radicals and permitted a functional recovery of 50 to 60%, mannitol being the more potent protective agent. Furthermore, these scavengers also significantly reduced norepinephrine washout.(ABSTRACT TRUNCATED AT 250 WORDS)

VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection).

PubMed

Wang, Yibo; Zhang, Weili; Zhang, Yuhui; Yang, Yuejin; Sun, Lizhong; Hu, Shengshou; Chen, Jilin; Zhang, Channa; Zheng, Yi; Zhen, Yisong; Sun, Kai; Fu, Chunyan; Yang, Tao; Wang, Jianwei; Sun, Jing; Wu, Haiying; Glasgow, Wayne C; Hui, Rutai

2006-03-28

The haplotypes in the gene vitamin K epoxide reductase complex subunit 1 (VKORC1) have been found to affect warfarin dose response through effects on the formation of reduced-form vitamin K, a cofactor for gamma-carboxylation of vitamin K-dependent proteins, which is involved in the coagulation cascade and has a potential impact on atherosclerosis. We hypothesized that VKORC1-dependent effects on the coagulation cascade and atherosclerosis would contribute to susceptibility for vascular diseases. To test the hypothesis, we studied the association of polymorphisms of VKORC1 with stroke (1811 patients), coronary heart disease (740 patients), and aortic dissection (253 patients) compared with matched controls (n=1811, 740, and 416, respectively). Five common noncoding single-nucleotide polymorphisms of VKORC1 were identified in a natural haplotype block with strong linkage disequilibrium (D'>0.9, r2>0.9), then single-nucleotide polymorphism (SNP) +2255 in the block was selected for the association study. We found that the presence of the C allele of the +2255 locus conferred almost twice the risk of vascular disease (odds ratio [OR] 1.95, 95% confidence interval [CI] .58 to 2.41, P<0.001 for stroke; OR 1.72, 95% CI 1.24 to 2.38, P<0.01 for coronary heart disease; and OR 1.90, 95% CI 1.04 to 3.48, P<0.05 for aortic dissection). We also observed that subjects with the CC and CT genotypes had lower levels of undercarboxylated osteocalcin (a regulator for the bone), probably vascular calcification, and lower levels of protein induced in vitamin K absence or antagonism II (PIVKA-II, a des-gamma-carboxy prothrombin) than those with TT genotypes. The haplotype of VKORC1 may serve as a novel genetic marker for the risk of stroke, coronary heart disease, and aortic dissection.

Downregulation of microRNA-29 by antisense inhibitors and a PPAR-gamma agonist protects against myocardial ischaemia-reperfusion injury.

PubMed

Ye, Yumei; Hu, Zhaoyong; Lin, Yu; Zhang, Congfang; Perez-Polo, Jose R

2010-08-01

MicroRNAs (miRNAs) regulate various cardiac processes including cell proliferation and apoptosis. Pioglitazone (PIO), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, protects against myocardial ischaemia-reperfusion (IR) injury. We assessed the effects of PPAR-gamma activation on myocardial miRNA levels and the role of miRNAs in IR injury. We evaluated the expression changes of miRNAs in the rat heart after PIO administration using miRNA arrays and then confirmed the result by northern blot. miR-29a and c levels decreased remarkably after 7-day treatment with PIO. In H9c2 cells, the effects of PIO and rosiglitazone on miR-29 expression levels were blocked by a selective PPAR-gamma inhibitor GW9662. Downregulation of miR-29 by antisense inhibitor or by PIO protected H9c2 cells from simulated IR injury, indicated as increased cell survival and decreased caspase-3 activity. In contrast, overexpressing miR-29 promoted apoptosis and completely blocked the protective effect of PIO. Antagomirs against miR-29a or -29c significantly reduced myocardial infarct size and apoptosis in hearts subjected to IR injury. Western blot analyses demonstrated that Mcl-2, an anti-apoptotic Bcl-2 family member, was increased by miR-29 inhibition. Downregulation of miR-29 protected hearts against IR injury. The modulation of miRNAs can be achieved by pharmacological intervention. These findings provide a rationale for the development of miRNA-based strategies for the attenuation of IR injury.

The electrocardiographic manifestations of athlete's heart and their association with exercise exposure.

PubMed

Bessem, Bram; De Bruijn, Matthijs C; Nieuwland, Wybe; Zwerver, Johannes; Van Den Berg, Maarten

2018-05-01

The aim of this study was to define the minimum amount of exercise per week ('current exposure') and the total amount of exercise ('lifetime exposure') needed to lead to the electrocardiographic changes fitting athlete's heart. All the pre-participation screenings (including electrocardiograms (ECGs)) from collegiate athletes performed at University Sports Medical Center in 2013 and 2014 were collected. Data on height, weight, sex, age, current sport(s) participation and lifetime sport(s) participation were collected. Current exposure was categorised into 0-3, 3-6, 6-10 and >10 hours/week. Lifetime sport exposure was divided into five categories: 0-1000, 1001-2000, 2001-3000, 3001-4000 and >4000 hours. The study population consisted of 1229 athletes (current exposure) and 1104 athletes (lifetime exposure). Current sport exposure: There was a significant increase in training-related ECG changes in the category 3-6 vs. <3 hours/week. When looking at individual parameters, we found an association with a significant difference in sinus bradycardia and QRS voltage (<3 vs. 3-6 hours/week) and first-degree AV-block (<3 vs. >10 hours/week).Lifetime sport exposure: There was an increase in training-related ECG changes that reached significance at an exposure >3000 hours. When looking at individual parameters, we found an association with a significant difference in sinus bradycardia (0-1000 vs. 2001-3000), QRS voltage (0-1000 vs. 3001-4000) and first-degree AV-block (0-1000 vs. >4000). A minimum of ≥3 hours/week of current exposure and a lifetime exposure of >3000 hours is needed to lead to the electrocardiographic changes fitting athlete's heart.

Regional Anesthesia to Scalp for Craniotomy: Innovation With Innervation.

PubMed

Jayaram, Kavitha; Srilata, Moningi; Kulkarni, Dilipkumar; Ramachandran, Gopinath

2016-01-01

Effective management and pain prevention is of great importance to avoid postoperative complications such as hypertension, agitation, and vomiting. All these adverse events may lead to elevation in intracranial pressure and, in turn, unfavorable outcome and prolonged hospital stay. Development of multiple methods of analgesia may contribute to the alleviation of problems due to pain. We tested the effectiveness of bilateral maxillary block with greater and lesser occipital nerve block for providing analgesia to the scalp. This study was undertaken in 40 patients scheduled for craniotomy. Before skin incision, patients were assigned randomly to receive either bilateral maxillary (group M) or scalp block (group S). Data on intraoperative hemodynamics, postoperative analgesia, and sedation were collected and analyzed for statistical significance. The primary outcome was the visual analog pain score. It was similar between the 2 groups at 1, 2, and 4 hours after extubation. At 12 hours, the maxillary block group had better analgesia (mean visual analog score: 3.4 cm for group M and 4.1 cm for group S with P-value of 0.0002) and sedation scores. Intraoperatively, there was no difference in the heart rate, blood pressure, and the anesthetic requirements between both the groups. Three patients in group S required fentanyl supplementation in the intraoperative period. There were no adverse events noted in the perioperative period among both the groups. Maxillary block along with greater and lesser occipital nerve block is an effective alternative to scalp block for craniotomy and has longer duration of analgesia.

Complete atrioventricular block following mediastinal irradiation: A report of six cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slama, M.S.; Le Guludec, D.; Sebag, C.

1991-07-01

Complete atrioventricular block (AVB) following radiotherapy has been reported rarely, usually after high dose mediastinal irradiation for Hodgkin's disease or lung or breast carcinoma. The authors report six new cases of episodic complete infranodal AVB, requiring permanent pacemaker implantation. The mean age was 48-years old (ranging from 25-60) at the first Adams Stokes attack, mean delay was 12 years after irradiation (10-18), and mean radiation dose was 5,200 rads (4,000-6,500). All patients had abnormal interval electrocardiograms (right bundle branch block in two, left bundle branch block in three, alternating left and right bundle branch block in one). Electrocardiograms during themore » episode of AVB or Holter recordings were consistent with infranodal block in all patients; electrophysiological study performed in five patients confirmed infranodal AVB in four, and one was normal. Pericardial disease was constant, which included pericardial constriction in four patients. Two patients died after failure of pericardiectomy to improve congestive heart failure, due to epicardial, myocardial, and endocardial involvement. Noncardiac mediastinal lesions were present in four cases. Since this delayed complication may occur in patients of such age that the relation between the AVB and the chest irradiation is questionable, they propose the following etiologic criteria; high radiation dose (over 4,000 rads); delay of 10 years or more; abnormal interval tracings; pericardial involvement; and associated cardiac or mediastinal radiation-induced lesions.« less

DDD versus VVIR pacing in patients, ages 70 and over, with complete heart block.

PubMed

Ouali, Sana; Neffeti, Elyes; Ghoul, Karima; Hammas, Sami; Kacem, Slim; Gribaa, Rim; Remedi, Fahmi; Boughzela, Essia

2010-05-01

Dual-chamber pacing is believed to have an advantage over single-chamber ventricular pacing. The aim of the study was to determine whether elderly patients with implanted pacemaker for complete atrioventricular block gain significant benefit from dual-chamber (DDD) compared with single-chamber ventricular demand (VVIR). The study was designed as a double-blind randomized two-period crossover study-each pacing mode was maintained for 3 months. Thirty patients (eight men, mean age 76.5 +/- 4.3 years) with implanted PM were submitted to a standard protocol, which included an interview, functional class assessment, quality of life (QoL) questionnaires, 6-minute walk test, and transthoracic echocardiographic examinations. QoL was measured by the SF-36. All these parameters were obtained on DDD mode pacing and VVIR mode pacing. Paired data were compared. QoL was significantly different between the two groups and showed the best values in DDD. Overall, no patient preferred VVIR mode, 18 preferred DDD mode, and 12 expressed no preference. No differences in mean walking distances were observed between patients with single-chamber and dual-chamber pacing. VVI pacing elicited marked decrease in left ventricle ejection fraction and significant enlargement of the left atrium. DDD pacing resulted in significant increase of the peak systolic velocities in lateral mitral annulus and septal mitral annulus. Early diastolic velocities on both sides of mitral annulus did not change. In active elderly patients with complete heart block, DDD pacing is associated with improved quality of life and systolic ventricular function compared with VVI pacing.

Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

PubMed

Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

2002-07-01

Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression.

PubMed

Fakherpour, Atousa; Ghaem, Haleh; Fattahi, Zeinabsadat; Zaree, Samaneh

2018-01-01

Although spinal anaesthesia (SA) is nowadays the preferred anaesthesia technique for caesarean section (CS), it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques) associated with the incidence of different degrees of SA-induced hypotension during elective CS. This prospective study was conducted on 511 mother-infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age) and anaesthesia-related risk factors (such as block height) were associated with occurance of SA-induced hypotension during elective CS. The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m 2 , 11-20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP) <120 mmHg and baseline heart rate >100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T 4 in anaesthesia-related modelling ( P < 0.05). Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS.

Clinical and electrophysiological characteristics of patients with paroxysmal intra-His block with narrow QRS complexes.

PubMed

Ragupathi, Loheetha; Johnson, Drew; Greenspon, Arnold; Frisch, Daniel; Ho, Reginald T; Pavri, Behzad B

2018-04-18

Atrioventricular (AV) block is usually due to infranodal disease and associated with a wide QRS complex; such patients often progress to complete AV block and pacemaker dependency. Uncommonly, infranodal AV block can occur within the His bundle with a narrow QRS complex. The aims of this study were to define clinical/echocardiographic characteristics of patients with AV block within the His bundle and report progression to pacemaker dependency. We retrospectively identified patients with narrow QRS complexes and documented intra-His delay or block at electrophysiology study (group A) or with electrocardiogram-documented Mobitz II AV block/paroxysmal AV block (group B). Clinical, electrophysiological, and echocardiographic variables at presentation and pacemaker parameters at the last follow-up visit were evaluated. Twenty-seven patients (19 women) were identified (mean age 64 ± 13 years; range, 38-85 years). Four patients who had <1 month of follow-up were excluded. There were 12 patients in group A and 11 in group B; 21 of 23 presented with syncope/presyncope. All patients received pacemakers: 8 single chamber and 15 dual chamber. After a median follow-up of 6.4 years, the median percentage of ventricular pacing was 1% (interquartile range 0%-4.66%). One patient developed true pacemaker dependency. Aortic and/or mitral annular calcification was present in 13 of 22 patients with available echocardiograms. Patients who present with syncope and narrow QRS complexes with intra-His delay or Mobitz II paroxysmal AV block with narrow QRS complexes rarely progress to pacemaker dependency and require infrequent pacing. This entity is more common in women, with a higher prevalence of aortic and/or mitral annular calcification. If confirmed by additional studies, single-chamber pacemaker may be sufficient. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Effects of an Isolated Complete Right Bundle Branch Block on Mechanical Ventricular Function.

PubMed

Zhang, Qin; Xue, Minghua; Li, Zhan; Wang, Haiyan; Zhu, Lei; Liu, Xinling; Meng, Haiyan; Hou, Yinglong

2015-12-01

The purpose of this study was to investigate the effects of an isolated complete right bundle branch block on mechanical ventricular function. Two groups of participants were enrolled in this study: a block group, consisting of 98 patients with isolated complete right bundle branch blocks without structural heart disease, and a control group, consisting of 92 healthy adults. The diameter, end-diastolic area, end-systolic area, and right ventricular (RV) fractional area change were obtained to evaluate morphologic and systolic function by 2-dimensional sonographic technology. Systolic and diastolic velocities and time interval parameters were measured to assess mechanical ventricular performance using pulsed wave tissue Doppler imaging. Although there was no significant difference in the RV fractional area change between the patients with blocks and controls, the diameter, end-diastolic area, and end-systolic area of the RV were significantly larger in the patients with blocks (P < .05). In the patients with blocks, the peak velocities during systole and early diastole and the ratio of the peak velocities during early and late diastole decreased. The block group had a prolonged pre-ejection period, electromechanical delay time, and isovolumic relaxation time, a decreased ejection time, and an increased pre-ejection period/ejection time ratio, and the myocardial performance index (Tei index) at the basal RV lateral wall was significantly increased. There were no significant differences in any echocardiographic parameters at different sites of the left ventricle. In patients with isolated complete right bundle branch blocks, systolic and diastolic functions are impaired in the RV, and follow-up is needed. © 2015 by the American Institute of Ultrasound in Medicine.

Loss of glycogen during preconditioning is not a prerequisite for protection of the rabbit heart.

PubMed

Weinbrenner, C; Wang, P; Downey, J M

1996-01-01

Depletion of glycogen has been proposed as the mechanism of protection from ischemic preconditioning. The hypothesis was tested by seeing whether pharmacological manipulation of preconditioning causes parallel changes in cardiac glycogen content. Five groups of isolated rabbit hearts were studied. Group 1 experienced 30 min of ischemia only. Group 2 (PC) was preconditioned with 5 min of global ischemia followed by 10 min of reperfusion. Group 3 was preconditioned with 5 min exposure to 400 nM bradykinin followed by a 10 min washout period. Group 4 experienced exposure to 10 microM adenosine followed by a 10 min washout period, and the fifth group was also preconditioned with 5 min ischemia and 10 min reperfusion but 100 microM 8-(p-sulfophenyl)theophylline (SPT), which blocks adenosine receptors, was included in the buffer to block preconditioning's protection. Transmural biopsies were taken before treatment, just prior to the 30 min period of global ischemia, and after 30 min of global ischemia. Glycogen in the samples was digested with amyloglucosidase and the resulting glucose was assayed. Baseline glycogen averaged 17.3 +/- 0.6 mumol glucose/g wet weight. After preconditioning glycogen decreased to 13.3 +/- 1.3 mumol glucose/g wet weight (p < 0.005 vs. baseline). Glycogen was similarly depleted after pharmacological preconditioning with adenosine (14.0 +/- 1.0 mumol glucose/g wet weight, p < 0.05 vs. baseline) suggesting a correlation. However, when preconditioning was performed in the presence of SPT, which blocks protection, glycogen was also depleted by the same amount (13.3 +/- 0.7 mumol glucose/g wet weight, p = ns vs. PC). Bradykinin, which also mimics preconditioning, caused no depletion of glycogen (16.3 +/- 0.8 mumol glucose/g wet weight, p = ns vs. baseline). Because preconditioning with bradykinin did not deplete glycogen and because glycogen continued to be low when protection from preconditioning was blocked with SPT, we conclude that loss of glycogen per se does not cause the protection of preconditioning.

Properties of the calcium-activated chloride current in heart.

PubMed

Zygmunt, A C; Gibbons, W R

1992-03-01

We used the whole cell patch clamp technique to study transient outward currents of single rabbit atrial cells. A large transient current, IA, was blocked by 4-aminopyridine (4AP) and/or by depolarized holding potentials. After block of IA, a smaller transient current remained. It was completely blocked by nisoldipine, cadmium, ryanodine, or caffeine, which indicates that all of the 4AP-resistant current is activated by the calcium transient that causes contraction. Neither calcium-activated potassium current nor calcium-activated nonspecific cation current appeared to contribute to the 4AP-resistant transient current. The transient current disappeared when ECl was made equal to the pulse potential; it was present in potassium-free internal and external solutions. It was blocked by the anion transport blockers SITS and DIDS, and the reversal potential of instantaneous current-voltage relations varied with extracellular chloride as predicted for a chloride-selective conductance. We concluded that the 4AP-resistant transient outward current of atrial cells is produced by a calcium-activated chloride current like the current ICl(Ca) of ventricular cells (1991. Circulation Research. 68:424-437). ICl(Ca) in atrial cells demonstrated outward rectification, even when intracellular chloride concentration was higher than extracellular. When ICa was inactivated or allowed to recover from inactivation, amplitudes of ICl(Ca) and ICa were closely correlated. The results were consistent with the view that ICl(Ca) does not undergo independent inactivation. Tentatively, we propose that ICl(Ca) is transient because it is activated by an intracellular calcium transient. Lowering extracellular sodium increased the peak outward transient current. The current was insensitive to the choice of sodium substitute. Because a recently identified time-independent, adrenergically activated chloride current in heart is reduced in low sodium, these data suggest that the two chloride currents are produced by different populations of channels.

An Experimental Evaluation of Stress-Management Training for the Airborne Soldier

DTIC Science & Technology

1980-06-01

skill takes considerable time and involves the learning of respiration control techniques and exercises to relax both the skeletal and smooth muscle...NUMBER 7. AUTHORia) 8. CONTRACT OR GRANT NUMBER(.) William P. Burke 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT, TASK US Army...block number) Jumpmaster training Performance under stress Stress-management training Stress reaction Respiration -control Heart rate response Deep

Attenuation of Cardiovascular Response with Lidocaine 1.5 mg/kg and Labetalol 10 mg

DTIC Science & Technology

1990-07-01

pressure may jeopardize tissue viability in subjects with valvular heart disease , coronary artery disease or elevations in intracranial pressure...this study are defined as follows: ASA I- Healthy Subject ASA II- Subject with mild systemic disease without functional limitations. Cardiovascular...bronchospastic disease or bronchodilator use, atrioventricular block, severe hepatic dysfunction, or current use of alpha- or beta- adrenergic drug

TRPM2 Channels Protect against Cardiac Ischemia-Reperfusion Injury

PubMed Central

Miller, Barbara A.; Hoffman, Nicholas E.; Merali, Salim; Zhang, Xue-Qian; Wang, JuFang; Rajan, Sudarsan; Shanmughapriya, Santhanam; Gao, Erhe; Barrero, Carlos A.; Mallilankaraman, Karthik; Song, Jianliang; Gu, Tongda; Hirschler-Laszkiewicz, Iwona; Koch, Walter J.; Feldman, Arthur M.; Madesh, Muniswamy; Cheung, Joseph Y.

2014-01-01

Cardiac TRPM2 channels were activated by intracellular adenosine diphosphate-ribose and blocked by flufenamic acid. In adult cardiac myocytes the ratio of GCa to GNa of TRPM2 channels was 0.56 ± 0.02. To explore the cellular mechanisms by which TRPM2 channels protect against cardiac ischemia/reperfusion (I/R) injury, we analyzed proteomes from WT and TRPM2 KO hearts subjected to I/R. The canonical pathways that exhibited the largest difference between WT-I/R and KO-I/R hearts were mitochondrial dysfunction and the tricarboxylic acid cycle. Complexes I, III, and IV were down-regulated, whereas complexes II and V were up-regulated in KO-I/R compared with WT-I/R hearts. Western blots confirmed reduced expression of the Complex I subunit and other mitochondria-associated proteins in KO-I/R hearts. Bioenergetic analyses revealed that KO myocytes had a lower mitochondrial membrane potential, mitochondrial Ca2+ uptake, ATP levels, and O2 consumption but higher mitochondrial superoxide levels. Additionally, mitochondrial Ca2+ uniporter (MCU) currents were lower in KO myocytes, indicating reduced mitochondrial Ca2+ uptake was likely due to both lower ψm and MCU activity. Similar to isolated myocytes, O2 consumption and ATP levels were also reduced in KO hearts. Under a simulated I/R model, aberrant mitochondrial bioenergetics was exacerbated in KO myocytes. Reactive oxygen species levels were also significantly higher in KO-I/R compared with WT-I/R heart slices, consistent with mitochondrial dysfunction in KO-I/R hearts. We conclude that TRPM2 channels protect the heart from I/R injury by ameliorating mitochondrial dysfunction and reducing reactive oxygen species levels. PMID:24492610

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

PubMed Central

Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest.

PubMed

Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO 2 -mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

Natural history of coronary heart disease and heart disease of uncertain etiology: Findings from a 50-year population study.

PubMed

Puddu, Paolo Emilio; Menotti, Alessandro

2015-10-15

To describe the natural history of common heart disease incidence on a population study. A sample of 1712 men aged 40-59 was enrolled in 1960 and followed-up for 50years. Coronary heart disease (CHD) was categorized if manifested as sudden death, fatal and non-fatal myocardial infarction and other acute coronary syndromes, and as Heart Disease of Uncertain Etiology (HDUE) if manifested as heart failure, chronic arrhythmia, blocks, diagnoses of chronic CHD or hypertensive heart disease. Their characteristics and prognosis in terms of age at event, mortality and expectancy of life up to 50years were analyzed. Incidence of first CHD and HDUE event or diagnosis was of 26.9 and 20.6%, respectively. First events were equally manifested as fatal or non-fatal occurrences among CHD, while non-fatal occurrences were almost always observed among HDUE. Cases of HDUE presented at a more advanced age and also average age at death was significantly more advanced than in CHD, respectively around 79 and 76years. Expectancy of life was significantly longer for HDUE (30.7years) than for CHD (27.6years). Strokes were more frequently ascertained among HDUE (14%) while 14% of death causes were due to cancer in both CHD and HDUE. Cancers were much higher (40%) among those never diagnosed CHD or HDUE who also had more stroke-due deaths (17%). This is the first investigation to report heart disease incidence and its natural history in a quasi-extinction cohort data from Italy in a pre-cardiac surgery era. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bisphenol A exposure and cardiac electrical conduction in excised rat hearts.

PubMed

Posnack, Nikki Gillum; Jaimes, Rafael; Asfour, Huda; Swift, Luther M; Wengrowski, Anastasia M; Sarvazyan, Narine; Kay, Matthew W

2014-04-01

Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown. The goal of our study was to measure the effect of BPA (0.1-100 μM) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats. We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1-100 μM BPA), prolonged action potential duration (1-100 μM BPA), and delayed atrioventricular conduction (10-100 μM BPA). These effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block. Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA's effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations.

Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study.

PubMed

Packer, Milton; Fowler, Michael B; Roecker, Ellen B; Coats, Andrew J S; Katus, Hugo A; Krum, Henry; Mohacsi, Paul; Rouleau, Jean L; Tendera, Michal; Staiger, Christoph; Holcslaw, Terry L; Amann-Zalan, Ildiko; DeMets, David L

2002-10-22

Beta-blocking agents improve functional status and reduce morbidity in mild-to-moderate heart failure, but it is not known whether they produce such benefits in severe heart failure. We randomly assigned 2289 patients with symptoms of heart failure at rest or on minimal exertion and with an ejection fraction <25% (but not volume-overloaded) to double-blind treatment with either placebo (n=1133) or carvedilol (n=1156) for an average of 10.4 months. Carvedilol reduced the combined risk of death or hospitalization for a cardiovascular reason by 27% (P=0.00002) and the combined risk of death or hospitalization for heart failure by 31% (P=0.000004). Patients in the carvedilol group also spent 27% fewer days in the hospital for any reason (P=0.0005) and 40% fewer days in the hospital for heart failure (P<0.0001). These differences were as a result of both a decrease in the number of hospitalizations and a shorter duration of each admission. More patients felt improved and fewer patients felt worse in the carvedilol group than in the placebo group after 6 months of maintenance therapy (P=0.0009). Carvedilol-treated patients were also less likely than placebo-treated patients to experience a serious adverse event (P=0.002), especially worsening heart failure, sudden death, cardiogenic shock, or ventricular tachycardia. In euvolemic patients with symptoms at rest or on minimal exertion, the addition of carvedilol to conventional therapy ameliorates the severity of heart failure and reduces the risk of clinical deterioration, hospitalization, and other serious adverse clinical events.

Mechanical preconditioning enables electrophysiologic coupling of skeletal myoblast cells to myocardium

PubMed Central

Treskes, Philipp; Cowan, Douglas B.; Stamm, Christof; Rubach, Martin; Adelmann, Roland; Wittwer, Thorsten; Wahlers, Thorsten

2015-01-01

Objective The effect of mechanical preconditioning on skeletal myoblasts in engineered tissue constructs was investigated to resolve issues associated with conduction block between skeletal myoblast cells and cardiomyocytes. Methods Murine skeletal myoblasts were used to generate engineered tissue constructs with or without application of mechanical strain. After in vitro myotube formation, engineered tissue constructs were co-cultured for 6 days with viable embryonic heart slices. With the use of sharp electrodes, electrical coupling between engineered tissue constructs and embryonic heart slices was assessed in the presence or absence of pharmacologic agents. Results The isolation and expansion procedure for skeletal myoblasts resulted in high yields of homogeneously desmin-positive (97.1% ± 0.1%) cells. Mechanical strain was exerted on myotubes within engineered tissue constructs during gelation of the matrix, generating preconditioned engineered tissue constructs. Electrical coupling between preconditioned engineered tissue constructs and embryonic heart slices was observed; however, no coupling was apparent when engineered tissue constructs were not subjected to mechanical strain. Coupling of cells from engineered tissue constructs to cells in embryonic heart slices showed slower conduction velocities than myocardial cells with the embryonic heart slices (preconditioned engineered tissue constructs vs embryonic heart slices: 0.04 ± 0.02 ms vs 0.10 ± 0.05 ms, P = .011), lower stimulation frequencies (preconditioned engineered tissue constructs vs maximum embryonic heart slices: 4.82 ± 1.42 Hz vs 10.58 ± 1.56 Hz; P = .0009), and higher sensitivities to the gap junction inhibitor (preconditioned engineered tissue constructs vs embryonic heart slices: 0.22 ± 0.07 mmol/L vs 0.93 ± 0.15 mmol/L; P = .0004). Conclusions We have generated skeletal myoblast–based transplantable grafts that electrically couple to myocardium. PMID:22980065

Transcriptional coactivators PGC-1α and PGC-lβ control overlapping programs required for perinatal maturation of the heart

PubMed Central

Lai, Ling; Leone, Teresa C.; Zechner, Christoph; Schaeffer, Paul J.; Kelly, Sean M.; Flanagan, Daniel P.; Medeiros, Denis M.; Kovacs, Attila; Kelly, Daniel P.

2008-01-01

Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARγ coactivator-1 (PGC-1) α and β have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1α and PGC-1β (PGC-1αβ−/− mice) were generated to investigate the convergence of their functions in vivo. The phenotype of PGC-1β−/− mice was minimal under nonstressed conditions, including normal heart function, similar to that of PGC-1α−/− mice generated previously. In striking contrast to the singly deficient PGC-1 lines, PGC-1αβ−/− mice died shortly after birth with small hearts, bradycardia, intermittent heart block, and a markedly reduced cardiac output. Cardiac-specific ablation of the PGC-1β gene on a PGC-1α-deficient background phenocopied the generalized PGC-1αβ−/− mice. The hearts of the PGC-1αβ−/− mice exhibited signatures of a maturational defect including reduced growth, a late fetal arrest in mitochondrial biogenesis, and persistence of a fetal pattern of gene expression. Brown adipose tissue (BAT) of PGC-1αβ−/− mice also exhibited a severe abnormality in function and mitochondrial density. We conclude that PGC-1α and PGC-1β share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT. PMID:18628400

Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate.

PubMed

Al Rasheed, N M; Al Sayed, M I; Al Zuhair, H H; Al Obaid, A R; Fatani, A J

2001-04-01

Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (P< 0.0001, ANOVA). Compound II was 14 and 6 times more potent in reducing blood pressure and 8 and 2 times more capable of reducing the heart rate than lidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl(2)significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential. Copyright 2001 Academic Press.

Utility of a super-flexible three-dimensional printed heart model in congenital heart surgery.

PubMed

Hoashi, Takaya; Ichikawa, Hajime; Nakata, Tomohiro; Shimada, Masatoshi; Ozawa, Hideto; Higashida, Akihiko; Kurosaki, Kenichi; Kanzaki, Suzu; Shiraishi, Isao

2018-05-28

The objective of this study was to assess the utility of 3D printed heart models of congenital heart disease for preoperative surgical simulation. Twenty patient-specific 3D models were created between March 2015 and August 2017. All operations were performed by a young consultant surgeon who had no prior experience with complex biventricular repair. All 15 patients with balanced ventricles had outflow tract malformations (double-outlet right ventricle in 7 patients, congenitally corrected transposition of great arteries in 5, transposition of great arteries in 1, interrupted aortic arch Type B in 1, tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries in 1). One patient had hypoplastic left heart complex, and the remaining 4 patients had a functional single ventricle. The median age at operation was 1.4 (range 0.1-5.9) years. Based on a multislice computed tomography data set, the 3D models were made of polyurethane resins using stereolithography as the printing technology and vacuum casting as the manufacturing method. All but 4 patients with a functional single ventricle underwent complete biventricular repair. The median cardiopulmonary bypass time and aortic cross-clamp time were 345 (110-570) min and 114 (35-293) min, respectively. During the median follow-up period of 1.3 (0.1-2.5) years, no mortality was observed. None of the patients experienced surgical heart block or systemic ventricular outflow tract obstruction. Three-dimensional printed heart models showed potential utility, especially in understanding the relationship between intraventricular communications and great vessels, as well as in simulation for creating intracardiac pathways.

Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip

NASA Technical Reports Server (NTRS)

Lee, F.; Shoemaker, J. K.; McQuillan, P. M.; Kunselman, A. R.; Smith, M. B.; Yang, Q. X.; Smith, H.; Gray, K.; Sinoway, L. I.

2000-01-01

We tested the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip protocol before and after forearm bier block with bretylium as forearm blood flow (Doppler) and metabolic (venous effluent metabolite concentration and (31)P-NMR indexes) and autonomic reflex responses (heart rate, blood pressure, and sympathetic nerve traffic) were measured. Bretylium inhibits the release of norepinephrine at the neurovascular junction. Bier block increased blood flow as well as oxygen consumption in the exercising forearm (P < 0.03 and P < 0.02, respectively). However, despite this increase in flow, venous K(+) release and H(+) release were both increased during exercise (P < 0.002 for both indexes). Additionally, minimal muscle pH measured during the first minute of recovery with NMR was lower after bier block (6.41 +/- 0.08 vs. 6.20 +/- 0.06; P < 0.036, simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier block. The results support the conclusion that sympathetic stimulation to muscle during exercise not only limits muscle blood flow but also appears to limit anaerobiosis and H(+) release, presumably through a preferential recruitment of oxidative fibers.

Doxorubicin Blocks Cardiomyocyte Autophagic Flux by Inhibiting Lysosome Acidification.

PubMed

Li, Dan L; Wang, Zhao V; Ding, Guanqiao; Tan, Wei; Luo, Xiang; Criollo, Alfredo; Xie, Min; Jiang, Nan; May, Herman; Kyrychenko, Viktoriia; Schneider, Jay W; Gillette, Thomas G; Hill, Joseph A

2016-04-26

The clinical use of doxorubicin is limited by cardiotoxicity. Histopathological changes include interstitial myocardial fibrosis and the appearance of vacuolated cardiomyocytes. Whereas dysregulation of autophagy in the myocardium has been implicated in a variety of cardiovascular diseases, the role of autophagy in doxorubicin cardiomyopathy remains poorly defined. Most models of doxorubicin cardiotoxicity involve intraperitoneal injection of high-dose drug, which elicits lethargy, anorexia, weight loss, and peritoneal fibrosis, all of which confound the interpretation of autophagy. Given this, we first established a model that provokes modest and progressive cardiotoxicity without constitutional symptoms, reminiscent of the effects seen in patients. We report that doxorubicin blocks cardiomyocyte autophagic flux in vivo and in cardiomyocytes in culture. This block was accompanied by robust accumulation of undegraded autolysosomes. We go on to localize the site of block as a defect in lysosome acidification. To test the functional relevance of doxorubicin-triggered autolysosome accumulation, we studied animals with diminished autophagic activity resulting from haploinsufficiency for Beclin 1. Beclin 1(+/-) mice exposed to doxorubicin were protected in terms of structural and functional changes within the myocardium. Conversely, animals overexpressing Beclin 1 manifested an amplified cardiotoxic response. Doxorubicin blocks autophagic flux in cardiomyocytes by impairing lysosome acidification and lysosomal function. Reducing autophagy initiation protects against doxorubicin cardiotoxicity. © 2016 American Heart Association, Inc.

Anesthetic efficacy of the intraosseous injection after an inferior alveolar nerve block.

PubMed

Dunbar, D; Reader, A; Nist, R; Beck, M; Meyers, W J

1996-09-01

The purpose of this study was to determine the contribution of the intraosseous (IO) injection to the inferior alveolar nerve (IAN) block in human first molars. Using a repeated-measures design, 40 subjects randomly received either a combination IAN block + IO injection (on the distal of the first molar) using 2% lidocaine with 1:100,000 epinephrine or an IAN block+mock IO injection (gingival penetration only) at two successive appointments. The first molar and adjacent teeth, and contralateral canine (+/-controls) were blindly tested with an Analytic Technology pulp tester at 2-min cycles for 60 min. An 80 reading was used as the criterion for pulpal anesthesia. One hundred percent of the subjects had lip numbness with the IAN block. For the first molar, anesthetic success, defined as achieving an 80 reading within 15 min and keeping this reading for 60 min, was 42% with the IAN and 90% with the IAN + IO. Anesthetic failure defined as never achieving two 80 readings during the 60 min was 32% with the IAN and 0% with the IAN + IO. The onset of anesthesia was immediate with the IO injection. Eighty percent of the subjects sampled had a subjective increase in heart rate with the IO injection. The IO injection and postinjection questionnaire recorded low pain ratings.

Worsening heart failure in the setting of dronedarone initiation.

PubMed

Coons, James C; Plauger, Kara M; Seybert, Amy L; Sokos, George G

2010-09-01

To describe a challenging patient case in which dronedarone was selected for a patient with atrial fibrillation and heart failure; the drug may have been associated with worsening heart failure, leading to acute renal and hepatic failure. A 47-year-old male with a history of heart failure with New York Heart Association class III-IV symptoms presented to our institution with ventricular fibrillation and ventricular tachycardia storm. Torsade de pointes secondary to a combination of dofetilide and hypokalemia was determined to be the etiology. Upon stabilization, the patient was initiated on dronedarone 400 mg orally twice daily by the electrophysiology service for atrial fibrillation. The patient had a questionable history of amiodarone intolerance. By hospital day 9 (day 4 of dronedarone therapy), the patient demonstrated a clinical picture consistent with acute renal and hepatic failure possibly due to worsening heart failure. Dronedarone was discontinued on hospital day 10. He was subsequently transferred to an outside hospital where he required milrinone therapy for cardiogenic shock. Laboratory markers of renal and hepatic function improved over the remainder of his hospitalization and he was discharged on hospital day 20. Dronedarone is a newly approved antiarrhythmic agent with multichannel blocking properties similar to amiodarone. Use of the Naranjo probability scale determined that this patient's worsening heart failure leading to acute renal and hepatic failure was possibly caused by dronedarone. The implication from the ANDROMEDA trial as well as our experience in this case is that dronedarone should be used cautiously in patients with heart failure and avoided in patients specifically outlined in the product labeling. This case report, to our knowledge, represents the first published postmarketing report of worsening heart failure complicated by multiorgan dysfunction in the setting of dronedarone initiation. Dronedarone use must be approached with caution in patients with a history of heart failure.

Low-Velocity Nail-Gun Injuries to the Interventricular Septum: Report of Two Cases, One in a Child.

PubMed

Michalsen, Kara L; Iguidbashian, John P; Kyser, James P; Long, William B

2015-08-01

Nail-gun injury to the heart is rare. Nail-gun injury to the interventricular septum is rarer: we could find only 5 reported cases, and none involving a child. We report 2 additional cases, in which nails penetrated the interventricular septum without causing acute pericardial tamponade, heart block, or shunt across the septum. Transesophageal echocardiography provides a dynamic way to evaluate the patient preoperatively, intraoperatively, and postoperatively. In the cases reported here, both the adult with multiple interventricular nails and the child with a single nail underwent foreign-object removal via median sternotomy. The child needed cardiopulmonary bypass for removal of the nail. There were no short-term or long-term sequelae from these interventricular septal injuries.

Minimally Invasive Implantable Fetal Micropacemaker: Mechanical Testing and Technical Refinements

PubMed Central

Zhou, Li; Vest, Adriana N.; Peck, Raymond A.; Sredl, Jonathan P.; Huang, Xuechen; Bar-Cohen, Yaniv; Silka, Michael J.; Pruetz, Jay D.; Chmait, Ramen H.; Loeb, Gerald E.

2016-01-01

This paper discusses the technical and safety requirements for cardiac pacing of a human fetus with heart failure and hydrops fetalis secondary to complete heart block. Engineering strategies to meet specific technical requirements were integrated into a systematic design and implementation consisting of a novel fetal micropacemaker, a percutaneous implantation system, and a sterile package that enables device storage and recharging maintenance in a clinical setting. We further analyzed observed problems on myocardial fixation and pacing lead fatigue previously reported in earlier preclinical trials. This paper describes the technical refinements of the implantable fetal micropacemaker to overcome these challenges. The mechanical performance has been extensively tested to verify the improvement of reliability and safety margins of the implantation system. PMID:27021067

Artifacts, assumptions, and ambiguity: Pitfalls in comparing experimental results to numerical simulations when studying electrical stimulation of the heart.

PubMed

Roth, Bradley J.

2002-09-01

Insidious experimental artifacts and invalid theoretical assumptions complicate the comparison of numerical predictions and observed data. Such difficulties are particularly troublesome when studying electrical stimulation of the heart. During unipolar stimulation of cardiac tissue, the artifacts include nonlinearity of membrane dyes, optical signals blocked by the stimulating electrode, averaging of optical signals with depth, lateral averaging of optical signals, limitations of the current source, and the use of excitation-contraction uncouplers. The assumptions involve electroporation, membrane models, electrode size, the perfusing bath, incorrect model parameters, the applicability of a continuum model, and tissue damage. Comparisons of theory and experiment during far-field stimulation are limited by many of these same factors, plus artifacts from plunge and epicardial recording electrodes and assumptions about the fiber angle at an insulating boundary. These pitfalls must be overcome in order to understand quantitatively how the heart responds to an electrical stimulus. (c) 2002 American Institute of Physics.

The marvel of percutaneous cardiovascular devices in the elderly.

PubMed

Guidoin, Robert; Douville, Yvan; Clavel, Marie-Annick; Zhang, Ze; Nutley, Mark; Pîbarot, Philippe; Dionne, Guy

2010-06-01

Thanks to minimally invasive procedures, frail and elderly patients can also benefit from innovative technologies. More than 14 million implanted pacemakers deliver impulses to the heart muscle to regulate the heart rate (treating bradycardias and blocks). The first human implantation of defibrillators was performed in early 2000. The defibrillator detects cardiac arrhythmias and corrects them by delivering electric shocks. The ongoing development of minimally invasive technologies has also broadened the scope of treatment for elderly patients with vascular stenosis and aneurysmal disease as well as other complex vascular pathologies. The nonsurgical cardiac valve replacement represents one of the most recent and exciting developments, demonstrating the feasibility of replacing a heart valve by way of placement through an intra-arterial or trans-ventricular sheath. Percutaneous devices are particularly well suited for the elderly as the surgical risks of minimally invasive surgery are considerably less as compared to open surgery, leading to a shorter hospital stay, a faster recovery, and improved quality of life.

Right ventricular sarcoidosis: is it time for updated diagnostic criteria?

PubMed

Vakil, Kairav; Minami, Elina; Fishbein, Daniel P

2014-04-01

A 55-year-old woman with a history of complete heart block, atrial flutter, and progressive right ventricular failure was referred to our tertiary care center to be evaluated for cardiac transplantation. The patient's clinical course included worsening right ventricular dysfunction for 3 years before the current evaluation. Our clinical findings raised concerns about arrhythmogenic right ventricular cardiomyopathy. Noninvasive imaging, including a positron emission tomographic scan, did not reveal obvious myocardial pathologic conditions. Given the end-stage nature of the patient's right ventricular failure and her dependence on inotropic agents, she underwent urgent listing and subsequent heart transplantation. Pathologic examination of the explanted heart revealed isolated right ventricular sarcoidosis with replacement fibrosis. Biopsy samples of the cardiac allograft 6 months after transplantation showed no recurrence of sarcoidosis. This atypical presentation of isolated cardiac sarcoidosis posed a considerable diagnostic challenge. In addition to discussing the patient's case, we review the relevant medical literature and discuss the need for updated differential diagnostic criteria for end-stage right ventricular failure that mimics arrhythmogenic right ventricular cardiomyopathy.

Comparison of the Effects of Benson Muscle Relaxation and Nature Sounds on the Fatigue in Patients With Heart Failure: A Randomized Controlled Clinical Trial.

PubMed

Seifi, Leila; Najafi Ghezeljeh, Tahereh; Haghani, Hamid

This study was conducted with the aim of comparing the effects of Benson muscle relaxation and nature sounds on fatigue in patients with heart failure. Fatigue and exercise intolerance as prevalent symptoms experienced by patients with heart failure can cause the loss of independence in the activities of daily living. It can also damage self-care and increase dependence to others, which subsequently can reduce the quality of life. This randomized controlled clinical trial was conducted in an urban area of Iran in 2016. Samples were consisted of 105 hospitalized patients with heart failure chosen using a convenience sampling method. They were assigned to relaxation, nature sounds, and control groups using a randomized block design. In addition to routine care, the Benson muscle relaxation and nature sounds groups received interventions in mornings and evenings twice a day for 20 minutes within 3 consecutive days. A 9-item questionnaire was used to collect data regarding fatigue before and after the interventions. Relaxation and nature sounds reduced fatigue in patients with heart failure in comparison to the control group. However, no statistically significant difference was observed between the interventions. Benson muscle relaxation and nature sounds are alternative methods for the reduction of fatigue in patients with heart failure. They are inexpensive and easy to be administered and upon patients' preferences can be used by nurses along with routine nursing interventions.

Mathematical modelling of the maternal cardiovascular system in the three stages of pregnancy.

PubMed

Corsini, Chiara; Cervi, Elena; Migliavacca, Francesco; Schievano, Silvia; Hsia, Tain-Yen; Pennati, Giancarlo

2017-09-01

In this study, a mathematical model of the female circulation during pregnancy is presented in order to investigate the hemodynamic response to the cardiovascular changes associated with each trimester of pregnancy. First, a preliminary lumped parameter model of the circulation of a non-pregnant female was developed, including the heart, the systemic circulation with a specific block for the uterine district and the pulmonary circulation. The model was first tested at rest; then heart rate and vascular resistances were individually varied to verify the correct response to parameter alterations characterising pregnancy. In order to simulate hemodynamics during pregnancy at each trimester, the main changes applied to the model consisted in reducing vascular resistances, and simultaneously increasing heart rate and ventricular wall volumes. Overall, reasonable agreement was found between model outputs and in vivo data, with the trends of the cardiac hemodynamic quantities suggesting correct response of the heart model throughout pregnancy. Results were reported for uterine hemodynamics, with flow tracings resembling typical Doppler velocity waveforms at each stage, including pulsatility indexes. Such a model may be used to explore the changes that happen during pregnancy in female with cardiovascular diseases. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

A centrally mediated prolonged hypotension produced by oxotremorine or pilocarpine

PubMed Central

Dage, R.C.

1979-01-01

1 Oxotremorine, methyloxotremorine, pilocarpine or arecoline were given intravenously to anaesthetized cats, dogs or rats, and intraperitoneally to conscious normotensive and spontaneously hypertensive rats, pretreated with doses of methylatropine that completely blocked peripheral muscarinic receptors, to ascertain their effects on blood pressure and heart rate. 2 Oxotremorine but not methyloxotremorine produced a prolonged hypotension in cats and dogs but not in rats. Heart rate was not changed. Pilocarpine, although less potent, produced an identical effect, whereas the effect of arecoline was short by comparison. The hypotensive effect of these drugs was reversed by atropine. 3 In dogs, oxotremorine produced a prolonged hypotension with no change in heart rate or cardiac output. 4 A decrease in spontaneous sympathetic nerve activity accompanied the hypotension in cats. Both effects were reversed by atropine but could be reinvoked by large doses of oxotremorine. 5 The oxotremorine-induced hypotension in cats was not altered by decerebration but was abolished by high cervical spinal section. 6 The results indicate that the prolonged hypotension elicited by oxotremorine is mediated by an action at muscarinic receptors in the brain stem resulting in a decrease in sympathetic nerve activity and peripheral resistance but not heart rate or cardiac output. PMID:760887

Evaluation of indoramin added to oxprenolol and bendrofluazide as a third agent in severe hypertension.

PubMed

Marshall, A J; Kettle, M A; Barritt, D W

1980-09-01

1 Indoramin, an alpha-adrenoreceptor blocking agent has been given as a third agent to patients with severe hypertension treated with adequate doses of a beta-adrenoceptor blocking drug and a thiazide diuretic. 2 A further fall in blood pressure followed the addition of indoramin. With 75 mg twice daily this was on average a fall of 12% of mean arterial pressure in the supine position, 16% standing an 17% after exercise. 3 The rise in blood pressure caused by isometric exercise was not altered by indoramin. 4 Indoramin slowed the heart rate. On 75 mg twice daily the reduction was 14% at rest and 19% after exercise. 5 Side effects of indoramin were sedation, sleep disturbance and vivid dreams.

Stress in mangrove forests: early detection and preemptive rehabilitation are essential for future successful worldwide mangrove forest management

USGS Publications Warehouse

Lewis, Roy R; Milbrandt, Eric C; Brown, Benjamin; Krauss, Ken W.; Rovai, Andre S.; Beever, James W.; Flynn, Laura L

2016-01-01

Mangrove forest rehabilitation should begin much sooner than at the point of catastrophic loss. We describe the need for “mangrove forest heart attack prevention”, and how that might be accomplished in a general sense by embedding plot and remote sensing monitoring within coastal management plans. The major cause of mangrove stress at many sites globally is often linked to reduced tidal flows and exchanges. Blocked water flows can reduce flushing not only from the seaward side, but also result in higher salinity and reduced sediments when flows are blocked landward. Long-term degradation of function leads to acute mortality prompted by acute events, but created by a systematic propensity for long-term neglect of mangroves. Often, mangroves are lost within a few years; however, vulnerability is re-set decades earlier when seemingly innocuous hydrological modifications are made (e.g., road construction, blocked tidal channels), but which remain undetected without reasonable large-scale monitoring.

Appendices for the Space Applications program, 1974

NASA Technical Reports Server (NTRS)

1974-01-01

To achieve truly low cost system design with direct evolution for inorbit shuttle resupply, a modular building block approach has been adopted. The heart of the modular building block concept lies in the ability to use a common set of nonoptimized subsystems in such a way that a wide variety of missions can be flown with no detrimental impact on performance. By standardizing the mechanical configurations and electrical interfaces of the subsystem modules, and by designing each of them to be structurally and thermally independent entities, it is possible to cluster these building blocks or modules about an instrument system so as to adequately perform the mission without the need for subsystem redevelopments for each mission. This system concept offers the following capabilities: (1) the ability to launch and orbit the observatory by either the Delta, the Titan, or the space shuttle. (2) the ability to completely reconfigure the spacecraft subsystems for different launch vehicles, and (3) the ability to perform in-orbit resupply and/or emergency retrieval of the observatory.

HRV analysis in local anesthesia using Continuous Wavelet Transform (CWT).

PubMed

Shafqat, K; Pal, S K; Kumari, S; Kyriacou, P A

2011-01-01

Spectral analysis of Heart Rate Variability (HRV) is used for the assessment of cardiovascular autonomic control. In this study Continuous Wavelet Transform (CWT) has been used to evaluate the effect of local anesthesia on HRV parameters in a group of fourteen patients undergoing axillary brachial plexus block. A new method which takes signal characteristics into account has been presented for the estimation of the variable boundaries associated with the low and the high frequency band of the HRV signal. The variable boundary method might be useful in cases when the power related to respiration component extends beyond the traditionally excepted range of the high frequency band (0.15-0.4 Hz). The statistical analysis (non-parametric Wilcoxon signed rank test) showed that the LF/HF ratio decreased within an hour of the application of the brachial plexus block compared to the values fifteen minutes prior to the application of the block. These changes were observed in thirteen of the fourteen patients included in this study.

[Ultrasound-guided Rectus Sheath Block vs Transversus Abdominis Plane Block in Children Undergoing Umbilical Hernia Repair].

PubMed

Torii, Naoko; Tachibana, Kazuya; Iwasaki, Mitsuo; Takeuchi, Muneyuki; Kinouchi, Keiko

2016-06-01

Although many reports describe the usefulness of the rectus sheath block (RSB) in the umbilical hernia repair, the efficacy of the transversus abdominis plane block (TAPB) is rarely reported. The purpose of this study was to compare the efficacy and technique of ultrasound-guided RSB and TAPB in children undergoing umbilical hernia repair. Thirty-four children younger than 12 years of age scheduled for umbilical hernia repair were enrolled in this prospective observer-blinded randomized clinical trial. They were randomly assigned either to RSB group (median age, 3.7 years) or TAPB group (median age, 3.8 years). After the induction of general anesthesia with sevoflurane, nitrous oxide, and oxygen children in both groups received regional anesthesia with 0.3 ml x kg(-1) of 0.25% ropivacaine on each side under ultrasound guidance. Hemodynamic changes at the skin incision, postoperative pain scores and parental satisfaction were recorded. Anesthesiologists rated the quality of ultrasound images and easiness of the block performance. The patients' demographics of the two groups were similar. There were no significant differences in the time needed for the block procedure, quality of ultrasound images and the change of the heart rate and blood pressure at the skin incision between the two groups. Postoperative pain score (immediately, 2 and 4 hours after the operation), need for rescue analgesia and satisfaction of the parents also did not differ. There were no major complications in the patients. TAPB provided comparable perioperative analgesia and easiness of block performance to RSB in the pediatric umbilical hernia repair.

Assessment of exit block following pulmonary vein isolation: far-field capture masquerading as entrance without exit block.

PubMed

Vijayaraman, Pugazhendhi; Dandamudi, Gopi; Naperkowski, Angela; Oren, Jess; Storm, Randle; Ellenbogen, Kenneth A

2012-10-01

Complete electrical isolation of pulmonary veins (PVs) remains the cornerstone of ablation therapy for atrial fibrillation. Entrance block without exit block has been reported to occur in 40% of the patients. Far-field capture (FFC) can occur during pacing from the superior PVs to assess exit block, and this may appear as persistent conduction from PV to left atrium (LA). To facilitate accurate assessment of exit block. Twenty consecutive patients with symptomatic atrial fibrillation referred for ablation were included in the study. Once PV isolation (entrance block) was confirmed, pacing from all the bipoles on the Lasso catheter was used to assess exit block by using a pacing stimulus of 10 mA at 2 ms. Evidence for PV capture without conduction to LA was necessary to prove exit block. If conduction to LA was noticed, pacing output was decreased until there was PV capture without conduction to LA or no PV capture was noted to assess for far-field capture in both the upper PVs. All 20 patients underwent successful isolation (entrance block) of all 76 (4 left common PV) veins: mean age 58 ± 9 years; paroxysmal atrial fibrillation 40%; hypertension 70%, diabetes mellitus 30%, coronary artery disease 15%; left ventricular ejection fraction 55% ± 10%; LA size 42 ± 11 mm. Despite entrance block, exit block was absent in only 16% of the PVs, suggesting persistent PV to LA conduction. FFC of LA appendage was noted in 38% of the left superior PVs. FFC of the superior vena cava was noted in 30% of the right superior PVs. The mean pacing threshold for FFC was 7 ± 4 mA. Decreasing pacing output until only PV capture (loss of FFC) is noted was essential to confirm true exit block. FFC of LA appendage or superior vena cava can masquerade as persistent PV to LA conduction. A careful assessment for PV capture at decreasing pacing output is essential to exclude FFC. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Computer model of cardiovascular control system responses to exercise

NASA Technical Reports Server (NTRS)

Croston, R. C.; Rummel, J. A.; Kay, F. J.

1973-01-01

Approaches of systems analysis and mathematical modeling together with computer simulation techniques are applied to the cardiovascular system in order to simulate dynamic responses of the system to a range of exercise work loads. A block diagram of the circulatory model is presented, taking into account arterial segments, venous segments, arterio-venous circulation branches, and the heart. A cardiovascular control system model is also discussed together with model test results.

Medical Standards for Experimental Human Use in Acceleration Stress Research

DTIC Science & Technology

1983-01-01

or re- teroposterior and lateral X-rays of the cervical , thoracic, sources, we consider a positive treadmill test to be dis- and lumbar spine. These...Gz stress. The requirement for a complete cervical , thoracic and dividuals who developed significant stress dysrhythmias lumbar spine X-ray series...hematoma h. Hernia Ill. Cardiac Stress: a. Dywrhythmla (Tachyarrhythmias and Bradyarrhythmim) b. Heart blocks c. Stress caadlomyopmt U244 Awono. spme

Effects of Social Exclusion on Cardiovascular and Affective Reactivity to a Socially Evaluative Stressor.

PubMed

Williamson, Timothy J; Thomas, KaMala S; Eisenberger, Naomi I; Stanton, Annette L

2018-04-03

Socially disconnected individuals have worse health than those who feel socially connected. The mechanisms through which social disconnection influences physiological and psychological outcomes warrant study. The current study tested whether experimental manipulations of social exclusion, relative to inclusion, influenced subsequent cardiovascular (CV) and affective reactivity to socially evaluative stress. Young adults (N = 81) were assigned through block randomization to experience either social exclusion or inclusion, using a standardized computer-based task (Cyberball). Immediately after exposure to Cyberball, participants either underwent a socially evaluative stressor or an active control task, based on block randomization. Physiological activity (systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)) and state anxiety were assessed throughout the experiment. Excluded participants evidenced a significant increase in cardiovascular and affective responses to a socially evaluative stressor. Included participants who underwent the stressor evidenced similar increases in anxiety, but systolic blood pressure, diastolic blood pressure, and heart rate did not change significantly in response to the stressor. Results contribute to the understanding of physiological consequences of social exclusion. Further investigation is needed to test whether social inclusion can buffer CV stress reactivity, which would carry implications for how positive social factors may protect against the harmful effects of stress.

Cardiovascular effects of substance P receptor stimulation in the ventrolateral medullary pressor and depressor areas.

PubMed

Urbanski, R W; Murugaian, J; Krieger, A J; Sapru, H N

1989-07-10

The pressor (VLPA) and the depressor (VLDA) areas in the ventrolateral medulla were identified with the microinjection of L-glutamate (1.77 nmol/site) in artificially ventilated urethane-anesthetized male Wistar rats. Bilateral microinjection of a stable substance P (SP) agonist [pGlu5, MePhe8, Sar9]-SP(5-11)], abbreviated as DiMe, into the VLPA (6-600 pmol/site) produced a dose-dependent increase in blood pressure (BP). The effects on heart rate (HR) were variable. Intravenous pretreatment with a ganglionic blocker chlorisondamine (3.0 mg/kg, i.v.), but not with a vasopressin antagonist, blocked these responses. Similar microinjection of DiMe (6-600 pmol/site) into the VLDA produced a dose-dependent decrease in HR but had no effect on BP levels. The DiMe-induced bradycardic response elicited from the VLDA was blocked by i.v. pretreatment with atropine methylbromide (0.5 mg/kg, i.v.). These findings indicate that there are SP receptors localized on sympathoexcitatory neurons in the VLPA and that SP may be an excitatory neurotransmitter in this area. In the VLDA, the SP receptors appear to be localized on a subpopulation of neurons that affect vagal, but not sympathetic, outflow to the heart.

Acetylcholine but not adenosine triggers preconditioning through PI3-kinase and a tyrosine kinase.

PubMed

Qin, Qining; Downey, James M; Cohen, Michael V

2003-02-01

Adenosine and acetylcholine (ACh) trigger preconditioning by different signaling pathways. The involvement of phosphatidylinositol 3-kinase (PI3-kinase), a protein tyrosine kinase, and Src family tyrosine kinase in preconditioning was evaluated in isolated rabbit hearts. Either wortmannin (PI3-kinase blocker), genistein (tyrosine kinase blocker), lavendustin A (tyrosine kinase blocker), or 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2; Src family tyrosine kinase blocker) was given for 15 min to bracket a 5-min infusion of either adenosine or ACh (trigger phase). The hearts then underwent 30 min of regional ischemia. Infarct size for ACh alone was 9.3 +/- 3.5% of the risk zone versus 34.3 +/- 4.1% in controls. All four inhibitors blocked ACh-induced protection. When wortmannin or PP2 was infused only during the 30-min ischemic period (mediator phase), ACh-induced protection was not affected (7.4 +/- 2.1% and 9.7 +/- 1.7% infarction, respectively). Adenosine-triggered protection was not blocked by any of the inhibitors. Therefore, PI3-kinase and at least one protein tyrosine kinase, probably Src kinase, are involved in the trigger phase of ACh-induced, but not adenosine-induced, preconditioning. Neither PI3-kinase nor Src kinase is a mediator of the protection of ACh.

Morbidity of Chagas heart disease in the microregion of Rio Negro, Amazonian Brazil: a case-control study

PubMed Central

Coura, José Rodrigues; Viñas, Pedro Albajar; Brum-Soares, Lucia Maria; de Sousa, Andréa Silvestre; Xavier, Sérgio Salles

2013-01-01

A case-control study on the morbidity of Chagas heart disease was carried out in the municipality of Barcelos in the microregion of the Rio Negro, state of Amazonas. One hundred and six individuals, who were serologically positive for Trypanosoma cruzi infection, as confirmed by at least two techniques with different principles, were matched according to age and sex with an equal number of seronegative individuals. The cases and controls were evaluated using an epidemiological questionnaire and clinical, electrocardiograph and echocardiograph examinations. In the seroepidemiological evaluation, 62% of the interviewees recognised triatomines and most of them confirmed that they had seen these insects in the piassava plantations of the riverside communities of the Negro River tributaries. Of the seropositive patients, 25.8% affirmed that they had been stung by the triatomines and 11.7% denied having been stung. The principal clinical manifestations of the seropositive individuals were palpitations, chest pain and dyspnoea upon effort. Cardiac auscultation revealed extrasystoles, bradycardia and systolic murmurs. The electrocardiographic alterations were ventricular extrasystoles, left and right bundle branch block, atrioventricular block and primary T wave alterations. The echocardiogram was altered in 22.6% of the seropositive individuals and in 8.5% of the seronegative individuals. PMID:24402153

Building a comprehensive team for the longitudinal care of single ventricle heart defects: Building blocks and initial results.

PubMed

Texter, Karen; Davis, Jo Ann M; Phelps, Christina; Cheatham, Sharon; Cheatham, John; Galantowicz, Mark; Feltes, Timothy F

2017-07-01

With increasing survival of children with HLHS and other single ventricle lesions, the complexity of medical care for these patients is substantial. Establishing and adhering to best practice models may improve outcome, but requires careful coordination and monitoring. In 2013 our Heart Center began a process to build a comprehensive Single Ventricle Team designed to target these difficult issues. Comprehensive Single Ventricle Team in 2014 was begun, to standardize care for children with single ventricle heart defects from diagnosis to adulthood within our institution. The team is a multidisciplinary group of providers committed to improving outcomes and quality of life for children with single ventricle heart defects, all functioning within the medical home of our heart center. Standards of care were developed and implemented in five target areas to standardize medical management and patient and family support. Under the team 100 patients have been cared for. Since 2014 a decrease in interstage mortality for HLHS were seen. Using a team approach and the tools of Quality Improvement they have been successful in reaching high protocol compliance for each of these areas. This article describes the process of building a successful Single Ventricle team, our initial results, and lessons learned. Additional study is ongoing to demonstrate the effects of these interventions on patient outcomes. © 2017 Wiley Periodicals, Inc.

A dual-input nonlinear system analysis of autonomic modulation of heart rate

NASA Technical Reports Server (NTRS)

Chon, K. H.; Mullen, T. J.; Cohen, R. J.

1996-01-01

Linear analyses of fluctuations in heart rate and other hemodynamic variables have been used to elucidate cardiovascular regulatory mechanisms. The role of nonlinear contributions to fluctuations in hemodynamic variables has not been fully explored. This paper presents a nonlinear system analysis of the effect of fluctuations in instantaneous lung volume (ILV) and arterial blood pressure (ABP) on heart rate (HR) fluctuations. To successfully employ a nonlinear analysis based on the Laguerre expansion technique (LET), we introduce an efficient procedure for broadening the spectral content of the ILV and ABP inputs to the model by adding white noise. Results from computer simulations demonstrate the effectiveness of broadening the spectral band of input signals to obtain consistent and stable kernel estimates with the use of the LET. Without broadening the band of the ILV and ABP inputs, the LET did not provide stable kernel estimates. Moreover, we extend the LET to the case of multiple inputs in order to accommodate the analysis of the combined effect of ILV and ABP effect on heart rate. Analyzes of data based on the second-order Volterra-Wiener model reveal an important contribution of the second-order kernels to the description of the effect of lung volume and arterial blood pressure on heart rate. Furthermore, physiological effects of the autonomic blocking agents propranolol and atropine on changes in the first- and second-order kernels are also discussed.

Cardiac HDAC6 Catalytic Activity is Induced in Response to Chronic Hypertension

PubMed Central

Lemon, Douglas D.; Horn, Todd R.; Cavasin, Maria A.; Jeong, Mark Y.; Haubold, Kurt W.; Long, Carlin S.; Irwin, David C.; McCune, Sylvia A.; Chung, Eunhee; Leinwand, Leslie A.; McKinsey, Timothy A.

2011-01-01

Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models of heart failure. The efficacious compounds target class I, class IIb and, to a lesser extent, class IIa HDACs. It is hypothesized that a selective inhibitor of a specific HDAC class (or an isoform within that class) will provide a favorable therapeutic window for the treatment of heart failure, although the optimal selectivity profile for such a compound remains unknown. Genetic studies have suggested that class I HDACs promote pathological cardiac remodeling, while class IIa HDACs are protective. In contrast, nothing is known about the function or regulation of class IIb HDACs in the heart. We developed assays to quantify catalytic activity of distinct HDAC classes in left and right ventricular cardiac tissue from animal models of hypertensive heart disease. Class I and IIa HDAC activity was elevated in some but not all diseased tissues. In contrast, catalytic activity of the class IIb HDAC, HDAC6, was consistently increased in stressed myocardium, but not in a model of physiologic hypertrophy. HDAC6 catalytic activity was also induced by diverse extracellular stimuli in cultured cardiac myocytes and fibroblasts. These findings suggest an unforeseen role for HDAC6 in the heart, and highlight the need for pre-clinical evaluation of HDAC6-selective inhibitors to determine whether this HDAC isoform is pathological or protective in the setting of cardiovascular disease. PMID:21539845

Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene.

PubMed

Gay, Maresha S; Dasgupta, Chiranjib; Li, Yong; Kanna, Angela; Zhang, Lubo

2016-08-01

Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene

PubMed Central

Gay, Maresha S.; Dasgupta, Chiranjib; Li, Yong; Kanna, Angela

2016-01-01

Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene. PMID:27302109

Does the volume of supplemental intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized-double blind clinical trial.

PubMed

Aggarwal, V; Singla, M; Miglani, S; Kohli, S; Sharma, V; Bhasin, S S

2018-01-01

To investigate the efficacy of 0.2 mL vs. 0.6 mL of 2% lidocaine when given as a supplementary intraligamentary injection after a failed inferior alveolar nerve block (IANB). Ninety-seven adult patients with symptomatic irreversible pulpits received an IANB and root canal treatment was initiated. Pain during treatment was recorded using a visual analogue scale (Heft-Parker VAS). Patients with unsuccessful anaesthesia (n = 78) randomly received intraligamentary injection of either 0.2 mL or 0.6 mL of 2% lidocaine with 1 : 80 000 epinephrine. Root canal treatment was reinitiated. Success after primary injection or supplementary injection was defined as no or mild pain (HP VAS score ≤54 mm) during access preparation and root canal instrumentation. Heart rate was monitored using a finger pulse oximeter. The anaesthetic success rates were analysed with Pearson chi-square test at 5% significance levels. The heart rate changes were analysed using t-tests. The intraligamentary injections with 0.2 mL solution gave an anaesthetic success rate of 64%, whilst the 0.6 mL was successful in 84% of cases with failed primary IANB. (χ 2  = 4.3, P = 0.03). There was no significant effect of the volume of intraligamentary injection on the change in heart rate. Increasing the volume of intraligamentary injection improved the success rates after a failed primary anaesthetic injection. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Mechanism of action of honey bee (Apis mellifera L.) venom on different types of muscles.

PubMed

Nabil, Z I; Hussein, A A; Zalat, S M; Rakha, M Kh

1998-03-01

1. The effect of crude honeybee (Apis mellifera) venom on the skeletal, smooth as well as cardiac muscles were studied in this investigation. 2. Perfusion of gastrocnemius-sciatic nerve preparation of frogs with 1 microgram/ml venom solution has weakened the mechanical contraction of the muscle without recovery. Blocking of nicotinic receptors with 3 micrograms/ml flaxedil before bee venom application sustained normal contraction of gastrocnemius muscle. 3. The electrical activity of duodenum rabbits was recorded before and after the application of 1 microgram/ml venom solution. The venom has depressed the amplitude of the muscle contraction after 15 min pretreatment with atropine nearly abolished the depressor effect of the venom on smooth muscle. 4. In concentrations from 0.5-2 micrograms/ml, bee venom caused decrease of heart rate of isolated perfused toad heart. This bradycardia was accompanied by elongation in the P-R interval. A gradual and progressive increase in the R-wave amplitude reflected a positive inotropism of the venom. Application of 5 micrograms/ml verapamil, a calcium channels blocking agent, abolished the noticed effect of the venom. 5. Marked electrocardiographic changes were produced within minutes of the venom application on the isolated perfused hearts, like marked injury current (elevation or depression of the S-T segment), atrioventricular conduction disturbances and sinus arrhythmias. Atropine and nicotine could decrease the toxic effect of the venom on the myocardium. 6. Results of the present work lead to the suggestion that bee venom is mediated through the peripheral cholinergic neurotransmitter system. General neurotoxicity of an inhibitory nature involving the autonomic as well as neuromuscular system are established as a result of the venom, meanwhile a direct effect on the myocardium membrane stabilization has been suggested.

Ventricular dilation and electrical dyssynchrony synergistically increase regional mechanical nonuniformity but not mechanical dyssynchrony: a computational model.

PubMed

Kerckhoffs, Roy C P; Omens, Jeffrey H; McCulloch, Andrew D; Mulligan, Lawrence J

2010-07-01

Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97+/-0.004, 0.010+/-0.002, and 78+/-1 milliseconds, respectively. With dilation alone, CURE decreased 2.0+/-0.07%, ISF increased 58+/-47%, and WTpeak increased 31+/-3%. With dyssynchronous activation alone, CURE decreased 15+/-0.6%, ISF increased 14-fold (+/-3), and WTpeak increased 121+/-4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23+/-0.8%, ISF increased 20-fold (+/-5), and WTpeak increased 147+/-5%. Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.

Long-term blockade of L/N-type Ca2+ channels by cilnidipine ameliorates repolarization abnormality of the canine hypertrophied heart

PubMed Central

Takahara, A; Nakamura, Y; Wagatsuma, H; Aritomi, S; Nakayama, A; Satoh, Y; Akie, Y; Sugiyama, A

2009-01-01

Background and purpose: The heart of the canine model of chronic atrioventricular block is known to have a ventricular electrical remodelling, which mimics the pathophysiology of long QT syndrome. Using this model, we explored a new pharmacological therapeutic strategy for the prevention of cardiac sudden death. Experimental approach: The L-type Ca2+ channel blocker amlodipine (2.5 mg·day−1), L/N-type Ca2+ channel blocker cilnidipine (5 mg·day−1), or the angiotensin II receptor blocker candesartan (12 mg·day−1) was administered orally to the dogs with chronic atrioventricular block for 4 weeks. Electropharmacological assessments with the monophasic action potential (MAP) recordings and blood sample analyses were performed before and 4 weeks after the start of drug administration. Key results: Amlodipine and cilnidipine decreased the blood pressure, while candesartan hardly affected it. The QT interval, MAP duration and beat-to-beat variability of the ventricular repolarization period were shortened only in the cilnidipine group, but such effects were not observed in the amlodipine or candesartan group. Plasma concentrations of adrenaline, angiotensin II and aldosterone decreased in the cilnidipine group. In contrast, plasma concentrations of angiotensin II and aldosterone were elevated in the amlodipine group, whereas in the candesartan group an increase in plasma levels of angiotensin II and a decrease in noradrenaline and adrenaline concentrations were observed. Conclusions and implications: Long-term blockade of L/N-type Ca2+ channels ameliorated the ventricular electrical remodelling in the hypertrophied heart which causes the prolongation of the QT interval. This could provide a novel therapeutic strategy for the treatment of cardiovascular diseases. PMID:19785655

Making Better Scar: Emerging Approaches for Modifying Mechanical and Electrical Properties Following Infarction and Ablation

PubMed Central

Holmes, Jeffrey W.; Laksman, Zachary; Gepstein, Lior

2015-01-01

Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function – maintaining integrity of the heart wall against enormous mechanical forces – but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches. PMID:26615948

Attentional focus and performance anxiety: effects on simulated race-driving performance and heart rate variability.

PubMed

Mullen, Richard; Faull, Andrea; Jones, Eleri S; Kingston, Kieran

2012-01-01

Previous studies have demonstrated that an external focus can enhance motor learning compared to an internal focus. The benefits of adopting an external focus are attributed to the use of less effortful automatic control processes, while an internal focus relies upon more effort-intensive consciously controlled processes. The aim of this study was to compare the effectiveness of a distal external focus with an internal focus in the acquisition of a simulated driving task and subsequent performance in a competitive condition designed to increase state anxiety. To provide further evidence for the automatic nature of externally controlled movements, the study included heart rate variability (HRV) as an index of mental effort. Sixteen participants completed eight blocks of four laps in either a distal external or internal focus condition, followed by two blocks of four laps in the competitive condition. During acquisition, the performance of both groups improved; however, the distal external focus group outperformed the internal focus group. The poorer performance of the internal focus group was accompanied by a larger reduction in HRV, indicating a greater investment of mental effort. In the competition condition, state anxiety increased, and for both groups, performance improved as a function of the increased anxiety. Increased heart rate and self-reported mental effort accompanied the performance improvement. The distal external focus group also outperformed the internal focus group across both neutral and competitive conditions and this more effective performance was again associated with lower levels of HRV. Overall, the results offer support for the suggestion that an external focus promotes a more automatic mode of functioning. In the competitive condition, both foci enhanced performance and while the improved performance may have been achieved at the expense of greater compensatory mental effort, this was not reflected in HRV scores.

The pacemaker-twiddler's syndrome: an infrequent cause of pacemaker failure.

PubMed

Salahuddin, Mohammad; Cader, Fathima Aaysha; Nasrin, Sahela; Chowdhury, Mashhud Zia

2016-01-20

The pacemaker-twiddler's syndrome is an uncommon cause of pacemaker malfunction. It occurs due to unintentional or deliberate manipulation of the pacemaker pulse generator within its skin pocket by the patient. This causes coiling of the lead and its dislodgement, resulting in failure of ventricular pacing. More commonly reported among elderly females with impaired cognition, the phenomenon usually occurs in the first year following pacemaker implantation. Treatment involves repositioning of the dislodged leads and suture fixation of the lead and pulse generator within its pocket. An 87 year old Bangladeshi lady who underwent a single chamber ventricular pacemaker (VVI mode: i.e. ventricle paced, ventricle sensed, inhibitory mode) implantation with the indication of complete heart block, and presented to us again 7 weeks later, with syncopal attacks. She admitted to repeatedly manipulating the pacemaker generator in her left pectoral region. Physical examination revealed a heart rate of 42 beats/minute, blood pressure 140/80 mmHg and bilateral crackles on lung auscultation. She had no cognitive deficit. An immediate electrocardiogram showed complete heart block with pacemaker spikes and failure to capture. Chest X-ray showed coiled and retracted right ventricular lead and rotated pulse generator. An emergent temporary pace maker was set at a rate of 60 beats per minute. Subsequently, she underwent successful lead repositioning with strong counselling to avoid further twiddling. Twiddler's syndrome should be considered as a cause of pacemaker failure in elderly patients presenting with bradyarrythmias following pacemaker implantation. Chest X-ray and electrocardiograms are simple and easily-available first line investigations for its diagnosis. Lead repositioning is required, however proper patient education and counselling against further manipulation is paramount to long-term management.

Upper thoracic epidural anaesthesia: effects of age on neural blockade and cardiovascular parameters.

PubMed

Wink, J; Wolterbeek, R; Aarts, L P H J; Koster, S C E; Versteegh, M I M; Veering, B T H

2013-07-01

Segmental dose reduction with increasing age after thoracic epidural anaesthesia (TEA) has been documented. We hypothesised that after a fixed loading dose of ropivacaine at the T3-T4 level, increasing age would result in more extended analgesic spread. In addition, other aspects of neural blockade and haemodynamic changes were studied. Thirty-five lung surgery patients were included in three age groups. Thirty-one patients received an epidural catheter at the T3-T4 interspace followed by an injection of 8-ml ropivacaine 0.75%. Analgesia was assessed with pinprick and temperature discrimination. Motor block was tested using the Bromage and epidural scoring scale for arm movements score. An arterial line was inserted for invasive measurement of blood pressure, cardiac index (CI) and stroke volume (SV). There was no influence of age on quality of TEA except for the caudal border of analgesia being somewhat lower in the middle and older age group compared with the young age group. Heart rate (6.0 ± 5.9, P < 0.001), mean arterial pressure (16.1 ± 15.6, P < 0.001), CI (0.55 ± 0.49, P < 0.001) and SV (9.6 ± 14.6, P = 0.001) decreased after TEA for the total group. Maximal reduction in heart rate after TEA was more extensive in the young age group compared with the other age groups. There was no effect of age on other cardiovascular parameters. We were unable to demonstrate an effect of age on the maximal number of spinal segments blocked after TEA; however, the caudad spread of analgesia increased with advancing age. In addition, reduction of heart rate was greater in the youngest group. © 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Epac2-Rap1 Signaling Regulates Reactive Oxygen Species Production and Susceptibility to Cardiac Arrhythmias

PubMed Central

Yang, Zhaokang; Kirton, Hannah M.; Al-Owais, Moza; Thireau, Jérôme; Richard, Sylvain; Peers, Chris

2017-01-01

Abstract Aims: In the heart, β1-adrenergic signaling involves cyclic adenosine monophosphate (cAMP) acting via both protein kinase-A (PKA) and exchange protein directly activated by cAMP (Epac): a guanine nucleotide exchange factor for the small GTPase Rap1. Inhibition of Epac-Rap1 signaling has been proposed as a therapeutic strategy for both cancer and cardiovascular disease. However, previous work suggests that impaired Rap1 signaling may have detrimental effects on cardiac function. The aim of the present study was to investigate the influence of Epac2-Rap1 signaling on the heart using both in vivo and in vitro approaches. Results: Inhibition of Epac2 signaling induced early afterdepolarization arrhythmias in ventricular myocytes. The underlying mechanism involved an increase in mitochondrial reactive oxygen species (ROS) and activation of the late sodium current (INalate). Arrhythmias were blocked by inhibition of INalate or the mitochondria-targeted antioxidant, mitoTEMPO. In vivo, inhibition of Epac2 caused ventricular tachycardia, torsades de pointes, and sudden death. The in vitro and in vivo effects of Epac2 inhibition were mimicked by inhibition of geranylgeranyltransferase-1, which blocks interaction of Rap1 with downstream targets. Innovation: Our findings show for the first time that Rap1 acts as a negative regulator of mitochondrial ROS production in the heart and that impaired Epac2-Rap1 signaling causes arrhythmias due to ROS-dependent activation of INalate. This has implications for the use of chemotherapeutics that target Epac2-Rap1 signaling. However, selective inhibition of INalate provides a promising strategy to prevent arrhythmias caused by impaired Epac2-Rap1 signaling. Conclusion: Epac2-Rap1 signaling attenuates mitochondrial ROS production and reduces myocardial arrhythmia susceptibility. Antioxid. Redox Signal. 27, 117–132. PMID:27649969

Cardiac Fibroblast-Specific Activating Transcription Factor 3 Protects Against Heart Failure by Suppressing MAP2K3-p38 Signaling.

PubMed

Li, Yulin; Li, Zhenya; Zhang, Congcong; Li, Ping; Wu, Yina; Wang, Chunxiao; Bond Lau, Wayne; Ma, Xin-Liang; Du, Jie

2017-05-23

Hypertensive ventricular remodeling is a common cause of heart failure. However, the molecular mechanisms regulating ventricular remodeling remain poorly understood. We used a discovery-driven/nonbiased approach to identify increased activating transcription factor 3 (ATF3) expression in hypertensive heart. We used loss/gain of function approaches to understand the role of ATF3 in heart failure. We also examined the mechanisms through transcriptome, chromatin immunoprecipitation sequencing analysis, and in vivo and in vitro experiments. ATF3 expression increased in murine hypertensive heart and human hypertrophic heart. Cardiac fibroblast cells are the primary cell type expressing high ATF3 levels in response to hypertensive stimuli. ATF3 knockout (ATF3KO) markedly exaggerated hypertensive ventricular remodeling, a state rescued by lentivirus-mediated/miRNA-aided cardiac fibroblast-selective ATF3 overexpression. Conversely, conditional cardiac fibroblast cell-specific ATF3 transgenic overexpression significantly ameliorated ventricular remodeling and heart failure. We identified Map2K3 as a novel ATF3 target. ATF3 binds with the Map2K3 promoter, recruiting HDAC1, resulting in Map2K3 gene-associated histone deacetylation, thereby inhibiting Map2K3 expression. Genetic Map2K3 knockdown rescued the profibrotic/hypertrophic phenotype in ATF3KO cells. Last, we demonstrated that p38 is the downstream molecule of Map2K3 mediating the profibrotic/hypertrophic effects in ATF3KO animals. Inhibition of p38 signaling reduced transforming growth factor-β signaling-related profibrotic and hypertrophic gene expression, and blocked exaggerated cardiac remodeling in ATF3KO cells. Our study provides the first evidence that ATF3 upregulation in cardiac fibroblasts in response to hypertensive stimuli protects the heart by suppressing Map2K3 expression and subsequent p38-transforming growth factor-β signaling. These results suggest that positive modulation of cardiac fibroblast ATF3 may represent a novel therapeutic approach against hypertensive cardiac remodeling. © 2017 American Heart Association, Inc.

Cardiac looping may be driven by compressive loads resulting from unequal growth of the heart and pericardial cavity. Observations on a physical simulation model

PubMed Central

Bayraktar, Meriç; Männer, Jörg

2014-01-01

The transformation of the straight embryonic heart tube into a helically wound loop is named cardiac looping. Such looping is regarded as an essential process in cardiac morphogenesis since it brings the building blocks of the developing heart into an approximation of their definitive topographical relationships. During the past two decades, a large number of genes have been identified which play important roles in cardiac looping. However, how genetic information is physically translated into the dynamic form changes of the looping heart is still poorly understood. The oldest hypothesis of cardiac looping mechanics attributes the form changes of the heart loop (ventral bending → simple helical coiling → complex helical coiling) to compressive loads resulting from growth differences between the heart and the pericardial cavity. In the present study, we have tested the physical plausibility of this hypothesis, which we call the growth-induced buckling hypothesis, for the first time. Using a physical simulation model, we show that growth-induced buckling of a straight elastic rod within the confined space of a hemispherical cavity can generate the same sequence of form changes as observed in the looping embryonic heart. Our simulation experiments have furthermore shown that, under bilaterally symmetric conditions, growth-induced buckling generates left- and right-handed helices (D-/L-loops) in a 1:1 ratio, while even subtle left- or rightward displacements of the caudal end of the elastic rod at the pre-buckling state are sufficient to direct the buckling process toward the generation of only D- or L-loops, respectively. Our data are discussed with respect to observations made in biological “models.” We conclude that compressive loads resulting from unequal growth of the heart and pericardial cavity play important roles in cardiac looping. Asymmetric positioning of the venous heart pole may direct these forces toward a biased generation of D- or L-loops. PMID:24772086

Cocaethylene, a metabolite of cocaine and ethanol, is a potent blocker of cardiac sodium channels.

PubMed

Xu, Y Q; Crumb, W J; Clarkson, C W

1994-10-01

Cocaethylene is an active metabolite of cocaine believed to play a causative role in the increased incidence of sudden death in individuals who coadminister ethanol with cocaine. However, the direct effects of cocaethylene on the heart have not been well defined. In this study, we defined the effects of cocaethylene on the cardiac Na current (INa) in guinea pig ventricular myocytes at 16 degrees C using the whole-cell patch-clamp method. Cocaethylene (10-50 microM) produced both a significant tonic block and a rate-dependent block of INa at cycle lengths between 2 and 0.2 sec. Cocaethylene produced a significantly greater tonic block than cocaine at a concentration of 50 microM and produced a significantly greater use-dependent block over a 5-fold range of drug concentrations (10-50 microM) and cycle lengths (0.2-1.0 sec). Analysis of channel-blocking characteristics revealed that cocaethylene had a significantly higher affinity for inactivated channels (Kdi = 5.1 +/- 0.6 microM, n = 15) compared with cocaine (Kdi = 7.9 +/- 0.5 microM, n = 10) (P < .01) and that cocaethylene produced a significantly greater hyperpolarizing shift of the steady-state INa inactivation curve (P < .05). Cocaethylene also had a significantly longer time constant for recovery from channel block at -140 mV (12.24 +/- 0.88 sec, n = 16) compared with cocaine (8.33 +/- 0.56 sec, n = 14) (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldose reductase modulates acute activation of mesenchymal markers via the β-catenin pathway during cardiac ischemia-reperfusion.

PubMed

Thiagarajan, Devi; O' Shea, Karen; Sreejit, Gopalkrishna; Ananthakrishnan, Radha; Quadri, Nosirudeen; Li, Qing; Schmidt, Ann Marie; Gabbay, Kenneth; Ramasamy, Ravichandran

2017-01-01

Aldose reductase (AR: human, AKR1B1; mouse, AKR1B3), the first enzyme in the polyol pathway, plays a key role in mediating myocardial ischemia/reperfusion (I/R) injury. In earlier studies, using transgenic mice broadly expressing human AKR1B1 to human-relevant levels, mice devoid of Akr1b3, and pharmacological inhibitors of AR, we demonstrated that AR is an important component of myocardial I/R injury and that inhibition of this enzyme protects the heart from I/R injury. In this study, our objective was to investigate if AR modulates the β-catenin pathway and consequent activation of mesenchymal markers during I/R in the heart. To test this premise, we used two different experimental models: in vivo, Akr1b3 null mice and wild type C57BL/6 mice (WT) were exposed to acute occlusion of the left anterior descending coronary artery (LAD) followed by recovery for 48 hours or 28 days, and ex-vivo, WT and Akr1b3 null murine hearts were perfused using the Langendorff technique (LT) and subjected to 30 min of global (zero-flow) ischemia followed by 60 min of reperfusion. Our in vivo results reveal reduced infarct size and improved functional recovery at 48 hours in mice devoid of Akr1b3 compared to WT mice. We demonstrate that the cardioprotection observed in Akr1b3 null mice was linked to acute activation of the β-catenin pathway and consequent activation of mesenchymal markers and genes linked to fibrotic remodeling. The increased activity of the β-catenin pathway at 48 hours of recovery post-LAD was not observed at 28 days post-infarction, thus indicating that the observed increase in β-catenin activity was transient in the mice hearts devoid of Akr1b3. In ex vivo studies, inhibition of β-catenin blocked the cardioprotection observed in Akr1b3 null mice hearts. Taken together, these data indicate that AR suppresses acute activation of β-catenin and, thereby, blocks consequent induction of mesenchymal markers during early reperfusion after myocardial ischemia. Inhibition of AR might provide a therapeutic opportunity to optimize cardiac remodeling after I/R injury.

Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cros, C., E-mail: caroline.cros@hotmail.co.uk; Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com; Moors, J.

Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau ofmore » each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three antiarrhythmics were enhanced. ► Detection of a drug-induced prolongation of QRS was improved at high heart rate.« less

Pulmonary artery closure in combination with patch technique for treating congenital heart disease combined with large patent ductus arteriosus: A clinical study of 9 cases

PubMed Central

Wen, Bing; Yang, Junya; Liu, Huiruo; Jiao, Zhouyang; Zhao, Wenzeng

2016-01-01

Objective: To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. Methods: Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. Results: Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac function of the patients also improved. Conclusion: Hybrid surgery is feasible and safe in treating patients with large patent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications. PMID:27375685

Pulmonary artery closure in combination with patch technique for treating congenital heart disease combined with large patent ductus arteriosus: A clinical study of 9 cases.

PubMed

Wen, Bing; Yang, Junya; Liu, Huiruo; Jiao, Zhouyang; Zhao, Wenzeng

2016-01-01

To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac function of the patients also improved. Hybrid surgery is feasible and safe in treating patients with large patent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications.

Acidosis slows electrical conduction through the atrio-ventricular node

PubMed Central

Nisbet, Ashley M.; Burton, Francis L.; Walker, Nicola L.; Craig, Margaret A.; Cheng, Hongwei; Hancox, Jules C.; Orchard, Clive H.; Smith, Godfrey L.

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis. PMID:25009505

Acidosis slows electrical conduction through the atrio-ventricular node.

PubMed

Nisbet, Ashley M; Burton, Francis L; Walker, Nicola L; Craig, Margaret A; Cheng, Hongwei; Hancox, Jules C; Orchard, Clive H; Smith, Godfrey L

2014-01-01

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis.

A comparison of the chronotropic and dromotropic actions between adenosine triphosphate and edrophonium in patients undergoing coronary artery bypass graft surgery.

PubMed

Watanabe, Seiji; Kono, Yasuo; Oishi-Tobinaga, Yoko; Yamada, Shin-ichi; Hara, Masato; Kano, Tatsuhiko

2002-10-01

To compare the effects of the stimulation of adenosine receptors and acetylcholine receptors in the cardiac conduction system in patients with ischemic heart disease. Prospective. University hospital. Patients scheduled for coronary artery bypass graft surgery (n = 37). The patients were divided into 3 groups: control group (n = 9), adenosine triphosphate (ATP) group (n = 12), and edrophonium group (n = 16). ATP (10 mg) or edrophonium (0.25 mg/kg) followed by saline or the same amount of saline was injected through a central venous catheter. ATP induced atrioventricular block in 10 of 12 patients (83%). The ATP injection produced a more prominent prolongation in the PQ duration (P-R interval) (139%) than in the P-P interval (105%) at the last beat before the development of atrioventricular block. The prolongation in the P-P interval (11%, average 85 msec) and PQ duration during atrioventricular block disappeared immediately after the restoration of atrioventricular conduction. After edrophonium, the maximal prolongation in P-P (118%, p < 0.01) and PQ (120%, p < 0.01) intervals was the same. P-P interval remained prolonged (p < 0.01) after PQ interval returned to baseline. Neither ATP nor edrophonium affected the QRS duration. These findings suggest that ATP predominantly inhibited atrioventricular conduction rather than the firing rate of sinoatrial nodes, and edrophonium inhibited both proportionally even with prolonged inhibitory action on the sinoatrial nodes. An injection of ATP is needed only when a transient cardiac standstill is requested, such as in endovascular grafting surgery. Edrophonium may be used to slow heart rate during coronary artery bypass graft surgery. Copyright 2002, Elsevier Science (USA). All rights reserved.

Mechanism of the cardiovascular effects of the GABAA receptors of the ventral tegmental area of the rat brain.

PubMed

Yeganeh, Fahimeh; Ranjbar, Afsaneh; Hatam, Masoumeh; Nasimi, Ali

2015-07-23

The ventral tegmental area (VTA) contains GABA terminals involved in the regulation of the cardiovascular system. Previously, we demonstrated that blocking GABAA but not GABAB receptors produced a pressor response accompanied by marked bradycardia. This study was performed to find the possible mechanisms involved in these responses by blocking ganglionic nicotinic receptors, peripheral muscarinic receptors or peripheral V1 vasopressin receptors. Experiments were performed on urethane anesthetized male Wistar rats. Drugs were microinjected unilaterally into the VTA (100 nl). The average changes in mean arterial pressure (MAP) and heart rate (HR) were compared between pre- and post-treatment using paired t-test. Injection of bicuculline methiodide (BMI), a GABAA antagonist, into the VTA caused a significant increase in MAP and a decrease in HR. Administration (i.v.) of the nicotinic receptor blocker, hexamethonium, enhanced the pressor response but abolished the bradycardic response to BMI, which ruled out involvement of the sympathetic nervous system. Blockade of the peripheral muscarinic receptors by homatropine (i.v.) abolished the bradycardic effect of BMI, but had no effect on the pressor response, indicating that bradycardia was produced by the parasympathetic outflow to the heart. Both the pressor and bradycardic responses to BMI were blocked by V1 receptor antagonist (i.v.), indicating that administration of BMI in the VTA disinhibited the release of vasopressin into the circulation. In conclusion, we demonstrated that GABAergic mechanism of the VTA exerts a tonic inhibition on vasopressin release through activation of GABAA receptors. The sympathetic system is not involved in the decrease of blood pressure by GABA of the VTA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cardiac rhythm and pacemaking abnormalities in patients affected by endemic pemphigus in Colombia may be the result of deposition of autoantibodies, complement, fibrinogen, and other molecules.

PubMed

Abreu Velez, Ana Maria; Howard, Michael S; Velazquez-Velez, Jorge Enrique

2018-05-01

We previously showed that one-third of patients affected by endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF), display autoreactivity to the heart. The purpose of this study was to investigate rhythm disturbances with the presence of autoantibodies and correlate them with ECG changes in these patients. We performed a study comparing 30 patients and 30 controls from the endemic area, matched by demographics, including age, sex, weight, work activities, and comorbidities. ECG as well as direct and indirect immunofluorescence, immunohistochemistry, and confocal microscopic studies focusing on cardiac node abnormalities were performed. Autopsies of 7 patients also were reviewed. The main ECG abnormalities seen in the El Bagre-EPF patients were sinus bradycardia (in one-half), followed by left bundle branch block, left posterior fascicular block, and left anterior fascicular block compared with the controls. One-third of the patients displayed polyclonal autoantibodies against the sinoatrial and/or AV nodes and the His bundle correlating with rhythm anomalies and delays in the cardiac conduction system (P <.01). The patient antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and myocardium-enriched zonula occludens-1-associated protein (MYZAP; Progen Biotechnik) (P <.01). One-third of the patients affected by El Bagre-EPF have rhythm abnormalities that slow the conduction of impulses in cardiac nodes and the cardiac conduction system. These abnormalities likely occur as a result of deposition of autoantibodies, complement, and other inflammatory molecules. We show for the first time that MYZAP is present in cardiac nodes. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Maternal and anaesthesia-related risk factors and incidence of spinal anaesthesia-induced hypotension in elective caesarean section: A multinomial logistic regression

PubMed Central

Fakherpour, Atousa; Ghaem, Haleh; Fattahi, Zeinabsadat; Zaree, Samaneh

2018-01-01

Background and Aims: Although spinal anaesthesia (SA) is nowadays the preferred anaesthesia technique for caesarean section (CS), it is associated with considerable haemodynamic effects, such as maternal hypotension. This study aimed to evaluate a wide range of variables (related to parturient and anaesthesia techniques) associated with the incidence of different degrees of SA-induced hypotension during elective CS. Methods: This prospective study was conducted on 511 mother–infant pairs, in which the mother underwent elective CS under SA. The data were collected through preset proforma containing three parts related to the parturient, anaesthetic techniques and a table for recording maternal blood pressure. It was hypothesized that some maternal (such as age) and anaesthesia-related risk factors (such as block height) were associated with occurance of SA-induced hypotension during elective CS. Results: The incidence of mild, moderate and severe hypotension was 20%, 35% and 40%, respectively. Eventually, ten risk factors were found to be associated with hypotension, including age >35 years, body mass index ≥25 kg/m2, 11–20 kg weight gain, gravidity ≥4, history of hypotension, baseline systolic blood pressure (SBP) <120 mmHg and baseline heart rate >100 beats/min in maternal modelling, fluid preloading ≥1000 ml, adding sufentanil to bupivacaine and sensory block height >T4in anaesthesia-related modelling (P < 0.05). Conclusion: Age, body mass index, weight gain, gravidity, history of hypotension, baseline SBP and heart rate, fluid preloading, adding sufentanil to bupivacaine and sensory block hieght were the main risk factors identified in the study for SA-induced hypotension during CS. PMID:29416149

Implant of permanent pacemaker during acute coronary syndrome: Mortality and associated factors in the ARIAM registry.

PubMed

Pola-Gallego-de-Guzmán, María Dolores; Ruiz-Bailén, Manuel; Martínez-Arcos, Maria-Angeles; Gómez-Blizniak, Artur; Castillo Rivera, Ana-Maria; Molinos, Jesus Cobo

2018-04-01

Patients with acute coronary syndrome complicated with high degree atrioventricular block still have a high mortality. A low percentage of these patients need a permanent pacemaker (PPM) but mortality and associated factors with the PPM implant in acute coronary syndrome patients are not known. We assess whether PPM implant is an independent variable in the mortality of acute coronary syndrome patients. Also, we explored the variables that remain independently associated with PPM implantation. This was an observational study on the Spanish ARIAM register. The inclusion period was from January 2001 to December 2011. This registry included all Andalusian acute coronary syndrome patients. Follow-up for global mortality was until November 2013. We selected 27,608 cases. In 62 patients a PPM was implanted (0.024%). The mean age in PPM patients was 70.71±11.214 years versus 64.46±12.985 years in patients with no PPM. PPM implant was associated independently with age (odds ratio (OR) 1.031, 95% confidence interval (CI) 1.007-1.055), with left ventricular branch block (OR 6.622, 95% CI 2.439-18.181), with any arrhythmia at intensive care unit admission (OR 2.754, 95% CI 1.506-5.025) and with heart failure (OR 3.344, 95% CI 1.78-8.333). PPM implant was independently associated with mortality (OR 11.436, 95% CI 1.576-83.009). In propensity score analysis PPM implant was still associated with mortality (OR 5.79, 95% CI 3.27-25.63). PPM implant is associated with mortality in the acute coronary syndrome population in the ARIAM registry. Advanced age, heart failure, arrhythmias and left ventricular branch block at intensive care unit admission were found associated factors with PPM implant in acute coronary syndrome patient.

Developing New Treatments for Heart Failure: Focus on the Heart.

PubMed

Gheorghiade, Mihai; Larson, Christopher J; Shah, Sanjiv J; Greene, Stephen J; Cleland, John G F; Colucci, Wilson S; Dunnmon, Preston; Epstein, Stephen E; Kim, Raymond J; Parsey, Ramin V; Stockbridge, Norman; Carr, James; Dinh, Wilfried; Krahn, Thomas; Kramer, Frank; Wahlander, Karin; Deckelbaum, Lawrence I; Crandall, David; Okada, Shunichiro; Senni, Michele; Sikora, Sergey; Sabbah, Hani N; Butler, Javed

2016-05-01

Compared with heart failure (HF) care 20 to 30 years ago, there has been tremendous advancement in therapy for ambulatory HF with reduced ejection fraction with the use of agents that block maladaptive neurohormonal pathways. However, during the past decade, with few notable exceptions, the frequency of successful drug development programs has fallen as most novel therapies have failed to offer incremental benefit or raised safety concerns (ie, hypotension). Moreover, no therapy has been approved specifically for HF with preserved ejection fraction or for worsening chronic HF (including acutely decompensated HF). Across the spectrum of HF, preliminary results from many phase II trials have been promising but are frequently followed by unsuccessful phase III studies, highlighting a disconnect in the translational process between basic science discovery, early drug development, and definitive clinical testing in pivotal trials. A major unmet need in HF drug development is the ability to identify homogeneous subsets of patients whose underlying disease is driven by a specific mechanism that can be targeted using a new therapeutic agent. Drug development strategies should increasingly consider therapies that facilitate reverse remodeling by directly targeting the heart itself rather than strictly focusing on agents that unload the heart or target systemic neurohormones. Advancements in cardiac imaging may allow for more focused and direct assessment of drug effects on the heart early in the drug development process. To better understand and address the array of challenges facing current HF drug development, so that future efforts may have a better chance for success, the Food and Drug Administration facilitated a meeting on February 17, 2015, which was attended by clinicians, researchers, regulators, and industry representatives. The following discussion summarizes the key takeaway dialogue from this meeting. © 2016 American Heart Association, Inc.

Modelling the interaction among several mechanisms in the short-term arterial pressure control.

PubMed

Ursino, M

2000-01-01

A Mathematical model of the short-term arterial pressure control in humans is presented. It includes a six-compartment description of the vascular system, an elastance variable model of the pulsating heart, two groups of baroreceptors (high-pressure or sinoaortic baroreceptors and low-pressure or cardiopulmonary baroreceptors), the efferent activity in the sympathetic nerves and in the vagus, and the response of four distinct effectors (heart period, systemic peripheral resistance, systemic venous unstressed volume and heart contractility). Several experimental results reported in the physiological literature can be reproduced with the model quite well. The examples presented in this work include the effect of combined sympathetic and vagal stimulation on heart rate, the baroreflex response to mild and severe acute haemorrhages, and the baroreflex response to ventricular pacing at different rates performed during atrioventricular block. The results suggest that: i) The sympathetic nerves and the vagus interact linearly in regulating heart period. The apparent negative interaction observed experimentally can be ascribed merely to the hyperbolic relationship which links heart rate to heart period. ii) The cardiopulmonary baroafferents play a significant role in the control of systemic arterial pressure during mild haemorrhages (lower than 3-4% of the overall blood volume). In this range, they may allow arterial pressure to be maintained at its normal level without the intervention of the sinoaortic baroreceptors. In contrast, the sinoaortic baroreceptors become the major responsible of the observed cardiovascular adjustments during more severe haemorrhages, when the role of cardiopulmonary baroreceptors becomes progressively exhausted. iii) The stability margin of the closed-loop system is quite low. Increasing the static gain of the baroreceptors or reducing the rate-dependent component may result in self-sustained oscillations similar to Mayer waves.

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits.

PubMed

Li, Yun-Wei; Li, Yan-Ming; Hon, Yan; Wan, Qi-Lin; He, Rui-Li; Wang, Zhi-Zhong; Zhao, Cui-Hua

2017-03-01

Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N 5 -(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.

Low proarrhythmic potential of citalopram and escitalopram in contrast to haloperidol in an experimental whole-heart model.

PubMed

Frommeyer, Gerrit; Brücher, Benedict; von der Ahe, Henning; Kaese, Sven; Dechering, Dirk G; Kochhäuser, Simon; Bogossian, Harilaos; Milberg, Peter; Eckardt, Lars

2016-10-05

In several case reports proarrhythmic effects of citalopram and escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available. The aim of the present study was to investigate if application of citalopram, escitalopram or haloperidol provokes polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of citalopram (2µM: +47ms, 4µM: +56ms, P<0.05) accompanied by an increase of action potential duration (APD) but not dispersion of repolarization. Reduced potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EAD) in 2 of 12 hearts but no polymorphic ventricular tachycardia (pVT). Application of escitalopram also increased QT-interval (2µM: +3ms, 4µM: +30ms, P<0.05) and APD without effects on dispersion. 3 of 10 hearts showed EAD and pVT in 2 of 10 hearts (32 episodes). The results were compared to 12 rabbits treated with haloperidol which led to an increase in QT-interval (1µM:+62ms; 2µM:+96ms; P<0.01), APD and dispersion (1µM:+15ms, 2µM:+40ms; P<0.01) and induced EAD in all 12 and pVT in 10 of 12 hearts (152 episodes). Citalopram and escitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast, haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of citalopram or escitalopram. These results imply that application of citalopram or escitalopram is not as proarrhythmic as some case reports might suggest while haloperidol is torsadogenic. Copyright © 2016 Elsevier B.V. All rights reserved.

The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model.

PubMed

Dare, Anna J; Logan, Angela; Prime, Tracy A; Rogatti, Sebastian; Goddard, Martin; Bolton, Eleanor M; Bradley, J Andrew; Pettigrew, Gavin J; Murphy, Michael P; Saeb-Parsy, Kourosh

2015-11-01

Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model. Hearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non-anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating score, and inflammatory markers 120 minutes or 24 hours post-transplant. MitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondrial DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient. IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

PubMed Central

Irion, Camila Iansen; Paredes, Bruno Diaz; Brasil, Guilherme Visconde; da Cunha, Sandro Torrentes; Paula, Luis Felipe; Carvalho, Alysson Roncally; de Carvalho, Antonio Carlos Campos; Carvalho, Adriana Bastos; Goldenberg, Regina Coeli dos Santos

2017-01-01

BACKGROUND Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. OBJECTIVES The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. METHODS To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. MAIN CONCLUSIONS iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice. PMID:28767980

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits

PubMed Central

Li, Yun-Wei; Hon, Yan; Wan, Qi-Lin; He, Rui-Li; Wang, Zhi-Zhong; Zhao, Cui-Hua

2017-01-01

Background and Objectives Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. Materials and Methods HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. Results Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N5-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). Conclusion Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC. PMID:28382073

Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease.

PubMed

Irion, Camila Iansen; Paredes, Bruno Diaz; Brasil, Guilherme Visconde; Cunha, Sandro Torrentes da; Paula, Luis Felipe; Carvalho, Alysson Roncally; Carvalho, Antonio Carlos Campos de; Carvalho, Adriana Bastos; Goldenberg, Regina Coeli Dos Santos

2017-08-01

Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.

Cardiac resynchronisation therapy in the presence of left-to-right intracardiac shunting: more good than harm?

PubMed

Kyu, Kyu; Seow, Swee Chong; Wong, Raymond; Kojodjojo, Pipin

2016-03-17

An elderly Chinese man with moderately impaired left ventricular function, left bundle branch block and ST-elevation myocardial infarction complicated by ventricular septal rupture had class IV heart failure symptoms refractory to medical and surgical interventions. As a treatment of last resort, a cardiac resynchronisation therapy (CRT) pacemaker was implanted apprehensively, as preoperative concerns were raised whether CRT could exacerbate left-to-right shunting, hence negating the potential benefits of CRT. Introduction of CRT significantly improved the patient's haemodynamic status and symptoms, allowing for successful discharge home. To the best of our knowledge, this is the first report of a patient with severely symptomatic acute heart failure, widened QRS and active left-to-right intracardiac shunting, treated successfully with CRT. 2016 BMJ Publishing Group Ltd.

Using the negative exponential distribution to quantitatively review the evidence on how rapidly the excess risk of ischaemic heart disease declines following quitting smoking.

PubMed

Lee, Peter N; Fry, John S; Hamling, Jan S

2012-10-01

No previous review has formally modelled the decline in IHD risk following quitting smoking. From PubMed searches and other sources we identified 15 prospective and eight case-control studies that compared IHD risk in current smokers, never smokers, and quitters by time period of quit, some studies providing separate blocks of results by sex, age or amount smoked. For each of 41 independent blocks, we estimated, using the negative exponential model, the time, H, when the excess risk reduced to half that caused by smoking. Goodness-of-fit to the model was adequate for 35 blocks, others showing a non-monotonic pattern of decline following quitting, with a variable pattern of misfit. After omitting one block with a current smoker RR 1.0, the combined H estimate was 4.40 (95% CI 3.26-5.95) years. There was considerable heterogeneity, H being <2years for 10 blocks and >10years for 12. H increased (p<0.001) with mean age at study start, but not clearly with other factors. Sensitivity analyses allowing for reverse causation, or varying assumed midpoint times for the final open-ended quitting period little affected goodness-of-fit of the combined estimate. The US Surgeon-General's view that excess risk approximately halves after a year's abstinence seems over-optimistic. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of the anaesthetic efficacy of and heart rate changes after periodontal ligament or intraosseous X-Tip injection in mandibular molars: a randomized controlled clinical trial.

PubMed

Zarei, M; Ghoddusi, J; Sharifi, E; Forghani, M; Afkhami, F; Marouzi, Parviz

2012-10-01

To compare the efficacy of supplemental anaesthesia using periodontal ligament injections (PDL) and intraosseous injections with the X-Tip system in terms of the measured heart rate and patient reported pain level. In this single-blind randomized clinical trial, 40 patients (22 women, 18 men) with irreversible pulpitis who had experienced unsuccessful pain management by inferior alveolar nerve block with 2% lidocaine and 1 : 100 000 epinephrine were selected. Patients were divided equally and randomly into two groups. Supplementary anaesthesia was provided through intraosseous injection with the X-Tip system (X-Tip group) or by PDL injection (PDL group). After each step of injection, pain severity was assessed using a visual analogue scale. Patient heart rate was recorded with a pulse oximeter. Data were coded and analysed using Mann-Whitney U-test with SPSS (version 16) software. Anaesthetic success was obtained in 100% of X-Tip and 70% of PDL group patients after the first supplemental injection. Compared with the first PDL injection, the first intraosseous injection resulted in a significant increase in heart rate (P = 0.001); however, this increase was short-lived (mean increase: 9-10 beats per min). No significant difference in heart rate or anaesthesia success was observed between men and women. Intraosseous injection using the X-Tip system was more effective than PDL injection as a supplementary anaesthetic for pulpectomy in mandibular molars or second premolars. However, the former resulted in a transient increase in heart rate. © 2012 International Endodontic Journal.

Cardio-protective signalling by glyceryl trinitrate and cariporide in a model of donor heart preservation.

PubMed

Kwan, Jair C; Gao, Ling; Macdonald, Peter S; Hicks, Mark

2015-03-01

Storage of donor hearts in cardioplegic solutions supplemented with agents that mimic the ischaemic preconditioning response enhanced their post-reperfusion function. The present study examines the minimisation of cell death and activation of pro-survival signalling directed towards maintenance of mitochondrial homeostasis in hearts arrested and stored in two such agents, glyceryl-trinitrate, a nitric oxide donor and cariporide, (a sodium-hydrogen exchange inhibitor). After baseline functional measurement, isolated working rat hearts were arrested and stored for 6h at 4°C in either Celsior(®), Celsior(®) containing 0.1mg/ml glyceryl-trinitrate, 10μM cariporide or both agents. After reperfusion, function was remeasured. Hearts were then processed for immunoblotting or histology. Necrotic and apoptotic markers present in the Celsior(®) group post-reperfusion were abolished by glyceryl-trinitrate, cariporide or both. Increased phosphorylation of ERK and Bcl2, after reperfusion in groups stored in glyceryl-trinitrate, cariporide or both along with increased phospho-STAT3 levels in the glyceryl-trinitrate/cariporide group correlated with functional recovery. Inhibition of STAT3 phosphorylation blocked recovery. No phospho-Akt increase was seen in any treatment. Activation of signalling pathways that favour mitophagy activation (ERK and Bcl2 phosphorylation) and maintenance of mitochondrial transition pore closure after reperfusion (STAT3 and ERK phosphorylation) were crucial for functional recovery of the donor heart. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases.

PubMed

Dinarello, Charles A; Simon, Anna; van der Meer, Jos W M

2012-08-01

Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function. This approach can therefore be effective in treating common conditions such as post-infarction heart failure, and trials targeting a broad spectrum of new indications are underway. So far, three IL-1-targeted agents have been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor rilonacept and the neutralizing monoclonal anti-IL-1β antibody canakinumab. In addition, a monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α antibody are in clinical trials.

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

PubMed Central

Ghazi, Lama; Drawz, Paul

2017-01-01

The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice. PMID:28413612

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy.

PubMed

Ghazi, Lama; Drawz, Paul

2017-01-01

The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice.

A Clinical and Follow-up Study of Right and Left Bundle Branch Block

DTIC Science & Technology

1974-09-03

atrial septal defects, one with a patent dnctus arteriosns. and one with coarctation of the aorta and aortic stenosis ), one case of rheumatic heart...disease with mild mitral and aortic insufficiency, one case of documented myocarditis, and two cases of nonrheumatic hemodynamiially in- Tuhle 3 .Si...f,’r(»i/() Aniiltjsi\\ of Clinical Evahtotion in EliliB Stihjcrts significant mitral insufficiency. Since some of the ECG subgroups

Compact Receiver Front Ends for Submillimeter-Wave Applications

NASA Technical Reports Server (NTRS)

Mehdi, Imran; Chattopadhyay, Goutam; Schlecht, Erich T.; Lin, Robert H.; Sin, Seth; Peralta, Alejandro; Lee, Choonsup; Gill, John J.; Gulkis, Samuel; Thomas, Bertrand C.

2012-01-01

The current generation of submillimeter-wave instruments is relatively mass and power-hungry. The receiver front ends (RFEs) of a submillimeter instrument form the heart of the instrument, and any mass reduction achieved in this subsystem is propagated through the instrument. In the current implementation, the RFE consists of different blocks for the mixer and LO circuits. The motivation for this work is to reduce the mass of the RFE by integrating the mixer and LO circuits in one waveguide block. The mixer and its associated LO chips will all be packaged in a single waveguide package. This will reduce the mass of the RFE and also provide a number of other advantages. By bringing the mixer and LO circuits close together, losses in the waveguide will be reduced. Moreover, the compact nature of the block will allow for better thermal control of the block, which is important in order to reduce gain fluctuations. A single waveguide block with a 600- GHz RFE functionality (based on a subharmonically pumped Schottky diode pair) has been demonstrated. The block is about 3x3x3 cubic centimeters. The block combines the mixer and multiplier chip in a single package. 3D electromagnetic simulations were carried out to design the waveguide circuit around the mixer and multiplier chip. The circuit is optimized to provide maximum output power and maximum bandwidth. An integrated submillimeter front end featuring a 520-600-GHz sub-harmonic mixer and a 260-300-GHz frequency tripler in a single cavity was tested. Both devices used GaAs MMIC membrane planar Schottky diode technology. The sub-harmonic mixer/tripler circuit has been tested using conventional metal-machined blocks. Measurement results on the metal block give best DSB (double sideband) mixer noise temperature of 2,360 K and conversion losses of 7.7 dB at 520 GHz. The LO input power required to pump the integrated tripler/sub-harmonic mixer is between 30 and 50 mW.

Evidence of reversible bradycardia and arrhythmias caused by immunogenic proteins secreted by T. cruzi in isolated rat hearts.

PubMed

Rodríguez-Angulo, Héctor O; Toro-Mendoza, Jhoan; Marques, Juan A; Concepción, Juan L; Bonfante-Cabarcas, Rafael; Higuerey, Yoliver; Thomas, Luz E; Balzano-Nogueira, Leandro; López, José R; Mijares, Alfredo

2015-02-01

Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.

Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts

PubMed Central

Rodríguez-Angulo, Héctor O.; Toro-Mendoza, Jhoan; Marques, Juan A.; Concepción, Juan L.; Bonfante-Cabarcas, Rafael; Higuerey, Yoliver; Thomas, Luz E.; Balzano-Nogueira, Leandro; López, José R.; Mijares, Alfredo

2015-01-01

Rationale Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. Objective The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. Methods and Results We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. Conclusions These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients. PMID:25647069

Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity.

PubMed Central

O'Malley, K; Velasco, M; Wells, J; McNay, J L

1975-01-01

A study was made of the possible mechanism(s) underlying minoxidil-induced increase in plasma renin activity (PRA). 10 patients with essential hypertension were treated with minoxidil and subsequently with a combination of minoxidil plus propranolol. Minoxidil lowered mean arterial pressure 31.6 plus or minus 3.3 mm Hg, mean plus or minus SEM. There was an associated increase in both PRA, 6.26 plus or minus 2.43 NG/ML/H, and heart rate, 21.4 plus or minus 2.7 beats/min. The changes in PRA and heart rate were positively correlated, r, 0.79. Addition of propranolol reduced mean arterial pressure by a further 10.1 plus or minus 1.5 mm Hg and returned heart rate to control levels. Propranolol reduced PRA significantly but not to control levels. Control PRA positively correlated with PRA on minoxidil, r, 0.97, and with PRA on minoxidil plus propranolol, r, 0.98. We conclude that control PRA is a major determinant of change in PRA with minoxidil. Minoxidil increased PRA by at least two mechanisms: (a) an adrenergic mechanism closely related to change in heart rate and blocked by propranolol, and (b) a mechanism(s) not sensitive to propranolol and possibly related to decrease in renal perfusion pressure. PMID:1127099

Inhibition of the reverse mode of the Na+/Ca2+ exchange by KB-R7943 augments arrhythmogenicity in the canine heart during rapid heart rates.

PubMed

Shinada, Takuro; Hirayama, Yoshiyuki; Maruyama, Mitsunori; Ohara, Toshihiko; Yashima, Masaaki; Kobayashi, Yoshinori; Atarashi, Hirotsugu; Takano, Teruo

2005-07-01

To test the hypothesis that the reverse mode of the Na+/Ca2+ exchange augmented by a rapid heart rate has an antiarrhythmic effect by shortening the action potential duration, we examined the effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), a selective inhibitor of the reverse mode of the Na+/Ca2+ exchange, to attenuate this effect. We recorded the electrocardiogram, monophasic action potential (MAP), and left ventricular pressure in canine beating hearts. In comparison to the control, KB-R7943 significantly increased the QTc value and MAP duration. MAP alternans and left ventricular pressure alternans were observed after changing the cycle length to 300 milliseconds in the control studies. KB-R7943 magnified both types of alternans and produced spatially discordant alternans between right and left ventricles. Early after-depolarizations and nonsustained ventricular tachycardia occurred in the presence of KB-R7943. Our data suggest that the reverse mode of the Na+/Ca2+ exchange may contribute to suppression of arrhythmias by abbreviating action potential duration under pathophysiological conditions. This conclusion is based on further confirmation by future studies of the specificity of KB-R7943 for block of the reverse mode of the Na+/Ca2+ exchange.

Association of cardiac implantable electronic devices with survival in bifascicular block and prolonged PR interval on electrocardiogram.

PubMed

Moulki, Naeem; Kealhofer, Jessica V; Benditt, David G; Gravely, Amy; Vakil, Kairav; Garcia, Santiago; Adabag, Selcuk

2018-06-16

Bifascicular block and prolonged PR interval on the electrocardiogram (ECG) have been associated with complete heart block and sudden cardiac death. We sought to determine if cardiac implantable electronic devices (CIED) improve survival in these patients. We assessed survival in relation to CIED status among 636 consecutive patients with bifascicular block and prolonged PR interval on the ECG. In survival analyses, CIED was considered as a time-varying covariate. Average age was 76 ± 9 years, and 99% of the patients were men. A total of 167 (26%) underwent CIED (127 pacemaker only) implantation at baseline (n = 23) or during follow-up (n = 144). During 5.4 ± 3.8 years of follow-up, 83 (13%) patients developed complete or high-degree atrioventricular block and 375 (59%) died. Patients with a CIED had a longer survival compared to those without a CIED in the traditional, static analysis (log-rank p < 0.0001) but not when CIED was considered as a time-varying covariate (log-rank p = 0.76). In the multivariable model, patients with a CIED had a 34% lower risk of death (hazard ratio 0.66, 95% confidence interval 0.52-0.83; p = 0.001) than those without CIED in the traditional analysis but not in the time-varying covariate analysis (hazard ratio 1.05, 95% confidence interval 0.79-1.38; p = 0.76). Results did not change in the subgroup with a pacemaker only. Bifascicular block and prolonged PR interval on ECG are associated with a high incidence of complete atrioventricular block and mortality. However, CIED implantation does not have a significant influence on survival when time-varying nature of CIED implantation is considered.

Real alerts and artifact classification in archived multi-signal vital sign monitoring data: implications for mining big data.

PubMed

Hravnak, Marilyn; Chen, Lujie; Dubrawski, Artur; Bose, Eliezer; Clermont, Gilles; Pinsky, Michael R

2016-12-01

Huge hospital information system databases can be mined for knowledge discovery and decision support, but artifact in stored non-invasive vital sign (VS) high-frequency data streams limits its use. We used machine-learning (ML) algorithms trained on expert-labeled VS data streams to automatically classify VS alerts as real or artifact, thereby "cleaning" such data for future modeling. 634 admissions to a step-down unit had recorded continuous noninvasive VS monitoring data [heart rate (HR), respiratory rate (RR), peripheral arterial oxygen saturation (SpO 2 ) at 1/20 Hz, and noninvasive oscillometric blood pressure (BP)]. Time data were across stability thresholds defined VS event epochs. Data were divided Block 1 as the ML training/cross-validation set and Block 2 the test set. Expert clinicians annotated Block 1 events as perceived real or artifact. After feature extraction, ML algorithms were trained to create and validate models automatically classifying events as real or artifact. The models were then tested on Block 2. Block 1 yielded 812 VS events, with 214 (26 %) judged by experts as artifact (RR 43 %, SpO 2 40 %, BP 15 %, HR 2 %). ML algorithms applied to the Block 1 training/cross-validation set (tenfold cross-validation) gave area under the curve (AUC) scores of 0.97 RR, 0.91 BP and 0.76 SpO 2 . Performance when applied to Block 2 test data was AUC 0.94 RR, 0.84 BP and 0.72 SpO 2 . ML-defined algorithms applied to archived multi-signal continuous VS monitoring data allowed accurate automated classification of VS alerts as real or artifact, and could support data mining for future model building.

Real Alerts and Artifact Classification in Archived Multi-signal Vital Sign Monitoring Data—Implications for Mining Big Data — Implications for Mining Big Data

PubMed Central

Hravnak, Marilyn; Chen, Lujie; Dubrawski, Artur; Bose, Eliezer; Clermont, Gilles; Pinsky, Michael R.

2015-01-01

PURPOSE Huge hospital information system databases can be mined for knowledge discovery and decision support, but artifact in stored non-invasive vital sign (VS) high-frequency data streams limits its use. We used machine-learning (ML) algorithms trained on expert-labeled VS data streams to automatically classify VS alerts as real or artifact, thereby “cleaning” such data for future modeling. METHODS 634 admissions to a step-down unit had recorded continuous noninvasive VS monitoring data (heart rate [HR], respiratory rate [RR], peripheral arterial oxygen saturation [SpO2] at 1/20Hz., and noninvasive oscillometric blood pressure [BP]) Time data were across stability thresholds defined VS event epochs. Data were divided Block 1 as the ML training/cross-validation set and Block 2 the test set. Expert clinicians annotated Block 1 events as perceived real or artifact. After feature extraction, ML algorithms were trained to create and validate models automatically classifying events as real or artifact. The models were then tested on Block 2. RESULTS Block 1 yielded 812 VS events, with 214 (26%) judged by experts as artifact (RR 43%, SpO2 40%, BP 15%, HR 2%). ML algorithms applied to the Block 1 training/cross-validation set (10-fold cross-validation) gave area under the curve (AUC) scores of 0.97 RR, 0.91 BP and 0.76 SpO2. Performance when applied to Block 2 test data was AUC 0.94 RR, 0.84 BP and 0.72 SpO2). CONCLUSIONS ML-defined algorithms applied to archived multi-signal continuous VS monitoring data allowed accurate automated classification of VS alerts as real or artifact, and could support data mining for future model building. PMID:26438655

Automated detection of heart ailments from 12-lead ECG using complex wavelet sub-band bi-spectrum features.

PubMed

Tripathy, Rajesh Kumar; Dandapat, Samarendra

2017-04-01

The complex wavelet sub-band bi-spectrum (CWSB) features are proposed for detection and classification of myocardial infarction (MI), heart muscle disease (HMD) and bundle branch block (BBB) from 12-lead ECG. The dual tree CW transform of 12-lead ECG produces CW coefficients at different sub-bands. The higher-order CW analysis is used for evaluation of CWSB. The mean of the absolute value of CWSB, and the number of negative phase angle and the number of positive phase angle features from the phase of CWSB of 12-lead ECG are evaluated. Extreme learning machine and support vector machine (SVM) classifiers are used to evaluate the performance of CWSB features. Experimental results show that the proposed CWSB features of 12-lead ECG and the SVM classifier are successful for classification of various heart pathologies. The individual accuracy values for MI, HMD and BBB classes are obtained as 98.37, 97.39 and 96.40%, respectively, using SVM classifier and radial basis function kernel function. A comparison has also been made with existing 12-lead ECG-based cardiac disease detection techniques.

GSK3- and PRMT-1–dependent modifications of desmoplakin control desmoplakin–cytoskeleton dynamics

PubMed Central

Albrecht, Lauren V.; Zhang, Lichao; Shabanowitz, Jeffrey; Purevjav, Enkhsaikhan; Towbin, Jeffrey A.; Hunt, Donald F.

2015-01-01

Intermediate filament (IF) attachment to intercellular junctions is required for skin and heart integrity, but how the strength and dynamics of this attachment are modulated during normal and pathological remodeling is poorly understood. We show that glycogen synthase kinase 3 (GSK3) and protein arginine methyltransferase 1 (PRMT-1) cooperate to orchestrate a series of posttranslational modifications on the IF-anchoring protein desmoplakin (DP) that play an essential role in coordinating cytoskeletal dynamics and cellular adhesion. Front-end electron transfer dissociation mass spectrometry analyses of DP revealed six novel serine phosphorylation sites dependent on GSK3 signaling and four novel arginine methylation sites including R2834, the mutation of which has been associated with arrhythmogenic cardiomyopathy (AC). Inhibition of GSK3 or PRMT-1 or overexpression of the AC-associated mutant R2834H enhanced DP–IF associations and delayed junction assembly. R2834H blocked the GSK3 phosphorylation cascade and reduced DP–GSK3 interactions in cultured keratinocytes and in the hearts of transgenic R2834H DP mice. Interference with this regulatory machinery may contribute to skin and heart diseases. PMID:25733715

Cardiac metabolism in the Myxinidae: physiological and phylogenetic considerations.

PubMed

Sidell, B D

1983-01-01

Cardiac muscle hearts of Atlantic hagfish continuously function under hypoxic conditions that would lead to cardiac failure in most other vertebrates. Contractile performance of hagfish systemic hearts is resistant to anoxia and respiratory poisons but shows a significant decrement when carbohydrate catabolism is blocked by 0.5 mM iodoacetic acid. Enzyme activity profiles of hagfish ventricle reveal a robust capacity for glycolysis of carbohydrate in comparison to that for general aerobic metabolism and catabolism of alternate metabolic fuels. Isolated working hagfish ventricles preferentially oxidize radiolabeled glucose even when fatty acid fuels are present in the incubation medium. Work output of the isolated ventricular preparation is maintained only in the presence of exogenous glucose. The results indicate that energy metabolism of the hagfish myocardium is predominantly carbohydrate-based and that energy demand of the tissue can be sustained by anaerobic glycolysis during extended periods of extreme hypoxia. Cardiac metabolism of this primitive species is compared with that of hearts from higher vertebrates and an evolutionary hypothesis relating cardiac workload to preferred metabolic fuel is discussed.

Computational Modeling of Blood Flow and Valve Dynamics in Hearts with Hypertrophic Cardiomyopathy

NASA Astrophysics Data System (ADS)

Zheng, Xudong; Mittal, Rajat; Abraham, Theodore; Pinheiro, Aurelio

2010-11-01

Hypertrophic Cardiomyopathy (HCM) is a cardiovascular disease manifested by the thickening of the ventricular wall and often leads to a partial obstruction to the blood flow out of the left ventricle. HCM is recognized as one of the most common causes of sudden cardiac death in athletes. In a heart with HCM, the hypertrophy usually narrows the blood flow pathway to the aorta and produces a low pressure zone between the mitral valve and the hypertrophy during systole. This low pressure can suck the mitral valve leaflet back and completely block the blood flow into the aorta. In the current study, a sharp interface immersed boundary method flow solver is employed to study the hemodynamics and valve dynamics inside a heart with HCM. The three-dimensional motion and configuration of the left ventricle including mitral valve leaflets and aortic valves are reconstructed based on echo-cardio data sets. The mechanisms of aortic obstruction associated with HCM are investigated. The long term objective of this study is to develop a computational tool to aid in the assessment and surgical management of HCM.

Post-repolarization refractoriness increases vulnerability to block and initiation of reentrant impulses in heterogeneous infarcted myocardium.

PubMed

Cabo, Candido

2015-10-01

Myocardial infarction causes remodeling of the tissue structure and the density and kinetics of several ion channels in the cell membrane. Heterogeneities in refractory period (ERP) have been shown to occur in the infarct border zone and have been proposed to lead to initiation of arrhythmias. The purpose of this study is to quantify the window of vulnerability (WV) to block and initiation of reentrant impulses in myocardium with ERP heterogeneities using computer simulations. We found that ERP transitions at the border between normal ventricular cells (NZ) with different ERPs are smooth, whereas ERP transitions between NZ and infarct border zone cells (IZ) are abrupt. The profile of the ERP transitions is a combination of electrotonic interaction between NZ and IZ cells and the characteristic post-repolarization refractoriness (PRR) of IZ cells. ERP heterogeneities between NZ and IZ cells are more vulnerable to block and initiation of reentrant impulses than ERP heterogeneities between NZ cells. The relationship between coupling intervals of premature impulses (V1V2) and coupling intervals between premature and first reentrant impulses (V2T1) at NZ/NZ and NZ/IZ borders is inverse (i.e. the longer the coupling intervals of premature impulses the shorter the coupling interval between the premature and first reentrant impulses); this is in contrast with the reported V1V2/V2T1 relationship measured during initiation of reentrant impulses in canine infarcted hearts which is direct. (1) ERP transitions at the NZ-IZ border are abrupt as a consequence of PRR; (2) PRR increases the vulnerability to block and initiation of reentrant impulses in heterogeneous myocardium; (3) V1V2/V2T1 relationships measured at ERP heterogeneities in the computer model and in experimental canine infarcts are not consistent. Therefore, it is likely that other mechanisms like micro and/or macro structural heterogeneities also contribute to initiation of reentrant impulses in infarcted hearts. Copyright © 2015 Elsevier Ltd. All rights reserved.

A review of the appropriate and inappropriate use of dronedarone: lessons learned from controlled studies and regulatory submission.

PubMed

Naccarelli, Gerald V; Wolbrette, Deborah L; Samii, Soraya; Banchs, Javier E; Penny-Peterson, Erica; Gonzalez, Mario D

2010-12-01

Dronedarone is a multichannel blocker with electrophysiologic effects similar to amiodarone. Dronedarone has been documented to prevent atrial fibrillation recurrences and also has efficacy in slowing the ventricular response during episodes of atrial fibrillation. However, in the ANDROMEDA trial, dronedarone was associated with increased mortality when tested in New York Heart Association (NYHA) III/IV patients with left ventricular ejection fractions of less than 35%, who also had a recent hospitalization for decompensated heart failure. When such high-risk patients with heart failure were excluded in the ATHENA trial, dronedarone treatment resulted in a statistical reduction in the composite primary end point of all-cause mortality or cardiovascular hospitalization. In ATHENA, dronedarone reduced cardiovascular hospitalizations even though in the DIONY-SOS trial dronedarone had less effect than amiodarone on suppressing atrial fibrillation recurrences. The most appropriate patients for treatment with dronedarone would be patients with a recent history of paroxysmal or persistent atrial fibrillation/atrial flutter (AF/AFL) that have associated risk factors per the inclusion criteria of ATHENA. Inappropriate patients would be those with class IV heart failure or recently hospitalized for heart failure within the last month from an acute decompensation, the main inclusion criteria in ANDROMEDA. Dronedarone is a novel, multichannel blocking antiarrhythmic agent that may have some pleiotropic effects in addition to its ability to suppress and maintain sinus rhythm and control the rate during AF/AFL recurrences.

Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.

PubMed

Malloy, Cole A; Ritter, Kyle; Robinson, Jonathan; English, Connor; Cooper, Robin L

2016-01-01

The Drosophila melanogaster heart is a popular model in which to study cardiac physiology and development. Progress has been made in understanding the role of endogenous compounds in regulating cardiac function in this model. It is well characterized that common neurotransmitters act on many peripheral and non-neuronal tissues as they flow through the hemolymph of insects. Many of these neuromodulators, including acetylcholine (ACh), have been shown to act directly on the D. melanogaster larval heart. ACh is a primary neurotransmitter in the central nervous system (CNS) of vertebrates and at the neuromuscular junctions on skeletal and cardiac tissue. In insects, ACh is the primary excitatory neurotransmitter of sensory neurons and is also prominent in the CNS. A full understanding regarding the regulation of the Drosophila cardiac physiology by the cholinergic system remains poorly understood. Here we use semi-intact D. melanogaster larvae to study the pharmacological profile of cholinergic receptor subtypes, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), in modulating heart rate (HR). Cholinergic receptor agonists, nicotine and muscarine both increase HR, while nAChR agonist clothianidin exhibits no significant effect when exposed to an open preparation at concentrations as low as 100 nM. In addition, both nAChR and mAChR antagonists increase HR as well but also display capabilities of blocking agonist actions. These results provide evidence that both of these receptor subtypes display functional significance in regulating the larval heart's pacemaker activity.

Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers.

PubMed

Feola, Iolanda; Volkers, Linda; Majumder, Rupamanjari; Teplenin, Alexander; Schalij, Martin J; Panfilov, Alexander V; de Vries, Antoine A F; Pijnappels, Daniël A

2017-11-01

Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers. Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca 2+ -translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting). Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation. © 2017 American Heart Association, Inc.

Comparison of Spinal Anaesthesia and Paravertebral Block in Unilateral Inguinal Hernia Repair.

PubMed

Işıl, Canan Tülay; Çınar, Ayşe Surhan Özer; Oba, Sibel; Işıl, Rıza Gürhan

2014-10-01

We aimed to compare the efficacy of spinal anaesthesia (SA) and paravertebral block (PVB) in unilateral inguinal hernia repair. Sixty American Society of Anesthesia physical status (ASA) I-III patients aged between 18-64 years with unilateral inguinal hernia were enrolled in this study. Two patients in Group SA and 4 patients in Group PVB were excluded, and statistical analyses were done on 54 patients. In regard to anaesthetic choice, patients were divided into two groups, with 30 patients in each: Group SA, spinal anaesthesia and Group PVB, paravertebral block. Standard monitoring was done, and mean arterial pressure (MAP) and heart rate (HR) were recorded during the surgical procedure. Demographic variables, surgical data, patient satisfaction, the onset times to reach T10 dermatome and to reach peak sensory level, and onset time to reach modified Bromage 3 motor block were recorded. Postoperative nausea and vomiting and pain at postoperative hours 0-24 with the visual analog scale (VAS) were also measured. Compared to pre-anaesthesia measurements, the decrease in HR and MAP during the 10(th)-90(th) minute period was significant in Group SA (p<0.01). In Group PVB, sensory block duration time was higher, whereas paralysis rate was higher in Group SA (p<0.01). Bromage scores were significantly different between the groups (p<0.01). In Group SA, VAS score at the 24(th) postoperative hour, nausea, and vomiting were significantly higher compared to Group PVB (p<0.01). In conclusion, paravertebral block provides acceptable surgical anaesthesia, maintaining good quality and long duration on postoperative analgesia in unilateral hernia repair.

Nuclear accumulation of myocyte muscle LIM protein is regulated by heme oxygenase 1 and correlates with cardiac function in the transition to failure

PubMed Central

Paudyal, Anju; Dewan, Sukriti; Ikie, Cindy; Whalley, Benjamin J; de Tombe, Pieter P.

2016-01-01

Key points The present study investigated the mechanism associated with impaired cardiac mechanosensing that leads to heart failure by examining the factors regulating muscle LIM protein subcellular distribution in myocytes.In myocytes, muscle LIM protein subcellular distribution is regulated by cell contractility rather than passive stretch via heme oxygenase‐1 and histone deacetylase signalling. The result of the present study provide new insights into mechanotransduction in cardiac myocytes.Myocyte mechanosensitivity, as indicated by the muscle LIM protein ratio, is also correlated with cardiac function in the transition to failure in a guinea‐pig model of disease. This shows that the loss mechanosensitivity plays an important role during the transition to failure in the heart.The present study provides the first indication that mechanosensing could be modified pharmacologically during the transition to heart failure. Abstract Impaired mechanosensing leads to heart failure and a decreased ratio of cytoplasmic to nuclear CSRP3/muscle LIM protein (MLP ratio) is associated with a loss of mechanosensitivity. In the present study, we tested whether passive or active stress/strain was important in modulating the MLP ratio and determined whether this correlated with heart function during the transition to failure. We exposed cultured neonatal rat myocytes to a 10% cyclic mechanical stretch at 1 Hz, or electrically paced myocytes at 6.8 V (1 Hz) for 48 h. The MLP ratio decreased by 50% (P < 0.05, n = 4) only in response to electrical pacing, suggesting impaired mechanosensitivity. Inhibition of contractility with 10 μm blebbistatin resulted in an ∼3‐fold increase in the MLP ratio (n = 8, P < 0.05), indicating that myocyte contractility regulates nuclear MLP. Inhibition of histone deacetylase (HDAC) signalling with trichostatin A increased nuclear MLP following passive stretch, suggesting that HDACs block MLP nuclear accumulation. Inhibition of heme oxygenase1 (HO‐1) activity with protoporphyrin IX zinc(II) blocked MLP nuclear accumulation. To examine how mechanosensitivity changes during the transition to heart failure, we studied a guinea‐pig model of angiotensin II infusion (400 ng kg–1 min–1) over 12 weeks. Using subcellular fractionation, we showed that the MLP ratio increased by 88% (n = 4, P < 0.01) during compensated hypertrophy but decreased significantly during heart failure (P < 0.001, n = 4). The MLP ratio correlated significantly with the E/A ratio (r = 0.71, P < 0.01, n = 12), a clinical measure of diastolic function. These data indicate for the first time that myocyte mechanosensitivity as indicated by the MLP ratio is regulated primarily by myocyte contractility via HO‐1 and HDAC signalling. PMID:26847743

Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

PubMed

Drolet, Benoit; Yang, Tao; Daleau, Pascal; Roden, Dan M; Turgeon, Jacques

2003-06-01

Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms. In human ether-a-go-go (HERG)-transfected Chinese hamster ovary cells (n = 16), risperidone caused concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current with an IC(50) for tail block of 261 nM. Risperidone did not block I(Ks). Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations. Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs).

Cardiac pacemaker dysfunction in children after thoracic drainage catheter manipulation.

PubMed

Lobdell, K W; Walters, H L; Hudson, C; Hakimi, M

1997-05-01

Two children underwent placement of permanent, epicardial-lead, dual-chamber, unipolar pacemaker systems for complete heart block. Postoperatively, both patients demonstrated subcutaneous emphysema-in the area of their pulse generators-temporally related to thoracic catheter manipulation. Acutely, each situation was managed with manual compression of the pulse generator, ascertaining appropriate pacemaker sensing and pacing. Maintenance of compression with pressure dressings, vigilant observation/monitoring, and education of the care givers resulted in satisfactory pacemaker function without invasive intervention.

The initial (earliest) report of polymorphous ventricular tachycardia.

PubMed

Jani, Sonal; Schweitzer, Paul

2006-07-01

In these short historical notes, we describe the early history of polymorphic ventricular tachycardia. Polymorphous ventricular tachycardia was probably first noted in 1918 by Wilson and Robinson. In a publication describing complete heart block and ventriculophasic arrhythmia, they noted a tachyarrhythmia characterized by multiple extrasystoles of different types at a rapid rate. Also, we briefly discuss the earliest recognized torsades de pointes by Dessertenes in 1966 and the first description of catecholaminergic polymorphic ventricular tachycardia, by Reid in 1977.

Toxicity of aerosol propellants in the respiratory and circulatory systems. VII. Influence of pulmonary emphysema and anesthesia in the rat.

PubMed

Watanabe, T; Aviado, D M

1975-01-01

Experimental induction of pulmonary emphysema caused an increase in sensitivity of the rat to toxicity from inhalation of propellants. The emphysematous rat showed an exaggerated reduction in pulmonary compliance in response to inhalation of trichlorofluoromethane (FC 11). In emphysematous and non emphysematous rats without anesthesia the inhalation of FC 11 caused tachycardia, arrhythmias and other abnormalities in the electrocardiogram. The tachycardiac response was eliminated by induction of barbiturate anesthesia, which increased the sensitivity of the heart to occurrence of abnormalities in the electrocardiogram in response to inhalation of FC 11 as well as of dichlorodifluoromethane (FC 12) and difluoroethane (FC 152a). The acceleration in heart rate in response to inhalation of FC 11, hypoxia or hypercapnea was prevented by prior treatment with a beta-blocking drug.

[Adenylate cyclase from rabbit heart: substrate binding site].

PubMed

Perfil'eva, E A; Khropov, Iu V; Khachatrian, L; Bulargina, T V; Baranova, L A

1981-08-01

The effects of 17 ATP analogs on the solubilized rabbit heart adenylate cyclase were studied. The triphosphate chain, position 8 of the adenine base and the ribose residue of the ATP molecule were modified. Despite the presence of the alkylating groups in two former types of the analogs tested, no covalent blocking of the active site of the enzyme was observed. Most of the compounds appeared to be competitive reversible inhibitors. The kinetic data confirmed the importance of the triphosphate chain for substrate binding in the active site of adenylate cyclase. (Formula: See Text) The inhibitors with different substituents in position 8 of the adenine base had a low affinity for the enzyme. The possible orientation of the triphosphate chain and the advantages of anti-conformation of the ATP molecule for their binding in the active site of adenylate cyclase are discussed.

Use of an Active-Fixation Coronary Sinus Lead to Implant a Biventricular Pacemaker via the Femoral Vein

PubMed Central

Shandling, Adrian; Donohue, Daniel; Tobias, Serge; Wu, Iris; Brar, Ramandeep

2010-01-01

Cardiac resynchronization therapy, which involves the placement of a pacing lead in the right atrium and in each ventricle, is effective in treating heart failure that is caused by left bundle branch block and cardiomyopathy. The left ventricular lead is usually placed into a lateral branch of the coronary sinus via the subclavian route. When the subclavian route is unavailable, insertion of a standard, passive-fixation coronary sinus lead via the femoral approach is feasible; however, the likelihood of subsequent dislodgment is high. Herein, we describe the placement of a novel, self-retaining, active-fixation coronary sinus lead—the Attain StarFix® Model 4195 OTW Lead—in an elderly heart-failure patient, via the femoral approach. We believe that this is the 1st report of this procedure. PMID:20200636

New developments in the management of periocular capillary hemangioma in children.

PubMed

Ni, Nina; Wagner, Rudolph S; Langer, Paul; Guo, Suqin

2011-01-01

The authors describe the theories of pathogenesis for capillary hemangioma and discuss the benefits and side effects of current treatment options, such as systemic and intralesional corticosteroids, laser therapy, and surgical excision. They also evaluate the recent systemic and topical applications of beta-blockers to treat infantile hemangioma. Although no major adverse events from beta-blocker treatment have been reported, the incidence of potential side effects such as bronchospasm, hypoglycemia, heart block, bradycardia, and congestive heart failure is unknown due to the novelty of the treatment. It has been postulated that topical application for localized superficial tumor may reduce systemic effects. Further research is necessary to compare the effectiveness of different treatments and to find the optimal dosing and delivery methods to minimize adverse effects in the treatment of this disorder. Copyright 2011, SLACK Incorporated.

Caring for the student with wolff-Parkinson-white syndrome.

PubMed

Prenni, Patricia G

2009-10-01

Wolff-Parkinson-White syndrome is a cardiac condition in which an extra electrical pathway within the heart causes an abnormal increase in heart rate. It affects one to three people of every 1,000 people worldwide, occurring more often in males. Diagnosis usually occurs during young adulthood, so it is important for school nurses to be familiar with the condition. Prophylactic treatments, as well as surgical intervention to permanently block the extra pathway, are options for people with Wolff-Parkinson-White syndrome. Tachycardia associated with Wolff-Parkinson-White syndrome can occur occasionally even when prophylactic treatment is administered. School nurses must know how to properly assess and treat episodes of tachycardia that may occur in the school setting. With proper education, school nurses can help provide a safe school environment for students with Wolff-Parkinson-White syndrome and promote successful academic achievement.

Technology Advances to Improve Response to Cardiac Resynchronization Therapy: What Clinicians Should Know.

PubMed

Auricchio, Angelo; Heggermont, Ward A

2018-06-01

Cardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure patients with reduced left ventricular ejection fraction, prolonged QRS duration, and abnormal QRS morphology. The ultimate goals of modern CRT are to improve the proportion of patients responding to CRT and to maximize the response to CRT in patients who do respond. While the rate of CRT nonresponders has moderately but progressively decreased over the last 20 years, mostly in patients with left bundle branch block, in patients without left bundle branch block the response rate is almost unchanged. A number of technological advances have already contributed to achieve some of the objectives of modern CRT. They include novel lead design (the left ventricular quadripolar lead, and multipoint pacing), or the possibility to go beyond conventional delivery of CRT (left ventricular endocardial pacing, His bundle pacing). Furthermore, to improve CRT response, a triad of actions is paramount: reducing the burden of atrial fibrillation, reducing the number of appropriate and inappropriate interventions, and adequately predicting heart failure episodes. As in other fields of cardiology, technology and innovations for CRT delivery have been at the forefront in transforming-improving-patient care; therefore, these innovations are discussed in this review. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Neurodevelopment in children with and without congenital heart block born to anti-Ro/SSA-positive mothers.

PubMed

Skog, Amanda; Tingström, Joanna; Salomonsson, Stina; Sonesson, Sven-Erik; Wahren-Herlenius, Marie

2013-01-01

To define factors influencing neurodevelopment in children with and without complete congenital heart block (CHB) born to mothers with Ro/SSA autoantibodies. Medical records of a population-based cohort of siblings with (n = 60) and without (n = 54) CHB born 1974-2009 to anti-Ro/SSA-positive mothers were retrieved from children primary healthcare centres and school health services and used to extract data on neurodevelopment. Impaired neurodevelopment was reported in 16% of the children (18/114) during the follow-up time of 13.0 (8.2-17.5) years, median (quartiles). Reported problems included speech (9%), motor (8%) and learning (8%) impairment, attention deficit (5%) and behavioural impairment (4%). Impairment in motor skill development was more common in boys (p < 0.001) if the child was born preterm (p < 0.001). Learning impairment was significantly influenced by maternal SLE (p < 0.005), while attention deficits was influenced by both maternal SLE (p < 0.05) and CHB in the child (p < 0.05). Our data indicate that in addition to well-established factors such as male sex and being born preterm, both maternal SLE and CHB may influence neurodevelopment. Follow-up of neurodevelopment should therefore be considered for children with CHB, especially if the mother is diagnosed with SLE. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica.

Carotid Space Mass Proximal to Vagus Nerve Causing Asystole and Syncope.

PubMed

Leviter, Julie; Wiznia, Daniel H

2016-01-01

Manipulation of vagal nerve rootlets, whether surgical or through mass effect of a neoplasm, can result in asystole and hypotension, accompanied by ST depression and right bundle branch block. There are few case reports of a neoplasm causing these effects, and this case describes a patient with such a mass presenting with syncopal episodes. A 43-year-old man with a past medical history of HIV, bipolar disorder, and epilepsy was admitted to the neurology service for a video electroencephalogram (vEEG) to characterize syncopal episodes that were felt to be epileptic in origin. During the study, he experienced symptoms of his typical aura, which correlated with a transient symptomatic high degree AV block on telemetry, and an absence of epileptic findings on vEEG. Magnetic Resonance Imaging (MRI) of the brain showed a mass in the left posterior carotid space at the skull base. The patient underwent permanent dual chamber MRI-compatible pacemaker placement for his heart block. His syncopal episodes resolved, but presyncopal symptoms persisted. We discuss the presentation and treatment of vagal neoplasms.

Wolff-Parkinson-white syndrome mimics a conduction disease.

PubMed

Marrakchi, S; Kammoun, I; Kachboura, S

2014-01-01

Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a "false positive" of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

Glucagon-like peptide-1 reduces contractile function and fails to boost glucose utilization in normal hearts in the presence of fatty acids.

PubMed

Nguyen, T Dung; Shingu, Yasushige; Amorim, Paulo A; Schwarzer, Michael; Doenst, Torsten

2013-10-09

GLP-1 and exendin-4, which are used as insulin sensitizers or weight reducing drugs, were shown to improve glucose uptake in the heart. However, the direct effects of GLP-1 or exendin-4 on normal hearts in the presence of fatty acids, the main cardiac substrates, have never been investigated. We therefore assessed the effects of GLP-1 or exendin-4 on myocardial glucose uptake (GU), glucose oxidation (GO) and cardiac performance (CP) under conditions of fatty acid utilization. Rat hearts were perfused with only glucose (5 mM) or glucose (5 mM) plus oleate (0.4 mM) as substrates for 60 min. After 30 min, GLP-1 or exendin-4 (0.5 nM or 5 nM) was added. In the absence of oleate, GLP-1 increased both GU and GO. Exendin-4 increased GO but showed no effect on GU. Neither GLP-1 nor exendin-4 affected CP. However, when oleate was present, GLP-1 failed to stimulate glucose utilization and exendin-4 even decreased GU. Furthermore, now GLP-1 reduced CP. In contrast to prior reports, this negative inotropic effect could not be blocked by the protein kinase A inhibitor H-89. We then measured myocardial GO and CP in rats receiving a 4-week GLP-1 infusion. Interestingly, this chronic treatment resulted in a significant reduction in both GO and CP. Under the influence of oleate, GLP-1 reduces contractile function and fails to stimulate glucose utilization in normal hearts. Exendin-4 may acutely reduce cardiac glucose uptake but not contractility. We suggest advanced investigation of heart function and metabolism in patients treating with these peptides. © 2013.

PPARβ/δ activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells.

PubMed

Alvarez-Guardia, David; Palomer, Xavier; Coll, Teresa; Serrano, Lucía; Rodríguez-Calvo, Ricardo; Davidson, Mercy M; Merlos, Manuel; El Kochairi, Ilhem; Michalik, Liliane; Wahli, Walter; Vázquez-Carrera, Manuel

2011-02-01

Owing to its high fat content, the classical Western diet has a range of adverse effects on the heart, including enhanced inflammation, hypertrophy, and contractile dysfunction. Proinflammatory factors secreted by cardiac cells, which are under the transcriptional control of nuclear factor-κB (NF-κB), may contribute to heart failure and dilated cardiomyopathy. The underlying mechanisms are complex, since they are linked to systemic metabolic abnormalities and changes in cardiomyocyte phenotype. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate metabolism and are capable of limiting myocardial inflammation and hypertrophy via inhibition of NF-κB. Since PPARβ/δ is the most prevalent PPAR isoform in the heart, we analyzed the effects of the PPARβ/δ agonist GW501516 on inflammatory parameters. A high-fat diet induced the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6, and enhanced the activity of NF-κB in the heart of mice. GW501516 abrogated this enhanced proinflammatory profile. Similar results were obtained when human cardiac AC16 cells exposed to palmitate were coincubated with GW501516. PPARβ/δ activation by GW501516 enhanced the physical interaction between PPARβ/δ and p65, which suggests that this mechanism may also interfere NF-κB transactivation capacity in the heart. GW501516-induced PPARβ/δ activation can attenuate the inflammatory response induced in human cardiac AC16 cells exposed to the saturated fatty acid palmitate and in mice fed a high-fat diet. This is relevant, especially taking into account that PPARβ/δ has been postulated as a potential target in the treatment of obesity and the insulin resistance state. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of poloxamer 407 administration on the serum lipids profile, anxiety level and protease activity in the heart and liver of mice

PubMed Central

Johnston, Thomas P.; Dubrovina, Nina I.; Kisarova, Yana A.; Zhanaeva, Svetlana Ya.; Cherkanova, Marina S.; Filjushina, Elena E.; Alexeenko, Tatyana V.; Machova, Eva; Zhukova, Natalya A.

2013-01-01

Chronic administration of the poloxamer 407 (P-407), a block copolymer, to elevate serum lipids in mice is a well-established mouse model of hyperlipidemia and atherosclerosis. We tested the hypothesis that the activity of several types of proteases in heart and liver tissue is changed in the early stages of atherosclerosis development. Additionally, we evaluated whether increased serum lipids would induce anxiety in mice, as determined by using a ‘plus-maze’ test. The mice were administered P-407 by intraperitoneal injection twice a week for one month. P-407 administration to mice resulted in a marked increase in total serum cholesterol, atherogenic non-HDL-cholesterol, and especially in total triglycerides, and it also increased anxiety. Morphological changes observed in P-407-treated mice included contractile type changes in cardiomyocytes and foamy macrophages in liver. A significant increase of cysteine proteases cathepsin B and cathepsin L (at 24 h) and aspartate protease cathepsin D (at both 24 h and 5 days) was determined in heart tissue following P-407 administration. However, no changes were noted in heart matrix metalloproteinase activity. The activity of cysteine and aspartate proteases was significantly increased in liver at both 24 hours and 5 days after P-407 administration. In conclusion, administration of P-407 to mice for one month resulted in increased anxiety, and more importantly, there was an increase in the activity of heart and liver proteases secondary to sustained dyslipidemia. It is suggested that heart and liver cysteine and aspartate proteases may represent potential therapeutic targets in the early stages of atherosclerosis. PMID:24170975

Angiotensin II induces tumor necrosis factor biosynthesis in the adult mammalian heart through a protein kinase C-dependent pathway.

PubMed

Kalra, Dinesh; Sivasubramanian, Natarajan; Mann, Douglas L

2002-05-07

Previous studies suggest that angiotensin II (Ang II) upregulates the expression of tumor necrosis factor (TNF) in nonmyocyte cell types; however, the effect of Ang II on TNF expression in the adult mammalian heart is not known. To determine whether Ang II was sufficient to provoke TNF biosynthesis in the adult heart, we examined the effects of Ang II in isolated buffer-perfused Langendorff feline hearts. Ang II (10(-7) mol/L) treatment resulted in a time- and dose-dependent increase in myocardial TNF mRNA and protein biosynthesis in the heart as well as in cultured adult cardiac myocytes. The effects of Ang II on myocardial TNF mRNA and protein synthesis were mediated through the angiotensin type 1 receptor (AT1R), insofar as an AT1R antagonist (AT1a) blocked the effects of Ang II, whereas an angiotensin type 2 receptor (AT2R) antagonist (AT2a) had no effect. Stimulation with Ang II led to the activation of nuclear factor-kappaB and activator protein-1 (AP-1), two transcription factors that are important for TNF gene expression. Nuclear factor-kappaB activation was accompanied by phosphorylation of IkappaBalpha on serine 32 as well as degradation of IkappaBalpha, suggesting that the effects of Ang II were mediated through an IkappaBalpha-dependent pathway. The important role of protein kinase C (PKC) was suggested by studies in which a phorbol ester triggered TNF biosynthesis, and a PKC inhibitor abrogated Ang II-induced TNF biosynthesis. These studies suggest that Ang II provokes TNF biosynthesis in the adult mammalian heart through a PKC-dependent pathway.

Chronic Losartan Treatment Up-Regulates AT1R and Increases the Heart Vulnerability to Acute Onset of Ischemia and Reperfusion Injury in Male Rats.

PubMed

Song, Minwoo A; Dasgupta, Chiranjib; Zhang, Lubo

2015-01-01

Inhibition of angiotensin II type 1 receptor (AT1R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT1R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT1R and PKCδ expression in the left ventricle. In contrast, AT2R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT1R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury.

Acute effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate, on cardiovascular parameters in anaesthetized, artificially ventilated rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, Yoshimasa; Itoh, Takeo, E-mail: titoh@med.nagoya-cu.ac.jp; Shiraishi, Hiroaki

The organophosphorus compound sarin irreversibly inhibits acetylcholinesterase. We examined the acute cardiovascular effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate (BIMP), in anaesthetized, artificially ventilated rats. Intravenous administration of BIMP (0.8 mg/kg; the LD50 value) induced a long-lasting increase in blood pressure and tended to increase heart rate. In rats pretreated with the non-selective muscarinic-receptor antagonist atropine, BIMP significantly increased both heart rate and blood pressure. In atropine-treated rats, hexamethonium (antagonist of ganglionic nicotinic receptors) greatly attenuated the BIMP-induced increase in blood pressure without changing the BIMP-induced increase in heart rate. In rats treated with atropine plus hexamethonium, intravenous phentolaminemore » (non-selective α-adrenergic receptor antagonist) plus propranolol (non-selective β-adrenergic receptor antagonist) completely blocked the BIMP-induced increases in blood pressure and heart rate. In atropine-treated rats, the reversible acetylcholinesterase inhibitor neostigmine (1 mg/kg) induced a transient increase in blood pressure, but had no effect on heart rate. These results suggest that in anaesthetized rats, BIMP induces powerful stimulation of sympathetic as well as parasympathetic nerves and thereby modulates heart rate and blood pressure. They may also indicate that an action independent of acetylcholinesterase inhibition contributes to the acute cardiovascular responses induced by BIMP. - Highlights: • A sarin-like agent BIMP markedly increased blood pressure in anaesthetized rats. • Muscarinic receptor blockade enhanced the BIMP-induced increase in blood pressure. • Ganglionic nicotinic receptor blockade attenuated the BIMP-induced response. • Blockade of α- as well as β-receptors attenuated the BIMP-induced response.« less

The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model

PubMed Central

Dare, Anna J.; Logan, Angela; Prime, Tracy A.; Rogatti, Sebastian; Goddard, Martin; Bolton, Eleanor M.; Bradley, J. Andrew; Pettigrew, Gavin J.; Murphy, Michael P.; Saeb-Parsy, Kourosh

2015-01-01

Background Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model. Methods Hearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non–anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating score, and inflammatory markers 120 minutes or 24 hours post-transplant. Results MitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondrial DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient. Conclusions IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury. PMID:26140808

Chronic Losartan Treatment Up-Regulates AT1R and Increases the Heart Vulnerability to Acute Onset of Ischemia and Reperfusion Injury in Male Rats

PubMed Central

Song, Minwoo A.; Dasgupta, Chiranjib; Zhang, Lubo

2015-01-01

Inhibition of angiotensin II type 1 receptor (AT1R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT1R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT1R and PKCδ expression in the left ventricle. In contrast, AT2R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT1R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury. PMID:26168042

[Fiessinger-Leroy-Reiter syndrome with non-obstructive cardiomyopathy treated with methotrexate].

PubMed

Blétry, O; De Prost, Y; Scheuble, C; Frank, R; Godeau, P

1979-07-01

The case of a 50 year old male with the Fiessinger-Leroy-Reiter syndrome, ankylosing spondylitis and generalised pustular psoriasis is reported. This condition wax complicated by non-obstructive cardiomyopathy, congestive cardiac failure and first-degree atrioventricular block, the site of which was localised by electrophysiological studies (nodal block with an infrahisian conduction defect). After failure of several therapeutic regimes, a spectacular improvement was obtained with Methotrexate associated with a diuretic; the signs of heart failure regressed and the cardiomyopathy stablised. A parallel improvement was seen in the skin, cardiac and articular lesions and has been maintained with an 18 months follow-up. Left ventricular performance was studied by echocardiography. The mechanism of the beneficial effect of Methotrexate is unclear; this therapeutic trial is to be extended to include other cases of primary cardiomyopathy without obstruction.

Efficacy of virtual block objects in reducing the lung dose in helical tomotherapy planning for cervical oesophageal cancer: a planning study.

PubMed

Ito, Makoto; Shimizu, Hidetoshi; Aoyama, Takahiro; Tachibana, Hiroyuki; Tomita, Natsuo; Makita, Chiyoko; Koide, Yutaro; Kato, Daiki; Ishiguchi, Tsuneo; Kodaira, Takeshi

2018-04-04

Intensity-modulated radiotherapy is useful for cervical oesophageal carcinoma (CEC); however, increasing low-dose exposure to the lung may lead to radiation pneumonitis. Nevertheless, an irradiation technique that avoids the lungs has never been examined due to the high difficulty of dose optimization. In this study, we examined the efficacy of helical tomotherapy that can restrict beamlets passing virtual blocks during dose optimization computing (block plan) in reducing the lung dose. Fifteen patients with CEC were analysed. The primary/nodal lesion and prophylactic nodal region with adequate margins were defined as the planning target volume (PTV)-60 Gy and PTV-48 Gy, respectively. Nineteen plans per patient were made and compared (total: 285 plans), including non-block and block plans with several shapes and sizes. The most appropriate block model was semi-circular, 8 cm outside of the tracheal bifurcation, with a significantly lower lung dose compared to that of non-block plans; the mean lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and the mean lung dose were 31.3% vs. 48.0% (p <  0.001), 22.4% vs. 39.4% (p <  0.001), 13.2% vs. 16.0% (p = 0.028), and 7.1 Gy vs. 9.6 Gy (p <  0.001), respectively. Both the block and non-block plans were comparable in terms of the homogeneity and conformity indexes of PTV-60 Gy: 0.05 vs. 0.04 (p = 0.100) and 0.82 vs. 0.85 (p = 0.616), respectively. The maximum dose of the spinal cord planning risk volume increased slightly (49.4 Gy vs. 47.9 Gy, p = 0.002). There was no significant difference in the mean doses to the heart and the thyroid gland. Prolongation of the delivery time was less than 1 min (5.6 min vs. 4.9 min, p = 0.010). The block plan for CEC could significantly reduce the lung dose, with acceptable increment in the spinal dose and a slightly prolonged delivery time.

Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck.

PubMed

Ansara, A J; Kolanczyk, D M; Koehler, J M

2016-04-01

Heart failure remains a leading cause of morbidity and mortality worldwide. Advanced therapies have prolonged survival in patients with advanced heart failure, but pharmacotherapeutic optimization remains the mainstay of treatment. It has been over 10 years since the last mortality-reducing medication has been approved by the Food and Drug Administration. This article reviews the background, current knowledge and data supporting the use of sacubitril/valsartan (Entresto(®) ), the newly FDA-approved medication that dually inhibits angiotensin and neprilysin, in the treatment of heart failure. A literature search was performed (January 1980 to August 2015) using PubMed and the search terms were as follows: neprilysin inhibitor, heart failure, endopeptidase, natriuretic peptides, angiotensin, omapatrilat, LCZ696, valsartan and sacubitril. Peer-reviewed, published clinical trials, review articles, relevant treatment guidelines and prescribing information documents were identified and reviewed for relevance. Additionally, reference citations from publications identified were reviewed. The inhibition of endopeptidases has been an area of extensive study for the treatment of heart failure. Previously published literature with the endopeptidase inhibitor omapatrilat failed to demonstrate a sufficient balance between clinical efficacy and safety to justify its approval. Omapatrilat blocked three pathways that break down bradykinin, leading to high rates of angioedema. Sacubitril, on the other hand, is metabolized to a form that is highly selective for neprilysin without possessing activity for the other two peptidases, ACE and APP. The combination of sacubitril with valsartan in a single formulation offers the benefit of concurrent blockade of the renin angiotensin aldosterone system and the inhibition of neprilysin while minimizing angioedema risk. When compared to ACE inhibitor therapy in systolic heart failure patients, sacubitril/valsartan demonstrated reductions in all-cause mortality and hospitalization due to heart failure while maintaining a similar safety profile. A formulation that contains both sacubitril and valsartan was manufactured and approved by the FDA in July 2015 for the reduction of mortality and hospitalization in systolic heart failure patients. The new medication offers a potentially superior alternative to ACE inhibitor therapy in the management of systolic heart failure. The effects of treatment with sacubitril/valsartan in the setting of diastolic heart failure are currently under investigation in clinical trials. © 2016 John Wiley & Sons Ltd.

The use of non-invasive fetal electrocardiography in diagnosing second-degree fetal atrioventricular block.

PubMed

Lakhno, Igor; Behar, Joachim A; Oster, Julien; Shulgin, Vyacheslav; Ostras, Oleksii; Andreotti, Fernando

2017-01-01

Complete atrioventricular block in fetuses is known to be mostly associated with autoimmune disease and can be irreversible if no steroids treatment is provided. Conventional methods used in clinical practice for diagnosing fetal arrhythmia are limited since they do not reflect the primary electrophysiological conduction processes that take place in the myocardium. The non-invasive fetal electrocardiogram has the potential to better support fetal arrhythmias diagnosis through the continuous analysis of the beat to beat variation of the fetal heart rate and morphological analysis of the PQRST complex. We present two retrospective case reports on which atrioventricular block diagnosis could have been supported by the non-invasive fetal electrocardiogram. The two cases comprised a 22-year-old pregnant woman with the gestational age of 31 weeks and a 25-year-old pregnant woman with the gestational age of 41 weeks. Both women were admitted to the Department of Maternal and Fetal Medicine at the Kyiv and Kharkiv municipal perinatal clinics. Patients were observed using standard fetal monitoring methods as well as the non-invasive fetal electrocardiogram. The non-invasive fetal electrocardiographic recordings were analyzed retrospectively, where it is possible to identify the presence of the atrioventricular block. This study demonstrates, for the first time, the feasibility of the non-invasive fetal electrocardiogram as a supplementary method to diagnose of the fetal atrioventricular block. Combined with current fetal monitoring techniques, non-invasive fetal electrocardiography could support clinical decisions.

Bisphenol A Exposure and Cardiac Electrical Conduction in Excised Rat Hearts

PubMed Central

Jaimes, Rafael; Asfour, Huda; Swift, Luther M.; Wengrowski, Anastasia M.; Sarvazyan, Narine; Kay, Matthew W.

2014-01-01

Background: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown. Objectives: The goal of our study was to measure the effect of BPA (0.1–100 μM) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats. Methods: We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. Results: Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1–100 μM BPA), prolonged action potential duration (1–100 μM BPA), and delayed atrioventricular conduction (10–100 μM BPA). These effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block. Conclusions: Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA’s effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations. Citation: Posnack NG, Jaimes R III, Asfour H, Swift LM, Wengrowski AM, Sarvazyan N, Kay MW. 2014. Bisphenol A exposure and cardiac electrical conduction in excised rat hearts. Environ Health Perspect 122:384–390; http://dx.doi.org/10.1289/ehp.1206157 PMID:24487307

The mechanism of protection from 5 (N-ethyl-N-isopropyl)amiloride differs from that of ischemic preconditioning in rabbit heart.

PubMed

Sato, H; Miki, T; Vallabhapurapu, R P; Wang, P; Liu, G S; Cohen, M V; Downey, J M

1997-10-01

We investigated the effects of 5-(N-ethyl-N-isopropyl)amiloride (EIPA) on infarction in isolated rabbit hearts and cardiomyocytes. Thirty min of regional ischemia caused 29.6 +/- 2.8% of the risk zone to infarct in untreated Krebs buffer-perfused hearts. Treatment with EIPA (1 microM) for 20 min starting either 15 min before ischemia or 15 min after the onset of ischemia significantly reduced infarction to 5.4 +/- 2.0% and 7.0 +/- 1.0%, respectively (p < 0.01 versus untreated hearts). In both cases salvage was very similar to that seen with ischemic preconditioning (PC) (7.1 +/- 1.5% infarction). Unlike the case with ischemic preconditioning, however, protection from EIPA was not blocked by 50 microM polymyxin B, a PKC inhibitor, or 1 microM glibenclamide, a KATP channel blocker. Forty-five min of regional ischemia caused 51.0 +/- 2.9% infarction in untreated hearts. Ischemic preconditioning reduced infarction to 23.4 +/- 3.1% (p < 0.001 versus untreated hearts). In these hearts with longer periods of ischemia pretreatment with EIPA reduced infarction similarly to 28.8 +/- 2.1% (p < 0.01 versus untreated hearts). However, when EIPA was combined with ischemic PC, no further reduction in infarction was seen (23.8 +/- 3.5% infarction). To further elucidate the mechanism of EIPA's cardioprotective effect, this agent was also examined in isolated rabbit cardiomyocytes. Preconditioning caused a delay of about 30 min in the progressive increase in osmotic fragility that occurs during simulated ischemia. In contrast, EIPA had no effect on the time course of ischemia-induced osmotic fragility. Furthermore, EIPA treatment did not alter the salutary effect of ischemic preconditioning when the two were combined in this model. We conclude that Na+/H+ exchange inhibition limits myocardial infarction in the isolated rabbit heart by a mechanism which is quite different from that of ischemic preconditioning. Despite the apparently divergent mechanisms, EIPA's cardioprotective effect could not be added to that of ischemic or metabolic preconditioning in these models.

Angiotensin-(1-7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity.

PubMed

Giani, Jorge F; Gironacci, Mariela M; Muñoz, Marina C; Turyn, Daniel; Dominici, Fernando P

2008-05-01

Angiotensin (ANG) II contributes to cardiac remodelling by inducing the activation of several signalling molecules, including ERK1/2, Rho kinase and members of the STAT family of proteins. Angiotensin-(1-7) is produced in the heart and inhibits the proliferative actions of ANG II, although the mechanisms of this inhibition are poorly understood. Accordingly, in the present study we examined whether ANG-(1-7) affects the ANG II-mediated activation of ERK1/2 and Rho kinase, STAT3 and STAT5a/b in rat heart in vivo. We hypothesized that ANG-(1-7) inhibits these growth-promoting pathways, counterbalancing the trophic action of ANG II. Solutions of normal saline (0.9% NaCl) containing ANG II (8 pmol kg(-1)) plus ANG-(1-7) in increasing doses (from 0.08 to 800 pmol kg(-1)) were administered via the inferior vena cava to anaesthetized male Sprague-Dawley rats. After 5 min, hearts were removed and ERK1/2, Rho kinase, STAT3 and STAT5a/b phosphorylation was determined by Western blotting using phosphospecific antibodies. Angiotensin II stimulated ERK1/2 and Rho kinase phosphorylation (2.3 +/- 0.2- and 2.1 +/- 0.2-fold increase over basal values, respectively), while ANG-(1-7) was without effect. The ANG II-mediated phosphorylation of ERK1/2 and Rho kinase was prevented in a dose-dependent manner by ANG-(1-7) and disappeared in the presence of the Mas receptor antagonist d-Ala7-ANG-(1-7). Both ANG II and ANG-(1-7) increased STAT3 and STAT5a/b phosphorylation to a similar extent (130-140% increase). The ANG-(1-7)-stimulated STAT phosphorylation was blocked by the AT(1) receptor antagonist losartan and not by d-Ala7-ANG-(1-7). Our results show a dual action of ANG-(1-7), that is, a stimulatory effect on STAT3 and 5a/b phosphorylation through AT(1) receptors and a blocking action on ANG II-stimulated ERK1/2 and Rho kinase phosphorylation through Mas receptor activation. The latter effect could be representative of a mechanism for a protective role of ANG-(1-7) in the heart by counteracting the effects of locally generated ANG II.

IMMEDIATE EFFECTS OF X-IRRADIATION ON THE HEART OF THE FROG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onkelinx, Cl.

1962-07-21

The effects of whole-body irradiations on the heartbeat of pithed frogs were studied. A strong bradycardia was observed after 1 to 5 min of irradiation and is reversible within 1 min after irradiation. A sino-auricular block was observed in some cases. No response was found in any of the frogs during the cold months. The effects of atropine, physostigmine, and eserine on the response were studied. The results suggest a vagal excitation or acetylcholine liberation from the irradiation. (D.L.C.)

Physiological Assessment of Aircraft Pilot Workload in Simulated Landing and Simulated Hostile Threat Environments

DTIC Science & Technology

1984-04-01

999949999999 17 * . TABLE 3.Inter- beat interval (131) changes over 14 blocks of 6 tone trials each f’or the 3...Tone3 were presented • .. 4 binaurally through Sennheiser Model HD 400 earphones. Tone duration was 200 msec at 65 dB. A *run* on this task was...canthus and superior ridge of the left eye. Heart rate (actually quantified as inter- beat -interal, or IBI, in msec) leads were placed on the left

KSC-02pd0793

NASA Image and Video Library

2002-05-28

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 17-A, Cape Canaveral Air Force Station, the Boeing Delta II rocket is lifted up the gantry. The rocket is the launch vehicle for the CONTOUR spacecraft, scheduled to launch July 1. CONTOUR will provide the first detailed look into the heart of a comet -- the nucleus. The spacecraft will fly close to at least two comets, Encke and Schwassmann-Wachmann 3, taking pictures of the nucleus while analyzing the gas and dust that surround these rocky, icy building blocks of the solar system.

KSC-02pd0812

NASA Image and Video Library

2002-05-29

KENNEDY SPACE CENTER, FLA. -- On Launch Pad 17-A, Cape Canaveral Air Force Station, a technician works beneath the Boeing Delta II rocket that will be the launch vehicle for the CONTOUR spacecraft, scheduled to launch July 1. CONTOUR will provide the first detailed look into the heart of a comet -- the nucleus. The spacecraft will fly close to at least two comets, Encke and Schwassmann-Wachmann 3, taking pictures of the nucleus while analyzing the gas and dust that surround these rocky, icy building blocks of the solar system.

Simulation of Cardiac Arrhythmias Using a 2D Heterogeneous Whole Heart Model

PubMed Central

Balakrishnan, Minimol; Chakravarthy, V. Srinivasa; Guhathakurta, Soma

2015-01-01

Simulation studies of cardiac arrhythmias at the whole heart level with electrocardiogram (ECG) gives an understanding of how the underlying cell and tissue level changes manifest as rhythm disturbances in the ECG. We present a 2D whole heart model (WHM2D) which can accommodate variations at the cellular level and can generate the ECG waveform. It is shown that, by varying cellular-level parameters like the gap junction conductance (GJC), excitability, action potential duration (APD) and frequency of oscillations of the auto-rhythmic cell in WHM2D a large variety of cardiac arrhythmias can be generated including sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinus pause, junctional rhythm, Wolf Parkinson White syndrome and all types of AV conduction blocks. WHM2D includes key components of the electrical conduction system of the heart like the SA (Sino atrial) node cells, fast conducting intranodal pathways, slow conducting atriovenctricular (AV) node, bundle of His cells, Purkinje network, atrial, and ventricular myocardial cells. SA nodal cells, AV nodal cells, bundle of His cells, and Purkinje cells are represented by the Fitzhugh-Nagumo (FN) model which is a reduced model of the Hodgkin-Huxley neuron model. The atrial and ventricular myocardial cells are modeled by the Aliev-Panfilov (AP) two-variable model proposed for cardiac excitation. WHM2D can prove to be a valuable clinical tool for understanding cardiac arrhythmias. PMID:26733873

(-)-Terpinen-4-ol changes intracellular Ca2+ handling and induces pacing disturbance in rat hearts.

PubMed

Gondim, Antonio Nei Santana; Lara, Aline; Santos-Miranda, Artur; Roman-Campos, Danilo; Lauton-Santos, Sandra; Menezes-Filho, José Evaldo Rodrigues; de Vasconcelos, Carla Maria Lins; Conde-Garcia, Eduardo Antonio; Guatimosim, Silvia; Cruz, Jader S

2017-07-15

(-)-Terpinen-4-ol is a naturally occurring plant monoterpene and has been shown to have a plethora of biological activities. The objective of this study was to investigate the effects of (-)-terpinen-4-ol on the rat heart, a key player in the control and maintenance of arterial blood pressure. The effects of (-)-terpinen-4-ol on the rat heart were investigated using isolated left atrium isometric force measurements, in vivo electrocardiogram (ECG) recordings, patch clamp technique, and confocal microscopy. It was observed that (-)-terpinen-4-ol reduced contraction force in an isolated left atrium at millimolar concentrations. Conversely, it induced a positive inotropic effect and extrasystoles at micromolar concentrations, suggesting that (-)-terpinen-4-ol may have arrhythmogenic activity on cardiac tissue. In anaesthetized animals, (-)-terpinen-4-ol also elicited rhythm disturbance, such as supraventricular tachycardia and atrioventricular block. To investigate the cellular mechanism underlying the dual effect of (-)-terpinen-4-ol on heart muscle, experiments were performed on isolated ventricular cardiomyocytes to determine the effect of (-)-terpinen-4-ol on L-type Ca 2+ currents, Ca 2+ sparks, and Ca 2+ transients. The arrhythmogenic activity of (-)-terpinen-4-ol in vitro and in vivo may be explained by its effect on intracellular Ca 2+ handling. Taken together, our data suggest that (-)-terpinen-4-ol has cardiac arrhythmogenic activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Tumor Necrosis Factor Is a Therapeutic Target for Immunological Unbalance and Cardiac Abnormalities in Chronic Experimental Chagas' Heart Disease

PubMed Central

Pereira, Isabela Resende; Vilar-Pereira, Glaucia; Silva, Andrea Alice; Moreira, Otacilio Cruz; Britto, Constança; Sarmento, Ellen Diana Marinho

2014-01-01

Background. Chagas disease (CD) is characterized by parasite persistence and immunological unbalance favoring systemic inflammatory profile. Chronic chagasic cardiomyopathy, the main manifestation of CD, occurs in a TNF-enriched milieu and frequently progresses to heart failure. Aim of the Study. To challenge the hypothesis that TNF plays a key role in Trypanosoma cruzi-induced immune deregulation and cardiac abnormalities, we tested the effect of the anti-TNF antibody Infliximab in chronically T. cruzi-infected C57BL/6 mice, a model with immunological, electrical, and histopathological abnormalities resembling Chagas' heart disease. Results. Infliximab therapy did not reactivate parasite but reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue and plasma TNF and IFNγ levels; diminished the frequency of IL-17A+ but increased IL-10+ CD4+ T-cells; reduced TNF+ but augmented IL-10+ Ly6C+ and F4/80+ cells. Further, anti-TNF therapy decreased cytotoxic activity but preserved IFNγ-producing VNHRFTLV-specific CD8+ T-cells in spleen and reduced the number of perforin+ cells infiltrating the myocardium. Importantly, Infliximab reduced the frequency of mice afflicted by arrhythmias and second degree atrioventricular blocks and decreased fibronectin deposition in the cardiac tissue. Conclusions. Our data support that TNF is a crucial player in the pathogenesis of Chagas' heart disease fueling immunological unbalance which contributes to cardiac abnormalities. PMID:25140115

Dronedarone for the treatment of atrial fibrillation and atrial flutter: approval and efficacy.

PubMed

Wolbrette, Deborah; Gonzalez, Mario; Samii, Soraya; Banchs, Javier; Penny-Peterson, Erica; Naccarelli, Gerald

2010-08-09

Dronedarone, a new Class III antiarrhythmic agent, has now been approved by the US Food and Drug Administration for use in patients with atrial fibrillation or atrial flutter. Approval came in March 2009 due to the positive results of the ATHENA trial showing significant reductions in all-cause mortality and cardiovascular hospitalization with dronedarone use. A post hoc analysis of the ATHENA data also suggested a decrease in stroke risk with this agent. However, due to safety concerns in the heart failure population in the earlier ANDROMEDA trial, dronedarone is not recommended for patients with an ejection fraction <35% and recent decompensated heart failure. Dronedarone is an amiodarone analog with multichannel blocking electrophysiologic properties similar to those of amiodarone, but several structural differences. Dronedarone's lack of the iodine moiety reduces its potential for thyroid and pulmonary toxicity. Preliminary data from the DIONYSOS trial, and an indirect meta-analysis comparing amiodarone with dronedarone, showed amiodarone to be more effective in maintaining sinus rhythm, while dronedarone was associated with fewer adverse effects resulting in early termination of the drug. Dronedarone is the first antiarrhythmic drug for the treatment of atrial fibrillation and atrial flutter shown to reduce cardiovascular hospitalizations. In patients with structural heart disease who have an ejection fraction >35% and no recent decompensated heart failure, dronedarone should be considered earlier than amiodarone in the treatment algorithm.

Bioactive natural constituents from food sources-potential use in hypertension prevention and treatment.

PubMed

Huang, Wu-Yang; Davidge, Sandra T; Wu, Jianping

2013-01-01

Prevention and management of hypertension are the major public health challenges worldwide. Uncontrolled high blood pressure may lead to a shortened life expectancy and a higher morbidity due to a high risk of cardiovascular complications such as coronary heart disease (which leads to heart attack) and stroke, congestive heart failure, heart rhythm irregularities, and kidney failure etc. In recent years, it has been recognized that many dietary constituents may contribute to human cardiovascular health. There has been an increased focus on identifying these natural components of foods, describing their physiological activities and mechanisms of actions. Grain, vegetables, fruits, milk, cheese, meat, chicken, egg, fish, soybean, tea, wine, mushrooms, and lactic acid bacteria are various food sources with potential antihypertensive effects. Their main bioactive constituents include angiotensin I-converting enzyme (ACE) inhibitory peptides, vitamins C and E, flavonoids, flavanols, cathecins, anthocyanins, phenolic acids, polyphenols, tannins, resveratrol, polysaccharides, fiber, saponin, sterols, as well as K, Ca, and P. They may reduce blood pressure by different mechanisms, such as ACE inhibition effect, antioxidant, vasodilatory, opiate-like, Ca(2+) channel blocking, and chymase inhibitory activities. These functional foods may provide new therapeutic applications for hypertension prevention and treatment, and contribute to a healthy cardiovascular population. The present review summarizes the antihypertensive food sources and their bioactive constituents, as well as physiological mechanisms of dietary products, especially focusing on ACE inhibitory activity.

Effect of PR interval prolongation on long-term outcomes in patients with left bundle branch block vs non-left bundle branch block morphologies undergoing cardiac resynchronization therapy.

PubMed

Rickard, John; Karim, Mohammad; Baranowski, Bryan; Cantillon, Daniel; Spragg, David; Tang, W H Wilson; Niebauer, Mark; Grimm, Richard; Trulock, Kevin; Wilkoff, Bruce; Varma, Niraj

2017-10-01

Although the influence of QRS duration (QRSd) and/or bundle branch block morphology on outcomes of cardiac resynchronization therapy (CRT) have been well studied, the effect of PR interval remains uncertain. The purpose of this study was to evaluate the impact of PR prolongation (PRp) before CRT on long-term outcomes, specifically taking into account bundle branch block morphology and QRSd. We extracted clinical data on consecutive patients undergoing CRT. Multivariate models were constructed to analyze the effect of PRp (≥200 ms) on the combined endpoint of death, heart transplant, or left ventricular assist device. Kaplan-Meier curves were constructed stratifying patients based on bundle branch block and QRSd (dichotomized by 150 ms). Of the 472 patients who met inclusion criteria, 197 (41.7%) had PR interval ≥200 ms. During follow-up (mean 5.1 ± 2.6 years) there were 214 endpoints, of which 109 (23.1%) occurred in patients with PRp. In multivariate analysis, PRp was independently associated with worsened outcomes (hazard ratio 1.34, 95% confidence interval 1.01-1.77, P = .04). When stratified by bundle branch block morphology, PRp was significantly associated with worsened outcomes (log-rank P <.001) in patients with LBBB but not in those with non-LBBB (log-rank P = .55). Among patients with LBBB, stratified by QRSd, patients without PRp had improved outcomes compared to those with PRp independent of QRSd (log-rank P <.001). PRp is an independent predictor of impaired long-term outcome after CRT among patients with LBBB but not in non-LBBB patients. Notably, among LBBB patients, PRp is a more important predictor than QRSd in assessing long-term outcomes. Copyright © 2017. Published by Elsevier Inc.

SU-C-19A-01: A Simple Deep Inspiration Breath Hold System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rasmussen, B; Kaznowski, L; Blackburn, J

2014-06-15

Purpose: Deep Inspiration Breath Hold (DIBH) Radiation therapy for left sided breast can reduce dose to the lungs and heart. The purpose of this work is to illustrate how to implement a simple method of DIBH for simulation and treatment using equipment readily available in most radiation oncology clinics. Methods: For simulation and treatment, a foam block is placed on the patient's abdomen or chest and a horizontal laser mounted on a movable slide is aimed at the center of the foam block. After a coaching session the block is marked at the average free breathing position and average DIBHmore » position. The position of block relative to laser can be seen by the patient via prism glasses as well as the radiation therapists via a video camera system. Simulation CT scans and treatment delivery are performed under DIBH conditions. Imaging and treatment are performed by manually turning the beam on once the patient has achieved DIBH after being given verbal instructions. Results: Manually triggered imaging was used daily to verify DIBH reproducibility for all patients treated using this system. Sets of before and during port images were used to ensure patient position was appropriate for treatment. Results of the laser on block method were compared to a sister facility using surface mapping techniques for DIBH and the two methods were found to have clinically equivalent reproducibility. Conclusion: The laser and block system was found to be simple to implement and robust during patient treatment. This system can be created from readily available materials at low cost and provides adequate feedback to patient and therapists. During treatment images document the reproducibility of setup and give confidence to clinicians that this method is reproducible from day to day.« less

Comparison of Spinal Anaesthesia and Paravertebral Block in Unilateral Inguinal Hernia Repair

PubMed Central

Işıl, Canan Tülay; Çınar, Ayşe Surhan Özer; Oba, Sibel; Işıl, Rıza Gürhan

2014-01-01

Objective We aimed to compare the efficacy of spinal anaesthesia (SA) and paravertebral block (PVB) in unilateral inguinal hernia repair. Methods Sixty American Society of Anesthesia physical status (ASA) I–III patients aged between 18–64 years with unilateral inguinal hernia were enrolled in this study. Two patients in Group SA and 4 patients in Group PVB were excluded, and statistical analyses were done on 54 patients. In regard to anaesthetic choice, patients were divided into two groups, with 30 patients in each: Group SA, spinal anaesthesia and Group PVB, paravertebral block. Standard monitoring was done, and mean arterial pressure (MAP) and heart rate (HR) were recorded during the surgical procedure. Demographic variables, surgical data, patient satisfaction, the onset times to reach T10 dermatome and to reach peak sensory level, and onset time to reach modified Bromage 3 motor block were recorded. Postoperative nausea and vomiting and pain at postoperative hours 0–24 with the visual analog scale (VAS) were also measured. Results Compared to pre-anaesthesia measurements, the decrease in HR and MAP during the 10th–90th minute period was significant in Group SA (p<0.01). In Group PVB, sensory block duration time was higher, whereas paralysis rate was higher in Group SA (p<0.01). Bromage scores were significantly different between the groups (p<0.01). In Group SA, VAS score at the 24th postoperative hour, nausea, and vomiting were significantly higher compared to Group PVB (p<0.01). Conclusion In conclusion, paravertebral block provides acceptable surgical anaesthesia, maintaining good quality and long duration on postoperative analgesia in unilateral hernia repair. PMID:27366432

Effect of interscalene block on intraocular pressure and ocular perfusion pressure.

PubMed

Basaran, Betul; Yilbas, Aysun Ankay; Gultekin, Zeki

2017-10-23

Interscalene block (ISB) is commonly associated with Horner's syndrome due to spread of local anesthetic to the cervical sympathetic chain. Postganglionic neurons that originate from superior cervical ganglia form the sympathetic innervation of eye. Decrease in sympathetic tone may change intraocular pressure (IOP) and ocular perfusion pressure (OPP). The aim of the study was to investigate whether ISB affects IOP and/or OPP. Thirty patients scheduled for ambulatory shoulder surgery under regional anesthesia with a single-shot ISB (15 mL 0.5% bupivacaine and 15 mL 2% lidocaine) were recruited. The IOP and OPP in both eyes, mean arterial pressure (MAP), heart rate (HR) and end-tidal CO 2 (ETCO 2 ) were measured before ISB and 5, 10, 20, 30 and 60 min after ISB in the beach-chair position. The baseline IOP and OPP were similar in the blocked and unblocked sides (IOP 17.60 ± 1.69 and 17.40 ± 1.96 respectively p = 0.432; OPP 49.80 ± 8.20 and 50 ± 8.07 respectively p = 0.432). The IOP in the blocked side significantly decreased between 10th to 60th min following ISB, compared to the baseline values (p < 0.001). The OPP in the blocked side significantly increased from 10th to 60th min (p < 0.001) whereas, there were no significant changes in IOP and OPP throughout the measurement period in the unblocked side. ISB decreased IOP in the blocked side. ISB could be considered as a safe regional technique of choice in elderly patients at high risk for developing glaucoma.

The BMP pathway acts to directly regulate Tbx20 in the developing heart

PubMed Central

Mandel, Elizabeth M.; Kaltenbrun, Erin; Callis, Thomas E.; Zeng, Xin-Xin I.; Marques, Sara R.; Yelon, Deborah; Wang, Da-Zhi; Conlon, Frank L.

2010-01-01

TBX20 has been shown to be essential for vertebrate heart development. Mutations within the TBX20 coding region are associated with human congenital heart disease, and the loss of Tbx20 in a wide variety of model systems leads to cardiac defects and eventually heart failure. Despite the crucial role of TBX20 in a range of cardiac cellular processes, the signal transduction pathways that act upstream of Tbx20 remain unknown. Here, we have identified and characterized a conserved 334 bp Tbx20 cardiac regulatory element that is directly activated by the BMP/SMAD1 signaling pathway. We demonstrate that this element is both necessary and sufficient to drive cardiac-specific expression of Tbx20 in Xenopus, and that blocking SMAD1 signaling in vivo specifically abolishes transcription of Tbx20, but not that of other cardiac factors, such as Tbx5 and MHC, in the developing heart. We further demonstrate that activation of Tbx20 by SMAD1 is mediated by a set of novel, non-canonical, high-affinity SMAD-binding sites located within this regulatory element and that phospho-SMAD1 directly binds a non-canonical SMAD1 site in vivo. Finally, we show that these non-canonical sites are necessary and sufficient for Tbx20 expression in Xenopus, and that reporter constructs containing these sites are expressed in a cardiac-specific manner in zebrafish and mouse. Collectively, our findings define Tbx20 as a direct transcriptional target of the BMP/SMAD1 signaling pathway during cardiac maturation. PMID:20460370

Slow Breathing and Hypoxic Challenge: Cardiorespiratory Consequences and Their Central Neural Substrates

PubMed Central

Critchley, Hugo D.; Nicotra, Alessia; Chiesa, Patrizia A.; Nagai, Yoko; Gray, Marcus A.; Minati, Ludovico; Bernardi, Luciano

2015-01-01

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge. PMID:25973923

Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.

PubMed

Downs, Anthony M; Jalloh, Hawa B; Prater, Kayla J; Fregoso, Santiago P; Bond, Cherie E; Hampton, Thomas G; Hoover, Donald B

2016-05-01

The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy

PubMed Central

Dees, Ellen; Miller, Paul M.; Moynihan, Katherine L.; Pooley, Ryan D.; Hunt, R. Pierre; Galindo, Cristi L.; Rottman, Jeffrey N.; Bader, David M.

2012-01-01

SUMMARY CENP-F is a large multifunctional protein with demonstrated regulatory roles in cell proliferation, vesicular transport and cell shape through its association with the microtubule (MT) network. Until now, analysis of CENP-F has been limited to in vitro analysis. Here, using a Cre-loxP system, we report the in vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type displaying high levels of CENP-F expression. Loss of CENP-F function in developing myocytes leads to decreased cell division, blunting of trabeculation and an initially smaller, thin-walled heart. Still, embryos are born at predicted mendelian ratios on an outbred background. After birth, hearts lacking CENP-F display disruption of their intercalated discs and loss of MT integrity particularly at the costamere; these two structures are essential for cell coupling/electrical conduction and force transduction in the heart. Inhibition of myocyte proliferation and cell coupling as well as loss of MT maintenance is consistent with previous reports of generalized CENP-F function in isolated cells. One hundred percent of these animals develop progressive dilated cardiomyopathy with heart block and scarring, and there is a 20% mortality rate. Importantly, although it has long been postulated that the MT cytoskeleton plays a role in the development of heart disease, this study is the first to reveal a direct genetic link between disruption of this network and cardiomyopathy. Finally, this study has broad implications for development and disease because CENP-F loss of function affects a diverse array of cell-type-specific activities in other organs. PMID:22563055

Role of aminophylline in refractory heart failure: a comparison to the vasodilator sodium nitroprusside, the old and the new.

PubMed

DiBianco, R; Rosenfeld, S P; Katz, R J; Simpson, A G; Fletcher, R D; Singh, S

1980-08-01

Aminophylline [(theophylline ethylene diamine (TED)] reportedly improved cardiac hemodynamics by lowering vascular resistances and increasing contractility. TED as used clinically has not been compared to the vasodilator sodium nitroprusside (NP). To assess the relative hemodynamic effects of these two commonly used agents, the following comparison was made. Ten patients with congestive cardiomyopathy in chronic refractory heart failure [New York Heart Association (NYHA) class IV] were studied. All patients demonstrated cardiomegaly by chest x ray and echocardiography (LVd = 6.3 +/- 0.7 cm) and markedly abnormal hemodynamics during baseline observations (see Table I). Hemodynamic measurements at baseline were compared after TED infusion (mean blood level = 16 +/- 12 micrograms/m/TED) and during intravenous NP. No significant changes in heart rate occurred during either therapeutic intervention; a fall in mean arterial pressure of 10 mmHg (p < 0.01) was observed during NP therapy; atrioventricular (AV) block with ventricular fibrillation was successfully treated in one patient after TED. Theophylline ethylene diamine demonstrated no detectable cardiac hemodynamic effects 60--90 min post infusion despite proven blood levels, whereas NP exhibited distinctly beneficial effects in this patient group. Previous studies demonstrating improved hemodynamics occurring with TED have been limited to the time of infusion or within the following 40 min, a time when TED blood levels are maximum and therefore closest to toxicity. The results of this study suggest that TED demonstrates no beneficial hemodynamic effects in refractory heart failure as early as 1 h after infusion despite blood levels in the therapeutic range.

Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells.

PubMed

El-Bizri, Nesrine; Bkaily, Ghassan; Wang, Shimin; Jacques, Danielle; Regoli, Domenico; D'Orléans-Juste, Pedro; Sukarieh, Rami

2003-03-01

Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (10(-10) M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1 or B2 receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (10(-6) M) had no effect on fast Na+ inward current and delayed outward potassium current. However, both L- and T-type Ca2+ currents were found to be increased by BK in a dose-dependent manner (10(-10)-10(-7) M). The effects of BK on T- and L-type Ca2+ currents were partially blocked by the B1 receptor antagonist [Leu8]des-Arg9-BK (R592) (10(-7) M) and completely reversed by the B2 receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (10(-7) M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+ currents in heart cells mainly via stimulation of B2 receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+ current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.

Chronic mercury exposure impairs the sympathovagal control of the rat heart.

PubMed

Simões, M R; Azevedo, B F; Fiorim, J; Jr Freire, D D; Covre, E P; Vassallo, D V; Dos Santos, L

2016-11-01

Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl 2 (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl 2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl 2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl 2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk. © 2016 John Wiley & Sons Australia, Ltd.

[Heart transplantation. Experience at La Pitié hospital. Apropos of 82 cases].

PubMed

Cabrol, C; Gandjbakhch, I; Pavie, A; Cabrol, A; Mattei, M F; Liénhart, A; Gluckmann, J C; Rottembourg, J

1984-12-01

Since 1968, 320 patients with severe irreversible myocardial failure, have been referred to our department for transplantation; 78 p. 100 had dilated cardiomyopathies; 14 p. 100 had ischaemic heart disease and 8 p. 100 had valvular heart disease. One hundred and five patients had absolute contra-indications and were excluded (pulmonary hypertension, diabetes, gastro-duodenal ulcer, age, or other major organic disease). Of the remaining 215 patients, only 82 were transplanted because of the limited number of available donor hearts. The most commonly used technique was orthotopic grafting as described by Lower and Shumway; Barnard's method of heterotopic grafting was used in 1 case and a block heart and lung transplantation by Reitz and Shumway's method was performed in 3 cases. The main postoperative complications, apart from technical problems (7 deaths), were related to rejection (107 episodes, 27 deaths), infection (82 episodes, 13 deaths), atherosclerosis of the graft (4 cases, 2 deaths, 1 retransplantation) and malignant tumours (3 deaths). After transplantation, 82 p. 100 of patients were discharged after an average hospital stay of 2 months; 47 p. 100 survived the first year and lead almost normal socio-professional activities. Thirty patients are still alive, the longest postoperative survival being 9 years. Significant advances have been made in the last 3 years. Classical immuno-suppressor therapy (steroids, azathioprine, horse antilymphocytic serum) has given way to more effective antilymphocytic sera and more powerful immuno-suppressor drugs (cyclosporine A). This treatment has greatly changed the postoperative course of events. Rejection phenomena, though still as common, are much less serious and, above all, more insidious.(ABSTRACT TRUNCATED AT 250 WORDS)

Dependence of Ca outflow and depression of frog myocardium contraction on ryodipine concentration.

PubMed

Narusevicius, E; Gendviliene, V; Macianskiene, R; Hmelj-Dunai, G; Velena, A; Duburs, G

1988-02-01

The effect of ryodipine on calcium outflow from tissues, on contraction force, the duration of action potentials and the relaxation phase time-constant in the contraction cycles of myocardial strips was studied using frog heart preparations. It was found that calcium outflow (delta Ca) as a function on ryodipine concentration can be represented as: (formula; see text) A linear correlation exists between Ca2+, contraction blocking and the shortening of the action potential in the presence of various ryodipine concentrations. Ryodipine (10(-5) mol/l) decreased the relaxation time-constant by about 20% as compared to controls. It was concluded that calcium outflow from myocardial tissues in response to ryodipine is due to blockade of calcium entry into the cells and their output through the Na+--Ca2+ exchange system. Frog heart myocardial contractions are essentially under the control of calcium entry through sarcolemmal calcium channels.

Electromechanical integration of cardiomyocytes derived from human embryonic stem cells.

PubMed

Kehat, Izhak; Khimovich, Leonid; Caspi, Oren; Gepstein, Amira; Shofti, Rona; Arbel, Gil; Huber, Irit; Satin, Jonathan; Itskovitz-Eldor, Joseph; Gepstein, Lior

2004-10-01

Cell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell-derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies.

What is the risk of hyperkalaemia in heart failure?

PubMed

Bielecka-Dabrowa, Agata; Rysz, Jacek; Mikhailidis, Dimitri P; Banach, Maciej

2011-10-01

Chronic heart failure (CHF) is the only major cardiovascular disease whose prevalence and incidence are thought to be increasing. Potassium balance may be lost both through the neurohormonal mechanisms involved in cardiovascular diseases and through the drugs used in their treatment. Avoiding both hypo- and hyperkalemia is difficult but beneficial in CHF. Aldosterone production is decreased in the elderly, diabetic patients, and those receiving drugs that block the production or action of renin and angiotensin II. As a result, these groups, as well as those with already impaired potassium excretion due to progressive age or disease-related decline in glomerular filtration rate, are particularly vulnerable to the development of hyperkalemia. Evidence from several studies suggests that, in patients with CHF, serum potassium should be maintained between 4.0 and 5.5 mEq/L. To gain the maximum benefit from aldosterone antagonists it is necessary to individualize their use; it is also necessary to carefully monitor electrolytes.

Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient

NASA Technical Reports Server (NTRS)

Sun, E.; Gao, Y.; Chen, J.; Roberts, A. I.; Wang, X.; Chen, Z.; Shi, Y.

2004-01-01

Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

INCREASED HYPOTHALAMIC ANGIOTENSIN-(1-7) LEVELS IN RATS WITH AORTIC COARCTATION-INDUCED HYPERTENSION

PubMed Central

Gironacci, Mariela M.; Brosnihan, K. Bridget; Ferrario, Carlos M.; Gorzalczany, Susana; Lopez Verrilli, María A.; Pascual, Mariano; Taira, Carlos; Peña, Clara

2007-01-01

Since angiotensin (Ang) (1-7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1-7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1-7) compared with the normotensive group, with Ang II being the predominant peptide in heart and kidney. In the hypothalamus, equimolar amounts of Ang II and Ang-(1-7) were found in the sham group, whereas only Ang-(1-7) levels increased in CH rats. We conclude that aortic coarctation activates systemic and tissue renin-angiotensin system. The increased central levels of Ang-(1-7) in the CH rats suggest a potential mitigating role of this peptide in central control of the hypertensive process. PMID:17646033

Dual renin-angiotensin-aldosterone blockade: promises and pitfalls.

PubMed

Chrysant, Steven G; Chrysant, George S

2015-01-01

Single renin-angiotensin-aldosterone system (RAAS) blockade has been shown to be effective and safe for the treatment of hypertension, coronary heart disease (CHD), heart failure (HF), diabetes, and chronic kidney disease (CKD) with proteinuria. Due to the action of RAAS blockers at various levels of the RAAS cascade, it was hypothesized that dual RAAS blockade would result in more complete inhibition of angiotensin II (Ang II) production and be more effective in blocking its detrimental cardiovascular remodeling effects. Unfortunately, several clinical trials in patients with hypertension, CHD, HF, and CKD with proteinuria have demonstrated no superiority of dual versus single RAAS blockade, but a higher incidence of adverse events. Based on these findings, dual RAAS blockade is no longer recommended for the routine treatment of various cardiovascular diseases, except diabetic nephropathy with proteinuria and HF with reduced ejection fraction. All the new information gathered from studies within the last 3 years will be presented in this review.

Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy.

PubMed

Fujiita, Takashi; Shimizu, Masami; Kaku, Bunji; Kanaya, Hounin; Horita, Yuki; Uno, Yoshihide; Yamazaki, Tsukasa; Ohka, Takio; Sakata, Kenji; Mabuchi, Hiroshi

2005-07-01

A 33-year-old man was admitted for general malaise and vomiting. An electrocardiogram showed a complete atrioventricular block and an echocardiogram showed right atrial dilatation and normal wall motion of left ventricle (LV). Gene analysis showed nonsense mutation in the STA gene, which codes for emerin, and Emery-Dreifuss muscular dystrophy was diagnosed. An endomyocardial biopsy of right ventricle showed mild hypertrophy of myocytes. Myocardial scintigraphic studies with Tc-99m methoxyisobutylisonitrile (MIBI) and I-123-betamethyl-p-iodophenylpentadecanoic acid (BMIPP) scintigrams showed no abnormalities. In contrast, I-123 metaiodobenzylguanidine (MIBG) scintigrams showed a diffuse and severe decrease in accumulation of MIBG in the heart. Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy.

Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation.

PubMed

Holmes, Jeffrey W; Laksman, Zachary; Gepstein, Lior

2016-01-01

Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function - maintaining integrity of the heart wall against enormous mechanical forces - but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inverse Relationship of Blood Pressure to Long-Term Outcomes and Benefit of Cardiac Resynchronization Therapy in Patients With Mild Heart Failure: A Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Long-Term Follow-Up Substudy.

PubMed

Biton, Yitschak; Moss, Arthur J; Kutyifa, Valentina; Mathias, Andrew; Sherazi, Saadia; Zareba, Wojciech; McNitt, Scott; Polonsky, Bronislava; Barsheshet, Alon; Brown, Mary W; Goldenberg, Ilan

2015-09-01

Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with left ventricular dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase systolic blood pressure (SBP). Therefore, we hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. The independent contribution of SBP to outcome was analyzed in 1267 patients with left bundle brunch block enrolled in Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death and CRT with defibrillator versus implantable cardioverter defibrillator benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the implantable cardioverter defibrillator arm, each 10-mm Hg decrement of SBP was independently associated with a significant 21% (P<0.001) increased risk for HF or death, and patients with lower quintile SBP (<110 mm Hg) experienced a corresponding >2-fold risk-increase. CRT with defibrillator provided the greatest HF or mortality risk reduction in patients with SBP<110 mm Hg hazard ratio of 0.34, P<0.001, when compared with hazard ratio of 0.52, P<0.001, in those with 110>SBP≥136 mm Hg and hazard ratio of 0.94, P=0.808, with SBP>136 mm Hg (P for trend=0.001). In patients with mild HF, prolonged QRS, and left bundle brunch block, low SBP is related to higher risk of mortality or HF with implantable cardioverter defibrillator therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline SBP values. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271. © 2015 American Heart Association, Inc.

Frailty syndrome in patients with heart rhythm disorders.

PubMed

Mlynarska, Agnieszka; Mlynarski, Rafal; Golba, Krzysztof S

2017-09-01

To assess the prevalence of frailty syndrome in patients with heart rhythm disorders that qualified for pacemaker implantation. The study included 171 patients (83 women, aged 73.9 ± 6.7 years) who qualified for pacemaker implantation as a result of sinus node dysfunction (81 patients) or atrio-ventricular blocks (AVB; 90 patients). A total of 60 patients (25 women, aged 72.40 ± 7.09 years) without heart rhythm disorders were included in the control group. Frailty syndrome was diagnosed using the Canadian Study of Health and Aging Clinical Frailty Scale test. Frailty syndrome was diagnosed in 25.15% of the patients, and pre-frailty in 36.84% of the patients. Frailty syndrome was diagnosed in 10% of the control group, and the average value of frailty was 3.35 ± 0.92. Frailty occurred significantly more often among patients with AVB (33.34%) compared with patients who were diagnosed with sinus node dysfunction (16.05%); P = 0.0081. The average score of frailty for sinus node dysfunction was 3.71 ± 0.89, and for AVB it was 4.14 ± 0.93; P = 0.0152. In the case of AVB, the women had a statistically more intense level of frailty of 4.54 ± 0.90 as compared with the men 3.87 ± 0.85; P = 0.0294. In the multiple logistic analysis, the presence of any arrhythmia was strongly associated with frailty syndrome (OR 2.1286, 95% CI 1.4594 - 3.1049; P = 0.0001). Frailty syndrome was diagnosed in one-quarter of patients with cardiac arrhythmias, whereas a further 40% were at a higher risk of frailty syndrome, and its occurrence was significantly higher if compared with the control group. Frailty occurred significantly more often among patients with atrio-ventricular blocks, especially in women. The results of the present research showed that there is a statistical association between frailty and arrhythmias. Geriatr Gerontol Int 2017; 17: 1313-1318. © 2016 Japan Geriatrics Society.

Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial.

PubMed

Konstam, Marvin A; Neaton, James D; Dickstein, Kenneth; Drexler, Helmut; Komajda, Michel; Martinez, Felipe A; Riegger, Gunter A J; Malbecq, William; Smith, Ronald D; Guptha, Soneil; Poole-Wilson, Philip A

2009-11-28

Angiotensin-receptor blockers (ARBs) are effective treatments for patients with heart failure, but the relation between dose and clinical outcomes has not been explored. We compared the effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure. This double-blind trial was undertaken in 255 sites in 30 countries. 3846 patients with heart failure of New York Heart Association class II-IV, left-ventricular ejection fraction 40% or less, and intolerance to angiotensin-converting-enzyme (ACE) inhibitors were randomly assigned to losartan 150 mg (n=1927) or 50 mg daily (n=1919). Allocation was by block randomisation stratified by centre and presence or absence of beta-blocker therapy, and all patients and investigators were masked to assignment. The primary endpoint was death or admission for heart failure. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00090259. Six patients in each group were excluded because of poor data quality. With 4.7-year median follow-up in each group (IQR 3.7-5.5 for losartan 150 mg; 3.4-5.5 for losartan 50 mg), 828 (43%) patients in the 150 mg group versus 889 (46%) in the 50 mg group died or were admitted for heart failure (hazard ratio [HR] 0.90, 95% CI 0.82-0.99; p=0.027). For the two primary endpoint components, 635 patients in the 150 mg group versus 665 in the 50 mg group died (HR 0.94, 95% CI 0.84-1.04; p=0.24), and 450 versus 503 patients were admitted for heart failure (0.87, 0.76-0.98; p=0.025). Renal impairment (n=454 vs 317), hypotension (203 vs 145), and hyperkalaemia (195 vs 131) were more common in the 150 mg group than in the 50 mg group, but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group. Losartan 150 mg daily reduced the rate of death or admission for heart failure in patients with heart failure, reduced left-ventricular ejection fraction, and intolerance to ACE inhibitors compared with losartan 50 mg daily. These findings show the value of up-titrating ARB doses to confer clinical benefit. Merck (USA).

Transforming the "unacceptable" donor: outcomes from the adoption of a standardized donor management technique.

PubMed

Wheeldon, D R; Potter, C D; Oduro, A; Wallwork, J; Large, S R

1995-01-01

Donor management remains one of the most neglected areas of transplantation. A comprehensive donor management regimen has been developed. The results of the application of this strategy form the basis of this report. Full hemodynamic data were collected from 150 multiorgan donors between October 1990 and August 1993. The data were collected at the time of donor team arrival, after insertion of a pulmonary artery floatation catheter and immediately before cardiac excision. Fifty-two donors (35%) fell well outside our minimum acceptance criteria on arrival. Twenty-one of fifty-two had a mean arterial pressure less than 55 mm Hg (mean 47 mm Hg) despite inotropic support in most cases; 10 of 52 had a central venous pressure greater than 15 mm Hg (mean 18.0 mm Hg); 2 of 52 had a high inotrope requirement greater than 20 micrograms/kg/min (mean 25 micrograms/kg/min). After the insertion of a pulmonary artery floatation catheter, an additional 13 of 52 donors were found to have a pulmonary capillary wedge pressure greater than 15 mm Hg (mean 19.8 mm Hg), and the final 6 of 52 had a low left ventricular stroke work index, less than 15 gm (mean 12.8 gm). After optimal management, including hormone replacement 44 of 52 donors yielded transplantable organs (29 hearts, 15 heart and lung blocks). Thirty-seven of forty-four patients (84%) were alive and well from 13 to 48 months after transplantation. There were five early deaths (11%) caused by infection (heart), adult respiratory distress syndrome (heart), arrhythmia (heart), cerebrovascular event (heart and lung), and infection (heart, lung, and liver). Two late deaths (5%) occurred as a result of tamponade (3 months, heart) and infection (14 months, heart and lung). Eight of fifty-two organs were still unsuitable for transplantation after optimum management during the splanchnic dissection as a result of inotrope dependency (n = 4), left ventricular hypertrophy (n = 2), and coronary artery disease (n = 2). The data indicate that, of the organs which initially fall outside our transplant acceptance criteria, 92% are capable of functional resuscitation. Conversely, superficial assessment may not show compromised function. Optimizing cardiovascular performance also has important implications for the viability of all transplantable organs. This aggressive approach to donor management has resulted in the transplantation of 44 donor hearts that may otherwise have been turned down or inappropriately managed.

How revealing are insertable loop recorders in pediatrics?

PubMed

Frangini, Patricia A; Cecchin, Frank; Jordao, Ligia; Martuscello, Maria; Alexander, Mark E; Triedman, John K; Walsh, Edward P; Berul, Charles I

2008-03-01

An insertable loop recorder (ILR) in patients with infrequent syncope or palpitations may be useful to decide management strategies, including clinical observation, medical therapy, pacemaker, or implantable cardioverter defibrillator (ICD). We sought to determine the diagnostic utility of the Reveal ILR (Medtronic, Inc., Minneapolis, MN, USA) in pediatric patients. Retrospective review of clinical data, indications, findings, and therapeutic decision in 27 consecutive patients who underwent ILR implantation from 1998-2007. The median age was 14.8 years (2-25 years). Indications were syncope in 24 patients and recurrent palpitations in three. Overall, eight patients had structural heart disease (six congenital heart disease, one hypertrophic cardiomyopathy, one Kawasaki), five had previous documented ventricular arrhythmias with negative evaluation including electrophysiology study, and three patients had QT prolongation. Tilt testing was performed in 10 patients, of which five had neurocardiogenic syncope but recurrent episodes despite medical therapy. After median three months (1-20 months), 17 patients presented with symptoms and the ILR memory was analyzed in 16 (no episode stored in one due to full device memory), showing asystole or transient atrioventricular (AV) block (2), sinus bradycardia (6), or normal sinus rhythm (8). Among asymptomatic patients, 3/10 had intermittent AV block or long pauses, automatically detected and stored by the ILR. In 19 of 20 patients, ILR was diagnostic (95%) and five subsequently underwent pacemaker implantation, while seven patients remained asymptomatic without ILR events. Notably, no life-threatening events were detected. The ILR was explanted in 22 patients after a median of 22 months, two due to pocket infection, 12 for battery depletion and eight after clear documentation of nonmalignant arrhythmia. The ILR in pediatrics is a useful adjunct to other diagnostic studies. Patient selection is critical as the ILR should not be utilized for malignant arrhythmias. A diagnosis is attained in the majority of symptomatic patients, predominantly bradyarrhythmias including pauses and intermittent AV block.

Effects of stellate ganglion block on sedation as assessed by bispectral index in normal healthy volunteers.

PubMed

Yeo, Jinseok; Jeon, Younghoon

2015-01-01

The sympathetic nervous system plays an important role in the arousal response. Recently, the stellate ganglion block (SGB) was found to effectively treat anxiety and night awakening in humans and decrease electroencephalogram (EEG) indices of arousal responses in rat. But, the role of the sympathetic block in human arousal responses has not yet been studied. We performed this prospective, double-blinded, controlled volunteer study to investigate the sedative effects and bispectral index (BIS) changes of SGB. A randomized, double-blind trial. Single academic medical center. This study was approved by the Ethics Committee of Kyungpook National University Hospital (ref: KNUH-10-1081) and registered with CRiS (Clinical Research Information Service, http://cris.cdc.go.kr, ref: KCT0000036, 2010. 9.24). Twenty healthy volunteers were enrolled in this study. The volunteers were randomly assigned to one of 2 groups: the SGB group (n = 10) and the sham group (n =10). Volunteers in SGB group received SGB and volunteers in the sham group received a sham procedure. BIS value, heart rate, and blood pressure were measured before and 5, 10, 20, and 30 minutes after the procedure. Observer's Assessment of Alertness/Sedation (OAA/S) scores were assessed before and 10 and 30 minutes after the intervention. In the SGB group, BIS values and OAA/S scores significantly decreased after the intervention as compared to baseline (P < 0.05). The values were also significantly decreased in the SGB group when compared to the values in sham group after the intervention (P < 0.05). There was a significant change of mean blood pressure 10 to 30 minutes after SGB (P < 0.05). There were no differences in heart rate during study period between groups. This study is limited by a relatively small sample size. This study showed that SGB has a sedative effect in normal healthy volunteers, as evidenced by decreased OAA/S scores and BIS values.

MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway.

PubMed

Cerniello, Flavia M; Carretero, Oscar A; Longo Carbajosa, Nadia A; Cerrato, Bruno D; Santos, Robson A; Grecco, Hernán E; Gironacci, Mariela M

2017-11-01

The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein). MAS1R internalization was evaluated by measuring the MAS1R present in the plasma membrane after agonist stimulation using a ligand-binding assay. MAS1R trafficking was evaluated by its colocalization with trafficking markers. MAS1R internalization was blocked in the presence of shRNAcaveolin-1 and with dominant negatives for Eps15 (a protein involved in endocytosed Rs by clathrin-coated pits) and for dynamin. After stimulation, MAS1R colocalized with Rab11-a slow recycling vesicle marker-and not with Rab4-a fast recycling vesicle marker-or LysoTracker-a lysosome marker. Cells transfected with MAS1R showed an increase in Akt and ERK1/2 activation on angiotensin-(1-7) stimulation, which was blocked when the clathrin-coated pits pathway was blocked. Suppression of β-arrestin2 by shRNA reduced the angiotensin-(1-7)-induced ERK1/2 activation, whereas Akt activation was not modified. We conclude that on agonist stimulation, MAS1R is internalized through clathrin-coated pits and caveolae in a dynamin-dependent manner and is then slowly recycled back to the plasma membrane. MAS1R induced Akt and ERK1/2 activation from early endosomes, and the activation of ERK1/2 was mediated by β-arrestin2. Thus, MAS1R activity and density may be tightly controlled by the cell. © 2017 American Heart Association, Inc.

An implantable nerve cooler for the exercising dog.

PubMed

Borgdorff, P; Versteeg, P G

1984-01-01

An implantable nerve cooler has been constructed to block cervical vago-sympathetic activity in the exercising dog reversibly. An insulated gilt brass container implanted around the nerve is perfused with cooled alcohol via silicone tubes. The flow of alcohol is controlled by an electromagnetic valve to keep nerve temperature at the required value. Nerve temperature is measured by a thermistor attached to the housing and in contact with the nerve. It is shown that, during cooling, temperature at this location differs less than 2 degrees C from nerve core temperature. Measurement of changes in heart rate revealed that complete vagal block in the conscious animal is obtained at a nerve temperature of 2 degrees C and can be achieved within 50 s. During steady-state cooling in the exercising animal nerve temperature varied less than 0.5 degree C. When the coolers after 2 weeks of implantation were removed they showed no oxydation and could be used again.

Crebanine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytes.

PubMed

Xiao-Shan, He; Qing, Lin; Yun-Shu, Ma; Ze-Pu, Yu

2014-01-01

To study the effects of crebanine on voltage-gated Na(+) channels in cardiac tissues. Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltage-dependent Na(+) current was recorded using the whole cell voltage-clamp technique. Crebanine reversibly inhibited Na(+) current with an IC50 value of 0.283 mmol·L(-1) (95% confidence range: 0.248-0.318 mmol·L(-1)). Crebanine at 0.262 mmol·L(-1) caused a negative shift (about 12 mV) in the voltage-dependence of steady-state inactivation of Na(+) current, and retarded its recovery from inactivation, but did not affect its activation curve. In addition to blocking other voltage-gated ion channels, crebanine blocked Na(+) channels in guinea-pig ventricular myocytes. Crebanine acted as an inactivation stabilizer of Na(+) channels in cardiac tissues. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Automated detection of heart ailments from 12-lead ECG using complex wavelet sub-band bi-spectrum features

PubMed Central

Dandapat, Samarendra

2017-01-01

The complex wavelet sub-band bi-spectrum (CWSB) features are proposed for detection and classification of myocardial infarction (MI), heart muscle disease (HMD) and bundle branch block (BBB) from 12-lead ECG. The dual tree CW transform of 12-lead ECG produces CW coefficients at different sub-bands. The higher-order CW analysis is used for evaluation of CWSB. The mean of the absolute value of CWSB, and the number of negative phase angle and the number of positive phase angle features from the phase of CWSB of 12-lead ECG are evaluated. Extreme learning machine and support vector machine (SVM) classifiers are used to evaluate the performance of CWSB features. Experimental results show that the proposed CWSB features of 12-lead ECG and the SVM classifier are successful for classification of various heart pathologies. The individual accuracy values for MI, HMD and BBB classes are obtained as 98.37, 97.39 and 96.40%, respectively, using SVM classifier and radial basis function kernel function. A comparison has also been made with existing 12-lead ECG-based cardiac disease detection techniques. PMID:28894589

Cardiotoxic and Cardioprotective Features of Chronic β-adrenergic Signaling

PubMed Central

Zhang, Xiaoying; Szeto, Christopher; Gao, Erhe; Tang, Mingxin; Jin, Jianguo; Fu, Qin; Makarewich, Catherine; Ai, Xiaojie; Li, Ying; Tang, Allen; Wang, Jenny; Gao, Hui; Wang, Fang; Ge, Xinyi Joy; Kunapuli, Satya P.; Zhou, Lin; Zeng, Chunyu; Xiang, Kevin Yang; Chen, Xiongwen

2012-01-01

Rationale In the failing heart, persistent β-adrenergic receptor (βAR) activation is thought to induce myocyte death by protein kinase A (PKA)-dependent and PKA-independent activation of calcium/calmodulin-dependent kinase II (CaMKII). β-Adrenergic signaling pathways are also capable of activating cardioprotective mechanisms. Objective This study used a novel PKA inhibitor peptide (PKI) to inhibit PKA activity to test the hypothesis that βAR signaling causes cell death through PKA-dependent pathways and cardioprotection through PKA-independent pathways. Methods and Results In PKI transgenic mice, chronic isoproterenol (ISO) failed to induce cardiac hypertrophy, fibrosis, myocyte apoptosis and depressed cardiac function. In cultured adult feline ventricular myocytes (AFVMs), PKA inhibition protected myocytes from death induced by β1-AR agonists by preventing cytosolic and SR Ca2+ overload and CaMKII activation. PKA inhibition revealed a cardioprotective role of β-adrenergic signaling via cAMP/EPAC /Rap1/Rac/ERK pathway. Selective PKA inhibition causes protection in the heart after myocardial infarction (MI) that was superior to β-blocker therapy. Conclusion These results suggest that selective block of PKA could be a novel heart failure therapy. PMID:23104882