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.

Identification of cardiac rhythm features by mathematical analysis of vector fields.

PubMed

Fitzgerald, Tamara N; Brooks, Dana H; Triedman, John K

2005-01-01

Automated techniques for locating cardiac arrhythmia features are limited, and cardiologists generally rely on isochronal maps to infer patterns in the cardiac activation sequence during an ablation procedure. Velocity vector mapping has been proposed as an alternative method to study cardiac activation in both clinical and research environments. In addition to the visual cues that vector maps can provide, vector fields can be analyzed using mathematical operators such as the divergence and curl. In the current study, conduction features were extracted from velocity vector fields computed from cardiac mapping data. The divergence was used to locate ectopic foci and wavefront collisions, and the curl to identify central obstacles in reentrant circuits. Both operators were applied to simulated rhythms created from a two-dimensional cellular automaton model, to measured data from an in situ experimental canine model, and to complex three-dimensional human cardiac mapping data sets. Analysis of simulated vector fields indicated that the divergence is useful in identifying ectopic foci, with a relatively small number of vectors and with errors of up to 30 degrees in the angle measurements. The curl was useful for identifying central obstacles in reentrant circuits, and the number of velocity vectors needed increased as the rhythm became more complex. The divergence was able to accurately identify canine in situ pacing sites, areas of breakthrough activation, and wavefront collisions. In data from human arrhythmias, the divergence reliably estimated origins of electrical activity and wavefront collisions, but the curl was less reliable at locating central obstacles in reentrant circuits, possibly due to the retrospective nature of data collection. The results indicate that the curl and divergence operators applied to velocity vector maps have the potential to add valuable information in cardiac mapping and can be used to supplement human pattern recognition.

Phantom evaluation of a cardiac SPECT/VCT system that uses a common set of solid-state detectors for both emission and transmission scans.

PubMed

Bai, Chuanyong; Conwell, Richard; Kindem, Joel; Babla, Hetal; Gurley, Mike; De Los Santos, Romer; Old, Rex; Weatherhead, Randy; Arram, Samia; Maddahi, Jamshid

2010-06-01

We developed a cardiac SPECT system (X-ACT) with low dose volume CT transmission-based attenuation correction (AC). Three solid-state detectors are configured to form a triple-head system for emission scans and reconfigured to form a 69-cm field-of-view detector arc for transmission scans. A near mono-energetic transmission line source is produced from the collimated fluorescence x-ray emitted from a lead target when the target is illuminated by a narrow polychromatic x-ray beam from an x-ray tube. Transmission scans can be completed in 1 min with insignificant patient dose (deep dose equivalent <5 muSv). We used phantom studies to evaluate (1) the accuracy of the reconstructed attenuation maps, (2) the effect of AC on image uniformity, and (3) the effect of AC on defect contrast (DC). The phantoms we used included an ACR phantom, an anthropomorphic phantom with a uniform cardiac insert, and an anthropomorphic phantom with two defects in the cardiac insert. The reconstructed attenuation coefficient of water at 140 keV was .150 +/- .003/cm in the uniform region of the ACR phantom, .151 +/- .003/cm and .151 +/- .002/cm in the liver and cardiac regions of the anthropomorphic phantom. The ACR phantom images with AC showed correction of the bowing effect due to attenuation in the images without AC (NC). The 17-segment scores of the images of the uniform cardiac insert were 78.3 +/- 6.5 before and 87.9 +/- 3.3 after AC (average +/- standard deviation). The inferior-to-anterior wall ratio and the septal-to-lateral wall ratio were .99 and 1.16 before and 1.02 and 1.00 after AC. The DC of the two defects was .528 and .156 before and .628 and .173 after AC. The X-ACT system generated accurate attenuation maps with 1-minute transmission scans. AC improved image quality and uniformity over NC.

Three-dimensional mapping in the electrophysiological laboratory.

PubMed

Maury, Philippe; Monteil, Benjamin; Marty, Lilian; Duparc, Alexandre; Mondoly, Pierre; Rollin, Anne

2018-06-07

Investigation and catheter ablation of cardiac arrhythmias are currently still based on optimal knowledge of arrhythmia mechanisms in relation to the cardiac anatomy involved, in order to target their crucial components. Currently, most complex arrhythmias are investigated using three-dimensional electroanatomical navigation systems, because these are felt to optimally integrate both the anatomical and electrophysiological features of a given arrhythmia in a given patient. In this article, we review the technical background of available three-dimensional electroanatomical navigation systems, and their potential use in complex ablations. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Novel Micropatterned Cardiac Cell Cultures with Realistic Ventricular Microstructure

PubMed Central

Badie, Nima; Bursac, Nenad

2009-01-01

Systematic studies of cardiac structure-function relationships to date have been hindered by the intrinsic complexity and variability of in vivo and ex vivo model systems. Thus, we set out to develop a reproducible cell culture system that can accurately replicate the realistic microstructure of native cardiac tissues. Using cell micropatterning techniques, we aligned cultured cardiomyocytes at micro- and macroscopic spatial scales to follow local directions of cardiac fibers in murine ventricular cross sections, as measured by high-resolution diffusion tensor magnetic resonance imaging. To elucidate the roles of ventricular tissue microstructure in macroscopic impulse conduction, we optically mapped membrane potentials in micropatterned cardiac cultures with realistic tissue boundaries and natural cell orientation, cardiac cultures with realistic tissue boundaries but random cell orientation, and standard isotropic monolayers. At 2 Hz pacing, both microscopic changes in cell orientation and ventricular tissue boundaries independently and synergistically increased the spatial dispersion of conduction velocity, but not the action potential duration. The realistic variations in intramural microstructure created unique spatial signatures in micro- and macroscopic impulse propagation within ventricular cross-section cultures. This novel in vitro model system is expected to help bridge the existing gap between experimental structure-function studies in standard cardiac monolayers and intact heart tissues. PMID:19413993

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

DOE PAGES

Qian, Fang; Huang, Chao; Lin, Yi-Dong; ...

2017-04-18

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

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

Qian, Fang; Huang, Chao; Lin, Yi-Dong

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

In Situ Optical Mapping of Voltage and Calcium in the Heart

PubMed Central

Ewart, Paul; Ashley, Euan A.; Loew, Leslie M.; Kohl, Peter; Bollensdorff, Christian; Woods, Christopher E.

2012-01-01

Electroanatomic mapping the interrelation of intracardiac electrical activation with anatomic locations has become an important tool for clinical assessment of complex arrhythmias. Optical mapping of cardiac electrophysiology combines high spatiotemporal resolution of anatomy and physiological function with fast and simultaneous data acquisition. If applied to the clinical setting, this could improve both diagnostic potential and therapeutic efficacy of clinical arrhythmia interventions. The aim of this study was to explore this utility in vivo using a rat model. To this aim, we present a single-camera imaging and multiple light-emitting-diode illumination system that reduces economic and technical implementation hurdles to cardiac optical mapping. Combined with a red-shifted calcium dye and a new near-infrared voltage-sensitive dye, both suitable for use in blood-perfused tissue, we demonstrate the feasibility of in vivo multi-parametric imaging of the mammalian heart. Our approach combines recording of electrophysiologically-relevant parameters with observation of structural substrates and is adaptable, in principle, to trans-catheter percutaneous approaches. PMID:22876327

Vasopressin responses to unloading arterial baroreceptors during cardiac nerve blockade in conscious dogs

NASA Technical Reports Server (NTRS)

O'Donnell, C. P.; Keil, L. C.; Thrasher, T. N.

1992-01-01

We examined the relative contributions of afferent input from the heart and from arterial baroreceptors in the stimulation of arginine vasopressin (AVP) secretion in response to hypotension caused by thoracic inferior vena caval constriction (TIVCC). Afferent input from cardiac receptors was reversibly blocked by infusing 2% procaine into the pericardial space to anesthetize the cardiac nerves. Acute cardiac nerve blockade (CNB) alone caused a rise in mean arterial pressure (MAP) of 24 +/- 3 mmHg but no change in plasma AVP. If the rise in MAP was prevented by TIVCC, plasma AVP increased by 39 +/- 15 pg/ml, and if MAP was allowed to increase and then was forced back to control by TIVCC, plasma AVP increased by 34 +/- 15 pg/ml. Thus the rise in MAP during CNB stimulated arterial baroreceptors, which in turn compensated for the loss of inhibitory input from cardiac receptors on AVP secretion. These results indicate that the maximum secretory response resulting from complete unloading of cardiac receptors at a normal MAP results in a mean increase in plasma AVP of 39 pg/ml in this group of dogs. When MAP was reduced 25% below control levels (from 95 +/- 5 to 69 +/- 3 mmHg) by TIVCC during pericardial saline infusion, plasma AVP increased by 79 +/- 42 pg/ml. However, the same degree of hypotension during CNB (MAP was reduced from 120 +/- 5 to 71 +/- 3 mmHg) led to a greater (P less than 0.05) increase in plasma AVP of 130 +/- 33 pg/ml. Because completely unloading cardiac receptors can account for an increase of only 39 pg/ml on average in this group of dogs, the remainder of the increase in plasma AVP must be due to other sources of stimulation. We suggest that the principal stimulus to AVP secretion after acute CNB in these studies arises from unloading the arterial baroreceptors.

Voltage-based device tracking in a 1.5 Tesla MRI during imaging: initial validation in swine models.

PubMed

Schmidt, Ehud J; Tse, Zion T H; Reichlin, Tobias R; Michaud, Gregory F; Watkins, Ronald D; Butts-Pauly, Kim; Kwong, Raymond Y; Stevenson, William; Schweitzer, Jeffrey; Byrd, Israel; Dumoulin, Charles L

2014-03-01

Voltage-based device-tracking (VDT) systems are commonly used for tracking invasive devices in electrophysiological cardiac-arrhythmia therapy. During electrophysiological procedures, electro-anatomic mapping workstations provide guidance by integrating VDT location and intracardiac electrocardiogram information with X-ray, computerized tomography, ultrasound, and MR images. MR assists navigation, mapping, and radiofrequency ablation. Multimodality interventions require multiple patient transfers between an MRI and the X-ray/ultrasound electrophysiological suite, increasing the likelihood of patient-motion and image misregistration. An MRI-compatible VDT system may increase efficiency, as there is currently no single method to track devices both inside and outside the MRI scanner. An MRI-compatible VDT system was constructed by modifying a commercial system. Hardware was added to reduce MRI gradient-ramp and radiofrequency unblanking pulse interference. VDT patches and cables were modified to reduce heating. Five swine cardiac VDT electro-anatomic mapping interventions were performed, navigating inside and thereafter outside the MRI. Three-catheter VDT interventions were performed at >12 frames per second both inside and outside the MRI scanner with <3 mm error. Catheters were followed on VDT- and MRI-derived maps. Simultaneous VDT and imaging was possible in repetition time >32 ms sequences with <0.5 mm errors, and <5% MRI signal-to-noise ratio (SNR) loss. At shorter repetition times, only intracardiac electrocardiogram was reliable. Radiofrequency heating was <1.5°C. An MRI-compatible VDT system is feasible. Copyright © 2013 Wiley Periodicals, Inc.

Hemodynamic comparison of mild and severe preeclampsia: concept of stroke systemic vascular resistance index.

PubMed

Scardo, J; Kiser, R; Dillon, A; Brost, B; Newman, R

1996-01-01

Our purpose was to compare baseline hemodynamic parameters of mild and severe preeclampsia. Patients admitted to the Medical University Labor and Delivery Unit with the diagnosis of preeclampsia who had not received prior antihypertensive or magnesium sulfate therapy were recruited for noninvasive hemodynamic monitoring with thoracic electrical bioimpedance. After stabilization in the lateral recumbent position, hemodynamic monitoring was begun. Baseline hemodynamic parameters, mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke index (SI) were recorded. Stroke systemic vascular resistance index (SSVRI), the resistance imposed by vasculature on each beat of the heart, was calculated for each patient by multiplying SVRI by HR. For statistical analysis, unpaired Student's t-tests (two-tailed) were utilized (P < 0.01). Forty-one preeclamptic patients (20 mild, 21 severe) were enrolled. Mean gestational age of severe patients was 32.2 +/- 4.0 and of mild patients was 37.0 +/- 3.5. MAP, SBP, diastolic blood pressure, HR, and SSVRI were higher in the severe group. SVRI, CI, cardiac output, and SI did not differ significantly between groups. Severe preclampsia appears to be a more intensely vasoconstricted state than mild preeclampsia. Although CI is inversely proportional to SVRI, increased HR in severe preeclampsia prevents this expected decrease in cardiac output.

Cardiac magnetic field map topology quantified by Kullback-Leibler entropy identifies patients with hypertrophic cardiomyopathy

NASA Astrophysics Data System (ADS)

Schirdewan, A.; Gapelyuk, A.; Fischer, R.; Koch, L.; Schütt, H.; Zacharzowsky, U.; Dietz, R.; Thierfelder, L.; Wessel, N.

2007-03-01

Hypertrophic cardiomyopathy (HCM) is a common primary inherited cardiac muscle disorder, defined clinically by the presence of unexplained left ventricular hypertrophy. The detection of affected patients remains challenging. Genetic testing is limited because only in 50%-60% of all HCM diagnoses an underlying mutation can be found. Furthermore, the disease has a varied clinical course and outcome, with many patients having little or no discernible cardiovascular symptoms, whereas others develop profound exercise limitation and recurrent arrhythmias or sudden cardiac death. Therefore prospective screening of HCM family members is strongly recommended. According to the current guidelines this includes serial echocardiographic and electrocardiographic examinations. In this study we investigated the capability of cardiac magnetic field mapping (CMFM) to detect patients suffering from HCM. We introduce for the first time a combined diagnostic approach based on map topology quantification using Kullback-Leibler (KL) entropy and regional magnetic field strength parameters. The cardiac magnetic field was recorded over the anterior chest wall using a multichannel-LT-SQUID system. CMFM was calculated based on a regular 36 point grid. We analyzed CMFM in patients with confirmed diagnosis of HCM (HCM, n =33, 43.8±13 years, 13 women, 20 men), a control group of healthy subjects (NORMAL, n =57, 39.6±8.9 years; 22 women and 35 men), and patients with confirmed cardiac hypertrophy due to arterial hypertension (HYP, n =42, 49.7±7.9 years, 15 women and 27 men). A subgroup analysis was performed between HCM patients suffering from the obstructive (HOCM, n =19) and nonobstructive (HNCM, n =14) form of the disease. KL entropy based map topology quantification alone identified HCM patients with a sensitivity of 78.8% and specificity of 86.9% (overall classification rate 84.8%). The combination of the KL parameters with a regional field strength parameter improved the overall classification rate to 87.9% (sensitivity: 84.8%, specificity: 88.9%, area under ROC curve: 0.94). KL measures applied to discriminate between HOCM and HNCM patients showed a correct classification of 78.8%. The combination of one KL and one regional parameter again improved the overall classification rate to 97%. A preliminary prospective analysis in two HCM families showed the feasibility of this diagnostic approach with a correct diagnosis of all 22 screened family members (1 HOCM, 4 HNCM, 17 normal). In conclusion, Cardiac Magnetic Field Mapping including KL entropy based topology quantifications is a suitable tool for HCM screening.

SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function

PubMed Central

Hatcher, Jeffrey; Gu, He; Cheng, Zixi (Jack)

2016-01-01

Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2 ∙−), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions of O2 ∙− may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and ΔHR versus ΔMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function. PMID:26823951

Myocardial effective transverse relaxation time T2* Correlates with left ventricular wall thickness: A 7.0 T MRI study.

PubMed

Huelnhagen, Till; Hezel, Fabian; Serradas Duarte, Teresa; Pohlmann, Andreas; Oezerdem, Celal; Flemming, Bert; Seeliger, Erdmann; Prothmann, Marcel; Schulz-Menger, Jeanette; Niendorf, Thoralf

2017-06-01

Myocardial effective relaxation time T2* is commonly regarded as a surrogate for myocardial tissue oxygenation. However, it is legitimate to assume that there are multiple factors that influence T2*. To this end, this study investigates the relationship between T2* and cardiac macromorphology given by left ventricular (LV) wall thickness and left ventricular radius, and provides interpretation of the results in the physiological context. High spatio-temporally resolved myocardial CINE T2* mapping was performed in 10 healthy volunteers using a 7.0 Tesla (T) full-body MRI system. Ventricular septal wall thickness, left ventricular inner radius, and T2* were analyzed. Macroscopic magnetic field changes were elucidated using cardiac phase-resolved magnetic field maps. Ventricular septal T2* changes periodically over the cardiac cycle, increasing in systole and decreasing in diastole. Ventricular septal wall thickness and T2* showed a significant positive correlation, whereas the inner LV radius and T2* were negatively correlated. The effect of macroscopic magnetic field gradients on T2* can be considered minor in the ventricular septum. Our findings suggest that myocardial T2* is related to tissue blood volume fraction. Temporally resolved T2* mapping could be beneficial for myocardial tissue characterization and for understanding cardiac (patho)physiology in vivo. Magn Reson Med 77:2381-2389, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

The Feasibility of a Completely Automated Total IV Anesthesia Drug Delivery System for Cardiac Surgery.

PubMed

Zaouter, Cedrick; Hemmerling, Thomas M; Lanchon, Romain; Valoti, Emanuela; Remy, Alain; Leuillet, Sébastien; Ouattara, Alexandre

2016-10-01

In this pilot study, we tested a novel automatic anesthesia system for closed-loop administration of IV anesthesia drugs for cardiac surgical procedures with cardiopulmonary bypass. This anesthesia drug delivery robot integrates all 3 components of general anesthesia: hypnosis, analgesia, and muscle relaxation. Twenty patients scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Propofol, remifentanil, and rocuronium were administered using closed-loop feedback control. The main objective was the feasibility of closed-loop anesthesia defined as successful automated cardiac anesthesia without manual override by the attending anesthesiologist. Secondary qualitative observations were clinical and controller performances. The clinical performance of hypnosis control was the efficacy to maintain a bispectral index (BIS) of 45. To evaluate the hypnosis performance, BIS values were stratified into 4 categories: "excellent," "good," "poor," and "inadequate" hypnosis control defined as BIS values within 10%, ranging from 11% to 20%, ranging from 21% to 30%, or >30% of the target value, respectively. The clinical performance of analgesia was the efficacy to maintain NociMap values close to 0. The analgesia performance was assessed classifying the NociMap values in 3 pain control groups: -33 to +33 representing excellent pain control, -34 to -66 and +34 to +66 representing good pain control, and -67 to -100 and +67 to +100 representing insufficient pain control. The controller performance was calculated using the Varvel parameters. Robotic anesthesia was successful in 16 patients, which is equivalent to 80% (97.5% confidence interval [CI], 53%-95%) of the patients undergoing cardiac surgery. Four patients were excluded from the final analysis because of technical problems with the automated anesthesia delivery system. The secondary qualitative observations revealed that the clinical performance of hypnosis allowed an excellent and good control during 70% (97.5% CI, 63%-76%) of maintenance time and an insufficient clinical performance of analgesia for only 3% (97.5% CI, 1%-6%) of maintenance time. The completely automated closed-loop system tested in this investigation could be used successfully and safely for cardiac surgery necessitating cardiopulmonary bypass. The results of the present trial showed satisfactory clinical performance of anesthesia control.

Phantom evaluation of a cardiac SPECT/VCT system that uses a common set of solid-state detectors for both emission and transmission scans

PubMed Central

Conwell, Richard; Kindem, Joel; Babla, Hetal; Gurley, Mike; De Los Santos, Romer; Old, Rex; Weatherhead, Randy; Arram, Samia; Maddahi, Jamshid

2010-01-01

Background We developed a cardiac SPECT system (X-ACT) with low dose volume CT transmission-based attenuation correction (AC). Three solid-state detectors are configured to form a triple-head system for emission scans and reconfigured to form a 69-cm field-of-view detector arc for transmission scans. A near mono-energetic transmission line source is produced from the collimated fluorescence x-ray emitted from a lead target when the target is illuminated by a narrow polychromatic x-ray beam from an x-ray tube. Transmission scans can be completed in 1 min with insignificant patient dose (deep dose equivalent <5 μSv). Methods We used phantom studies to evaluate (1) the accuracy of the reconstructed attenuation maps, (2) the effect of AC on image uniformity, and (3) the effect of AC on defect contrast (DC). The phantoms we used included an ACR phantom, an anthropomorphic phantom with a uniform cardiac insert, and an anthropomorphic phantom with two defects in the cardiac insert. Results The reconstructed attenuation coefficient of water at 140 keV was .150 ± .003/cm in the uniform region of the ACR phantom, .151 ± .003/cm and .151 ± .002/cm in the liver and cardiac regions of the anthropomorphic phantom. The ACR phantom images with AC showed correction of the bowing effect due to attenuation in the images without AC (NC). The 17-segment scores of the images of the uniform cardiac insert were 78.3 ± 6.5 before and 87.9 ± 3.3 after AC (average ± standard deviation). The inferior-to-anterior wall ratio and the septal-to-lateral wall ratio were .99 and 1.16 before and 1.02 and 1.00 after AC. The DC of the two defects was .528 and .156 before and .628 and .173 after AC. Conclusion The X-ACT system generated accurate attenuation maps with 1-minute transmission scans. AC improved image quality and uniformity over NC. PMID:20169476

What is needed to implement a web-based audit and feedback intervention with outreach visits to improve care quality: A concept mapping study among cardiac rehabilitation teams.

PubMed

van Engen-Verheul, Mariëtte M; Peek, Niels; Haafkens, Joke A; Joukes, Erik; Vromen, Tom; Jaspers, Monique W M; de Keizer, Nicolette F

2017-01-01

Evidence on successful quality improvement (QI) in health care requires quantitative information from randomized clinical trials (RCTs) on the effectiveness of QI interventions, but also qualitative information from professionals to understand factors influencing QI implementation. Using a structured qualitative approach, concept mapping, this study determines factors identified by cardiac rehabilitation (CR) teams on what is needed to successfully implement a web-based audit and feedback (A&F) intervention with outreach visits to improve the quality of CR care. Participants included 49 CR professionals from 18 Dutch CR centres who had worked with the A&F system during a RCT. In three focus group sessions participants formulated statements on factors needed to implement QI successfully. Subsequently, participants rated all statements for importance and feasibility and grouped them thematically. Multi dimensional scaling was used to produce a final concept map. Forty-two unique statements were formulated and grouped into five thematic clusters in the concept map. The cluster with the highest importance was QI team commitment, followed by organisational readiness, presence of an adequate A&F system, access to an external quality assessor, and future use and functionalities of the A&F system. Concept mapping appeared efficient and useful to understand contextual factors influencing QI implementation as perceived by healthcare teams. While presence of a web-based A&F system and external quality assessor were seen as instrumental for gaining insight into performance and formulating QI actions, QI team commitment and organisational readiness were perceived as essential to actually implement and carry out these actions. These two sociotechnical factors should be taken into account when implementing and evaluating the success of QI implementations in future research. Copyright © 2016. Published by Elsevier Ireland Ltd.

A Fiber-Based Ratiometric Optical Cardiac Mapping Channel Using a Diffraction Grating and Split Detector

PubMed Central

Brown, Ninita H.; Dobrovolny, Hana M.; Gauthier, Daniel J.; Wolf, Patrick D.

2007-01-01

Optical fiber-based mapping systems are used to record the cardiac action potential (AP) throughout the myocardium. The optical AP contains a contraction-induced motion artifact (MA), which makes it difficult to accurately measure the action potential duration (APD). MA is removed by preventing contraction with electrical-mechanical uncoupling drugs, such as 2,3-butanedione monoxime (BDM). We designed a novel fiber-based ratiometric optical channel using a blue light emitting diode, a diffraction grating, and a split photodetector that can accurately measure the cardiac AP without the need for BDM. The channel was designed based on simulations using the optical design software ZEMAX. The channel has an electrical bandwidth of 150 Hz and an root mean-square dark noise of 742 μV. The channel successfully recorded the cardiac AP from the wall of five rabbit heart preparations without the use of BDM. After 20-point median filtering, the mean signal/noise ratio was 25.3 V/V. The APD measured from the base of a rabbit heart was 134 ± 8.4 ms, compared to 137.6 ± 3.3 ms from simultaneous microelectrode recordings. This difference was not statistically significant (p-value = 0.3). The quantity of MA removed was also measured using the motion ratio. The reduction in MA was significant (p-value = 0.0001). This fiber-based system is the first of its kind to enable optical APD measurements in the beating heart wall without the use of BDM. PMID:17416627

Recent advances in the Laboratory of Molecular and Cellular Cardiology.

PubMed

Breitbart, R E; London, B; Nguyen, H T; Satler, C A

1995-12-01

This article highlights some of the research in cardiac molecular biology in progress in the Department of Cardiology at Children's Hospital. It provides a sampling of investigative approaches to key questions in cardiovascular development and function and, as such, is intended as an overview rather than a comprehensive treatment of these problems. The featured projects, encompassing four different "model" systems, include (1) genetic analysis of the mef2 gene required for fruit fly cardial cell differentiation, (2) cardiac-specific homeobox factors in zebrafish cardiovascular development, (3) mouse transgenic and gene knockout models of cardiac potassium ion channel function, and (4) mapping and identification of human gene mutations causing long QT syndrome.

T1 mapping and survival in systemic light-chain amyloidosis

PubMed Central

Banypersad, Sanjay M.; Fontana, Marianna; Maestrini, Viviana; Sado, Daniel M.; Captur, Gabriella; Petrie, Aviva; Piechnik, Stefan K.; Whelan, Carol J.; Herrey, Anna S.; Gillmore, Julian D.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Hawkins, Philip N.; Moon, James C.

2015-01-01

Aims To assess the prognostic value of myocardial pre-contrast T1 and extracellular volume (ECV) in systemic amyloid light-chain (AL) amyloidosis using cardiovascular magnetic resonance (CMR) T1 mapping. Methods and results One hundred patients underwent CMR and T1 mapping pre- and post-contrast. Myocardial ECV was calculated at contrast equilibrium (ECVi) and 15 min post-bolus (ECVb). Fifty-four healthy volunteers served as controls. Patients were followed up for a median duration of 23 months and survival analyses were performed. Mean ECVi was raised in amyloid (0.44 ± 0.12) as was ECVb (mean 0.44 ± 0.12) compared with healthy volunteers (0.25 ± 0.02), P < 0.001. Native pre-contrast T1 was raised in amyloid (mean 1080 ± 87 ms vs. 954 ± 34 ms, P < 0.001). All three correlated with pre-test probability of cardiac involvement, cardiac biomarkers, and systolic and diastolic dysfunction. During follow-up, 25 deaths occurred. An ECVi of >0.45 carried a hazard ratio (HR) for death of 3.84 [95% confidence interval (CI): 1.53–9.61], P = 0.004 and pre-contrast T1 of >1044 ms = HR 5.39 (95% CI: 1.24–23.4), P = 0.02. Extracellular volume after primed infusion and ECVb performed similarly. Isolated post-contrast T1 was non-predictive. In Cox regression models, ECVi was independently predictive of mortality (HR = 4.41, 95% CI: 1.35–14.4) after adjusting for E:E′, ejection fraction, diastolic dysfunction grade, and NT-proBNP. Conclusion Myocardial ECV (bolus or infusion technique) and pre-contrast T1 are biomarkers for cardiac AL amyloid and they predict mortality in systemic amyloidosis. PMID:25411195

Optogenetic control of the cardiac conduction system (Conference Presentation)

NASA Astrophysics Data System (ADS)

Crocini, Claudia; Ferrantini, Cecilia; Coppini, Raffaele; Loew, Leslie M.; Cerbai, Elisabetta; Poggesi, Corrado; Pavone, Francesco S.; Sacconi, Leonardo

2016-03-01

Fatal cardiac arrhythmias are a major medical and social issue in Western countries. Current implantable pacemaker/defibrillators have limited effectiveness and are plagued by frequent malfunctions and complications. Here, we aim at setting up a new method to map and control the electrical activity of whole isolated mouse hearts. We employ a transgenic mouse model expressing Channel Rhodopsin-2 (ChR2) in the heart coupled with voltage optical mapping to monitor and control action potential propagation. The whole heart is loaded with the fluorinated red-shifted voltage sensitive dye (di-4-ANBDQPQ) and imaged with the central portion (128 x 128 pixel) of sCMOS camera operating at frame rate of 1.6 kHz. The wide-field imaging system is implemented with a random access ChR2 activation developed using two orthogonally-mounted acousto-optical deflectors (AODs). AODs rapidly scan different sites of the sample with a commutation time of 4 μs, allowing us to design ad hoc ChR2-stimulation pattern. First, we demonstrate the capability of our system in manipulating the conduction system of the whole mouse heart by changing the electrical propagation features. Then, we explore the efficacy of the random access ChR2 stimulation in inducing arrhythmias as well as to restore the cardiac sinus rhythm during an arrhythmic event. This work shows the potentiality of this new method for studying the mechanisms of arrhythmias and reentry in healthy and diseased hearts, as well as the basis of intra-ventricular dyssynchrony.

Using a Combined Platform of Swarm Intelligence Algorithms and GIS to Provide Land Suitability Maps for Locating Cardiac Rehabilitation Defibrillators

PubMed Central

KAFFASH-CHARANDABI, Neda; SADEGHI-NIARAKI, Abolghasem; PARK, Dong-Kyun

2015-01-01

Background: Cardiac arrest is a condition in which the heart is completely stopped and is not pumping any blood. Although most cardiac arrest cases are reported from homes or hospitals, about 20% occur in public areas. Therefore, these areas need to be investigated in terms of cardiac arrest incidence so that places of high incidence can be identified and cardiac rehabilitation defibrillators installed there. Methods: In order to investigate a study area in Petersburg, Pennsylvania State, and to determine appropriate places for installing defibrillators with 5-year period data, swarm intelligence algorithms were used. Moreover, the location of the defibrillators was determined based on the following five evaluation criteria: land use, altitude of the area, economic conditions, distance from hospitals and approximate areas of reported cases of cardiac arrest for public places that were created in geospatial information system (GIS). Results: The A-P HADEL algorithm results were more precise about 27.36%. The validation results indicated a wider coverage of real values and the verification results confirmed the faster and more exact optimization of the cost function in the PSO method. Conclusion: The study findings emphasize the necessity of applying optimal optimization methods along with GIS and precise selection of criteria in the selection of optimal locations for installing medical facilities because the selected algorithm and criteria dramatically affect the final responses. Meanwhile, providing land suitability maps for installing facilities across hot and risky spots has the potential to save many lives. PMID:26587471

Cardiac tissue slices: preparation, handling, and successful optical mapping.

PubMed

Wang, Ken; Lee, Peter; Mirams, Gary R; Sarathchandra, Padmini; Borg, Thomas K; Gavaghan, David J; Kohl, Peter; Bollensdorff, Christian

2015-05-01

Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and optical mapping of transmembrane potential and intracellular free calcium concentration transients (CaT) in ventricular tissue slices from guinea pigs and rabbits. Slices cut in the epicardium-tangential plane contained well-aligned in-slice myocardial cell strands ("fibers") in subepicardial and midmyocardial sections. Cut with a high-precision slow-advancing microtome at a thickness of 350 to 400 μm, tissue slices preserved essential action potential (AP) properties of the precutting Langendorff-perfused heart. We identified the need for a postcutting recovery period of 36 min (guinea pig) and 63 min (rabbit) to reach 97.5% of final steady-state values for AP duration (APD) (identified by exponential fitting). There was no significant difference between the postcutting recovery dynamics in slices obtained using 2,3-butanedione 2-monoxime or blebistatin as electromechanical uncouplers during the cutting process. A rapid increase in APD, seen after cutting, was caused by exposure to ice-cold solution during the slicing procedure, not by tissue injury, differences in uncouplers, or pH-buffers (bicarbonate; HEPES). To characterize intrinsic patterns of CaT, AP, and conduction, a combination of multipoint and field stimulation should be used to avoid misinterpretation based on source-sink effects. In summary, we describe in detail the preparation, mapping, and data analysis approaches for reproducible cardiac tissue slice-based investigations into AP and CaT dynamics. Copyright © 2015 the American Physiological Society.

Cardiac tissue slices: preparation, handling, and successful optical mapping

PubMed Central

Wang, Ken; Lee, Peter; Mirams, Gary R.; Sarathchandra, Padmini; Borg, Thomas K.; Gavaghan, David J.; Kohl, Peter

2015-01-01

Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and optical mapping of transmembrane potential and intracellular free calcium concentration transients (CaT) in ventricular tissue slices from guinea pigs and rabbits. Slices cut in the epicardium-tangential plane contained well-aligned in-slice myocardial cell strands (“fibers”) in subepicardial and midmyocardial sections. Cut with a high-precision slow-advancing microtome at a thickness of 350 to 400 μm, tissue slices preserved essential action potential (AP) properties of the precutting Langendorff-perfused heart. We identified the need for a postcutting recovery period of 36 min (guinea pig) and 63 min (rabbit) to reach 97.5% of final steady-state values for AP duration (APD) (identified by exponential fitting). There was no significant difference between the postcutting recovery dynamics in slices obtained using 2,3-butanedione 2-monoxime or blebistatin as electromechanical uncouplers during the cutting process. A rapid increase in APD, seen after cutting, was caused by exposure to ice-cold solution during the slicing procedure, not by tissue injury, differences in uncouplers, or pH-buffers (bicarbonate; HEPES). To characterize intrinsic patterns of CaT, AP, and conduction, a combination of multipoint and field stimulation should be used to avoid misinterpretation based on source-sink effects. In summary, we describe in detail the preparation, mapping, and data analysis approaches for reproducible cardiac tissue slice-based investigations into AP and CaT dynamics. PMID:25595366

Localization of premature ventricular contractions from the papillary muscles using the standard 12-lead electrocardiogram: a feasibility study using a novel cardiac isochrone positioning system.

PubMed

van Dam, Peter M; Boyle, Noel G; Laks, Michael M; Tung, Roderick

2016-12-01

The precise localization of the site of origin of a premature ventricular contraction (PVC) prior to ablation can facilitate the planning and execution of the electrophysiological procedure. In clinical practice, the targeted ablation site is estimated from the standard 12-lead ECG. The accuracy of this qualitative estimation has limitations, particularly in the localization of PVCs originating from the papillary muscles. Clinical available electrocardiographic imaging (ECGi) techniques that incorporate patient-specific anatomy may improve the localization of these PVCs, but require body surface maps with greater specificity for the epicardium. The purpose of this report is to demonstrate that a novel cardiac isochrone positioning system (CIPS) program can accurately detect the specific location of the PVC on the papillary muscle using only a 12-lead ECG. Cardiac isochrone positioning system uses three components: (i) endocardial and epicardial cardiac anatomy and torso geometry derived from MRI, (ii) the patient-specific electrode positions derived from an MRI model registered 3D image, and (iii) the 12-lead ECG. CIPS localizes the PVC origin by matching the anatomical isochrone vector with the ECG vector. The predicted PVC origin was compared with the site of successful ablation or stimulation. Three patients who underwent electrophysiological mapping and ablation of PVCs originating from the papillary muscles were studied. CIPS localized the PVC origin for all three patients to the correct papillary muscle and specifically to the base, mid, or apical region. A simplified form of ECGi utilizing only 12 standard electrocardiographic leads may facilitate accurate localization of the origin of papillary muscle PVCs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Magnetic resonance imaging-compatible circular mapping catheter: an in vivo feasibility and safety study.

PubMed

Elbes, Delphine; Magat, Julie; Govari, Assaf; Ephrath, Yaron; Vieillot, Delphine; Beeckler, Christopher; Weerasooriya, Rukshen; Jais, Pierre; Quesson, Bruno

2017-03-01

Interventional cardiac catheter mapping is routinely guided by X-ray fluoroscopy, although radiation exposure remains a significant concern. Feasibility of catheter ablation for common flutter has recently been demonstrated under magnetic resonance imaging (MRI) guidance. The benefit of catheter ablation under MRI could be significant for complex arrhythmias such as atrial fibrillation (AF), but MRI-compatible multi-electrode catheters such as Lasso have not yet been developed. This study aimed at demonstrating the feasibility and safety of using a multi-electrode catheter [magnetic resonance (MR)-compatible Lasso] during MRI for cardiac mapping. We also aimed at measuring the level of interference between MR and electrophysiological (EP) systems. Experiments were performed in vivo in sheep (N = 5) using a multi-electrode, circular, steerable, MR-compatible diagnostic catheter. The most common MRI sequences (1.5T) relevant for cardiac examination were run with the catheter positioned in the right atrium. High-quality electrograms were recorded while imaging with a maximal signal-to-noise ratio (peak-to-peak signal amplitude/peak-to-peak noise amplitude) ranging from 5.8 to 165. Importantly, MRI image quality was unchanged. Artefacts induced by MRI sequences during mapping were demonstrated to be compatible with clinical use. Phantom data demonstrated that this 10-pole circular catheter can be used safely with a maximum of 4°C increase in temperature. This new MR-compatible 10-pole catheter appears to be safe and effective. Combining MR and multipolar EP in a single session offers the possibility to correlate substrate information (scar, fibrosis) and EP mapping as well as online monitoring of lesion formation and electrical endpoint. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Novel cardiac magnetic resonance biomarkers: native T1 and extracellular volume myocardial mapping.

PubMed

Cannaò, Paola Maria; Altabella, Luisa; Petrini, Marcello; Alì, Marco; Secchi, Francesco; Sardanelli, Francesco

2016-04-28

Cardiac magnetic resonance (CMR) is a non-invasive diagnostic tool playing a key role in the assessment of cardiac morphology and function as well as in tissue characterization. Late gadolinium enhancement is a fundamental CMR technique for detecting focal or regional abnormalities such as scar tissue, replacement fibrosis, or inflammation using qualitative, semi-quantitative, or quantitative methods, but not allowing for evaluating the whole myocardium in the presence of diffuse disease. The novel T1 mapping approach permits a quantitative assessment of the entire myocardium providing a voxel-by-voxel map of native T1 relaxation time, obtained before the intravenous administration of gadolinium-based contrast material. Combining T1 data obtained before and after contrast injection, it is also possible to calculate the voxel-by-voxel extracellular volume (ECV), resulting in another myocardial parametric map. This article describes technical challenges and clinical perspectives of these two novel CMR biomarkers: myocardial native T1 and ECV mapping.

Register cardiac fiber orientations from 3D DTI volume to 2D ultrasound image of rat hearts

NASA Astrophysics Data System (ADS)

Qin, Xulei; Wang, Silun; Shen, Ming; Zhang, Xiaodong; Lerakis, Stamatios; Wagner, Mary B.; Fei, Baowei

2015-03-01

Two-dimensional (2D) ultrasound or echocardiography is one of the most widely used examinations for the diagnosis of cardiac diseases. However, it only supplies the geometric and structural information of the myocardium. In order to supply more detailed microstructure information of the myocardium, this paper proposes a registration method to map cardiac fiber orientations from three-dimensional (3D) magnetic resonance diffusion tensor imaging (MR-DTI) volume to the 2D ultrasound image. It utilizes a 2D/3D intensity based registration procedure including rigid, log-demons, and affine transformations to search the best similar slice from the template volume. After registration, the cardiac fiber orientations are mapped to the 2D ultrasound image via fiber relocations and reorientations. This method was validated by six images of rat hearts ex vivo. The evaluation results indicated that the final Dice similarity coefficient (DSC) achieved more than 90% after geometric registrations; and the inclination angle errors (IAE) between the mapped fiber orientations and the gold standards were less than 15 degree. This method may provide a practical tool for cardiologists to examine cardiac fiber orientations on ultrasound images and have the potential to supply additional information for diagnosis of cardiac diseases.

An observational study describing the geographic-time distribution of cardiac arrests in Singapore: what is the utility of geographic information systems for planning public access defibrillation? (PADS Phase I).

PubMed

Ong, Marcus Eng Hock; Tan, Eng Hoe; Yan, Xiuyuan; Anushia, P; Lim, Swee Han; Leong, Benjamin Sieu-Hon; Ong, Victor Yeok Kein; Tiah, Ling; Yap, Susan; Overton, Jerry; Anantharaman, V

2008-03-01

Public access defibrillation (PAD) has shown potential to increase cardiac arrest survival rates. To describe the geographic epidemiology of prehospital cardiac arrest in Singapore using geographic information systems (GIS) technology and assess the potential for deployment of a PAD program. We conducted an observational prospective study looking at the geographic location of pre-hospital cardiac arrests in Singapore. Included were all patients with out-of-hospital cardiac arrest (OHCA) presented to emergency departments. Patient characteristics, cardiac arrest circumstances, emergency medical service (EMS) response and outcomes were recorded according to the Utstein style. Location of cardiac arrests was spot-mapped using GIS. From 1 October 2001 to 14 October 2004, 2428 patients were enrolled into the study. Mean age for arrests was 60.6 years with 68.0% male. 67.8% of arrests occurred in residences, with 54.5% bystander witnessed and another 10.5% EMS witnessed. Mean EMS response time was 9.6 min with 21.7% receiving prehospital defibrillation. Cardiac arrest occurrence was highest in the suburban town centers in the Eastern and Southern part of the country. We also identified communities with the highest arrest rates. About twice as many arrests occurred during the day (07:00-18:59 h) compared to night (19:00-06:59 h). The categories with the highest frequencies of occurrence included residential areas, in vehicles, healthcare facilities, along roads, shopping areas and offices/industrial areas. We found a definite geographical distribution pattern of cardiac arrest. This study demonstrates the utility of GIS with a national cardiac arrest database and has implications for implementing a PAD program, targeted CPR training, AED placement and ambulance deployment.

Software development, nomenclature schemes, and mapping strategies for an international pediatric cardiac surgery database system.

PubMed

Jacobs, Jeffrey P

2002-01-01

The field of congenital heart surgery has the opportunity to create the first comprehensive international database for a medical subspecialty. An understanding of the demographics of congenital heart disease and the rapid growth of computer technology leads to the realization that creating a comprehensive international database for pediatric cardiac surgery represents an important and achievable goal. The evolution of computer-based data analysis creates an opportunity to develop software to manage an international congenital heart surgery database and eventually become an electronic medical record. The same database data set for congenital heart surgery is now being used in Europe and North America. Additional work is under way to involve Africa, Asia, Australia, and South America. The almost simultaneous publication of the European Association for Cardio-thoracic Surgery/Society of Thoracic Surgeons coding system and the Association for European Paediatric Cardiology coding system resulted in the potential for multiple coding. Representatives of the Association for European Paediatric Cardiology, Society of Thoracic Surgeons, European Association for Cardio-thoracic Surgery, and European Congenital Heart Surgeons Foundation agree that these hierarchical systems are complementary and not competitive. An international committee will map the two systems. The ideal coding system will permit a diagnosis or procedure to be coded only one time with mapping allowing this code to be used for patient care, billing, practice management, teaching, research, and reporting to governmental agencies. The benefits of international data gathering and sharing are global, with the long-term goal of the continued upgrade in the quality of congenital heart surgery worldwide. Copyright 2002 by W.B. Saunders Company

Mechanisms of action of sacubitril/valsartan on cardiac remodeling: a systems biology approach.

PubMed

Iborra-Egea, Oriol; Gálvez-Montón, Carolina; Roura, Santiago; Perea-Gil, Isaac; Prat-Vidal, Cristina; Soler-Botija, Carolina; Bayes-Genis, Antoni

2017-01-01

Sacubitril/Valsartan, proved superiority over other conventional heart failure management treatments, but its mechanisms of action remains obscure. In this study, we sought to explore the mechanistic details for Sacubitril/Valsartan in heart failure and post-myocardial infarction remodeling, using an in silico, systems biology approach. Myocardial transcriptome obtained in response to myocardial infarction in swine was analyzed to address post-infarction ventricular remodeling. Swine transcriptome hits were mapped to their human equivalents using Reciprocal Best (blast) Hits, Gene Name Correspondence, and InParanoid database. Heart failure remodeling was studied using public data available in gene expression omnibus (accession GSE57345, subseries GSE57338), processed using the GEO2R tool. Using the Therapeutic Performance Mapping System technology, dedicated mathematical models trained to fit a set of molecular criteria, defining both pathologies and including all the information available on Sacubitril/Valsartan, were generated. All relationships incorporated into the biological network were drawn from public resources (including KEGG, REACTOME, INTACT, BIOGRID, and MINT). An artificial neural network analysis revealed that Sacubitril/Valsartan acts synergistically against cardiomyocyte cell death and left ventricular extracellular matrix remodeling via eight principal synergistic nodes. When studying each pathway independently, Valsartan was found to improve cardiac remodeling by inhibiting members of the guanine nucleotide-binding protein family, while Sacubitril attenuated cardiomyocyte cell death, hypertrophy, and impaired myocyte contractility by inhibiting PTEN. The complex molecular mechanisms of action of Sacubitril/Valsartan upon post-myocardial infarction and heart failure cardiac remodeling were delineated using a systems biology approach. Further, this dataset provides pathophysiological rationale for the use of Sacubitril/Valsartan to prevent post-infarct remodeling.

Gender-related differences in β-adrenergic receptor-mediated cardiac remodeling.

PubMed

Zhu, Baoling; Liu, Kai; Yang, Chengzhi; Qiao, Yuhui; Li, Zijian

2016-12-01

Cardiac remodeling is the pathological basis of various cardiovascular diseases. In this study, we found gender-related differences in β-adrenergic receptor (AR)-mediated pathological cardiac remodeling. Cardiac remodeling model was established by subcutaneous injection of isoprenaline (ISO) for 14 days. Heart rate (HR), mean arterial pressure (MAP), and echocardiography were obtained on 7th and 14th days during ISO administration. Myocardial cross-sectional area and the ratio of heart mass to tibia length (HM/TL) were detected to assess cardiac hypertrophy. Picro-Sirius red staining (picric acid + Sirius red F3B) was used to evaluate cardiac fibrosis. Myocardial capillary density was assessed by immunohistochemistry for von Willebrand factor. Further, real-time PCR was used to measure the expression of β1-AR and β2-AR. Results showed that ISO induced cardiac remodeling, the extent of which was different between female and male mice. The extent of increase in cardiac wall thickness, myocardial cross-sectional area, and collagen deposition in females was less than that in males. However, no gender-related difference was observed in HR, MAP, cardiac function, and myocardial capillary density. The distinctive decrease of β2-AR expression, rather than a decrease of β1-AR expression, seemed to result in gender-related differences in cardiac remodeling.

A single bout of exhaustive exercise affects integrated baroreflex function after 16 days of head-down tilt

NASA Technical Reports Server (NTRS)

Engelke, K. A.; Doerr, D. F.; Convertino, V. A.

1995-01-01

We tested the hypothesis that one bout of maximal exercise performed 24 h before reambulation from 16 days of 6 degrees head-down tilt (HDT) could increase integrated baroreflex sensitivity. Isolated carotid-cardiac and integrated baroreflex function was assessed in seven subjects before and after two periods of HDT separated by 11 mo. On the last day of one HDT period, subjects performed a single bout of maximal cycle ergometry (exercise). Subjects did not exercise after the other HDT period (control). Carotid-cardiac baroreflex sensitivity was evaluated using a neck collar device. Integrated baroreflex function was assessed by recording heart rate (HR) and blood pressure (MAP) during a 15-s Valsalva maneuver (VM) at a controlled expiratory pressure of 30 mmHg. The ratio of change in HR to change in MAP (delta HR/ delta MAP) during phases II and IV of the VM was used as an index of cardiac baroreflex sensitivity. Baroreflex-mediated vasoconstriction was assessed by measuring the late phase II rise in MAP. Following HDT, carotid-cardiac baroreflex sensitivity was reduced (2.8 to 2.0 ms/mmHg; P = 0.05) as was delta HR/ delta MAP during phase II (-1.5 to -0.8 beats/mmHg; P = 0.002). After exercise, isolated carotid baroreflex activity and phase II delta HR/ delta MAP returned to pre-HDT levels but remained attenuated in the control condition. Phase IV delta HR/ delta MAP was not altered by HDT or exercise. The late phase II increase of MAP was 71% greater after exercise compared with control (7 vs. 2 mmHg; P = 0.041).(ABSTRACT TRUNCATED AT 250 WORDS).

Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy

PubMed Central

Kim, Dae-Hyeong; Ghaffari, Roozbeh; Lu, Nanshu; Wang, Shuodao; Lee, Stephen P.; Keum, Hohyun; D’Angelo, Robert; Klinker, Lauren; Su, Yewang; Lu, Chaofeng; Kim, Yun-Soung; Ameen, Abid; Li, Yuhang; Zhang, Yihui; de Graff, Bassel; Hsu, Yung-Yu; Liu, ZhuangJian; Ruskin, Jeremy; Xu, Lizhi; Lu, Chi; Omenetto, Fiorenzo G.; Huang, Yonggang; Mansour, Moussa; Slepian, Marvin J.; Rogers, John A.

2012-01-01

Curved surfaces, complex geometries, and time-dynamic deformations of the heart create challenges in establishing intimate, nonconstraining interfaces between cardiac structures and medical devices or surgical tools, particularly over large areas. We constructed large area designs for diagnostic and therapeutic stretchable sensor and actuator webs that conformally wrap the epicardium, establishing robust contact without sutures, mechanical fixtures, tapes, or surgical adhesives. These multifunctional web devices exploit open, mesh layouts and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way that yields, after dissolution, exceptionally low mechanical moduli and thicknesses. In vivo studies in rabbit and pig animal models demonstrate the effectiveness of these device webs for measuring and spatially mapping temperature, electrophysiological signals, strain, and physical contact in sheet and balloon-based systems that also have the potential to deliver energy to perform localized tissue ablation. PMID:23150574

Cardiovascular effects of vasopressin following V(1) receptor blockade compared to effects of nitroglycerin.

PubMed

Cooke, C R; Wall, B M; Huch, K M; Mangold, T

2001-09-01

Studies to more clearly determine the mechanisms associated with arginine vasopressin (AVP)-induced vasodilation were performed in normal subjects and in quadriplegic subjects with impaired efferent sympathetic responses. Studies to compare the effects of AVP with the hemodynamic effects of nitroglycerin, an agent that primarily affects venous capacitance vessels, were also performed in normal subjects. Incremental infusions of AVP following V(1)-receptor blockade resulted in equivalent reductions in systemic vascular resistance (SVRI) in normal and in quadriplegic subjects. However, there were major differences in the effect on mean arterial pressure (MAP), which was reduced in quadriplegic subjects but did not change in normal subjects. This difference in MAP can be attributed to a difference in the magnitude of increase in cardiac output (CI), which was twofold greater in normal than in quadriplegic subjects. These observations are consistent with AVP-induced vasodilation of arterial resistance vessels with reflex sympathetic enhancement of CI and are clearly different from the hemodynamic effects of nitroglycerin, i.e., reductions in MAP, CI, and indexes of cardiac preload, with only minor changes in SVRI.

In vivo quantification of amyloid burden in TTR-related cardiac amyloidosis

PubMed Central

Kollikowski, Alexander Marco; Kahles, Florian; Kintsler, Svetlana; Hamada, Sandra; Reith, Sebastian; Knüchel, Ruth; Röcken, Christoph; Mottaghy, Felix Manuel; Marx, Nikolaus; Burgmaier, Mathias

2017-01-01

Summary Cardiac transthyretin-related (ATTR) amyloidosis is a severe cardiomyopathy for which therapeutic approaches are currently under development. Because non-invasive imaging techniques such as cardiac magnetic resonance imaging and echocardiography are non-specific, the diagnosis of ATTR amyloidosis is still based on myocardial biopsy. Thus, diagnosis of ATTR amyloidosis is difficult in patients refusing myocardial biopsy. Furthermore, myocardial biopsy does not allow 3D-mapping and quantification of myocardial ATTR amyloid. In this report we describe a 99mTc-DPD-based molecular imaging technique for non-invasive single-step diagnosis, three-dimensional mapping and semiquantification of cardiac ATTR amyloidosis in a patient with suspected amyloid heart disease who initially rejected myocardial biopsy. This report underlines the clinical value of SPECT-based nuclear medicine imaging to enable non-invasive diagnosis of cardiac ATTR amyloidosis, particularly in patients rejecting biopsy. PMID:29259858

How to use concept mapping to identify barriers and facilitators of an electronic quality improvement intervention.

PubMed

van Engen-Verheul, Mariëtte; Peek, Niels; Vromen, Tom; Jaspers, Monique; de Keizer, Nicolette

2015-01-01

Systematic quality improvement (QI) interventions are increasingly used to change complex health care systems. Results of randomized clinical trials can provide quantitative evidence whether QI interventions were effective but they do not teach us why and how QI was (not) achieved. Qualitative research methods can answer these questions but typically involve only a small group of respondents against high resources. Concept mapping methodology overcomes these drawbacks by integrating results from qualitative group sessions with multivariate statistical analysis to represent ideas of diverse stakeholders visually on maps in an efficient way. This paper aims to describe how to use concept mapping to qualitatively gain insight into barriers and facilitators of an electronic QI intervention and presents experiences with the method from an ongoing case study to evaluate a QI system in the field of cardiac rehabilitation in the Netherlands.

T1 and T2 Mapping in Cardiology: "Mapping the Obscure Object of Desire".

PubMed

Mavrogeni, Sophie; Apostolou, Dimitris; Argyriou, Panayiotis; Velitsista, Stella; Papa, Lilika; Efentakis, Stelios; Vernardos, Evangelos; Kanoupaki, Mikela; Kanoupakis, George; Manginas, Athanassios

The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing. © 2017 S. Karger AG, Basel.

Causal Scale of Rotors in a Cardiac System

NASA Astrophysics Data System (ADS)

Ashikaga, Hiroshi; Prieto-Castrillo, Francisco; Kawakatsu, Mari; Dehghani, Nima

2018-04-01

Rotors of spiral waves are thought to be one of the potential mechanisms that maintain atrial fibrillation (AF). However, disappointing clinical outcomes of rotor mapping and ablation to eliminate AF raise a serious doubt on rotors as a macro-scale mechanism that causes the micro-scale behavior of individual cardiomyocytes to maintain spiral waves. In this study, we aimed to elucidate the causal relationship between rotors and spiral waves in a numerical model of cardiac excitation. To accomplish the aim, we described the system in a series of spatiotemporal scales by generating a renormalization group, and evaluated the causal architecture of the system by quantifying causal emergence. Causal emergence is an information-theoretic metric that quantifies emergence or reduction between micro- and macro-scale behaviors of a system by evaluating effective information at each scale. We found that the cardiac system with rotors has a spatiotemporal scale at which effective information peaks. A positive correlation between the number of rotors and causal emergence was observed only up to the scale of peak causation. We conclude that rotors are not the universal mechanism to maintain spiral waves at all spatiotemporal scales. This finding may account for the conflicting benefit of rotor ablation in clinical studies.

Site-specific microtubule-associated protein 4 dephosphorylation causes microtubule network densification in pressure overload cardiac hypertrophy.

PubMed

Chinnakkannu, Panneerselvam; Samanna, Venkatesababa; Cheng, Guangmao; Ablonczy, Zsolt; Baicu, Catalin F; Bethard, Jennifer R; Menick, Donald R; Kuppuswamy, Dhandapani; Cooper, George

2010-07-09

In severe pressure overload-induced cardiac hypertrophy, a dense, stabilized microtubule network forms that interferes with cardiocyte contraction and microtubule-based transport. This is associated with persistent transcriptional up-regulation of cardiac alpha- and beta-tubulin and microtubule-stabilizing microtubule-associated protein 4 (MAP4). There is also extensive microtubule decoration by MAP4, suggesting greater MAP4 affinity for microtubules. Because the major determinant of this affinity is site-specific MAP4 dephosphorylation, we characterized this in hypertrophied myocardium and then assessed the functional significance of each dephosphorylation site found by mimicking it in normal cardiocytes. We first isolated MAP4 from normal and pressure overload-hypertrophied feline myocardium; volume-overloaded myocardium, which has an equal degree and duration of hypertrophy but normal functional and cytoskeletal properties, served as a control for any nonspecific growth-related effects. After cloning cDNA-encoding feline MAP4 and obtaining its deduced amino acid sequence, we characterized by mass spectrometry any site-specific MAP4 dephosphorylation. Solely in pressure overload-hypertrophied myocardium, we identified striking MAP4 dephosphorylation at Ser-472 in the MAP4 N-terminal projection domain and at Ser-924 and Ser-1056 in the assembly-promoting region of the C-terminal microtubule-binding domain. Site-directed mutagenesis of MAP4 cDNA was then used to switch each serine to non-phosphorylatable alanine. Wild-type and mutated cDNAs were used to construct adenoviruses; microtubule network density, stability, and MAP4 decoration were assessed in normal cardiocytes following an equivalent level of MAP4 expression. The Ser-924 --> Ala MAP4 mutant produced a microtubule phenotype indistinguishable from that seen in pressure overload hypertrophy, such that Ser-924 MAP4 dephosphorylation during pressure overload hypertrophy may be central to this cytoskeletal abnormality.

Myocardial Tissue Characterization by Magnetic Resonance Imaging

PubMed Central

Ferreira, Vanessa M.; Piechnik, Stefan K.; Robson, Matthew D.; Neubauer, Stefan

2014-01-01

Cardiac magnetic resonance (CMR) imaging is a well-established noninvasive imaging modality in clinical cardiology. Its unsurpassed accuracy in defining cardiac morphology and function and its ability to provide tissue characterization make it well suited for the study of patients with cardiac diseases. Late gadolinium enhancement was a major advancement in the development of tissue characterization techniques, allowing the unique ability of CMR to differentiate ischemic heart disease from nonischemic cardiomyopathies. Using T2-weighted techniques, areas of edema and inflammation can be identified in the myocardium. A new generation of myocardial mapping techniques are emerging, enabling direct quantitative assessment of myocardial tissue properties in absolute terms. This review will summarize recent developments involving T1-mapping and T2-mapping techniques and focus on the clinical applications and future potential of these evolving CMR methodologies. PMID:24576837

An infrared optical pacing system for high-throughput screening of cardiac electrophysiology in human cardiomyocytes (Conference Presentation)

NASA Astrophysics Data System (ADS)

McPheeters, Matt T.; Wang, Yves T.; Laurita, Kenneth R.; Jenkins, Michael W.

2017-02-01

Cardiomyocytes derived from human induced pluripotent stem cells (hiPS-HCM) have the potential to provide individualized therapies for patients and to test drug candidates for cardiac toxicity. In order for hiPS-CM to be useful for such applications, there is a need for high-throughput technology to rapidly assess cardiac electrophysiology parameters. Here, we designed and tested a fully contactless optical mapping (OM) and optical pacing (OP) system capable of imaging and point stimulation of hiPS-CM in small wells. OM allowed us to characterize cardiac electrophysiological parameters (conduction velocity, action potential duration, etc.) using voltage-sensitive dyes with high temporal and spatial resolution over the entire well. To improve OM signal-to-noise ratio, we tested a new voltage-sensitive dye (Fluovolt) for accuracy and phototoxicity. Stimulation is essential because most electrophysiological parameters are rate dependent; however, traditional methods utilizing electrical stimulation is difficult in small wells. To overcome this limitation, we utilized OP (λ = 1464 nm) to precisely control heart rate with spatial precision without the addition of exogenous agents. We optimized OP parameters (e.g., well size, pulse width, spot size) to achieve robust pacing and minimize the threshold radiant exposure. Finally, we tested system sensitivity using Flecainide, a drug with well described action on multiple electrophysiological properties.

Myocardial T2* Mapping at Ultrahigh Field: Physics and Frontier Applications

NASA Astrophysics Data System (ADS)

Huelnhagen, Till; Paul, Katharina; Ku, Min-Chi; Serradas Duarte, Teresa; Niendorf, Thoralf

2017-06-01

Cardiovascular magnetic resonance imaging (CMR) has become an indispensable clinical tool for the assessment of morphology, function and structure of the heart muscle. By exploiting quantification of the effective transverse relaxation time (T2*) CMR also affords myocardial tissue characterization and probing of cardiac physiology, both being in the focus of ongoing research. These developments are fueled by the move to ultrahigh magnetic field strengths, which permits enhanced sensitivity and spatial resolution that help to overcome limitations of current clinical MR systems with the goal to contribute to a better understanding of myocardial (patho)physiology in vivo. In this context, the aim of this report is to introduce myocardial T2* mapping at ultrahigh magnetic fields as a promising technique to non-invasively assess myocardial (patho)physiology. For this purpose the basic principles of T2* assessment, the biophysical mechanisms determining T2* and (pre)clinical applications of myocardial T2* mapping are presented. Technological challenges and solutions for T2* sensitized CMR at ultrahigh magnetic field strengths are discussed followed by a review of acquisition techniques and post processing approaches. Preliminary results derived from myocardial T2* mapping in healthy subjects and cardiac patients at 7.0 Tesla are presented. A concluding section discusses remaining questions and challenges and provides an outlook on future developments and potential clinical applications.

Performance of Automated Software in the Assessment of Segmental Left Ventricular Function in Cardiac CT: Comparison with Cardiac Magnetic Resonance.

PubMed

Wang, Rui; Meinel, Felix G; Schoepf, U Joseph; Canstein, Christian; Spearman, James V; De Cecco, Carlo N

2015-12-01

To evaluate the accuracy, reliability and time saving potential of a novel cardiac CT (CCT)-based, automated software for the assessment of segmental left ventricular function compared to visual and manual quantitative assessment of CCT and cardiac magnetic resonance (CMR). Forty-seven patients with suspected or known coronary artery disease (CAD) were enrolled in the study. Wall thickening was calculated. Segmental LV wall motion was automatically calculated and shown as a colour-coded polar map. Processing time for each method was recorded. Mean wall thickness in both systolic and diastolic phases on polar map, CCT, and CMR was 9.2 ± 0.1 mm and 14.9 ± 0.2 mm, 8.9 ± 0.1 mm and 14.5 ± 0.1 mm, 8.3 ± 0.1 mm and 13.6 ± 0.1 mm, respectively. Mean wall thickening was 68.4 ± 1.5 %, 64.8 ± 1.4 % and 67.1 ± 1.4 %, respectively. Agreement for the assessment of LV wall motion between CCT, CMR and polar maps was good. Bland-Altman plots and ICC indicated good agreement between CCT, CMR and automated polar maps of the diastolic and systolic segmental wall thickness and thickening. The processing time using polar map was significantly decreased compared with CCT and CMR. Automated evaluation of segmental LV function with polar maps provides similar measurements to manual CCT and CMR evaluation, albeit with substantially reduced analysis time. • Cardiac computed tomography (CCT) can accurately assess segmental left ventricular wall function. • A novel automated software permits accurate and fast evaluation of wall function. • The software may improve the clinical implementation of segmental functional analysis.

Inhibition of beta-adrenergic receptor trafficking in adult cardiocytes by MAP4 decoration of microtubules.

PubMed

Cheng, Guangmao; Qiao, Fei; Gallien, Thomas N; Kuppuswamy, Dhandapani; Cooper, George

2005-03-01

Decreased beta-adrenergic receptor (beta-AR) number occurs both in animal models of cardiac hypertrophy and failure and in patients. beta-AR recycling is an important mechanism for the beta-AR resensitization that maintains a normal complement of cell surface beta-ARs. We have shown that 1) in severe pressure overload cardiac hypertrophy, there is extensive microtubule-associated protein 4 (MAP4) decoration of a dense microtubule network; and 2) MAP4 microtubule decoration inhibits muscarinic acetylcholine receptor recycling in neuroblastoma cells. We asked here whether MAP4 microtubule decoration inhibits beta-AR recycling in adult cardiocytes. [(3)H]CGP-12177 was used as a beta-AR ligand, and feline cardiocytes were isolated and infected with adenovirus containing MAP4 (AdMAP4) or beta-galactosidase (Adbeta-gal) cDNA. MAP4 decorated the microtubules extensively only in AdMAP4 cardiocytes. beta-AR agonist exposure reduced cell surface beta-AR number comparably in AdMAP4 and Adbeta-gal cardiocytes; however, after agonist withdrawal, the cell surface beta-AR number recovered to 78.4 +/- 2.9% of the pretreatment value in Adbeta-gal cardiocytes but only to 56.8 +/- 1.4% in AdMAP4 cardiocytes (P < 0.01). This result was confirmed in cardiocytes isolated from transgenic mice having cardiac-restricted MAP4 overexpression. In functional terms of cAMP generation, beta-AR agonist responsiveness of AdMAP4 cells was 47% less than that of Adbeta-gal cells. We conclude that MAP4 microtubule decoration interferes with beta-AR recycling and that this may be one mechanism for beta-AR downregulation in heart failure.

Ultrasound Current Source Density Imaging in live rabbit hearts using clinical intracardiac catheter

NASA Astrophysics Data System (ADS)

Li, Qian

Ultrasound Current Source Density Imaging (UCSDI) is a noninvasive modality for mapping electrical activities in the body (brain and heart) in 4-dimensions (space + time). Conventional cardiac mapping technologies for guiding the radiofrequency ablation procedure for treatment of cardiac arrhythmias have certain limitations. UCSDI can potentially overcome these limitations and enhance the electrophysiology mapping of the heart. UCSDI exploits the acoustoelectric (AE) effect, an interaction between ultrasound pressure and electrical resistivity. When an ultrasound beam intersects a current path in a material, the local resistivity of the material is modulated by the ultrasonic pressure, and a change in voltage signal can be detected based on Ohm's Law. The degree of modulation is determined by the AE interaction constant K. K is a fundamental property of any type of material, and directly affects the amplitude of the AE signal detected in UCSDI. UCSDI requires detecting a small AE signal associated with electrocardiogram. So sensitivity becomes a major challenge for transferring UCSDI to the clinic. This dissertation will determine the limits of sensitivity and resolution for UCSDI, balancing the tradeoff between them by finding the optimal parameters for electrical cardiac mapping, and finally test the optimized system in a realistic setting. This work begins by describing a technique for measuring K, the AE interaction constant, in ionic solution and biological tissue, and reporting the value of K in excised rabbit cardiac tissue for the first time. K was found to be strongly dependent on concentration for the divalent salt CuSO4, but not for the monovalent salt NaCl, consistent with their different chemical properties. In the rabbit heart tissue, K was determined to be 0.041 +/- 0.012 %/MPa, similar to the measurement of K in physiologic saline: 0.034 +/- 0.003 %/MPa. Next, this dissertation investigates the sensitivity limit of UCSDI by quantifying the relation between the recording electrode distance and the measured AE signal amplitude in gel phantoms and excised porcine heart tissue using a clinical intracardiac catheter. Sensitivity of UCSDI with catheter was 4.7 microV/mA (R2 = 0.999) in cylindrical gel (0.9% NaCl), and 3.2 microV/mA (R2 = 0.92) in porcine heart tissue. The AE signal was detectable more than 25 mm away from the source in cylindrical gel (0.9% NaCl). Effect of transducer properties on UCSDI sensitivity is also investigated using simulation. The optimal ultrasound transducer parameters chosen for cardiac imaging are center frequency = 0.5 MHz and f/number = 1.4. Last but not least, this dissertation shows the result of implementing the optimized ultrasound parameters in live rabbit heart preparation, the comparison of different recording electrode configuration and multichannel UCSDI recording and reconstruction. The AE signal detected using the 0.5 MHz transducer was much stronger (2.99 microV/MPa) than the 1.0 MHz transducer (0.42 microV/MPa). The clinical lasso catheter placed on the epicardium exhibited excellent sensitivity without being too invasive. 3-dimensional cardiac activation maps of the live rabbit heart using only one pair of recording electrodes were also demonstrated for the first time. Cardiac conduction velocity for atrial (1.31 m/s) and apical (0.67 m/s) pacing were calculated based on the activation maps. The future outlook of this dissertation includes integrating UCSDI with 2-dimensional ultrasound transducer array for fast imaging, and developing a multi-modality catheter with 4-dimensional UCSDI, multi-electrode recording and echocardiography capacity.

Two-Term Asymptotic Approximation of a Cardiac Restitution Curve*

PubMed Central

Cain, John W.; Schaeffer, David G.

2007-01-01

If spatial extent is neglected, ionic models of cardiac cells consist of systems of ordinary differential equations (ODEs) which have the property of excitability, i.e., a brief stimulus produces a prolonged evolution (called an action potential in the cardiac context) before the eventual return to equilibrium. Under repeated stimulation, or pacing, cardiac tissue exhibits electrical restitution: the steady-state action potential duration (APD) at a given pacing period B shortens as B is decreased. Independent of ionic models, restitution is often modeled phenomenologically by a one-dimensional mapping of the form APDnext = f(B – APDprevious). Under some circumstances, a restitution function f can be derived as an asymptotic approximation to the behavior of an ionic model. In this paper, extending previous work, we derive the next term in such an asymptotic approximation for a particular ionic model consisting of two ODEs. The two-term approximation exhibits excellent quantitative agreement with the actual restitution curve, whereas the leading-order approximation significantly underestimates actual APD values. PMID:18080006

A novel intra-operative, high-resolution atrial mapping approach.

PubMed

Yaksh, Ameeta; van der Does, Lisette J M E; Kik, Charles; Knops, Paul; Oei, Frans B S; van de Woestijne, Pieter C; Bekkers, Jos A; Bogers, Ad J J C; Allessie, Maurits A; de Groot, Natasja M S

2015-12-01

A new technique is demonstrated for extensive high-resolution intra-operative atrial mapping that will facilitate the localization of atrial fibrillation (AF) sources and identification of the substrate perpetuating AF. Prior to the start of extra-corporal circulation, a 8 × 24-electrode array (2-mm inter-electrode distance) is placed subsequently on all the right and left epicardial atrial sites, including Bachmann's bundle, for recording of unipolar electrograms during sinus rhythm and (induced) AF. AF is induced by high-frequency pacing at the right atrial free wall. A pacemaker wire stitched to the right atrium serves as a reference signal. The indifferent pole is connected to a steal wire fixed to subcutaneous tissue. Electrograms are recorded by a computerized mapping system and, after amplification (gain 1000), filtering (bandwidth 0.5-400 Hz), sampling (1 kHz) and analogue to digital conversion (16 bits), automatically stored on hard disk. During the mapping procedure, real-time visualization secures electrogram quality. Analysis will be performed offline. This technique was performed in 168 patients of 18 years and older, with coronary and/or structural heart disease, with or without AF, electively scheduled for cardiac surgery and a ventricular ejection fraction above 40 %. The mean duration of the entire mapping procedure including preparation time was 9 ± 2 min. Complications related to the mapping procedure during or after cardiac surgery were not observed. We introduce the first epicardial atrial mapping approach with a high resolution of ≥1728 recording sites which can be performed in a procedure time of only 9±2 mins. This mapping technique can potentially identify areas responsible for initiation and persistence of AF and hopefully can individualize both diagnosis and therapy of AF.

Theoretical considerations for mapping activation in human cardiac fibrillation

NASA Astrophysics Data System (ADS)

Rappel, Wouter-Jan; Narayan, Sanjiv M.

2013-06-01

Defining mechanisms for cardiac fibrillation is challenging because, in contrast to other arrhythmias, fibrillation exhibits complex non-repeatability in spatiotemporal activation but paradoxically exhibits conserved spatial gradients in rate, dominant frequency, and electrical propagation. Unlike animal models, in which fibrillation can be mapped at high spatial and temporal resolution using optical dyes or arrays of contact electrodes, mapping of cardiac fibrillation in patients is constrained practically to lower resolutions or smaller fields-of-view. In many animal models, atrial fibrillation is maintained by localized electrical rotors and focal sources. However, until recently, few studies had revealed localized sources in human fibrillation, so that the impact of mapping constraints on the ability to identify rotors or focal sources in humans was not described. Here, we determine the minimum spatial and temporal resolutions theoretically required to detect rigidly rotating spiral waves and focal sources, then extend these requirements for spiral waves in computer simulations. Finally, we apply our results to clinical data acquired during human atrial fibrillation using a novel technique termed focal impulse and rotor mapping (FIRM). Our results provide theoretical justification and clinical demonstration that FIRM meets the spatio-temporal resolution requirements to reliably identify rotors and focal sources for human atrial fibrillation.

Cardiac conduction velocity estimation from sequential mapping assuming known Gaussian distribution for activation time estimation error.

PubMed

Shariat, Mohammad Hassan; Gazor, Saeed; Redfearn, Damian

2016-08-01

In this paper, we study the problem of the cardiac conduction velocity (CCV) estimation for the sequential intracardiac mapping. We assume that the intracardiac electrograms of several cardiac sites are sequentially recorded, their activation times (ATs) are extracted, and the corresponding wavefronts are specified. The locations of the mapping catheter's electrodes and the ATs of the wavefronts are used here for the CCV estimation. We assume that the extracted ATs include some estimation errors, which we model with zero-mean white Gaussian noise values with known variances. Assuming stable planar wavefront propagation, we derive the maximum likelihood CCV estimator, when the synchronization times between various recording sites are unknown. We analytically evaluate the performance of the CCV estimator and provide its mean square estimation error. Our simulation results confirm the accuracy of the proposed method and the error analysis of the proposed CCV estimator.

Development of a Web GIS Application for Visualizing and Analyzing Community Out of Hospital Cardiac Arrest Patterns

PubMed Central

Semple, Hugh; Qin, Han; Sasson, Comilla

2013-01-01

Improving survival rates at the neighborhood level is increasingly seen as a priority for reducing overall rates of out-of-hospital cardiac arrest (OHCA) in the United States. Since wide disparities exist in OHCA rates at the neighborhood level, it is important for public health officials and residents to be able to quickly locate neighborhoods where people are at elevated risk for cardiac arrest and to target these areas for educational outreach and other mitigation strategies. This paper describes an OHCA web mapping application that was developed to provide users with interactive maps and data for them to quickly visualize and analyze the geographic pattern of cardiac arrest rates, bystander CPR rates, and survival rates at the neighborhood level in different U.S. cities. The data comes from the CARES Registry and is provided over a period spanning several years so users can visualize trends in neighborhood out-of-hospital cardiac arrest patterns. Users can also visualize areas that are statistical hot and cold spots for cardiac arrest and compare OHCA and bystander CPR rates in the hot and cold spots. Although not designed as a public participation GIS (PPGIS), this application seeks to provide a forum around which data and maps about local patterns of OHCA can be shared, analyzed and discussed with a view of empowering local communities to take action to address the high rates of OHCA in their vicinity. PMID:23923097

Cardiac T1 Imaging

PubMed Central

Jerosch-Herold, Michael; Kwong, Raymond Y.

2014-01-01

T1 mapping of the heart has evolved into a valuable tool to evaluate myocardial tissue properties, with or without contrast injection, including assessment of myocardial edema and free water content, extra-cellular volume (expansion), and most recently cardiomyocyte hypertrophy. The MRI pulse sequence techniques developed for these applications have had to address at least two important considerations for cardiac applications: measure magnetization inversion recoveries during cardiac motion with sufficient temporal resolution for the shortest expected T1 values, and, secondly, obtain these measurements within a time during which a patient can comfortably suspend breathing. So-called Look-Locker techniques, and variants thereof, which all sample multiple points of a magnetization recovery after each magnetization preparation have therefore become a mainstay in this field. The rapid pace of advances and new findings based on cardiac T1 mapping for assessment of diffuse fibrosis, or myocardial edema show that these techniques enrich the capabilities of MRI for myocardial tissue profiling, which is arguably unmatched by other cardiac imaging modalities. PMID:24509619

A method to improve the B0 homogeneity of the heart in vivo.

PubMed

Jaffer, F A; Wen, H; Balaban, R S; Wolff, S D

1996-09-01

A homogeneous static (B0) magnetic field is required for many NMR experiments such as echo planar imaging, localized spectroscopy, and spiral scan imaging. Although semi-automated techniques have been described to improve the B0 field homogeneity, none has been applied to the in vivo heart. The acquisition of cardiac field maps is complicated by motion, blood flow, and chemical shift artifact from epicardial fat. To overcome these problems, an ungated three-dimensional (3D) chemical shift image (CSI) was collected to generate a time and motion-averaged B0 field map. B0 heterogeneity in the heart was minimized by using a previous algorithm that solves for the optimal shim coil currents for an input field map, using up to third-order current-bounded shims (1). The method improved the B0 homogenelty of the heart in all 11 normal volunteers studied. After application of the algorithm to the unshimmed cardiac field maps, the standard deviation of proton frequency decreased by 43%, the magnitude 1H spectral linewidth decreased by 24%, and the peak-peak gradient decreased by 35%. Simulations of the high-order (second- and third-order) shims in B0 field correction of the heart show that high order shims are important, resulting for nearly half of the improvement in homogeneity for several subjects. The T2* of the left ventricular anterior wall before and after field correction was determined at 4.0 Tesis. Finally, results show that cardiac shimming is of benefit in cardiac 31P NMR spectroscopy and cardiac echo planar imaging.

Toward standardized mapping for left atrial analysis and cardiac ablation guidance

NASA Astrophysics Data System (ADS)

Rettmann, M. E.; Holmes, D. R.; Linte, C. A.; Packer, D. L.; Robb, R. A.

2014-03-01

In catheter-based cardiac ablation, the pulmonary vein ostia are important landmarks for guiding the ablation procedure, and for this reason, have been the focus of many studies quantifying their size, structure, and variability. Analysis of pulmonary vein structure, however, has been limited by the lack of a standardized reference space for population based studies. Standardized maps are important tools for characterizing anatomic variability across subjects with the goal of separating normal inter-subject variability from abnormal variability associated with disease. In this work, we describe a novel technique for computing flat maps of left atrial anatomy in a standardized space. A flat map of left atrial anatomy is created by casting a single ray through the volume and systematically rotating the camera viewpoint to obtain the entire field of view. The technique is validated by assessing preservation of relative surface areas and distances between the original 3D geometry and the flat map geometry. The proposed methodology is demonstrated on 10 subjects which are subsequently combined to form a probabilistic map of anatomic location for each of the pulmonary vein ostia and the boundary of the left atrial appendage. The probabilistic map demonstrates that the location of the inferior ostia have higher variability than the superior ostia and the variability of the left atrial appendage is similar to the superior pulmonary veins. This technique could also have potential application in mapping electrophysiology data, radio-frequency ablation burns, or treatment planning in cardiac ablation therapy.

Cardiac shear-wave elastography using a transesophageal transducer: application to the mapping of thermal lesions in ultrasound transesophageal cardiac ablation

NASA Astrophysics Data System (ADS)

Kwiecinski, Wojciech; Bessière, Francis; Constanciel Colas, Elodie; Apoutou N'Djin, W.; Tanter, Mickaël; Lafon, Cyril; Pernot, Mathieu

2015-10-01

Heart rhythm disorders, such as atrial fibrillation or ventricular tachycardia can be treated by catheter-based thermal ablation. However, clinically available systems based on radio-frequency or cryothermal ablation suffer from limited energy penetration and the lack of lesion’s extent monitoring. An ultrasound-guided transesophageal device has recently successfully been used to perform High-Intensity Focused Ultrasound (HIFU) ablation in targeted regions of the heart in vivo. In this study we investigate the feasibility of a dual therapy and imaging approach on the same transesophageal device. We demonstrate in vivo that quantitative cardiac shear-wave elastography (SWE) can be performed with the device and we show on ex vivo samples that transesophageal SWE can map the extent of the HIFU lesions. First, SWE was validated with the transesophageal endoscope in one sheep in vivo. The stiffness of normal atrial and ventricular tissues has been assessed during the cardiac cycle (n=11 ) and mapped (n= 7 ). Second, HIFU ablation has been performed with the therapy-imaging transesophageal device in ex vivo chicken breast samples (n  =  3), then atrial (left, n= 2 ) and ventricular (left n=1 , right n=1 ) porcine heart tissues. SWE provided stiffness maps of the tissues before and after ablation. Areas of the lesions were obtained by tissue color change with gross pathology and compared to SWE. During the cardiac cycle stiffness varied from 0.5   ±   0.1 kPa to 6.0   ±   0.3 kPa in the atrium and from 1.3   ±   0.3 kPa to 13.5   ±   9.1 kPa in the ventricles. The thermal lesions were visible on all SWE maps performed after ablation. Shear modulus of the ablated zones increased to 16.3   ±   5.5 kPa (versus 4.4   ±   1.6 kPa before ablation) in the chicken breast, to 30.3   ±   10.3 kPa (versus 12.2   ±   4.3 kPa) in the atria and to 73.8   ±   13.9 kPa (versus 21.2   ±   3.3 kPa) in the ventricles. On gross pathology, the size of the lesions ranged from 0.1 to 1.5 cm2 in the imaging plane area. Elasticity-estimated depths and widths of the lesions differed respectively with a median of 0.2 mm (first quartile Q1:  -0.8 mm third quartile Q3: 2.6 mm) for a mean squared error (MSE) of 5.1 mm2 and a median of 0.2 mm (Q1:  -2.7 mm Q3: 2.7 mm) for a MSE of 11.1 mm2 from gross pathology. We have demonstrated the feasibility of the HIFU thermal ablation monitoring using a dual therapy and imaging transesophageal device. The combination of HIFU, ultrasound imaging and SWE on the same transesophageal system could lead to a new clinical device for a safer and controlled treatment of a wide variety of cardiac arrhythmias.

Cardiac shear-wave elastography using a transesophageal transducer: application to the mapping of thermal lesions in ultrasound transesophageal cardiac ablation.

PubMed

Kwiecinski, Wojciech; Bessière, Francis; Colas, Elodie Constanciel; N'Djin, W Apoutou; Tanter, Mickaël; Lafon, Cyril; Pernot, Mathieu

2015-10-21

Heart rhythm disorders, such as atrial fibrillation or ventricular tachycardia can be treated by catheter-based thermal ablation. However, clinically available systems based on radio-frequency or cryothermal ablation suffer from limited energy penetration and the lack of lesion's extent monitoring. An ultrasound-guided transesophageal device has recently successfully been used to perform High-Intensity Focused Ultrasound (HIFU) ablation in targeted regions of the heart in vivo. In this study we investigate the feasibility of a dual therapy and imaging approach on the same transesophageal device. We demonstrate in vivo that quantitative cardiac shear-wave elastography (SWE) can be performed with the device and we show on ex vivo samples that transesophageal SWE can map the extent of the HIFU lesions. First, SWE was validated with the transesophageal endoscope in one sheep in vivo. The stiffness of normal atrial and ventricular tissues has been assessed during the cardiac cycle (n = 11) and mapped (n = 7). Second, HIFU ablation has been performed with the therapy-imaging transesophageal device in ex vivo chicken breast samples (n  =  3), then atrial (left, n = 2) and ventricular (left n = 1, right n = 1) porcine heart tissues. SWE provided stiffness maps of the tissues before and after ablation. Areas of the lesions were obtained by tissue color change with gross pathology and compared to SWE. During the cardiac cycle stiffness varied from 0.5   ±   0.1 kPa to 6.0   ±   0.3 kPa in the atrium and from 1.3   ±   0.3 kPa to 13.5   ±   9.1 kPa in the ventricles. The thermal lesions were visible on all SWE maps performed after ablation. Shear modulus of the ablated zones increased to 16.3   ±   5.5 kPa (versus 4.4   ±   1.6 kPa before ablation) in the chicken breast, to 30.3   ±   10.3 kPa (versus 12.2   ±   4.3 kPa) in the atria and to 73.8   ±   13.9 kPa (versus 21.2   ±   3.3 kPa) in the ventricles. On gross pathology, the size of the lesions ranged from 0.1 to 1.5 cm(2) in the imaging plane area. Elasticity-estimated depths and widths of the lesions differed respectively with a median of 0.2 mm (first quartile Q1:  -0.8 mm; third quartile Q3: 2.6 mm) for a mean squared error (MSE) of 5.1 mm(2) and a median of 0.2 mm (Q1:  -2.7 mm; Q3: 2.7 mm) for a MSE of 11.1 mm(2) from gross pathology. We have demonstrated the feasibility of the HIFU thermal ablation monitoring using a dual therapy and imaging transesophageal device. The combination of HIFU, ultrasound imaging and SWE on the same transesophageal system could lead to a new clinical device for a safer and controlled treatment of a wide variety of cardiac arrhythmias.

Recurrence-plot-based measures of complexity and their application to heart-rate-variability data.

PubMed

Marwan, Norbert; Wessel, Niels; Meyerfeldt, Udo; Schirdewan, Alexander; Kurths, Jürgen

2002-08-01

The knowledge of transitions between regular, laminar or chaotic behaviors is essential to understand the underlying mechanisms behind complex systems. While several linear approaches are often insufficient to describe such processes, there are several nonlinear methods that, however, require rather long time observations. To overcome these difficulties, we propose measures of complexity based on vertical structures in recurrence plots and apply them to the logistic map as well as to heart-rate-variability data. For the logistic map these measures enable us not only to detect transitions between chaotic and periodic states, but also to identify laminar states, i.e., chaos-chaos transitions. The traditional recurrence quantification analysis fails to detect the latter transitions. Applying our measures to the heart-rate-variability data, we are able to detect and quantify the laminar phases before a life-threatening cardiac arrhythmia occurs thereby facilitating a prediction of such an event. Our findings could be of importance for the therapy of malignant cardiac arrhythmias.

Evaluation of Rigid-Body Motion Compensation in Cardiac Perfusion SPECT Employing Polar-Map Quantification

PubMed Central

Pretorius, P. Hendrik; Johnson, Karen L.; King, Michael A.

2016-01-01

We have recently been successful in the development and testing of rigid-body motion tracking, estimation and compensation for cardiac perfusion SPECT based on a visual tracking system (VTS). The goal of this study was to evaluate in patients the effectiveness of our rigid-body motion compensation strategy. Sixty-four patient volunteers were asked to remain motionless or execute some predefined body motion during an additional second stress perfusion acquisition. Acquisitions were performed using the standard clinical protocol with 64 projections acquired through 180 degrees. All data were reconstructed with an ordered-subsets expectation-maximization (OSEM) algorithm using 4 projections per subset and 5 iterations. All physical degradation factors were addressed (attenuation, scatter, and distance dependent resolution), while a 3-dimensional Gaussian rotator was used during reconstruction to correct for six-degree-of-freedom (6-DOF) rigid-body motion estimated by the VTS. Polar map quantification was employed to evaluate compensation techniques. In 54.7% of the uncorrected second stress studies there was a statistically significant difference in the polar maps, and in 45.3% this made a difference in the interpretation of segmental perfusion. Motion correction reduced the impact of motion such that with it 32.8 % of the polar maps were statistically significantly different, and in 14.1% this difference changed the interpretation of segmental perfusion. The improvement shown in polar map quantitation translated to visually improved uniformity of the SPECT slices. PMID:28042170

Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans

PubMed Central

Niewinski, Piotr; Tubek, Stanislaw; Banasiak, Waldemar; Paton, Julian F R; Ponikowski, Piotr

2014-01-01

Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function. PMID:24396060

Wideband Arrhythmia-Insensitive-Rapid (AIR) Pulse Sequence for Cardiac T1 mapping without Image Artifacts induced by ICD

PubMed Central

Hong, KyungPyo; Jeong, Eun-Kee; Wall, T. Scott; Drakos, Stavros G.; Kim, Daniel

2015-01-01

Purpose To develop and evaluate a wideband arrhythmia-insensitive-rapid (AIR) pulse sequence for cardiac T1 mapping without image artifacts induced by implantable-cardioverter-defibrillator (ICD). Methods We developed a wideband AIR pulse sequence by incorporating a saturation pulse with wide frequency bandwidth (8.9 kHz), in order to achieve uniform T1 weighting in the heart with ICD. We tested the performance of original and “wideband” AIR cardiac T1 mapping pulse sequences in phantom and human experiments at 1.5T. Results In 5 phantoms representing native myocardium and blood and post-contrast blood/tissue T1 values, compared with the control T1 values measured with an inversion-recovery pulse sequence without ICD, T1 values measured with original AIR with ICD were considerably lower (absolute percent error >29%), whereas T1 values measured with wideband AIR with ICD were similar (absolute percent error <5%). Similarly, in 11 human subjects, compared with the control T1 values measured with original AIR without ICD, T1 measured with original AIR with ICD was significantly lower (absolute percent error >10.1%), whereas T1 measured with wideband AIR with ICD was similar (absolute percent error <2.0%). Conclusion This study demonstrates the feasibility of a wideband pulse sequence for cardiac T1 mapping without significant image artifacts induced by ICD. PMID:25975192

The characterisation of blood rotation in a human heart chamber based on statistical analysis of vorticity maps

NASA Astrophysics Data System (ADS)

Wong, Kelvin K. L.; Kelso, Richard M.; Worthley, Stephen G.; Sanders, Prashanthan; Mazumdar, Jagannath; Abbott, Derek

2008-12-01

Modelling of non-stationary cardiac structures is complicated by the complexity of their intrinsic and extrinsic motion. The first known study of haemodynamics due to the beating of heart was made by Leonardo Da Vinci, giving the idea of fluid-solid interaction by describing how vortices develop during cardiac structural interaction with the blood. Heart morphology affects in changes of cardio dynamics during the systolic and diastolic phrases. In a chamber of the heart, vortices are discovered to exist as the result of the unique morphological changes of the cardiac chamber wall by using flow-imaging techniques such as phase contrast magnetic resonance imaging. The first part of this paper attempts to quantify vortex characteristics by means of calculating vorticity numerically and devising two dimensional vortical flow maps. The technique relies on determining the properties of vorticity using a statistical quantification of the flow maps and comparison of these quantities based on different scenarios. As the characteristics of our vorticity maps vary depending on the phase of a cardiac cycle, there is a need for robust quantification method to analyse vorticity. In the second part of the paper, the approach is then utilised for examining vortices within the human right atrium. Our study has shown that a proper quantification of vorticity for the flow field can indicate the strength and number of vortices within a heart chamber.

Site-specific Microtubule-associated Protein 4 Dephosphorylation Causes Microtubule Network Densification in Pressure Overload Cardiac Hypertrophy*

PubMed Central

Chinnakkannu, Panneerselvam; Samanna, Venkatesababa; Cheng, Guangmao; Ablonczy, Zsolt; Baicu, Catalin F.; Bethard, Jennifer R.; Menick, Donald R.; Kuppuswamy, Dhandapani; Cooper, George

2010-01-01

In severe pressure overload-induced cardiac hypertrophy, a dense, stabilized microtubule network forms that interferes with cardiocyte contraction and microtubule-based transport. This is associated with persistent transcriptional up-regulation of cardiac α- and β-tubulin and microtubule-stabilizing microtubule-associated protein 4 (MAP4). There is also extensive microtubule decoration by MAP4, suggesting greater MAP4 affinity for microtubules. Because the major determinant of this affinity is site-specific MAP4 dephosphorylation, we characterized this in hypertrophied myocardium and then assessed the functional significance of each dephosphorylation site found by mimicking it in normal cardiocytes. We first isolated MAP4 from normal and pressure overload-hypertrophied feline myocardium; volume-overloaded myocardium, which has an equal degree and duration of hypertrophy but normal functional and cytoskeletal properties, served as a control for any nonspecific growth-related effects. After cloning cDNA-encoding feline MAP4 and obtaining its deduced amino acid sequence, we characterized by mass spectrometry any site-specific MAP4 dephosphorylation. Solely in pressure overload-hypertrophied myocardium, we identified striking MAP4 dephosphorylation at Ser-472 in the MAP4 N-terminal projection domain and at Ser-924 and Ser-1056 in the assembly-promoting region of the C-terminal microtubule-binding domain. Site-directed mutagenesis of MAP4 cDNA was then used to switch each serine to non-phosphorylatable alanine. Wild-type and mutated cDNAs were used to construct adenoviruses; microtubule network density, stability, and MAP4 decoration were assessed in normal cardiocytes following an equivalent level of MAP4 expression. The Ser-924 → Ala MAP4 mutant produced a microtubule phenotype indistinguishable from that seen in pressure overload hypertrophy, such that Ser-924 MAP4 dephosphorylation during pressure overload hypertrophy may be central to this cytoskeletal abnormality. PMID:20436166

Assessment of cardiac sympathetic neuronal function using PET imaging.

PubMed

Bengel, Frank M; Schwaiger, Markus

2004-01-01

The autonomic nervous system plays a key role for regulation of cardiac performance, and the importance of alterations of innervation in the pathophysiology of various heart diseases has been increasingly emphasized. Nuclear imaging techniques have been established that allow for global and regional investigation of the myocardial nervous system. The guanethidine analog iodine 123 metaiodobenzylguanidine (MIBG) has been introduced for scintigraphic mapping of presynaptic sympathetic innervation and is available today for imaging on a broad clinical basis. Not much later than MIBG, positron emission tomography (PET) has also been established for characterizing the cardiac autonomic nervous system. Although PET is methodologically demanding and less widely available, it provides substantial advantages. High spatial and temporal resolution along with routinely available attenuation correction allows for detailed definition of tracer kinetics and makes noninvasive absolute quantification a reality. Furthermore, a series of different radiolabeled catecholamines, catecholamine analogs, and receptor ligands are available. Those are often more physiologic than MIBG and well understood with regard to their tracer physiologic properties. PET imaging of sympathetic neuronal function has been successfully applied to gain mechanistic insights into myocardial biology and pathology. Available tracers allow dissection of processes of presynaptic and postsynaptic innervation contributing to cardiovascular disease. This review summarizes characteristics of currently available PET tracers for cardiac neuroimaging along with the major findings derived from their application in health and disease.

Attenuation-emission alignment in cardiac PET∕CT based on consistency conditions

PubMed Central

Alessio, Adam M.; Kinahan, Paul E.; Champley, Kyle M.; Caldwell, James H.

2010-01-01

Purpose: In cardiac PET and PET∕CT imaging, misaligned transmission and emission images are a common problem due to respiratory and cardiac motion. This misalignment leads to erroneous attenuation correction and can cause errors in perfusion mapping and quantification. This study develops and tests a method for automated alignment of attenuation and emission data. Methods: The CT-based attenuation map is iteratively transformed until the attenuation corrected emission data minimize an objective function based on the Radon consistency conditions. The alignment process is derived from previous work by Welch et al. [“Attenuation correction in PET using consistency information,” IEEE Trans. Nucl. Sci. 45, 3134–3141 (1998)] for stand-alone PET imaging. The process was evaluated with the simulated data and measured patient data from multiple cardiac ammonia PET∕CT exams. The alignment procedure was applied to simulations of five different noise levels with three different initial attenuation maps. For the measured patient data, the alignment procedure was applied to eight attenuation-emission combinations with initially acceptable alignment and eight combinations with unacceptable alignment. The initially acceptable alignment studies were forced out of alignment a known amount and quantitatively evaluated for alignment and perfusion accuracy. The initially unacceptable studies were compared to the proposed aligned images in a blinded side-by-side review. Results: The proposed automatic alignment procedure reduced errors in the simulated data and iteratively approaches global minimum solutions with the patient data. In simulations, the alignment procedure reduced the root mean square error to less than 5 mm and reduces the axial translation error to less than 1 mm. In patient studies, the procedure reduced the translation error by >50% and resolved perfusion artifacts after a known misalignment for the eight initially acceptable patient combinations. The side-by-side review of the proposed aligned attenuation-emission maps and initially misaligned attenuation-emission maps revealed that reviewers preferred the proposed aligned maps in all cases, except one inconclusive case. Conclusions: The proposed alignment procedure offers an automatic method to reduce attenuation correction artifacts in cardiac PET∕CT and provides a viable supplement to subjective manual realignment tools. PMID:20384256

State of the Art: Clinical Applications of Cardiac T1 Mapping.

PubMed

Schelbert, Erik B; Messroghli, Daniel R

2016-03-01

While cardiovascular magnetic resonance (MR) has become the noninvasive tool of choice for the assessment of myocardial viability and for the detection of acute myocardial edema, cardiac T1 mapping is believed to further extend the ability of cardiovascular MR to characterize the myocardium. Fundamentally, cardiovascular MR can improve diagnosis of disease that historically has been challenging to establish with other imaging modalities. For example, decreased native T1 values appear highly specific to detect and quantify disease severity related to myocardial iron overload states or glycosphingolipid accumulation in Anderson-Fabry disease, whereas high native T1 values are observed with edema, amyloid, and other conditions. Cardiovascular MR can also improve the assessment of prognosis with parameters that relate to myocardial structure and composition that complement the familiar functional parameters around which contemporary cardiology decision making revolves. In large cohorts, extracellular volume fraction (ECV) has been shown to quantify the full extent of myocardial fibrosis in noninfarcted myocardium. ECV may predict outcomes at least as effectively as left ventricular ejection fraction. This uncommon statistical observation (of potentially being more strongly associated with outcomes than ejection fraction) suggests prime biologic importance for the cardiac interstitium that may rank highly in the hierarchy of vast myocardial changes occurring in cardiac pathophysiology. This article presents current and developing clinical applications of cardiac T1 mapping and reviews the existing evidence on their diagnostic and prognostic value in various clinical conditions. This article also contextualizes these advances and explores how T1 mapping and ECV may affect major "global" issues such as diagnosis of disease, risk stratification, and paradigms of disease, and ultimately how we conceptualize patient vulnerability.

Endovascular brain intervention and mapping in a dog experimental model using magnetically-guided micro-catheter technology.

PubMed

Kara, Tomas; Leinveber, Pavel; Vlasin, Michal; Jurak, Pavel; Novak, Miroslav; Novak, Zdenek; Chrastina, Jan; Czechowicz, Krzysztof; Belehrad, Milos; Asirvatham, Samuel J

2014-06-01

Despite the substantial progress that has been achieved in interventional cardiology and cardiac electrophysiology, endovascular intervention for the diagnosis and treatment of central nervous system (CNS) disorders such as stroke, epilepsy and CNS malignancy is still limited, particularly due to highly tortuous nature of the cerebral arterial and venous system. Existing interventional devices and techniques enable only limited and complicated access especially into intra-cerebral vessels. The aim of this study was to develop a micro-catheter magnetically-guided technology specifically designed for endovascular intervention and mapping in deep CNS vascular structures. Mapping of electrical brain activity was performed via the venous system on an animal dog model with the support of the NIOBE II system. A novel micro-catheter specially designed for endovascular interventions in the CNS, with the support of the NIOBE II technology, was able to reach safely deep intra-cerebral venous structures and map the electrical activity there. Such structures are not currently accessible using standard catheters. This is the first study demonstrating successful use of a new micro-catheter in combination with NIOBE II technology for endovascular intervention in the brain.

Design of parallel transmission radiofrequency pulses robust against respiration in cardiac MRI at 7 Tesla.

PubMed

Schmitter, Sebastian; Wu, Xiaoping; Uğurbil, Kâmil; Van de Moortele, Pierre-François

2015-11-01

Two-spoke parallel transmission (pTX) radiofrequency (RF) pulses have been demonstrated in cardiac MRI at 7T. However, current pulse designs rely on a single set of B1(+)/B0 maps that may not be valid for subsequent scans acquired at another phase of the respiration cycle because of organ displacement. Such mismatches may yield severe excitation profile degradation. B1(+)/B0 maps were obtained, using 16 transmit channels at 7T, at three breath-hold positions: exhale, half-inhale, and inhale. Standard and robust RF pulses were designed using maps obtained at exhale only, and at multiple respiratory positions, respectively. Excitation patterns were analyzed for all positions using Bloch simulations. Flip-angle homogeneity was compared in vivo in cardiac CINE acquisitions. Standard one- and two-spoke pTX RF pulses are sensitive to breath-hold position, primarily due to B1(+) alterations, with high dependency on excitation trajectory for two spokes. In vivo excitation inhomogeneity varied from nRMSE = 8.2% (exhale) up to 32.5% (inhale) with the standard design; much more stable results were obtained with the robust design with nRMSE = 9.1% (exhale) and 10.6% (inhale). A new pTX RF pulse design robust against respiration induced variations of B1(+)/B0 maps is demonstrated and is expected to have a positive impact on cardiac MRI in breath-hold, free-breathing, and real-time acquisitions. © 2014 Wiley Periodicals, Inc.

Magnetic resonance evaluation of cardiac thrombi and masses by T1 and T2 mapping: an observational study.

PubMed

Caspar, Thibault; El Ghannudi, Soraya; Ohana, Mickaël; Labani, Aïssam; Lawson, Aubrietia; Ohlmann, Patrick; Morel, Olivier; De Mathelin, Michel; Roy, Catherine; Gangi, Afshin; Germain, Philippe

2017-04-01

The purpose of this work was to evaluate CMR T1 and T2 mapping sequences in patients with intracardiac thrombi and masses in order to assess T1 and T2 relaxometry usefulness and to allow better etiological diagnosis. This observational study of patients scheduled for routine CMR was performed from September 2014 to August 2015. All patients referred to our department for a 1.5 T CMR were screened to participate. T1 mapping were acquired before and after Gadolinium injection; T2 mapping images were obtained before injection. 41 patients were included. 22 presented with cardiac thrombi and 19 with cardiac masses. The native T1 of thrombi was 1037 ± 152 ms (vs 1032 ± 39 ms for myocardium, p = 0.88; vs 1565 ± 88 ms for blood pool, p < 0.0001). T2 were 74 ± 13 ms (vs 51 ± 3 ms for myocardium, p < 0.0001; vs 170 ± 32 ms for blood pool, p < 0.0001). Recent thrombi had a native T1 shorter than old thrombi (911 ± 177 vs 1169 ± 107 ms, p = 0.01). The masses having a shorter T1 than the myocardium were lipomas (278 ± 29 ms), calcifications (621 ± 218 ms), and melanoma (736 ms). All other masses showed T1 values higher than myocardial T1, with T2 consistently >70 ms. T1 and T2 mapping CMR sequences can be useful and represent a new approach for the evaluation of cardiac thrombi and masses.

Assessment of myocardial fibrosis with T1 mapping MRI.

PubMed

Everett, R J; Stirrat, C G; Semple, S I R; Newby, D E; Dweck, M R; Mirsadraee, S

2016-08-01

Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in an intact pig model

PubMed Central

2010-01-01

Introduction We developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming. Methods Twelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls. Results During progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dtmin), indexes of LV contractility (preload recruitable stroke work, PRSW, and maximal acceleration of pressure in the cardiac cycle, dP/dtmax) and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased. Conclusions Progressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments. PMID:21092272

Mesenchymal-endothelial-transition contributes to cardiac neovascularization

PubMed Central

Ubil, Eric; Duan, Jinzhu; Pillai, Indulekha C.L.; Rosa-Garrido, Manuel; Wu, Yong; Bargiacchi, Francesca; Lu, Yan; Stanbouly, Seta; Huang, Jie; Rojas, Mauricio; Vondriska, Thomas M.; Stefani, Enrico; Deb, Arjun

2014-01-01

Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal-transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial cell like phenotype after acute ischemic cardiac injury. Fibroblast derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast derived endothelial cells, reduces post infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal to endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial-transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair. PMID:25317562

Magnetic resonance-compatible model of isolated working heart from large animal for multimodal assessment of cardiac function, electrophysiology, and metabolism.

PubMed

Vaillant, Fanny; Magat, Julie; Bour, Pierre; Naulin, Jérôme; Benoist, David; Loyer, Virginie; Vieillot, Delphine; Labrousse, Louis; Ritter, Philippe; Bernus, Olivier; Dos Santos, Pierre; Quesson, Bruno

2016-05-15

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications. Copyright © 2016 the American Physiological Society.

Probability mapping of scarred myocardium using texture and intensity features in CMR images

PubMed Central

2013-01-01

Background The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. Methods In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. Results In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. Conclusion The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium). PMID:24053280

Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

PubMed

Torlasco, Camilla; Cassinerio, Elena; Roghi, Alberto; Faini, Andrea; Capecchi, Marco; Abdel-Gadir, Amna; Giannattasio, Cristina; Parati, Gianfranco; Moon, James C; Cappellini, Maria D; Pedrotti, Patrizia

2018-01-01

Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

Analysis of chaos attractors of MCG-recordings.

PubMed

Jiang, Shiqin; Yang, Fan; Yi, Panke; Chen, Bo; Luo, Ming; Wang, Lemin

2006-01-01

By studying the chaos attractor of cardiac magnetic induction strength B(z) generated by the electrical activity of the heart, we found that its projection in the reconstructed phase space has a similar shape with the map of the total current dipole vector. It is worth noting that the map of the total current dipole vector is computed with MCG recordings measured at 36 locations, whereas the chaos attractor of B(z) is generated by only one cardiac magnetic field recordings on the measured plan. We discuss only two subjects of different ages in this paper.

Electromechanical Wave Imaging (EWI) validation in all four cardiac chambers with 3D electroanatomic mapping in canines in vivo

PubMed Central

Costet, Alexandre; Wan, Elaine; Bunting, Ethan; Grondin, Julien; Garan, Hasan; Konofagou, Elisa

2016-01-01

Characterization and mapping of arrhythmias is currently performed through invasive insertion and manipulation of cardiac catheters. Electromechanical wave imaging (EWI) is a non-invasive ultrasound-based imaging technique, which tracks the electromechanical activation that immediately follows electrical activation. Electrical and electromechanical activations were previously found to be linearly correlated in the left ventricle, but the relationship has not yet been investigated in the three other chambers of the heart. The objective of this study was to investigate the relationship between electrical and electromechanical activations and validate EWI in all four chambers of the heart with conventional 3D electroanatomical mapping. Six (n = 6) normal adult canines were used in this study. The electrical activation sequence was mapped in all four chambers of the heart, both endocardially and epicardially using the St Jude's EnSite 3D mapping system (St. Jude Medical, Secaucus, NJ). EWI acquisitions were performed in all four chambers during normal sinus rhythm, and during pacing in the left ventricle. Isochrones of the electromechanical activation were generated from standard echocardiographic imaging views. Electrical and electromechanical activation maps were co-registered and compared, and electrical and electromechanical activation times were plotted against each other and linear regression was performed for each pair of activation maps. Electromechanical and electrical activations were found to be directly correlated with slopes of the correlation ranging from 0.77 to 1.83, electromechanical delays between 9 and 58 ms and R2 values from 0.71 to 0.92. The linear correlation between electrical and electromechanical activations and the agreement between the activation maps indicate that the electromechanical activation follows the pattern of propagation of the electrical activation. This suggests that EWI may be used as a novel non-invasive method to accurately characterize and localize sources of arrhythmias. PMID:27782003

Electromechanical wave imaging (EWI) validation in all four cardiac chambers with 3D electroanatomic mapping in canines in vivo.

PubMed

Costet, Alexandre; Wan, Elaine; Bunting, Ethan; Grondin, Julien; Garan, Hasan; Konofagou, Elisa

2016-11-21

Characterization and mapping of arrhythmias is currently performed through invasive insertion and manipulation of cardiac catheters. Electromechanical wave imaging (EWI) is a non-invasive ultrasound-based imaging technique, which tracks the electromechanical activation that immediately follows electrical activation. Electrical and electromechanical activations were previously found to be linearly correlated in the left ventricle, but the relationship has not yet been investigated in the three other chambers of the heart. The objective of this study was to investigate the relationship between electrical and electromechanical activations and validate EWI in all four chambers of the heart with conventional 3D electroanatomical mapping. Six (n  =  6) normal adult canines were used in this study. The electrical activation sequence was mapped in all four chambers of the heart, both endocardially and epicardially using the St Jude's EnSite 3D mapping system (St. Jude Medical, Secaucus, NJ). EWI acquisitions were performed in all four chambers during normal sinus rhythm, and during pacing in the left ventricle. Isochrones of the electromechanical activation were generated from standard echocardiographic imaging views. Electrical and electromechanical activation maps were co-registered and compared, and electrical and electromechanical activation times were plotted against each other and linear regression was performed for each pair of activation maps. Electromechanical and electrical activations were found to be directly correlated with slopes of the correlation ranging from 0.77 to 1.83, electromechanical delays between 9 and 58 ms and R 2 values from 0.71 to 0.92. The linear correlation between electrical and electromechanical activations and the agreement between the activation maps indicate that the electromechanical activation follows the pattern of propagation of the electrical activation. This suggests that EWI may be used as a novel non-invasive method to accurately characterize and localize sources of arrhythmias.

Interventional endocardial motion estimation from electroanatomical mapping data: application to scar characterization.

PubMed

Porras, Antonio R; Piella, Gemma; Berruezo, Antonio; Hoogendoorn, Corne; Andreu, David; Fernandez-Armenta, Juan; Sitges, Marta; Frangi, Alejandro F

2013-05-01

Scar presence and its characteristics play a fundamental role in several cardiac pathologies. To accurately define the extent and location of the scar is essential for a successful ventricular tachycardia ablation procedure. Nowadays, a set of widely accepted electrical voltage thresholds applied to local electrograms recorded are used intraoperatively to locate the scar. Information about cardiac mechanics could be considered to characterize tissues with different viability properties. We propose a novel method to estimate endocardial motion from data obtained with an electroanatomical mapping system together with the endocardial geometry segmented from preoperative 3-D magnetic resonance images, using a statistical atlas constructed with bilinear models. The method was validated using synthetic data generated from ultrasound images of nine volunteers and was then applied to seven ventricular tachycardia patients. Maximum bipolar voltages, commonly used to intraoperatively locate scar tissue, were compared to endocardial wall displacement and strain for all the patients. The results show that the proposed method allows endocardial motion and strain estimation and that areas with low-voltage electrograms also present low strain values.

[Sudden cardiac death, a major scientific challenge].

PubMed

Haissaguerre, Michel; Hocini, Meleze; Sacher, Frédéric; Shah, Ashok

2010-06-01

Sudden death is responsible for 350,000 deaths each year in Europe, or 1000 deaths each day, equivalent to the combined mortality from the most lethal cancers (breast, lung and colorectal). Unfortunately, sudden death is widely considered to be "natural", being due to unknown but critical cardiac disorders leading to sudden arrest of cardiac activity. Awareness of its potential preventability is inadequate. Indeed, 80% of cases of sudden death are associated with extremely rapid heartbeats, an "electric tornado" called ventricular fibrillation, caused by ultrarapid firing of ectopic foci or chaotic wave propagation. This arrhythmia strikes like lightning Although it can be associated with myocardial infarction, most victims have structurally normal or slightly altered hearts. The cells which cause this ultrarapid firing originate from the Purkinje system, which constitutes just a fraction (2%) of total cardiac mass. This is borne out by the fact that the risk of fatal arrhythmic events can be reduced by focal thermoablation. What is most important is to identify subjects at risk of such events. It has been suggested that there exists an unidentified subclinical electrical disharmony, which converts into a tornado of ultimately fatal clinical events at a certain threshold level. High-resolution bioelectrical cardiac mapping, functional imaging, and treatment of electrical field disorders are major scientific challenges given their complexity, intraindividual dynamics and interindividual variability.

Myocardial Mapping With Cardiac Magnetic Resonance: The Diagnostic Value of Novel Sequences.

PubMed

Sanz, Javier; LaRocca, Gina; Mirelis, Jesús G

2016-09-01

Cardiac magnetic resonance has evolved into a crucial modality for the evaluation of cardiomyopathy due to its ability to characterize myocardial structure and function. In the last few years, interest has increased in the potential of "mapping" techniques that provide direct and objective quantification of myocardial properties such as T1, T2, and T2* times. These approaches enable the detection of abnormalities that affect the myocardium in a diffuse fashion and/or may be too subtle for visual recognition. This article reviews the current state of myocardial T1 and T2-mapping in both health and disease. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Registration of 4D cardiac CT sequences under trajectory constraints with multichannel diffeomorphic demons.

PubMed

Peyrat, Jean-Marc; Delingette, Hervé; Sermesant, Maxime; Xu, Chenyang; Ayache, Nicholas

2010-07-01

We propose a framework for the nonlinear spatiotemporal registration of 4D time-series of images based on the Diffeomorphic Demons (DD) algorithm. In this framework, the 4D spatiotemporal registration is decoupled into a 4D temporal registration, defined as mapping physiological states, and a 4D spatial registration, defined as mapping trajectories of physical points. Our contribution focuses more specifically on the 4D spatial registration that should be consistent over time as opposed to 3D registration that solely aims at mapping homologous points at a given time-point. First, we estimate in each sequence the motion displacement field, which is a dense representation of the point trajectories we want to register. Then, we perform simultaneously 3D registrations of corresponding time-points with the constraints to map the same physical points over time called the trajectory constraints. Under these constraints, we show that the 4D spatial registration can be formulated as a multichannel registration of 3D images. To solve it, we propose a novel version of the Diffeomorphic Demons (DD) algorithm extended to vector-valued 3D images, the Multichannel Diffeomorphic Demons (MDD). For evaluation, this framework is applied to the registration of 4D cardiac computed tomography (CT) sequences and compared to other standard methods with real patient data and synthetic data simulated from a physiologically realistic electromechanical cardiac model. Results show that the trajectory constraints act as a temporal regularization consistent with motion whereas the multichannel registration acts as a spatial regularization. Finally, using these trajectory constraints with multichannel registration yields the best compromise between registration accuracy, temporal and spatial smoothness, and computation times. A prospective example of application is also presented with the spatiotemporal registration of 4D cardiac CT sequences of the same patient before and after radiofrequency ablation (RFA) in case of atrial fibrillation (AF). The intersequence spatial transformations over a cardiac cycle allow to analyze and quantify the regression of left ventricular hypertrophy and its impact on the cardiac function.

Utility and Clinical Profile of Dexmedetomidine in Pediatric Cardiac Catheterization Procedures: A Matched Controlled Analysis.

PubMed

Riveros, Ricardo; Makarova, Natalya; Riveros-Perez, Efrain; Chodavarapu, Praneeta; Saasouh, Wael; Yılmaz, Hüseyin Oğuz; Cuko, Evis; Babazade, Rovnat; Kimatian, Stephen; Turan, Alparslan

2017-12-01

Dexmedetomidine is increasingly used in children undergoing cardiac catheterization procedures. We compared the percentage of surgical time with hemodynamic instability and the incidence of postoperative agitation between pediatric cardiac catheterization patients who received dexmedetomidine infusion and those who did not and the incidence of postoperative agitation. We matched 653 pediatric patients scheduled for cardiac catheterization. Two separate multivariable linear mixed models were used to assess the association between dexmedetomidine use and intraoperative blood pressure and heart rate instability. A multivariate logistic regression was used for relationship between dexmedetomidine and postoperative agitation. No difference between the study groups was found in the duration of MAP ( P = .867) or heart rate (HR) instabilities ( P = .224). The relationship between dexmedetomidine use and the duration of negative hemodynamic effects does not depend on any of the considered CHD types (all P > .001) or intervention ( P = .453 for MAP and P = .023 for HR). No difference in postoperative agitation was found between the study groups ( P = .590). Our study demonstrated no benefit in using dexmedetomidine infusion compared with other general anesthesia techniques to maintain hemodynamic stability or decrease agitation in pediatric patients undergoing cardiac catheterization procedures.

Mapping of Cardiac Electrical Activation with Electromechanical Wave Imaging: An in silico-in vivo Reciprocity Study

PubMed Central

Provost, Jean; Gurev, Viatcheslav; Trayanova, Natalia; Konofagou, Elisa E.

2011-01-01

Background Electromechanical Wave Imaging (EWI) is an entirely non-invasive, ultrasound-based imaging method capable of mapping the electromechanical activation sequence of the ventricles in vivo. Given the broad accessibility of ultrasound scanners in the clinic, the application of EWI could constitute a flexible surrogate for the 3D electrical activation. Objective The purpose of this report is to reproduce the electromechanical wave (EW) using an anatomically-realistic electromechanical model, and establish the capability of EWI to map the electrical activation sequence in vivo when pacing from different locations. Methods EWI was performed in one canine during pacing from three different sites. A high-resolution dynamic model of coupled cardiac electromechanics of the canine heart was used to predict the experimentally recorded electromechanical wave. The simulated 3D electrical activation sequence was then compared with the experimental EW. Results The electrical activation sequence and the EW were highly correlated for all pacing sites. The relationship between the electrical activation and the EW onset was found to be linear with a slope of 1.01 to 1.17 for different pacing schemes and imaging angles. Conclusions The accurate reproduction of the EW in simulations indicates that the model framework is capable of accurately representing the cardiac electromechanics and thus testing new hypotheses. The one-to-one correspondence between the electrical activation sequence and the EW indicates that EWI could be used to map the cardiac electrical activity. This opens the door for further exploration of the technique in assisting in the early detection, diagnosis and treatment monitoring of rhythm dysfunction. PMID:21185403

Invasion of Peripheral Immune Cells into Brain Parenchyma after Cardiac Arrest and Resuscitation.

PubMed

Zhang, Can; Brandon, Nicole R; Koper, Kerryann; Tang, Pei; Xu, Yan; Dou, Huanyu

2018-06-01

Although a direct link has long been suspected between systemic immune responses and neuronal injuries after stroke, it is unclear which immune cells play an important role. A question remains as to whether the blood brain barrier (BBB) is transiently disrupted after circulatory arrest to allow peripheral immune cells to enter brain parenchyma. Here, we developed a clinically relevant cardiac arrest and resuscitation model in mice to investigate the BBB integrity using noninvasive magnetic resonance imaging. Changes in immune signals in the brain and periphery were assayed by immunohistochemistry and flow cytometry. Quantitative variance maps from T1-weighted difference images before and after blood-pool contrast clearance revealed BBB disruptions immediately after resuscitation and one day after reperfusion. Time profiles of hippocampal CA1 neuronal injuries correlated with the morphological changes of microglia activation. Cytotoxic T cells, CD11b + CD11c + dendritic cells, and CD11b + CD45 +hi monocytes and macrophages were significantly increased in the brain three days after cardiac arrest and resuscitation, suggesting direct infiltration of these cells following the BBB disruption. Importantly, these immune cell changes were coupled with a parallel increase in the same subset of immune cell populations in the bone marrow and blood. We conclude that neurovascular breakdown during the initial reperfusion phase contributes to the systemic immune cell invasion and subsequent neuropathogenesis affecting the long-term outcome after cardiac arrest and resuscitation.

Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

PubMed

Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

2007-05-01

3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues.

PubMed

Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M

2016-09-01

Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

Three-dimensional mapping and regulation of action potential propagation in nanoelectronics innervated tissues

PubMed Central

Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

2016-01-01

Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could impact broadly fundamental scientific and clinical studies, yet realization lacks effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and sub-millisecond time-resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues, and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multi-site stimulation and mapping to manipulate actively the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics. PMID:27347837

3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium

NASA Astrophysics Data System (ADS)

Xu, Lizhi; Gutbrod, Sarah R.; Bonifas, Andrew P.; Su, Yewang; Sulkin, Matthew S.; Lu, Nanshu; Chung, Hyun-Joong; Jang, Kyung-In; Liu, Zhuangjian; Ying, Ming; Lu, Chi; Webb, R. Chad; Kim, Jong-Seon; Laughner, Jacob I.; Cheng, Huanyu; Liu, Yuhao; Ameen, Abid; Jeong, Jae-Woong; Kim, Gwang-Tae; Huang, Yonggang; Efimov, Igor R.; Rogers, John A.

2014-02-01

Means for high-density multiparametric physiological mapping and stimulation are critically important in both basic and clinical cardiology. Current conformal electronic systems are essentially 2D sheets, which cannot cover the full epicardial surface or maintain reliable contact for chronic use without sutures or adhesives. Here we create 3D elastic membranes shaped precisely to match the epicardium of the heart via the use of 3D printing, as a platform for deformable arrays of multifunctional sensors, electronic and optoelectronic components. Such integumentary devices completely envelop the heart, in a form-fitting manner, and possess inherent elasticity, providing a mechanically stable biotic/abiotic interface during normal cardiac cycles. Component examples range from actuators for electrical, thermal and optical stimulation, to sensors for pH, temperature and mechanical strain. The semiconductor materials include silicon, gallium arsenide and gallium nitride, co-integrated with metals, metal oxides and polymers, to provide these and other operational capabilities. Ex vivo physiological experiments demonstrate various functions and methodological possibilities for cardiac research and therapy.

Memory-induced nonlinear dynamics of excitation in cardiac diseases.

PubMed

Landaw, Julian; Qu, Zhilin

2018-04-01

Excitable cells, such as cardiac myocytes, exhibit short-term memory, i.e., the state of the cell depends on its history of excitation. Memory can originate from slow recovery of membrane ion channels or from accumulation of intracellular ion concentrations, such as calcium ion or sodium ion concentration accumulation. Here we examine the effects of memory on excitation dynamics in cardiac myocytes under two diseased conditions, early repolarization and reduced repolarization reserve, each with memory from two different sources: slow recovery of a potassium ion channel and slow accumulation of the intracellular calcium ion concentration. We first carry out computer simulations of action potential models described by differential equations to demonstrate complex excitation dynamics, such as chaos. We then develop iterated map models that incorporate memory, which accurately capture the complex excitation dynamics and bifurcations of the action potential models. Finally, we carry out theoretical analyses of the iterated map models to reveal the underlying mechanisms of memory-induced nonlinear dynamics. Our study demonstrates that the memory effect can be unmasked or greatly exacerbated under certain diseased conditions, which promotes complex excitation dynamics, such as chaos. The iterated map models reveal that memory converts a monotonic iterated map function into a nonmonotonic one to promote the bifurcations leading to high periodicity and chaos.

Memory-induced nonlinear dynamics of excitation in cardiac diseases

NASA Astrophysics Data System (ADS)

Landaw, Julian; Qu, Zhilin

2018-04-01

Excitable cells, such as cardiac myocytes, exhibit short-term memory, i.e., the state of the cell depends on its history of excitation. Memory can originate from slow recovery of membrane ion channels or from accumulation of intracellular ion concentrations, such as calcium ion or sodium ion concentration accumulation. Here we examine the effects of memory on excitation dynamics in cardiac myocytes under two diseased conditions, early repolarization and reduced repolarization reserve, each with memory from two different sources: slow recovery of a potassium ion channel and slow accumulation of the intracellular calcium ion concentration. We first carry out computer simulations of action potential models described by differential equations to demonstrate complex excitation dynamics, such as chaos. We then develop iterated map models that incorporate memory, which accurately capture the complex excitation dynamics and bifurcations of the action potential models. Finally, we carry out theoretical analyses of the iterated map models to reveal the underlying mechanisms of memory-induced nonlinear dynamics. Our study demonstrates that the memory effect can be unmasked or greatly exacerbated under certain diseased conditions, which promotes complex excitation dynamics, such as chaos. The iterated map models reveal that memory converts a monotonic iterated map function into a nonmonotonic one to promote the bifurcations leading to high periodicity and chaos.

The benefits of soluble non-bacterial fraction of kefir on blood pressure and cardiac hypertrophy in hypertensive rats are mediated by an increase in baroreflex sensitivity and decrease in angiotensin-converting enzyme activity.

PubMed

Brasil, Girlandia Alexandre; Silva-Cutini, Mirian de Almeida; Moraes, Flávia de Souza Andrade; Pereira, Thiago de Melo Costa; Vasquez, Elisardo Corral; Lenz, Dominik; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Lima, Ewelyne Miranda; Biancardi, Vinícia Campana; Maia, June Ferreira; de Andrade, Tadeu Uggere

We aimed to evaluate whether long-term treatment with the soluble non-bacterial fraction of kefir affects mean arterial pressure (MAP) and cardiac hypertrophy through the modulation of baroreflex sensitivity, ACE activity, and the inflammatory-to-anti-inflammatory cytokine ratio in spontaneously hypertensive rats (SHRs). SHRs were treated with the soluble non-bacterial kefir fraction (SHR-kefir) or with kefir vehicle (SHR-soluble fraction of milk). Normotensive control Wistar Kyoto animals received the soluble fraction of milk. All treatments were administered by gavage (0.3 mL/100g/body weight), once daily for eight weeks. At the end, after basal MAP and Heart Rate (HT) measurement, barorreflex sensitivity was evaluated through in bolus administrations of sodium nitroprusside and phenylephrine (AP 50 [arterial pressure 50%], the lower plateau, and HR range were measured). ACE activity and cytokines (TNF-α and IL-10) were evaluated by ELISA. Cardiac hypertrophy was analysed morphometrically. Compared to SHR control, SHR-kefir exhibited a significant decrease in both MAP (SHR: 184 ± 5; SHR-Kefir: 142 ± 8 mmHg), and HR (SHR: 360 ± 10; SHR-kefir: 310 ± 14 bpm). The non-bacterial fraction of kefir also reduced cardiac hypertrophy, TNF-α-to-IL10 ratio, and ACE activity in SHRs. SHR-kefir baroreflex sensitivity, resulted in a partial but significant recovery of baroreflex gain, as demonstrated by improvements in AP 50 , the lower plateau, and HR range. In summary, our results indicate that long-term administration of the non-bacterial fraction of kefir promotes a significant decrease in both MAP and HR, by improving baroreflex, and reduces cardiac hypertrophy in SHRs, likely via ACE inhibition, and reduction of the TNF-α-to-IL10 ratio. Copyright © 2018 Elsevier Inc. All rights reserved.

Optical Mapping of Membrane Potential and Epicardial Deformation in Beating Hearts.

PubMed

Zhang, Hanyu; Iijima, Kenichi; Huang, Jian; Walcott, Gregory P; Rogers, Jack M

2016-07-26

Cardiac optical mapping uses potentiometric fluorescent dyes to image membrane potential (Vm). An important limitation of conventional optical mapping is that contraction is usually arrested pharmacologically to prevent motion artifacts from obscuring Vm signals. However, these agents may alter electrophysiology, and by abolishing contraction, also prevent optical mapping from being used to study coupling between electrical and mechanical function. Here, we present a method to simultaneously map Vm and epicardial contraction in the beating heart. Isolated perfused swine hearts were stained with di-4-ANEPPS and fiducial markers were glued to the epicardium for motion tracking. The heart was imaged at 750 Hz with a video camera. Fluorescence was excited with cyan or blue LEDs on alternating camera frames, thus providing a 375-Hz effective sampling rate. Marker tracking enabled the pixel(s) imaging any epicardial site within the marked region to be identified in each camera frame. Cyan- and blue-elicited fluorescence have different sensitivities to Vm, but other signal features, primarily motion artifacts, are common. Thus, taking the ratio of fluorescence emitted by a motion-tracked epicardial site in adjacent frames removes artifacts, leaving Vm (excitation ratiometry). Reconstructed Vm signals were validated by comparison to monophasic action potentials and to conventional optical mapping signals. Binocular imaging with additional video cameras enabled marker motion to be tracked in three dimensions. From these data, epicardial deformation during the cardiac cycle was quantified by computing finite strain fields. We show that the method can simultaneously map Vm and strain in a left-sided working heart preparation and can image changes in both electrical and mechanical function 5 min after the induction of regional ischemia. By allowing high-resolution optical mapping in the absence of electromechanical uncoupling agents, the method relieves a long-standing limitation of optical mapping and has potential to enhance new studies in coupled cardiac electromechanics. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Single-shot turbo spin echo acquisition for in vivo cardiac diffusion MRI.

PubMed

Edalati, Masoud; Lee, Gregory R; Hui Wang; Taylor, Michael D; Li, Yu Y

2016-08-01

Diffusion MRI offers the ability to noninvasively characterize the microstructure of myocardium tissue and detect disease related pathology in cardiovascular examination. This study investigates the feasibility of in vivo cardiac diffusion MRI under free-breathing condition. A high-speed imaging technique, correlation imaging, is used to enable single-shot turbo spin echo for free-breathing cardiac data acquisition. The obtained in vivo cardiac diffusion-weighted images illustrate robust image quality and minor geometry distortions. The resultant diffusion scalar maps show reliable quantitative values consistent with those previously published in the literature. It is demonstrated that this technique has the potential for in vivo free-breathing cardiac diffusion MRI.

Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents

PubMed Central

Hou, Jennifer H.; Kralj, Joel M.; Douglass, Adam D.; Engert, Florian; Cohen, Adam E.

2014-01-01

The cardiac action potential (AP) and the consequent cytosolic Ca2+ transient are key indicators of cardiac function. Natural developmental processes, as well as many drugs and pathologies change the waveform, propagation, or variability (between cells or over time) of these parameters. Here we apply a genetically encoded dual-function calcium and voltage reporter (CaViar) to study the development of the zebrafish heart in vivo between 1.5 and 4 days post fertilization (dpf). We developed a high-sensitivity spinning disk confocal microscope and associated software for simultaneous three-dimensional optical mapping of voltage and calcium. We produced a transgenic zebrafish line expressing CaViar under control of the heart-specific cmlc2 promoter, and applied ion channel blockers at a series of developmental stages to map the maturation of the action potential in vivo. Early in development, the AP initiated via a calcium current through L-type calcium channels. Between 90 and 102 h post fertilization (hpf), the ventricular AP switched to a sodium-driven upswing, while the atrial AP remained calcium driven. In the adult zebrafish heart, a sodium current drives the AP in both the atrium and ventricle. Simultaneous voltage and calcium imaging with genetically encoded reporters provides a new approach for monitoring cardiac development, and the effects of drugs on cardiac function. PMID:25309445

Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents.

PubMed

Hou, Jennifer H; Kralj, Joel M; Douglass, Adam D; Engert, Florian; Cohen, Adam E

2014-01-01

The cardiac action potential (AP) and the consequent cytosolic Ca(2+) transient are key indicators of cardiac function. Natural developmental processes, as well as many drugs and pathologies change the waveform, propagation, or variability (between cells or over time) of these parameters. Here we apply a genetically encoded dual-function calcium and voltage reporter (CaViar) to study the development of the zebrafish heart in vivo between 1.5 and 4 days post fertilization (dpf). We developed a high-sensitivity spinning disk confocal microscope and associated software for simultaneous three-dimensional optical mapping of voltage and calcium. We produced a transgenic zebrafish line expressing CaViar under control of the heart-specific cmlc2 promoter, and applied ion channel blockers at a series of developmental stages to map the maturation of the action potential in vivo. Early in development, the AP initiated via a calcium current through L-type calcium channels. Between 90 and 102 h post fertilization (hpf), the ventricular AP switched to a sodium-driven upswing, while the atrial AP remained calcium driven. In the adult zebrafish heart, a sodium current drives the AP in both the atrium and ventricle. Simultaneous voltage and calcium imaging with genetically encoded reporters provides a new approach for monitoring cardiac development, and the effects of drugs on cardiac function.

Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells

PubMed Central

Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; Robb MacLellan, W.; Marbán, Eduardo; Wang, Charles

2015-01-01

It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

Hemodynamic effects of nitroglycerin ointment in emergency department patients.

PubMed

Mumma, Bryn E; Dhingra, Kapil R; Kurlinkus, Charley; Diercks, Deborah B

2014-08-01

Nitroglycerin ointment is commonly used in the treatment of emergency department (ED) patients with suspected acute heart failure (AHF) or suspected acute coronary syndrome (ACS), but its hemodynamic effects in this population are not well described. Our objective was to assess the effect of nitroglycerin ointment on mean arterial pressure (MAP) and systemic vascular resistance (SVR) in ED patients receiving nitroglycerin. We hypothesized that nitroglycerin ointment would result in a reduction of MAP and SVR in the acute treatment of patients. We conducted a prospective, observational pilot study in a convenience sample of adult patients from a single ED who were treated with nitroglycerin ointment. Impedance cardiography was used to measure MAP, SVR, cardiac output (CO), stroke volume (SV), and thoracic fluid content (TFC) at baseline and at 30, 60, and 120 min after application of nitroglycerin ointment. Mixed effects regression models with random slope and random intercept were used to analyze changes in hemodynamic parameters from baseline to 30, 60, and 120 min after adjusting for age, sex, and final ED diagnosis of AHF. Sixty-four subjects with mean age of 55 years (interquartile range, 48-67 years) were enrolled; 59% were male. In the adjusted analysis, MAP and TFC decreased after application of nitroglycerin ointment (p=0.001 and p=0.043, respectively). Cardiac index, CO, SVR, and SV showed no change (p=0.113, p=0.085, p=0.570, and p=0.076, respectively) over time. Among ED patients who are treated with nitroglycerin ointment, MAP and TFC decrease over time. However, other hemodynamic parameters do not change after application of nitroglycerin ointment in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

[Rhythm disorders and cardiac crypto-malformations].

PubMed

Davy, J M; Raczka, F; Cung, T T; Combes, N; Bortone, A; Gaty, D

2005-12-01

Faced with a cardiac arrhythmia occuring in an apparently healthy heart, it is necessary to perform an anatomical investigation to detect any unsuspected anomalies. Congenital cardiopathy must certainly be excluded, as this is often responsible for rhythm disorders and/or cardiac conduction defects. Similarly, any acquired conditions, cardiomyopathy, or cardiac tumour must be sought. However, the possibility should always be considered of a minimal congenital malformation, which could be repsonsible for: any type of cardiac arrhythmia: rhythm disorder or conduction defect at the atrial, junctional or ventricular level, with a benign or serious prognosis. Unexpected therapeutic difficulties during radiofrequency ablation procedures or at implantation of pacemakers or defibrillators. Together with rhythm studies, the investigation of choice is high quality imaging, either the classic left or right angiography or the more modern cardiac CT or intracardiac mapping.

Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation

PubMed Central

Epelman, Slava; Lavine, Kory J.; Beaudin, Anna E.; Sojka, Dorothy K.; Carrero, Javier A.; Calderon, Boris; Brija, Thaddeus; Gautier, Emmanuel L.; Ivanov, Stoyan; Satpathy, Ansuman T.; Schilling, Joel D.; Schwendener, Reto; Sergin, Ismail; Razani, Babak; Forsberg, E. Camilla; Yokoyama, Wayne; Unanue, Emil R.; Colonna, Marco; Randolph, Gwendalyn J.; Mann, Douglas L.

2014-01-01

Summary Cardiac macrophages are crucial for tissue repair after cardiac injury but have not been well characterized. Here we identify four populations of cardiac macrophages. At steady state, resident macrophages were primarily maintained through local proliferation. However, after macrophage depletion or during cardiac inflammation, Ly6chi monocytes contributed to all four macrophage populations, whereas resident macrophages also expanded numerically through proliferation. Genetic fate mapping revealed that yolk-sac and fetal monocyte progenitors gave rise to the majority of cardiac macrophages, and the heart was among a minority of organs in which substantial numbers of yolk-sac macrophages persisted in adulthood. CCR2 expression and dependence distinguished cardiac macrophages of adult monocyte versus embryonic origin. Transcriptional and functional data revealed that monocyte-derived macrophages coordinate cardiac inflammation, while playing redundant but lesser roles in antigen sampling and efferocytosis. These data highlight the presence of multiple cardiac macrophage subsets, with different functions, origins and strategies to regulate compartment. PMID:24439267

Cardiac imaging at 7 Tesla: Single- and two-spoke radiofrequency pulse design with 16-channel parallel excitation.

PubMed

Schmitter, Sebastian; DelaBarre, Lance; Wu, Xiaoping; Greiser, Andreas; Wang, Dingxin; Auerbach, Edward J; Vaughan, J Thomas; Uğurbil, Kâmil; Van de Moortele, Pierre-François

2013-11-01

Higher signal to noise ratio (SNR) and improved contrast have been demonstrated at ultra-high magnetic fields (≥7 Tesla [T]) in multiple targets, often with multi-channel transmit methods to address the deleterious impact on tissue contrast due to spatial variations in B1 (+) profiles. When imaging the heart at 7T, however, respiratory and cardiac motion, as well as B0 inhomogeneity, greatly increase the methodological challenge. In this study we compare two-spoke parallel transmit (pTX) RF pulses with static B1 (+) shimming in cardiac imaging at 7T. Using a 16-channel pTX system, slice-selective two-spoke pTX pulses and static B1 (+) shimming were applied in cardiac CINE imaging. B1 (+) and B0 mapping required modified cardiac triggered sequences. Excitation homogeneity and RF energy were compared in different imaging orientations. Two-spoke pulses provide higher excitation homogeneity than B1 (+) shimming, especially in the more challenging posterior region of the heart. The peak value of channel-wise RF energy was reduced, allowing for a higher flip angle, hence increased tissue contrast. Image quality with two-spoke excitation proved to be stable throughout the entire cardiac cycle. Two-spoke pTX excitation has been successfully demonstrated in the human heart at 7T, with improved image quality and reduced RF pulse energy when compared with B1 (+) shimming. Copyright © 2013 Wiley Periodicals, Inc.

Tripolar Laplacian electrocardiogram and moment of activation isochronal mapping.

PubMed

Besio, W; Chen, T

2007-05-01

The electrocardiogram (ECG) provides useful global temporal assessment of the cardiac activity, but has limited spatial capabilities. The Laplacian electrocardiogram (LECG), an improvement over the ECG, provides high spatiotemporal distributed information about cardiac electrical activation. We designed and developed LECG tripolar concentric ring electrode active sensors based on the finite element algorithm 'nine-point method' (NPM). The active sensors were used in an array of 6 by 12 (72) locations to record bipolar and tripolar LECG from the body surface over the anterolateral chest. Compared to bipolar LECG, tripolar LECG showed significantly higher spatial selectivity which may be helpful in inferring information about cardiac activations detected on the body surface. In this study the moment of activation (MOA), an indicator of a depolarization wave passing below the active sensors, was used to surmise possible timing information of the cardiac electrical activation below the active sensors' recording sites. The MOA on the body surface was used to generate isochronal maps that may some day be used by clinicians in diagnosing arrhythmias and assessing the efficacy of therapies.

Extracellular Volume Detects Amyloidotic Cardiomyopathy and Correlates With Neurological Impairment in Transthyretin-familial Amyloidosis.

PubMed

Gallego-Delgado, María; González-López, Esther; Muñoz-Beamud, Francisco; Buades, Juan; Galán, Lucía; Muñoz-Blanco, Jose Luis; Sánchez-González, Javier; Ibáñez, Borja; Mirelis, Jesus G; García-Pavía, Pablo

2016-10-01

Cardiac involvement determines prognosis and treatment options in transthyretin-familial amyloidosis. Cardiac magnetic resonance T 1 mapping techniques are useful to assess myocardial extracellular volume. This study hypothesized that myocardial extracellular volume allows identification of amyloidotic cardiomyopathy and correlates with the degree of neurological impairment in transthyretin-familial amyloidosis. A total of 31 transthyretin-familial amyloidosis patients (19 mean age, 49 ± 12 years; 26 with the Val30Met mutation) underwent a T 1 mapping cardiac magnetic resonance study and a neurological evaluation with Neuropathy Impairment Score of the Lower Limb score, Norfolk Quality of Life questionnaire, and Karnofsky index. Five patients had cardiac amyloidosis (all confirmed by 99m Tc-DPD scintigraphy). Mean extracellular volume was increased in patients with cardiac amyloidosis (0.490 ± 0.131 vs 0.289 ± 0.035; P = .026). Extracellular volume correlated with age (R = 0.467; P = .008), N-terminal pro-B-type natriuretic peptide (R S = 0.846; P < .001), maximum wall thickness (R = 0.621; P < .001), left ventricular mass index (R = 0.685; P < .001), left ventricular ejection fraction (R = -0.378; P = .036), Neuropathy Impairment Score of the Lower Limb (R S = 0.604; P = .001), Norfolk Quality of Life questionnaire (R S = 0.529; P = .003) and Karnofsky index (R S = -0.517; P = .004). A cutoff value of extracellular volume of 0.357 was diagnostic of cardiac amyloidosis with 100% sensitivity and specificity (P < .001). Extracellular volume and N-terminal pro-B-type natriuretic peptide were the only cardiac parameters that significantly correlated with neurologic scores. Extracellular volume quantification allows identification of cardiac amyloidosis and correlates with the degree of neurological impairment in transthyretin-familial amyloidosis. This noninvasive technique could be a useful tool for early diagnosis of cardiac amyloidosis and to track cardiac and extracardiac amyloid disease. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Nandrolone decanoate determines cardiac remodelling and injury by an imbalance in cardiac inflammatory cytokines and ACE activity, blunting of the Bezold-Jarisch reflex, resulting in the development of hypertension.

PubMed

Franquni, João Vicente Maggioni; do Nascimento, Andrews Marques; de Lima, Eweliny Miranda; Brasil, Girlândia Alexandre; Heringer, Otávio Arruda; Cassaro, Karla Oliveira Dos Santos; da Cunha, Thony Vinicius Pita; Musso, Carlos; Silva Santos, Maria Carmen L F; Kalil, Ieda Carneiro; Endringer, Denise Coutinho; Boëchat, Giovanna Assis Pereirra; Bissoli, Nazaré Souza; de Andrade, Tadeu Uggere

2013-03-01

The aims of this study were to evaluate the effects of nandrolone (ND) on cardiac inflammatory cytokines, ACE activity, troponin I, and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were administered either ND (20 mg/kg; DECA) or vehicle (control animals; CONT) for 4 weeks. BJR was analyzed by measuring the bradycardia and hypotension responses elicited by serotonin administration (2-32 μg/kg). Mean arterial pressure (MAP) was assessed and myocyte hypertrophy was determined by the heart weight/body weight ratio and by morphometric analysis. Matrix collagen deposition was assessed by histological analysis of the picrosirius red-stained samples. Mesenteric vascular reactivity was performed and central venous pressure (CVP) evaluated. Cardiac inflammatory cytokine levels and angiotensin-converting enzyme (ACE) activity were studied as well the biomarker of cardiac lesion, troponin I. DECA group showed enhancement of matrix type I collagen deposition (p < 0.01) and cardiac ACE activity (p < 0.01) compared with the CONT. Interleukin (IL)-10 was reduced (p < 0.01) and pro-inflammatory cytokines (TNF-α and IL-6; p < 0.01) were increased in the DECA group compared with CONT. Cardiac injury was observed in the DECA group shown by the reduction in cardiac troponin I (p < 0.01) compared with the CONT group. Animals in the DECA group also developed myocyte hypertrophy and reduction of BJR sensitivity. The MAP of animals treated with ND reached hypertensive levels (p < 0.01; compared with CONT). No changes in CVP and vascular reactivity were observed in both experimental groups. We conclude that high doses of ND elicit cardiotoxic effects with cardiac remodelling and injury. Cardiac changes reduce the BJR sensitivity. Together, these abnormalities contributed to the development of hypertension in animals in the DECA group. Copyright © 2012 Elsevier Inc. All rights reserved.

Dynamical density delay maps: simple, new method for visualising the behaviour of complex systems

PubMed Central

2014-01-01

Background Physiologic signals, such as cardiac interbeat intervals, exhibit complex fluctuations. However, capturing important dynamical properties, including nonstationarities may not be feasible from conventional time series graphical representations. Methods We introduce a simple-to-implement visualisation method, termed dynamical density delay mapping (“D3-Map” technique) that provides an animated representation of a system’s dynamics. The method is based on a generalization of conventional two-dimensional (2D) Poincaré plots, which are scatter plots where each data point, x(n), in a time series is plotted against the adjacent one, x(n + 1). First, we divide the original time series, x(n) (n = 1,…, N), into a sequence of segments (windows). Next, for each segment, a three-dimensional (3D) Poincaré surface plot of x(n), x(n + 1), h[x(n),x(n + 1)] is generated, in which the third dimension, h, represents the relative frequency of occurrence of each (x(n),x(n + 1)) point. This 3D Poincaré surface is then chromatised by mapping the relative frequency h values onto a colour scheme. We also generate a colourised 2D contour plot from each time series segment using the same colourmap scheme as for the 3D Poincaré surface. Finally, the original time series graph, the colourised 3D Poincaré surface plot, and its projection as a colourised 2D contour map for each segment, are animated to create the full “D3-Map.” Results We first exemplify the D3-Map method using the cardiac interbeat interval time series from a healthy subject during sleeping hours. The animations uncover complex dynamical changes, such as transitions between states, and the relative amount of time the system spends in each state. We also illustrate the utility of the method in detecting hidden temporal patterns in the heart rate dynamics of a patient with atrial fibrillation. The videos, as well as the source code, are made publicly available. Conclusions Animations based on density delay maps provide a new way of visualising dynamical properties of complex systems not apparent in time series graphs or standard Poincaré plot representations. Trainees in a variety of fields may find the animations useful as illustrations of fundamental but challenging concepts, such as nonstationarity and multistability. For investigators, the method may facilitate data exploration. PMID:24438439

Noninvasive reconstruction of the three-dimensional ventricular activation sequence during pacing and ventricular tachycardia in the rabbit heart.

PubMed

Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

2011-01-01

Ventricular arrhythmias represent one of leading causes for sudden cardiac death, a significant problem in public health. Noninvasive imaging of cardiac electric activities associated with ventricular arrhythmias plays an important role in better our understanding of the mechanisms and optimizing the treatment options. The present study aims to rigorously validate a novel three-dimensional (3-D) cardiac electrical imaging (3-DCEI) technique with the aid of 3-D intra-cardiac mapping during paced rhythm and ventricular tachycardia (VT) in the rabbit heart. Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in thirteen healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous norepinephrine (NE). The non-invasively imaged activation sequence correlated well with invasively measured counterparts, with a correlation coefficient of 0.72 and a relative error of 0.30 averaged over all paced beats and NE-induced PVCs and VT beats. The averaged distance from imaged site of initial activation to measured site determined from intra-cardiac mapping was ∼5mm. These promising results suggest that 3-DCEI is feasible to non-invasively localize the origins and image activation sequence of focal ventricular arrhythmias.

Importance of Calibration Method in Central Blood Pressure for Cardiac Structural Abnormalities.

PubMed

Negishi, Kazuaki; Yang, Hong; Wang, Ying; Nolan, Mark T; Negishi, Tomoko; Pathan, Faraz; Marwick, Thomas H; Sharman, James E

2016-09-01

Central blood pressure (CBP) independently predicts cardiovascular risk, but calibration methods may affect accuracy of central systolic blood pressure (CSBP). Standard central systolic blood pressure (Stan-CSBP) from peripheral waveforms is usually derived with calibration using brachial SBP and diastolic BP (DBP). However, calibration using oscillometric mean arterial pressure (MAP) and DBP (MAP-CSBP) is purported to provide more accurate representation of true invasive CSBP. This study sought to determine which derived CSBP could more accurately discriminate cardiac structural abnormalities. A total of 349 community-based patients with risk factors (71±5years, 161 males) had CSBP measured by brachial oscillometry (Mobil-O-Graph, IEM GmbH, Stolberg, Germany) using 2 calibration methods: MAP-CSBP and Stan-CSBP. Left ventricular hypertrophy (LVH) and left atrial dilatation (LAD) were measured based on standard guidelines. MAP-CSBP was higher than Stan-CSBP (149±20 vs. 128±15mm Hg, P < 0.0001). Although they were modestly correlated (rho = 0.74, P < 0.001), the Bland-Altman plot demonstrated a large bias (21mm Hg) and limits of agreement (24mm Hg). In receiver operating characteristic (ROC) curve analyses, MAP-CSBP significantly better discriminated LVH compared with Stan-CSBP (area under the curve (AUC) 0.66 vs. 0.59, P = 0.0063) and brachial SBP (0.62, P = 0.027). Continuous net reclassification improvement (NRI) (P < 0.001) and integrated discrimination improvement (IDI) (P < 0.001) corroborated superior discrimination of LVH by MAP-CSBP. Similarly, MAP-CSBP better distinguished LAD than Stan-CSBP (AUC 0.63 vs. 0.56, P = 0.005) and conventional brachial SBP (0.58, P = 0.006), whereas Stan-CSBP provided no better discrimination than conventional brachial BP (P = 0.09). CSBP is calibration dependent and when oscillometric MAP and DBP are used, the derived CSBP is a better discriminator for cardiac structural abnormalities. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early patterning and specification of cardiac progenitors in gastrulating mesoderm

PubMed Central

Devine, W Patrick; Wythe, Joshua D; George, Matthew; Koshiba-Takeuchi, Kazuko; Bruneau, Benoit G

2014-01-01

Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor ‘fields’ has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies. DOI: http://dx.doi.org/10.7554/eLife.03848.001 PMID:25296024

Promoting Early Diagnosis of Hemodynamic Instability during Simulated Hemorrhage with the Use of a Real-time Decision-assist Algorithm

DTIC Science & Technology

2013-01-01

vilian trauma systems and in military casualty care rely on standard vital signs (blood pressure, arterial oxygen saturation , heart rate [HR...acting to maintain blood pressure and arterial oxygen saturation (i.e., standard vital signs are not changing) in the presence of re- duced...assessments in austere environments. Profiles of changes in mean arterial pressure (MAP), cardiac output, and venous oxygen saturation during LBNP have been

In vitro quantitation of human femoral artery atherosclerosis using near-infrared Raman spectroscopy

NASA Astrophysics Data System (ADS)

Dykes, Ava C.; Anastasiadis, Pavlos; Allen, John S., III; Sharma, Shiv K.

2012-06-01

Near-infrared Raman spectroscopy has been used in vitro to identify calcified atherosclerotic plaques in human femoral arteries. Raman techniques allow for the identification of these plaques in a nondestructive manner, which may allow for the diagnosis of coronary artery disease in cardiac patients in the future. As Raman spectroscopy also reveals chemical information about the composition of the arteries, it can also be used as a prognostic tool. The in vivo detection of atherosclerotic plaques at risk for rupture in cardiac patients will enhance treatment methods while improving clinical outcomes for these procedures. Raman spectra were excited by an Invictus 785-nm NIR laser and measured with a fiber-coupled micro-Raman RXN system (Kaiser Optical Systems, Inc., Ann Arbor, MI) equipped with a 785 nm CW laser and CCD detector. Chemical mapping of arteries obtained post mortem allowed for the discrete location of atherosclerotic plaques. Raman peaks at 961 and 1073 cm-1 reveal the presence of calcium hydroxyapatite and carbonate apatite, which are known to be present in calcified plaques. By mapping the locations of these peaks the boundaries of the plaques can be precisely determined. Areas of varying degrees of calcification were also identified. Because this can be useful in determining the degree of plaque calcification and vessel stenosis, this may have a significant impact on the clinical treatment of atherosclerotic plaques in the future.

Registration of 4D time-series of cardiac images with multichannel Diffeomorphic Demons.

PubMed

Peyrat, Jean-Marc; Delingette, Hervé; Sermesant, Maxime; Pennec, Xavier; Xu, Chenyang; Ayache, Nicholas

2008-01-01

In this paper, we propose a generic framework for intersubject non-linear registration of 4D time-series images. In this framework, spatio-temporal registration is defined by mapping trajectories of physical points as opposed to spatial registration that solely aims at mapping homologous points. First, we determine the trajectories we want to register in each sequence using a motion tracking algorithm based on the Diffeomorphic Demons algorithm. Then, we perform simultaneously pairwise registrations of corresponding time-points with the constraint to map the same physical points over time. We show this trajectory registration can be formulated as a multichannel registration of 3D images. We solve it using the Diffeomorphic Demons algorithm extended to vector-valued 3D images. This framework is applied to the inter-subject non-linear registration of 4D cardiac CT sequences.

Attenuation correction for flexible magnetic resonance coils in combined magnetic resonance/positron emission tomography imaging.

PubMed

Eldib, Mootaz; Bini, Jason; Calcagno, Claudia; Robson, Philip M; Mani, Venkatesh; Fayad, Zahi A

2014-02-01

Attenuation correction for magnetic resonance (MR) coils is a new challenge that came about with the development of combined MR and positron emission tomography (PET) imaging. This task is difficult because such coils are not directly visible on either PET or MR acquisitions with current combined scanners and are therefore not easily localized in the field of view. This issue becomes more evident when trying to localize flexible MR coils (eg, cardiac or body matrix coil) that change position and shape from patient to patient and from one imaging session to another. In this study, we proposed a novel method to localize and correct for the attenuation and scatter of a flexible MR cardiac coil, using MR fiducial markers placed on the surface of the coil to allow for accurate registration of a template computed tomography (CT)-based attenuation map. To quantify the attenuation properties of the cardiac coil, a uniform cylindrical water phantom injected with 18F-fluorodeoxyglucose (18F-FDG) was imaged on a sequential MR/PET system with and without the flexible cardiac coil. After establishing the need to correct for the attenuation of the coil, we tested the feasibility of several methods to register a precomputed attenuation map to correct for the attenuation. To accomplish this, MR and CT visible markers were placed on the surface of the cardiac flexible coil. Using only the markers as a driver for registration, the CT image was registered to the reference image through a combination of rigid and deformable registration. The accuracy of several methods was compared for the deformable registration, including B-spline, thin-plate spline, elastic body spline, and volume spline. Finally, we validated our novel approach both in phantom and patient studies. The findings from the phantom experiments indicated that the presence of the coil resulted in a 10% reduction in measured 18F-FDG activity when compared with the phantom-only scan. Local underestimation reached 22% in regions of interest close to the coil. Various registration methods were tested, and the volume spline was deemed to be the most accurate, as measured by the Dice similarity metric. The results of our phantom experiments showed that the bias in the 18F-FDG quantification introduced by the presence of the coil could be reduced by using our registration method. An overestimation of only 1.9% of the overall activity for the phantom scan with the coil attenuation map was measured when compared with the baseline phantom scan without coil. A local overestimation of less than 3% was observed in the ROI analysis when using the proposed method to correct for the attenuation of the flexible cardiac coil. Quantitative results from the patient study agreed well with the phantom findings. We presented and validated an accurate method to localize and register a CT-based attenuation map to correct for the attenuation and scatter of flexible MR coils. This method may be translated to clinical use to produce quantitatively accurate measurements with the use of flexible MR coils during MR/PET imaging.

Visualization and appearance of artifacts of leadless pacemaker systems in cardiac MRI : An experimental ex vivo study.

PubMed

Edlinger, Christoph; Granitz, Marcel; Paar, Vera; Jung, Christian; Pfeil, Alexander; Eder, Sarah; Wernly, Bernhard; Kammler, Jürgen; Hergan, Klaus; Hoppe, Uta C; Steinwender, Clemens; Lichtenauer, Michael; Kypta, Alexander

2018-05-23

Leadless pacemaker systems are an important upcoming device in clinical rhythmology. Currently two different products are available with the Micra system (Medtronic) being the most used in the clinical setting to date. The possibility to perform magnetic resonance imaging (MRI) is an important feature of modern pacemaker devices. Even though the Micra system is suitable for MRI, little is yet known about its impact on artifacts within the images. The aim of our ex vivo study was to perform cardiac MRI to quantify the artifacts and to evaluate if artifacts limit or inhibit the assessment of the surrounding myocardium. After ex vivo implantation of the leadless pacemaker (LP) in a porcine model, hearts were filled with saline solution and fixed on wooden sticks on a plastic container. The model was examined at 1.5 T and at 3 T using conventional sequences and T2 mapping sequences. In addition, conventional X‑rays and computed tomography (CT) scans were performed. Correct implantation of the LP could be performed in all hearts. In almost all MRI sequences the right ventricle and the septal region surrounding the (LP) were altered by an artifact and therefore would sustain limited assessment; however, the rest of the myocardium remained free of artifacts and evaluable for common radiologic diagnoses. A characteristic shamrock-shaped artifact was generated which appeared to be even more intense in magnitude and brightness when using 3 T compared to 1.5 T. The use of the Micra system in cardiac MRI appeared to be feasible. In our opinion, it will still be possible to make important clinical cardiac MRI diagnoses (the detection of major ischemic areas or inflammatory processes) in patients using the Micra system. We suggest the use of 1.5 T as the preferred method in clinical practice.

Resolution of abnormal cardiac MRI T2 signal following immune suppression for cardiac sarcoidosis.

PubMed

Crouser, Elliott D; Ruden, Emily; Julian, Mark W; Raman, Subha V

2016-08-01

Cardiac MR (CMR) with late gadolinium enhancement is commonly used to detect cardiac damage in the setting of cardiac sarcoidosis. The addition of T2 mapping to CMR was recently shown to enhance cardiac sarcoidosis detection and correlates with increased cardiac arrhythmia risk. This study was conducted to determine if CMR T2 abnormalities and related arrhythmias are reversible following immune suppression therapy. A retrospective study of subjects with cardiac sarcoidosis with abnormal T2 signal on baseline CMR and a follow-up CMR study at least 4 months later was conducted at The Ohio State University from 2011 to 2015. Immune suppression treated participants had a significant reduction in peak myocardial T2 value (70.0±5.5 vs 59.2±6.1 ms, pretreatment vs post-treatment; p=0.017), and 83% of immune suppression treated subjects had objective improvement in cardiac arrhythmias. Two subjects who had received inadequate immune suppression treatment experienced progression of cardiac sarcoidosis. This report indicates that abnormal CMR T2 signal represents an acute inflammatory manifestation of cardiac sarcoidosis that is potentially reversible with adequate immune suppression therapy. Copyright © 2016 American Federation for Medical Research.

Probing myocardium biomechanics using quantitative optical coherence elastography

NASA Astrophysics Data System (ADS)

Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

2015-03-01

We present a quantitative optical coherence elastographic method for noncontact assessment of the myocardium elasticity. The method is based on shear wave imaging optical coherence tomography (SWI-OCT), where a focused air-puff system is used to induce localized tissue deformation through a low-pressure short-duration air stream and a phase-sensitive OCT system is utilized to monitor the propagation of the induced tissue displacement with nanoscale sensitivity. The 1-D scanning of M-mode OCT imaging and the application of optical phase retrieval and mapping techniques enable the reconstruction and visualization of 2-D depth-resolved shear wave propagation in tissue with ultra-high frame rate. The feasibility of this method in quantitative elasticity measurement is demonstrated on tissue-mimicking phantoms with the estimated Young's modulus compared with uniaxial compression tests. We also performed pilot experiments on ex vivo mouse cardiac muscle tissues with normal and genetically altered cardiomyocytes. Our results indicate this noncontact quantitative optical coherence elastographic method can be a useful tool for the cardiac muscle research and studies.

Developing a novel comprehensive framework for the investigation of cellular and whole heart electrophysiology in the in situ human heart: historical perspectives, current progress and future prospects.

PubMed

Taggart, Peter; Orini, Michele; Hanson, Ben; Hayward, Martin; Clayton, Richard; Dobrzynski, Halina; Yanni, Joseph; Boyett, Mark; Lambiase, Pier D

2014-08-01

Understanding the mechanisms of fatal ventricular arrhythmias is of great importance. In view of the many electrophysiological differences that exist between animal species and humans, the acquisition of basic electrophysiological data in the intact human heart is essential to drive and complement experimental work in animal and in-silico models. Over the years techniques have been developed to obtain basic electrophysiological signals directly from the patients by incorporating these measurements into routine clinical procedures which access the heart such as cardiac catheterisation and cardiac surgery. Early recordings with monophasic action potentials provided valuable information including normal values for the in vivo human heart, cycle length dependent properties, the effect of ischaemia, autonomic nervous system activity, and mechano-electric interaction. Transmural recordings addressed the controversial issue of the mid myocardial "M" cell. More recently, the technique of multielectrode mapping (256 electrodes) developed in animal models has been extended to humans, enabling mapping of activation and repolarisation on the entire left and right ventricular epicardium in patients during cardiac surgery. Studies have examined the issue of whether ventricular fibrillation was driven by a "mother" rotor with inhomogeneous and fragmented conduction as in some animal models, or by multiple wavelets as in other animal studies; results showed that both mechanisms are operative in humans. The simpler spatial organisation of human VF has important implications for treatment and prevention. To link in-vivo human electrophysiological mapping with cellular biophysics, multielectrode mapping is now being combined with myocardial biopsies. This technique enables region-specific electrophysiology changes to be related to underlying cellular biology, for example: APD alternans, which is a precursor of VF and sudden death. The mechanism is incompletely understood but related to calcium cycling and APD restitution. Multielectrode sock mapping during incremental pacing enables epicardial sites to be identified which exhibit marked APD alternans and sites where APD alternans is absent. Whole heart electrophysiology is assessed by activation repolarisation mapping and analysis is performed immediately on-site in order to guide biopsies to specific myocardial sites. Samples are analysed for ion channel expression, Ca(2+)-handling proteins, gap junctions and extracellular matrix. This new comprehensive approach to bridge cellular and whole heart electrophysiology allowed to identify 20 significant changes in mRNA for ion channels Ca(2+)-handling proteins, a gap junction channel, a Na(+)-K(+) pump subunit and receptors (particularly Kir 2.1) between the positive and negative alternans sites. Copyright © 2014 Elsevier Ltd. All rights reserved.

Robotics in invasive cardiac electrophysiology.

PubMed

Shurrab, Mohammed; Schilling, Richard; Gang, Eli; Khan, Ejaz M; Crystal, Eugene

2014-07-01

Robotic systems allow for mapping and ablation of different arrhythmia substrates replacing hand maneuvering of intracardiac catheters with machine steering. Currently there are four commercially available robotic systems. Niobe magnetic navigation system (Stereotaxis Inc., St Louis, MO) and Sensei robotic navigation system (Hansen Medical Inc., Mountain View, CA) have an established platform with at least 10 years of clinical studies looking at their efficacy and safety. AMIGO Remote Catheter System (Catheter Robotics, Inc., Mount Olive, NJ) and Catheter Guidance Control and Imaging (Magnetecs, Inglewood, CA) are in the earlier phases of implementations with ongoing feasibility and some limited clinical studies. This review discusses the advantages and limitations related to each existing system and highlights the ideal futuristic robotic system that may include the most promising features of the current ones.

Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.

PubMed

Joers, Valerie; Seneczko, Kailie; Goecks, Nichole C; Kamp, Timothy J; Hacker, Timothy A; Brunner, Kevin G; Engle, Jonathan W; Barnhart, Todd E; Nickles, R Jerome; Holden, James E; Emborg, Marina E

2012-01-01

Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog (11)C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia.

3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium

PubMed Central

Xu, Lizhi; Gutbrod, Sarah R.; Bonifas, Andrew P.; Su, Yewang; Sulkin, Matthew S.; Lu, Nanshu; Chung, Hyun-Joong; Jang, Kyung-In; Liu, Zhuangjian; Ying, Ming; Lu, Chi; Webb, R. Chad; Kim, Jong-Seon; Laughner, Jacob I.; Cheng, Huanyu; Liu, Yuhao; Ameen, Abid; Jeong, Jae-Woong; Kim, Gwang-Tae; Huang, Yonggang; Efimov, Igor R.; Rogers, John A.

2015-01-01

Means for high-density multiparametric physiological mapping and stimulation are critically important in both basic and clinical cardiology. Current conformal electronic systems are essentially 2D sheets, which cannot cover the full epicardial surface or maintain reliable contact for chronic use without sutures or adhesives. Here we create 3D elastic membranes shaped precisely to match the epicardium of the heart via the use of 3D printing, as a platform for deformable arrays of multifunctional sensors, electronic and optoelectronic components. Such integumentary devices completely envelop the heart, in a form-fitting manner, and possess inherent elasticity, providing a mechanically stable bioti-/abiotic interface during normal cardiac cycles. Component examples range from actuators for electrical, thermal and optical stimulation, to sensors for pH, temperature and mechanical strain. The semiconductor materials include silicon, gallium arsenide and gallium nitride, co-integrated with metals, metal oxides and polymers, to provide these and other operational capabilities. Ex vivo physiological experiments demonstrate various functions and methodological possibilities for cardiac research and therapy. PMID:24569383

The road ahead: working towards effective clinical translation of myocardial gene therapies

PubMed Central

Katz, Michael G; Fargnoli, Anthony S; Williams, Richard D; Bridges, Charles R

2014-01-01

During the last two decades the fields of molecular and cellular cardiology, and more recently molecular cardiac surgery, have developed rapidly. The concept of delivering cDNA encoding a therapeutic gene to cardiomyocytes using a vector system with substantial cardiac tropism, allowing for long-term expression of a therapeutic protein, has moved from hypothesis to bench to clinical application. However, the clinical results to date are still disappointing. The ideal gene transfer method should be explored in clinically relevant animal models of heart disease to evaluate the relative roles of specific molecular pathways in disease pathogenesis, helping to validate the potential targets for therapeutic intervention. Successful clinical cardiovascular gene therapy also requires the use of nonimmunogenic cardiotropic vectors capable of expressing the requisite amount of therapeutic protein in vivo and in situ. Depending on the desired application either regional or global myocardial gene delivery is required. Cardiac-specific delivery techniques incorporating mapping technologies for regional delivery and highly efficient methodologies for global delivery should improve the precision and specificity of gene transfer to the areas of interest and minimize collateral organ gene expression. PMID:24341816

Dual regression physiological modeling of resting-state EPI power spectra: Effects of healthy aging.

PubMed

Viessmann, Olivia; Möller, Harald E; Jezzard, Peter

2018-02-02

Aging and disease-related changes in the arteriovasculature have been linked to elevated levels of cardiac cycle-induced pulsatility in the cerebral microcirculation. Functional magnetic resonance imaging (fMRI), acquired fast enough to unalias the cardiac frequency contributions, can be used to study these physiological signals in the brain. Here, we propose an iterative dual regression analysis in the frequency domain to model single voxel power spectra of echo planar imaging (EPI) data using external recordings of the cardiac and respiratory cycles as input. We further show that a data-driven variant, without external physiological traces, produces comparable results. We use this framework to map and quantify cardiac and respiratory contributions in healthy aging. We found a significant increase in the spatial extent of cardiac modulated white matter voxels with age, whereas the overall strength of cardiac-related EPI power did not show an age effect. Copyright © 2018. Published by Elsevier Inc.

Coi-wiz: An interactive computer wizard for analyzing cardiac optical signals.

PubMed

Yuan, Xiaojing; Uyanik, Ilyas; Situ, Ning; Xi, Yutao; Cheng, Jie

2009-01-01

A number of revolutionary techniques have been developed for cardiac electrophysiology research to better study the various arrhythmia mechanisms that can enhance ablating strategies for cardiac arrhythmias. Once the three-dimensional high resolution cardiac optical imaging data is acquired, it is time consuming to manually go through them and try to identify the patterns associated with various arrhythmia symptoms. In this paper, we present an interactive computer wizard that helps cardiac electrophysiology researchers to visualize and analyze the high resolution cardiac optical imaging data. The wizard provides a file interface that accommodates different file formats. A series of analysis algorithms output waveforms, activation and action potential maps after spatial and temporal filtering, velocity field and heterogeneity measure. The interactive GUI allows the researcher to identify the region of interest in both the spatial and temporal domain, thus enabling them to study different heart chamber at their choice.

Image based cardiac acceleration map using statistical shape and 3D+t myocardial tracking models; in-vitro study on heart phantom

NASA Astrophysics Data System (ADS)

Pashaei, Ali; Piella, Gemma; Planes, Xavier; Duchateau, Nicolas; de Caralt, Teresa M.; Sitges, Marta; Frangi, Alejandro F.

2013-03-01

It has been demonstrated that the acceleration signal has potential to monitor heart function and adaptively optimize Cardiac Resynchronization Therapy (CRT) systems. In this paper, we propose a non-invasive method for computing myocardial acceleration from 3D echocardiographic sequences. Displacement of the myocardium was estimated using a two-step approach: (1) 3D automatic segmentation of the myocardium at end-diastole using 3D Active Shape Models (ASM); (2) propagation of this segmentation along the sequence using non-rigid 3D+t image registration (temporal di eomorphic free-form-deformation, TDFFD). Acceleration was obtained locally at each point of the myocardium from local displacement. The framework has been tested on images from a realistic physical heart phantom (DHP-01, Shelley Medical Imaging Technologies, London, ON, CA) in which the displacement of some control regions was known. Good correlation has been demonstrated between the estimated displacement function from the algorithms and the phantom setup. Due to the limited temporal resolution, the acceleration signals are sparse and highly noisy. The study suggests a non-invasive technique to measure the cardiac acceleration that may be used to improve the monitoring of cardiac mechanics and optimization of CRT.

Lagrangian displacement tracking using a polar grid between endocardial and epicardial contours for cardiac strain imaging.

PubMed

Ma, Chi; Varghese, Tomy

2012-04-01

Accurate cardiac deformation analysis for cardiac displacement and strain imaging over time requires Lagrangian description of deformation of myocardial tissue structures. Failure to couple the estimated displacement and strain information with the correct myocardial tissue structures will lead to erroneous result in the displacement and strain distribution over time. Lagrangian based tracking in this paper divides the tissue structure into a fixed number of pixels whose deformation is tracked over the cardiac cycle. An algorithm that utilizes a polar-grid generated between the estimated endocardial and epicardial contours for cardiac short axis images is proposed to ensure Lagrangian description of the pixels. Displacement estimates from consecutive radiofrequency frames were then mapped onto the polar grid to obtain a distribution of the actual displacement that is mapped to the polar grid over time. A finite element based canine heart model coupled with an ultrasound simulation program was used to verify this approach. Segmental analysis of the accumulated displacement and strain over a cardiac cycle demonstrate excellent agreement between the ideal result obtained directly from the finite element model and our Lagrangian approach to strain estimation. Traditional Eulerian based estimation results, on the other hand, show significant deviation from the ideal result. An in vivo comparison of the displacement and strain estimated using parasternal short axis views is also presented. Lagrangian displacement tracking using a polar grid provides accurate tracking of myocardial deformation demonstrated using both finite element and in vivo radiofrequency data acquired on a volunteer. In addition to the cardiac application, this approach can also be utilized for transverse scans of arteries, where a polar grid can be generated between the contours delineating the outer and inner wall of the vessels from the blood flowing though the vessel.

A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression.

PubMed

Kuhl, U; Lassner, D; Dorner, A; Rohde, M; Escher, F; Seeberg, B; Hertel, E; Tschope, C; Skurk, C; Gross, U M; Schultheiss, H-P; Poller, W

2013-09-01

Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.

4D blood flow mapping using SPIM-microPIV in the developing zebrafish heart

NASA Astrophysics Data System (ADS)

Zickus, Vytautas; Taylor, Jonathan M.

2018-02-01

Fluid-structure interaction in the developing heart is an active area of research in developmental biology. However, investigation of heart dynamics is mostly limited to computational uid dynamics simulations using heart wall structure information only, or single plane blood ow information - so there is a need for 3D + time resolved data to fully understand cardiac function. We present an imaging platform combining selective plane illumination microscopy (SPIM) with micro particle image velocimetry (μPIV) to enable 3D-resolved flow mapping in a microscopic environment, free from many of the sources of error and bias present in traditional epi uorescence-based μPIV systems. By using our new system in conjunction with optical heart beat synchronization, we demonstrate the ability obtain non-invasive 3D + time resolved blood flow measurements in the heart of a living zebrafish embryo.

Creation of an ensemble of simulated cardiac cases and a human observer study: tools for the development of numerical observers for SPECT myocardial perfusion imaging

NASA Astrophysics Data System (ADS)

O'Connor, J. Michael; Pretorius, P. Hendrik; Gifford, Howard C.; Licho, Robert; Joffe, Samuel; McGuiness, Matthew; Mehurg, Shannon; Zacharias, Michael; Brankov, Jovan G.

2012-02-01

Our previous Single Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging (MPI) research explored the utility of numerical observers. We recently created two hundred and eighty simulated SPECT cardiac cases using Dynamic MCAT (DMCAT) and SIMIND Monte Carlo tools. All simulated cases were then processed with two reconstruction methods: iterative ordered subset expectation maximization (OSEM) and filtered back-projection (FBP). Observer study sets were assembled for both OSEM and FBP methods. Five physicians performed an observer study on one hundred and seventy-nine images from the simulated cases. The observer task was to indicate detection of any myocardial perfusion defect using the American Society of Nuclear Cardiology (ASNC) 17-segment cardiac model and the ASNC five-scale rating guidelines. Human observer Receiver Operating Characteristic (ROC) studies established the guidelines for the subsequent evaluation of numerical model observer (NO) performance. Several NOs were formulated and their performance was compared with the human observer performance. One type of NO was based on evaluation of a cardiac polar map that had been pre-processed using a gradient-magnitude watershed segmentation algorithm. The second type of NO was also based on analysis of a cardiac polar map but with use of a priori calculated average image derived from an ensemble of normal cases.

Cardiac sarcoidosis: challenges in clinical practice.

PubMed

Bakker, Anne L; Grutters, Jan C; Keijsers, Ruth G; Post, Martijn C

2017-09-01

To address the current recommendations for screening, diagnosis, and treatment of cardiac sarcoidosis and the difficulties to put these recommendations into clinical practice. The incidence of cardiac sarcoidosis appears to be higher than earlier reported, probably because of improved imaging techniques. Late gadolinium enhancement with cardiac MRI (LGE-CMR) and fluorodeoxyglucose positron emission tomography obtained a central role in the diagnostic algorithm and monitoring of disease activity. New techniques are being investigated: T1 and T2 mapping for early detection in CMR, a sarcoid-specific tracer in PET, integrated positron emission tomography/MRI scanners, and assessment of scar with LGE in cardiac computed tomography. Isolated cardiac sarcoidosis is an increasingly recognized phenotype, but still an enormous challenge in clinical practice. The prognostic value of (and extent of) LGE-CMR should be taken into account for risk assessment and internal cardiac defbrillator therapy, even in patients with preserved left ventricular function. Unfortunately, randomized controlled trials to guide immunosuppressive therapy are still lacking. A multidisciplinary approach to diagnose and treat cardiac sarcoidosis patients in specialized centers is strongly recommendable. Cardiac sarcoidosis is increasingly recognized because of improved imaging techniques; however, treatment of cardiac sarcoidosis is still mainly based on expert opinion.

Connective tissue growth factor induces cardiac hypertrophy through Akt signaling

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

Hayata, Nozomi; Fujio, Yasushi; Yamamoto, Yasuhiro

2008-05-30

In the process of cardiac remodeling, connective tissue growth factor (CTGF/CCN2) is secreted from cardiac myocytes. Though CTGF is well known to promote fibroblast proliferation, its pathophysiological effects in cardiac myocytes remain to be elucidated. In this study, we examined the biological effects of CTGF in rat neonatal cardiomyocytes. Cardiac myocytes stimulated with full length CTGF and its C-terminal region peptide showed the increase in cell surface area. Similar to hypertrophic ligands for G-protein coupled receptors, such as endothelin-1, CTGF activated amino acid uptake; however, CTGF-induced hypertrophy is not associated with the increased expression of skeletal actin or BNP, analyzedmore » by Northern-blotting. CTGF treatment activated ERK1/2, p38 MAPK, JNK and Akt. The inhibition of Akt by transducing dominant-negative Akt abrogated CTGF-mediated increase in cell size, while the inhibition of MAP kinases did not affect the cardiac hypertrophy. These findings indicate that CTGF is a novel hypertrophic factor in cardiac myocytes.« less

Omega-3 fatty acid supplementation enhances stroke volume and cardiac output during dynamic exercise.

PubMed

Walser, Buddy; Stebbins, Charles L

2008-10-01

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have beneficial effects on cardiovascular function. We tested the hypotheses that dietary supplementation with DHA (2 g/day) + EPA (3 g/day) enhances increases in stroke volume (SV) and cardiac output (CO) and decreases in systemic vascular resistance (SVR) during dynamic exercise. Healthy subjects received DHA + EPA (eight men, four women) or safflower oil (six men, three women) for 6 weeks. Both groups performed 20 min of bicycle exercise (10 min each at a low and moderate work intensity) before and after DHA + EPA or safflower oil treatment. Mean arterial pressure (MAP), heart rate (HR), SV, CO, and SVR were assessed before exercise and during both workloads. HR was unaffected by DHA + EPA and MAP was reduced, but only at rest (88 +/- 5 vs. 83 +/- 4 mm Hg). DHA + EPA augmented increases in SV (14.1 +/- 6.3 vs. 32.3 +/- 8.7 ml) and CO (8.5 +/- 1.0 vs. 10.3 +/- 1.2 L/min) and tended to attenuate decreases in SVR (-7.0 +/- 0.6 vs. -10.1 +/- 1.6 mm Hg L(-1) min(-1)) during the moderate workload. Safflower oil treatment had no effects on MAP, HR, SV, CO or SVR at rest or during exercise. DHA + EPA-induced increases in SV and CO imply that dietary supplementation with these fatty acids can increase oxygen delivery during exercise, which may have beneficial clinical implications for individuals with cardiovascular disease and reduced exercise tolerance.

Use of Intracardiac Echocardiography in Interventional Cardiology: Working With the Anatomy Rather Than Fighting It.

PubMed

Enriquez, Andres; Saenz, Luis C; Rosso, Raphael; Silvestry, Frank E; Callans, David; Marchlinski, Francis E; Garcia, Fermin

2018-05-22

The indications for catheter-based structural and electrophysiological procedures have recently expanded to more complex scenarios, in which an accurate definition of the variable individual cardiac anatomy is key to obtain optimal results. Intracardiac echocardiography (ICE) is a unique imaging modality able to provide high-resolution real-time visualization of cardiac structures, continuous monitoring of catheter location within the heart, and early recognition of procedural complications, such as pericardial effusion or thrombus formation. Additional benefits are excellent patient tolerance, reduction of fluoroscopy time, and lack of need for general anesthesia or a second operator. For these reasons, ICE has largely replaced transesophageal echocardiography as ideal imaging modality for guiding certain procedures, such as atrial septal defect closure and catheter ablation of cardiac arrhythmias, and has an emerging role in others, including mitral valvuloplasty, transcatheter aortic valve replacement, and left atrial appendage closure. In electrophysiology procedures, ICE allows integration of real-time images with electroanatomic maps; it has a role in assessment of arrhythmogenic substrate, and it is particularly useful for mapping structures that are not visualized by fluoroscopy, such as the interatrial or interventricular septum, papillary muscles, and intracavitary muscular ridges. Most recently, a three-dimensional (3D) volumetric ICE system has also been developed, with potential for greater anatomic information and a promising role in structural interventions. In this state-of-the-art review, we provide guidance on how to conduct a comprehensive ICE survey and summarize the main applications of ICE in a variety of structural and electrophysiology procedures. © 2018 American Heart Association, Inc.

Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT.

PubMed

Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia; Fanti, Stefano; Sambuceti, Gianmario

2015-11-01

Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III-IV) after CRT using (11)C-hydroxyephedrine (HED) PET/CT. Ten IHF patients (mean age = 68; range = 55-81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with "impaired innervation" (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation. This work might contribute to identify imaging parameters that could predict the response to CRT therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Zebrafish heart as a model to study the integrative autonomic control of pacemaker function

PubMed Central

Stoyek, Matthew R.; Quinn, T. Alexander; Croll, Roger P.

2016-01-01

The cardiac pacemaker sets the heart's primary rate, with pacemaker discharge controlled by the autonomic nervous system through intracardiac ganglia. A fundamental issue in understanding the relationship between neural activity and cardiac chronotropy is the identification of neuronal populations that control pacemaker cells. To date, most studies of neurocardiac control have been done in mammalian species, where neurons are embedded in and distributed throughout the heart, so they are largely inaccessible for whole-organ, integrative studies. Here, we establish the isolated, innervated zebrafish heart as a novel alternative model for studies of autonomic control of heart rate. Stimulation of individual cardiac vagosympathetic nerve trunks evoked bradycardia (parasympathetic activation) and tachycardia (sympathetic activation). Simultaneous stimulation of both vagosympathetic nerve trunks evoked a summative effect. Effects of nerve stimulation were mimicked by direct application of cholinergic and adrenergic agents. Optical mapping of electrical activity confirmed the sinoatrial region as the site of origin of normal pacemaker activity and identified a secondary pacemaker in the atrioventricular region. Strong vagosympathetic nerve stimulation resulted in a shift in the origin of initial excitation from the sinoatrial pacemaker to the atrioventricular pacemaker. Putative pacemaker cells in the sinoatrial and atrioventricular regions expressed adrenergic β2 and cholinergic muscarinic type 2 receptors. Collectively, we have demonstrated that the zebrafish heart contains the accepted hallmarks of vertebrate cardiac control, establishing this preparation as a viable model for studies of integrative physiological control of cardiac function by intracardiac neurons. PMID:27342878

Intrapericardial echocardiography: a novel catheter-based approach to cardiac imaging.

PubMed

Rodrigues, Ana Clara Tude; d'Avila, Andre; Houghtaling, Christopher; Ruskin, Jeremy N; Picard, Michael; Reddy, Vivek Y

2004-03-01

Transvascular catheter-based intracardiac echocardiography has been successfully used to help guide catheter ablation and electrophysiologic procedures. It has recently been demonstrated that catheters can be safely placed into the pericardial space to allow for epicardial cardiac mapping and ablation. We evaluated the feasibility of catheter-based intrapericardial echocardiography (IPE) during such procedures to identify cardiac structures and visualize intracardiac catheters. IPE was performed in 7 goats by placing a phased-array ultrasound transducer contained within a 10F steerable catheter into the pericardial space using the same transthoracic subxyphoid approach as used to map and ablate epicardial ventricular tachycardia. Images were obtained of cardiac structures and of intracardiac ablation catheters. After the procedure, the hearts were harvested to assess for possible IPE-related lesions. The IPE catheter could be easily placed inside the pericardial space in all animals. In 7 of 7 cases, longitudinal and short-axis views of right- and left-sided chambers and valves were obtained, similar in orientation to transesophageal echocardiography. Visualization of atrial appendages (6/7), pulmonary veins (6/7), coronary arteries (6/7), and coronary sinus (3/6) was also feasible. Assessment of intracardiac transvalvar and venous blood flow was achieved by spectral and color Doppler. The ablation catheter could be clearly visualized inside cardiac chambers. No arrhythmias were induced with IPE catheter manipulation. After harvesting the hearts, no lesions resulting from the procedure were observed. In this experimental setting, IPE was able to provide detailed images of cardiac structures and establish the relative position of the ablation catheter.

Use of light absorbers to alter optical interrogation with epi-illumination and transillumination in three-dimensional cardiac models

NASA Astrophysics Data System (ADS)

Ramshesh, Venkat K.; Knisley, Stephen B.

2006-03-01

Cardiac optical mapping currently provides 2-D maps of transmembrane voltage-sensitive fluorescence localized near the tissue surface. Methods for interrogation at different depths are required for studies of arrhythmias and the effects of defibrillation shocks in 3-D cardiac tissue. We model the effects of coloading with a dye that absorbs excitation or fluorescence light on the radius and depth of the interrogated region with specific illumination and collection techniques. Results indicate radii and depths of interrogation are larger for transillumination versus epi-illumination, an effect that is more pronounced for broad-field excitation versus laser scanner. Coloading with a fluorescence absorber lessens interrogated depth for epi-illumination and increases it for transillumination, which is confirmed with measurements using transillumination of heart tissue slices. Coloading with an absorber of excitation light consistently decreases the interrogated depths. Transillumination and coloading also decrease the intensities of collected fluorescence. Thus, localization can be modified with wavelength-specific absorbers at the expense of a reduction in fluorescence intensity.

Human Induced Pluripotent Stem Cell-Derived Cardiac Cell Sheets Expressing Genetically Encoded Voltage Indicator for Pharmacological and Arrhythmia Studies.

PubMed

Shaheen, Naim; Shiti, Assad; Huber, Irit; Shinnawi, Rami; Arbel, Gil; Gepstein, Amira; Setter, Noga; Goldfracht, Idit; Gruber, Amit; Chorna, Snizhanna V; Gepstein, Lior

2018-06-05

Fulfilling the potential of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes for studying conduction and arrhythmogenesis requires development of multicellular models and methods for long-term repeated tissue phenotyping. We generated confluent hiPSC-derived cardiac cell sheets (hiPSC-CCSs), expressing the genetically encoded voltage indicator ArcLight. ArcLight-based optical mapping allowed generation of activation and action-potential duration (APD) maps, which were validated by mapping the same hiPSC-CCSs with the voltage-sensitive dye, Di-4-ANBDQBS. ArcLight mapping allowed long-term assessment of electrical remodeling in the hiPSC-CCSs and evaluation of drug-induced conduction slowing (carbenoxolone, lidocaine, and quinidine) and APD prolongation (quinidine and dofetilide). The latter studies also enabled step-by-step depiction of drug-induced arrhythmogenesis ("torsades de pointes in the culture dish") and its prevention by MgSO 4 and rapid pacing. Phase-mapping analysis allowed biophysical characterization of spiral waves induced in the hiPSC-CCSs and their termination by electrical cardioversion and overdrive pacing. In conclusion, ArcLight mapping of hiPSC-CCSs provides a powerful tool for drug testing and arrhythmia investigation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Use of radiotelemetry to assess perinatal cardiac function in the ovine fetus and newborn.

PubMed

Antolic, A; Wood, C E; Keller-Wood, M

2017-12-01

The late gestation fetal ECG (fECG) has traditionally been difficult to characterize due to the low fECG signal relative to high maternal noise. Although new technologies have improved the feasibility of its acquisition and separation, little is known about its development in late gestation, a period in which the fetal heart undergoes extensive maturational changes. Here, we describe a method for the chronic implantation of radiotelemetry devices into late gestation ovine fetuses to characterize parameters of the fECG following surgery, throughout late gestation, and in the perinatal period. We found no significant changes in mean aortic pressure (MAP), heart rate (HR), or ECG in the 5 days following implantation; however, HR decreased in the first 24 h following the end of surgery, with associated increases in RR, PR, and QRS intervals. Over the last 14 days of fetal life, fetal MAP significantly increased, and HR significantly decreased, as expected. MAP and HR increased as labor progressed. Although there were no significant changes over time in the ECG during late gestation, the duration of the PR interval initially decreased and then increased as birth approached. These results indicate that although critical maturational changes occur in the late gestation fetal myocardium, the mechanisms that control the cardiac conduction are relatively mature in late gestation. The study demonstrates that radiotelemetry can be successfully used to assess fetal cardiac function, in particular conduction, through the process of labor and delivery, and may therefore be a useful tool for study of peripartum cardiac events. Copyright © 2017 the American Physiological Society.

Intravenous administration of hypertonic sodium chloride solution with dextran or isotonic sodium chloride solution for treatment of septic shock secondary to pyometra in dogs.

PubMed

Fantoni, D T; Auler Junior, J O; Futema, F; Cortopassi, S R; Migliati, E R; Faustino, M; de Oliveira, C M

1999-11-01

To determine effects of i.v. administration of hypertonic saline (7.5% NaCl) solution with 6% dextran 70 (HSSD) or isotonic saline (0.9% NaCl) solution (ISS) to dogs with septic shock secondary to pyometra. Prospective, randomized, clinical study. 14 client-owned dogs with septic shock secondary to pyometra. Prior to emergency ovariohysterectomy, catheters were placed in pulmonary and femoral arteries of each dog to evaluate hemodynamic and oxygenation status. Immediately prior to surgery, 7 dogs received HSSD (4 ml/kg [1.82 ml/lb] of body weight, i.v.) and 7 dogs received ISS (32 ml/kg [14.54 ml/lb], i.v.) during a 5-minute period. Measurements of hemodynamic and oxygenation variables were obtained before and 5 and 20 minutes after administration of fluids. Mean arterial pressure (MAP) increased significantly 5 and 20 minutes after administration of HSSD, whereas ISS did not affect MAP. However, cardiac output, cardiac index, and oxygen delivery increased and hematocrit decreased after both treatments. Oxygen consumption and extraction rate and degree of acidosis did not improve after either treatment. Intravenous administration of small volumes of HSSD to dogs with septic shock secondary to pyometra resulted in improvement of hemodynamic and oxygenation status. Although cardiac output, cardiac index, and oxygen delivery improved after administration of a volume of ISS equal to 8 times that of HSSD, MAP increased to > 80 mm Hg only after treatment with HSSD. Administration of HSSD may be an effective treatment for septic shock in dogs.

Computational Cardiac Anatomy Using MRI

PubMed Central

Beg, Mirza Faisal; Helm, Patrick A.; McVeigh, Elliot; Miller, Michael I.; Winslow, Raimond L.

2005-01-01

Ventricular geometry and fiber orientation may undergo global or local remodeling in cardiac disease. However, there are as yet no mathematical and computational methods for quantifying variation of geometry and fiber orientation or the nature of their remodeling in disease. Toward this goal, a landmark and image intensity-based large deformation diffeomorphic metric mapping (LDDMM) method to transform heart geometry into common coordinates for quantification of shape and form was developed. Two automated landmark placement methods for modeling tissue deformations expected in different cardiac pathologies are presented. The transformations, computed using the combined use of landmarks and image intensities, yields high-registration accuracy of heart anatomies even in the presence of significant variation of cardiac shape and form. Once heart anatomies have been registered, properties of tissue geometry and cardiac fiber orientation in corresponding regions of different hearts may be quantified. PMID:15508155

Applying an artificial neural network model for developing a severity score for patients with hereditary amyloid polyneuropathy.

PubMed

Novis, Shenia; Machado, Felipe; Costa, Victor B; Foguel, Debora; Cruz, Marcia W; de Seixas, José Manoel

2017-09-01

Hereditary (familial) amyloid polyneuropathy (FAP) is a systemic disease that includes a sensorimotor polyneuropathy related to transthyretin (TTR) mutations. So far, a scale designed to classify the severity of this disease has not yet been validated. This work proposes the implementation of an artificial neural network (ANN) in order to develop a severity scale for monitoring the disease progression in FAP patients. In order to achieve this goal, relevant symptoms and laboratory findings were collected from 98 Brazilian patients included in THAOS - the Transthyretin Amyloidosis Outcomes Survey. Ninety-three percent of them bore Val30Met, the most prevalent variant of TTR worldwide; 63 were symptomatic and 35 were asymptomatic. These data were numerically codified for the purpose of constructing a Self-Organizing Map (SOM), which maps data onto a grid of artificial neurons. Mapped data could be clustered by similarity into five groups, based on increasing FAP severity (from Groups 1 to 5). Most symptoms were virtually absent from patients who mapped to Group 1, which also includes the asymptomatic patients. Group 2 encompasses the patients bearing symptoms considered to be initial markers of FAP, such as first signs of walking disabilities and lack of sensitivity to temperature and pain. Interestingly, the patients with cardiac symptoms, which also carry cardiac-associated mutations of the TTR gene (such as Val112Ile and Ala19Asp), were concentrated in Group 3. Symptoms such as urinary and fecal incontinence and diarrhea characterized particularly Groups 4 and 5. Renal impairment was found almost exclusively in Group 5. Model validation was accomplished by considering the symptoms from a sample with 48 additional Brazilian patients. The severity scores proposed here not only identify the current stage of a patient's disease but also offer to the physician an easy-to-read, 2D map that makes it possible to track disease progression.

Role of angiotensin in renal sympathetic activation in cirrhotic rats.

PubMed

Voigt, M D; Jones, S Y; DiBona, G F

1999-08-01

Central nervous system (CNS) renin-angiotensin activity influences the basal level of renal sympathetic nerve activity (RSNA) and its reflex regulation. The effect of type 1 angiotensin II (ANG II)-receptor antagonist treatment (losartan) on cardiac baroreflex regulation of RSNA and renal sodium handling was examined in rats with cirrhosis due to common bile duct ligation (CBDL). Basal levels of heart rate, mean arterial pressure (MAP), RSNA, and urinary sodium excretion were not affected by intracerebroventricular administration of either losartan or vehicle to CBDL rats. After acute intravenous isotonic saline loading (10% body wt) in vehicle-treated CBDL rats, MAP was unchanged and the decrease in RSNA seen in normal rats did not occur. However, in losartan-treated CBDL rats, there were significant concurrent but transient decreases in MAP (-20 +/- 2 mmHg) and RSNA (-25 +/- 3%). The natriuretic response to acute volume loading in losartan-treated CBDL rats was significantly less than that in vehicle-treated CBDL rats only at those time points where there were significant decreases in MAP. Antagonism of CNS ANG II type 1 receptors augments the renal sympathoinhibitory response to acute volume loading in CBDL. However, the natriuretic response to the acute volume loading is not improved, likely due to the strong antinatriuretic influence of the concomitant marked decrease in MAP (renal perfusion pressure) mediated by widespread sympathetic withdrawal from the systemic vasculature.

Cardiac-driven Pulsatile Motion of Intracranial Cerebrospinal Fluid Visualized Based on a Correlation Mapping Technique.

PubMed

Yatsushiro, Satoshi; Sunohara, Saeko; Hayashi, Naokazu; Hirayama, Akihiro; Matsumae, Mitsunori; Atsumi, Hideki; Kuroda, Kagayaki

2018-04-10

A correlation mapping technique delineating delay time and maximum correlation for characterizing pulsatile cerebrospinal fluid (CSF) propagation was proposed. After proofing its technical concept, this technique was applied to healthy volunteers and idiopathic normal pressure hydrocephalus (iNPH) patients. A time-resolved three dimensional-phase contrast (3D-PC) sampled the cardiac-driven CSF velocity at 32 temporal points per cardiac period at each spatial location using retrospective cardiac gating. The proposed technique visualized distributions of propagation delay and correlation coefficient of the PC-based CSF velocity waveform with reference to a waveform at a particular point in the CSF space. The delay time was obtained as the amount of time-shift, giving the maximum correlation for the velocity waveform at an arbitrary location with that at the reference location. The validity and accuracy of the technique were confirmed in a flow phantom equipped with a cardiovascular pump. The technique was then applied to evaluate the intracranial CSF motions in young, healthy (N = 13), and elderly, healthy (N = 13) volunteers and iNPH patients (N = 13). The phantom study demonstrated that root mean square error of the delay time was 2.27%, which was less than the temporal resolution of PC measurement used in this study (3.13% of a cardiac cycle). The human studies showed a significant difference (P < 0.01) in the mean correlation coefficient between the young, healthy group and the other two groups. A significant difference (P < 0.05) was also recognized in standard deviation of the correlation coefficients in intracranial CSF space among all groups. The result suggests that the CSF space compliance of iNPH patients was lower than that of healthy volunteers. The correlation mapping technique allowed us to visualize pulsatile CSF velocity wave propagations as still images. The technique may help to classify diseases related to CSF dynamics, such as iNPH.

Could missile attacks trigger acute myocardial infarction?

PubMed

Zubaid, Mohammad; Suresh, Cheiyil G; Thalib, Lukman; Rashed, Wafa

2006-08-01

During the Gulf war in 2003, Kuwait was targeted with missile attacks for 10 consecutive days. Our objective is to evaluate the influence of missile attacks on the incidence of acute myocardial infarction (AMI). We retrospectively compared the number of admissions for AMI presenting to a major general hospital during missile attacks period (MAP) in 2003 with four control periods. MAP and each control period consisted of the same number of days (10 days). The four control periods were the 10 days immediately before and after MAP; and the same time period as MAP for the years 2001 and 2002. The number of admissions for AMI was highest during MAP, 21 cases compared to 14-16 cases in the four control periods, with a trend towards increase during MAP (incidence rate ratio = 1.59; 95% CI 0.95 to 2.66, p < 0.07). The number of admissions for AMI during the first 5 days of MAP was significantly higher compared to the first 5 days of the four control periods (incidence rate ratio = 2.43; 95% CI 1.23 to 4.26, p < 0.01). The observed AMI admission rate during the first 5 days of MAP was significantly higher than expected for a 5-day period in the years 2001, 2002 and 2003. This increase was specific to AMI and did not affect other acute cardiac conditions. Missile attacks were associated with an increase in the incidence of AMI. This increase was specific to AMI and did not influence acute cardiac conditions.

Myocardial lipid content in Fabry disease: a combined 1H-MR spectroscopy and MR imaging study at 3 Tesla.

PubMed

Petritsch, B; Köstler, H; Weng, A M; Horn, M; Gassenmaier, T; Kunz, A S; Weidemann, F; Wanner, C; Bley, T A; Beer, M

2016-10-28

Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by 1 H magnetic resonance spectroscopy (MRS) at 3 Tesla. Myocardial lipid content was quantified in vivo by 1 H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined 1 H-MRS with cardiac cine imaging and LGE MRI in a single examination. Myocardial lipid content was not significantly elevated in Fabry disease (p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI (LGE negative; n = 12) to patients with signs of fibrosis (LGE positive; n = 18) revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076). This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by 1 H-MRS. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections (LGE; 1 H-MRS; T 1 mapping), could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.

Arrhythmia Mechanism and Scaling Effect on the Spectral Properties of Electroanatomical Maps With Manifold Harmonics.

PubMed

Sanroman-Junquera, Margarita; Mora-Jimenez, Inmaculada; Garcia-Alberola, Arcadio; Caamano, Antonio J; Trenor, Beatriz; Rojo-Alvarez, Jose L

2018-04-01

Spatial and temporal processing of intracardiac electrograms provides relevant information to support the arrhythmia ablation during electrophysiological studies. Current cardiac navigation systems (CNS) and electrocardiographic imaging (ECGI) build detailed 3-D electroanatomical maps (EAM), which represent the spatial anatomical distribution of bioelectrical features, such as activation time or voltage. We present a principled methodology for spectral analysis of both EAM geometry and bioelectrical feature in CNS or ECGI, including their spectral representation, cutoff frequency, or spatial sampling rate (SSR). Existing manifold harmonic techniques for spectral mesh analysis are adapted to account for a fourth dimension, corresponding to the EAM bioelectrical feature. Appropriate scaling is required to address different magnitudes and units. With our approach, simulated and real EAM showed strong SSR dependence on both the arrhythmia mechanism and the cardiac anatomical shape. For instance, high frequencies increased significantly the SSR because of the "early-meets-late" in flutter EAM, compared with the sinus rhythm. Besides, higher frequency components were obtained for the left atrium (more complex anatomy) than for the right atrium in sinus rhythm. The proposed manifold harmonics methodology opens the field toward new signal processing tools for principled EAM spatiofeature analysis in CNS and ECGI, and to an improved knowledge on arrhythmia mechanisms.

STRUCTURAL AND FUNCTIONAL BASES OF CARDIAC FIBRILLATION. DIFFERENCES AND SIMILARITIES BETWEEN ATRIA AND VENTRICLES

PubMed Central

Filgueiras-Rama, David; Jalife, José

2016-01-01

Evidence accumulated over the last 25 years suggests that, whether in the atria or ventricles, fibrillation may be explained by the self-organization of the cardiac electrical activity into rapidly spinning rotors giving way to spiral waves that break intermittently and result in fibrillatory conduction. The dynamics and frequency of such rotors depend on the ion channel composition, excitability and refractory properties of the tissues involved, as well as on the thickness and respective three-dimensional fiber structure of the atrial and ventricular chambers. Therefore, improving the understanding of fibrillation has required the use of multidisciplinary research approaches, including optical mapping, patch clamping and molecular biology, and the application of concepts derived from the theory of wave propagation in excitable media. Moreover, translation of such concepts to the clinic has recently opened new opportunities to apply novel mechanistic approaches to therapy, particularly during atrial fibrillation ablation. Here we review the current understanding of the manner in which the underlying myocardial structure and function influence rotor initiation and maintenance during cardiac fibrillation. We also examine relevant underlying differences and similarities between atrial fibrillation and ventricular fibrillation and evaluate the latest clinical mapping technologies used to identify rotors in either arrhythmia. Altogether, the data being discussed have significantly improved our understanding of the cellular and structural bases of cardiac fibrillation and pointed toward potentially exciting new avenues for more efficient and effective identification and therapy of the most complex cardiac arrhythmias. PMID:27042693

Cardiac elastography: detecting pathological changes in myocardium tissues

NASA Astrophysics Data System (ADS)

Konofagou, Elisa E.; Harrigan, Timothy; Solomon, Scott

2003-05-01

Estimation of the mechanical properties of the cardiac muscle has been shown to play a crucial role in the detection of cardiovascular disease. Elastography was recently shown feasible on RF cardiac data in vivo. In this paper, the role of elastography in the detection of ischemia/infarct is explored with simulations and in vivo experiments. In finite-element simulations of a portion of the cardiac muscle containing an infarcted region, the cardiac cycle was simulated with successive compressive and tensile strains ranging between -30% and 20%. The incremental elastic modulus was also mapped uisng adaptive methods. We then demonstrated this technique utilizing envelope-detected sonographic data (Hewlett-Packard Sonos 5500) in a patient with a known myocardial infarction. In cine-loop and M-Mode elastograms from both normal and infarcted regions in simulations and experiments, the infarcted region was identifed by the up to one order of magnitude lower incremental axial displacements and strains, and higher modulus. Information on motion, deformation and mechanical property should constitute a unique tool for noninvasive cardiac diagnosis.

Feasibility Study on Cardiac Arrhythmia Ablation Using High-Energy Heavy Ion Beams

NASA Astrophysics Data System (ADS)

Lehmann, H. Immo; Graeff, Christian; Simoniello, Palma; Constantinescu, Anna; Takami, Mitsuru; Lugenbiel, Patrick; Richter, Daniel; Eichhorn, Anna; Prall, Matthias; Kaderka, Robert; Fiedler, Fine; Helmbrecht, Stephan; Fournier, Claudia; Erbeldinger, Nadine; Rahm, Ann-Kathrin; Rivinius, Rasmus; Thomas, Dierk; Katus, Hugo A.; Johnson, Susan B.; Parker, Kay D.; Debus, Jürgen; Asirvatham, Samuel J.; Bert, Christoph; Durante, Marco; Packer, Douglas L.

2016-12-01

High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40-55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction.

Novel anisotropic engineered cardiac tissues: studies of electrical propagation.

PubMed

Bursac, Nenad; Loo, Yihua; Leong, Kam; Tung, Leslie

2007-10-05

The goal of this study was to engineer cardiac tissue constructs with uniformly anisotropic architecture, and to evaluate their electrical function using multi-site optical mapping of cell membrane potentials. Anisotropic polymer scaffolds made by leaching of aligned sucrose templates were seeded with neonatal rat cardiac cells and cultured in rotating bioreactors for 6-14 days. Cells aligned and interconnected inside the scaffolds and when stimulated by a point electrode, supported macroscopically continuous, anisotropic impulse propagation. By culture day 14, the ratio of conduction velocities along vs. across cardiac fibers reached a value of 2, similar to that in native neonatal ventricles, while action potential duration and maximum capture rate, respectively, decreased to 120ms and increased to approximately 5Hz. The shorter culture time and larger scaffold thickness were associated with increased incidence of sustained reentrant arrhythmias. In summary, this study is the first successful attempt to engineer a cm(2)-size, functional anisotropic cardiac tissue patch.

An infrared optical pacing system for screening cardiac electrophysiology in human cardiomyocytes.

PubMed

McPheeters, Matthew T; Wang, Yves T; Werdich, Andreas A; Jenkins, Michael W; Laurita, Kenneth R

2017-01-01

Human cardiac myocytes derived from pluripotent stem cells (hCM) have invigorated interest in genetic disease mechanisms and cardiac safety testing; however, the technology to fully assess electrophysiological function in an assay that is amenable to high throughput screening has lagged. We describe a fully contactless system using optical pacing with an infrared (IR) laser and multi-site high fidelity fluorescence imaging to assess multiple electrophysiological parameters from hCM monolayers in a standard 96-well plate. Simultaneous multi-site action potentials (FluoVolt) or Ca2+ transients (Fluo4-AM) were measured, from which high resolution maps of conduction velocity and action potential duration (APD) were obtained in a single well. Energy thresholds for optical pacing were determined for cell plating density, laser spot size, pulse width, and wavelength and found to be within ranges reported previously for reliable pacing. Action potentials measured using FluoVolt and a microelectrode exhibited the same morphology and rate of depolarization. Importantly, we show that this can be achieved accurately with minimal damage to hCM due to optical pacing or fluorescence excitation. Finally, using this assay we demonstrate that hCM exhibit reproducible changes in repolarization and impulse conduction velocity for Flecainide and Quinidine, two well described reference compounds. In conclusion, we demonstrate a high fidelity electrophysiological screening assay that incorporates optical pacing with IR light to control beating rate of hCM monolayers.

Noninvasive Imaging of Three-dimensional Cardiac Activation Sequence during Pacing and Ventricular Tachycardia

PubMed Central

Han, Chengzong; Pogwizd, Steven M.; Killingsworth, Cheryl R.; He, Bin

2011-01-01

Background Imaging cardiac excitation within ventricular myocardium is important in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. Objective This study aims to rigorously assess the imaging performance of a three-dimensional (3-D) cardiac electrical imaging (3-DCEI) technique with the aid of 3-D intra-cardiac mapping from up to 216 intramural sites during paced rhythm and norepinephrine (NE) induced ventricular tachycardia (VT) in the rabbit heart. Methods Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in thirteen healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous NE. Computer tomography images were obtained to construct geometry model. Results The non-invasively imaged activation sequence correlated well with invasively measured counterparts, with a correlation coefficient of 0.72±0.04, and a relative error of 0.30±0.02 averaged over 520 paced beats as well as 73 NE-induced PVCs and VT beats. All PVCs and VT beats initiated in the subendocardium by a nonreentrant mechanism. The averaged distance from imaged site of initial activation to pacing site or site of arrhythmias determined from intra-cardiac mapping was ~5mm. For dual-site pacing, the double origins were identified when they were located at contralateral sides of ventricles or at the lateral wall and the apex. Conclusion 3-DCEI can non-invasively delineate important features of focal or multi-focal ventricular excitation. It offers the potential to aid in localizing the origins and imaging activation sequence of ventricular arrhythmias, and to provide noninvasive assessment of the underlying arrhythmia mechanisms. PMID:21397046

Detomidine and the combination of detomidine and MK-467, a peripheral alpha-2 adrenoceptor antagonist, as premedication in horses anaesthetized with isoflurane.

PubMed

Pakkanen, Soile Ae; Raekallio, Marja R; Mykkänen, Anna K; Salla, Kati M; de Vries, Annemarie; Vuorilehto, Lauri; Scheinin, Mika; Vainio, Outi M

2015-09-01

To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane. Experimental, crossover study with a 14 day wash-out period. Seven healthy horses. The horses received either detomidine (20 μg kg(-1) IV) and butorphanol (20 μg kg(-1) IV) alone (DET) or with MK-467 (200 μg kg(-1) IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg(-1) ) and midazolam (0.06 mg kg(-1) ) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2 ) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (Pa O2 /FiO2 ) and tissue oxygen delivery (DO2 ) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p < 0.05. The induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and Pa O2 /FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller. MK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Dynamic positional fate map of the primary heart-forming region.

PubMed

Cui, Cheng; Cheuvront, Tracey J; Lansford, Rusty D; Moreno-Rodriguez, Ricardo A; Schultheiss, Thomas M; Rongish, Brenda J

2009-08-15

Here we show the temporal-spatial orchestration of early heart morphogenesis at cellular level resolution, in vivo, and reconcile conflicting positional fate mapping data regarding the primary heart-forming field(s). We determined the positional fates of precardiac cells using a precision electroporation approach in combination with wide-field time-lapse microscopy in the quail embryo, a warm-blooded vertebrate (HH Stages 4 through 10). Contrary to previous studies, the results demonstrate the existence of a "continuous" circle-shaped heart field that spans the midline, appearing at HH Stage 4, which then expands to form a wide arc of progenitors at HH Stages 5-7. Our time-resolved image data show that a subset of these cardiac progenitor cells do not overlap with the expression of common cardiogenic factors, Nkx-2.5 and Bmp-2, until HH Stage 10, when a tubular heart has formed, calling into question when cardiac fate is specified and by which key factors. Sub-groups and anatomical bands (cohorts) of heart precursor cells dramatically change their relative positions in a process largely driven by endodermal folding and other large-scale tissue deformations. Thus, our novel dynamic positional fate maps resolve the origin of cardiac progenitor cells in amniotes. The data also establish the concept that tissue motion contributes significantly to cellular position fate - i.e., much of the cellular displacement that occurs during assembly of a midline heart tube (HH Stage 9) is NOT due to "migration" (autonomous motility), a commonly held belief. Computational analysis of our time-resolved data lays the foundation for more precise analyses of how cardiac gene regulatory networks correlate with early heart tissue morphogenesis in birds and mammals.

Underutilisation of public access defibrillation is related to retrieval distance and time-dependent availability.

PubMed

Deakin, Charles D; Anfield, Steve; Hodgetts, Gillian A

2018-05-14

Public access defibrillation doubles the chances of neurologically intact survival following out-of-hospital cardiac arrest (OHCA). Although there are increasing numbers of defibrillators (automated external defibrillator (AEDs)) available in the community, they are used infrequently, despite often being available. We aimed to match OHCAs with known AED locations in order to understand AED availability, the effects of reduced AED availability at night and the operational radius at which they can be effectively retrieved. All emergency calls to South Central Ambulance Service from April 2014 to April 2016 were screened to identify cardiac arrests. Each was mapped to the nearest AED, according to the time of day. Mapping software was used to calculate the actual walking distance for a bystander between each OHCA and respective AED, when travelling at a brisk walking speed (4 mph). 4012 cardiac arrests were identified and mapped to one of 2076 AEDs. All AEDs were available during daytime hours, but only 713 at night (34.3%). 5.91% of cardiac arrests were within a retrieval (walking) radius of 100 m during the day, falling to 1.59% out-of-hours. Distances to rural AEDs were greater than in urban areas (P<0.0001). An AED could potentially have been retrieved prior to actual ambulance arrival in 25.3% cases. Existing AEDs are underused; 36.4% of OHCAs are located within 500 m of an AED. Although more AEDs will improve availability, greater use can be made of existing AEDs, particularly by ensuring they are all available on a 24/7 basis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Interactive visualization for scar transmurality in cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Reiml, Sabrina; Toth, Daniel; Panayiotou, Maria; Fahn, Bernhard; Karim, Rashed; Behar, Jonathan M.; Rinaldi, Christopher A.; Razavi, Reza; Rhode, Kawal S.; Brost, Alexander; Mountney, Peter

2016-03-01

Heart failure is a serious disease affecting about 23 million people worldwide. Cardiac resynchronization therapy is used to treat patients suffering from symptomatic heart failure. However, 30% to 50% of patients have limited clinical benefit. One of the main causes is suboptimal placement of the left ventricular lead. Pacing in areas of myocardial scar correlates with poor clinical outcomes. Therefore precise knowledge of the individual patient's scar characteristics is critical for delivering tailored treatments capable of improving response rates. Current research methods for scar assessment either map information to an alternative non-anatomical coordinate system or they use the image coordinate system but lose critical information about scar extent and scar distribution. This paper proposes two interactive methods for visualizing relevant scar information. A 2-D slice based approach with a scar mask overlaid on a 16 segment heart model and a 3-D layered mesh visualization which allows physicians to scroll through layers of scar from endocardium to epicardium. These complementary methods enable physicians to evaluate scar location and transmurality during planning and guidance. Six physicians evaluated the proposed system by identifying target regions for lead placement. With the proposed method more target regions could be identified.

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.

3D and 4D echo--applications in EP laboratory procedures.

PubMed

Kautzner, Josef; Peichl, Petr

2008-08-01

3D echocardiography allows imaging and analysis of cardiovascular structures as they move in time and space, thus creating possibility for creation of 4D datasets (3D + time). Intracardiac echocardiography (ICE) further broadens the spectrum of echocardiographic techniques by allowing detailed imaging of intracardiac anatomy with 3D reconstructions. The paper reviews the current status of development of 3D and 4D echocardiography in electrophysiology. In ablation area, 3D echocardiography can enhance the performance of catheter ablation for complex arrhythmias such as atrial fibrillation. Currently, several strategies to obtain 3D reconstructions from ICE are available. One involves combination with electroanatomical mapping system; others create reconstruction from standard phased-array or single-element ICE catheter using special rotational or pull-back devices. Secondly, 3D echocardiography may be used for precise assessment of cardiac dyssynchrony before cardiac resynchronization therapy. Its reliable detection is expected to minimize number of non-responders to this treatment and optimize left ventricular lead positioning to get maximum hemodynamic benefit. The main potential benefit of 3D and 4D echocardiography in electrophysiology lie in real-time guidance of complex ablation procedures and precise assessment of cardiac dyssynchrony.

Impact of vitamin D3 on cardiovascular responses to glucocorticoid excess.

PubMed

Ahmed, Mona A

2013-06-01

Although the cardiovascular system is not a classical target for 1,25-dihydroxyvitamin D3, both cardiac myocytes and vascular smooth muscle cells respond to this hormone. The present study aimed to elucidate the effect of active vitamin D3 on cardiovascular functions in rats exposed to glucocorticoid excess. Adult male Wistar rats were allocated into three groups: control group, dexamethasone (Dex)-treated group receiving Dex (200 μg/kg) subcutaneously for 12 days, and vitamin D3-Dex-treated group receiving 1,25-(OH)2D3 (100 ng/kg) and Dex (200 μg/kg) subcutaneously for 12 days. Rats were subjected to measurement of systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures and heart rate. Rate pressure product (RPP) was calculated. Rats' isolated hearts were perfused in Langendorff preparation and studied for basal activities (heart rate, peaked developed tension, time to peak tension, half relaxation time, and myocardial flow rate) and their responses to isoproterenol infusion. Blood samples were collected for determination of plasma level of nitrite, nitric oxide surrogate. Dex-treated group showed significant increase in SBP, DBP, MAP, and RPP, as well as cardiac hypertrophy and enhancement of basal cardiac performance evidenced by increased heart rate, rapid and increased contractility, and accelerated lusitropy, together with impaired contractile and myocardial flow rate responsiveness to beta-adrenergic activation and depressed inotropic and coronary vascular reserves. Such alterations were accompanied by low plasma nitrite. These changes were markedly improved by vitamin D3 treatment. In conclusion, vitamin D3 is an efficacious modulator of the deleterious cardiovascular responses induced by glucocorticoid excess, probably via accentuation of nitric oxide.

A real time QRS detection using delay-coordinate mapping for the microcontroller implementation.

PubMed

Lee, Jeong-Whan; Kim, Kyeong-Seop; Lee, Bongsoo; Lee, Byungchae; Lee, Myoung-Ho

2002-01-01

In this article, we propose a new algorithm using the characteristics of reconstructed phase portraits by delay-coordinate mapping utilizing lag rotundity for a real-time detection of QRS complexes in ECG signals. In reconstructing phase portrait the mapping parameters, time delay, and mapping dimension play important roles in shaping of portraits drawn in a new dimensional space. Experimentally, the optimal mapping time delay for detection of QRS complexes turned out to be 20 ms. To explore the meaning of this time delay and the proper mapping dimension, we applied a fill factor, mutual information, and autocorrelation function algorithm that were generally used to analyze the chaotic characteristics of sampled signals. From these results, we could find the fact that the performance of our proposed algorithms relied mainly on the geometrical property such as an area of the reconstructed phase portrait. For the real application, we applied our algorithm for designing a small cardiac event recorder. This system was to record patients' ECG and R-R intervals for 1 h to investigate HRV characteristics of the patients who had vasovagal syncope symptom and for the evaluation, we implemented our algorithm in C language and applied to MIT/BIH arrhythmia database of 48 subjects. Our proposed algorithm achieved a 99.58% detection rate of QRS complexes.

QUest for the Arrhythmogenic Substrate of Atrial fibRillation in Patients Undergoing Cardiac Surgery (QUASAR Study): Rationale and Design.

PubMed

van der Does, Lisette J M E; Yaksh, Ameeta; Kik, Charles; Knops, Paul; Lanters, Eva A H; Teuwen, Christophe P; Oei, Frans B S; van de Woestijne, Pieter C; Bekkers, Jos A; Bogers, Ad J J C; Allessie, Maurits A; de Groot, Natasja M S

2016-06-01

The heterogeneous presentation and progression of atrial fibrillation (AF) implicate the existence of different pathophysiological processes. Individualized diagnosis and therapy of the arrhythmogenic substrate underlying AF may be required to improve treatment outcomes. Therefore, this single-center study aims to identify the arrhythmogenic areas underlying AF by intra-operative, high-resolution, multi-site epicardial mapping in 600 patients with different heart diseases. Participants are divided into 12 groups according to the underlying heart diseases and presence of prior AF episodes. Mapping is performed with a 192-electrode array for 5-10 s during sinus rhythm and (induced) AF of the entire atrial surface. Local activation times are converted into activation and wave maps from which various electrophysiological parameters are derived. Postoperative cardiac rhythm registrations and a 5-year follow-up will show the incidence of postoperative and persistent AF. This project provides the first step in the development of a tool for individual AF diagnosis and treatment.

AEDs at your fingertips: automated external defibrillators on college campuses and a novel approach for increasing accessibility.

PubMed

Berger, Ryan J; O'Shea, Jesse G

2014-01-01

The use of automated external defibrillators (AEDs) increases survival in cardiac arrest events. Due to the success of previous efforts and free, readily available mobile mapping software, the discussion is to emphasize the importance of the use of AEDs to prevent sudden cardiac arrest-related deaths on college campuses and abroad, while suggesting a novel approach to aiding in access and awareness issues. A user-friendly mobile application (a low-cost iOS map) was developed at Florida State University to decrease AED retrieval distance and time. The development of mobile AED maps is feasible for a variety of universities and other entities, with the potential to save lives. Just having AEDs installed is not enough--they need to be easily locatable. Society increasingly relies on phones to provide information, and there are opportunities to use mobile technology to locate and share information about relevant emergency devices; these should be incorporated into the chain of survival.

Investigation of optimal acquisition time of myocardial perfusion scintigraphy using cardiac focusing-collimator

NASA Astrophysics Data System (ADS)

Niwa, Arisa; Abe, Shinji; Fujita, Naotoshi; Kono, Hidetaka; Odagawa, Tetsuro; Fujita, Yusuke; Tsuchiya, Saki; Kato, Katsuhiko

2015-03-01

Recently myocardial perfusion SPECT imaging acquired using the cardiac focusing-collimator (CF) has been developed in the field of nuclear cardiology. Previously we have investigated the basic characteristics of CF using physical phantoms. This study was aimed at determining the acquisition time for CF that enables to acquire the SPECT images equivalent to those acquired by the conventional method in 201TlCl myocardial perfusion SPECT. In this study, Siemens Symbia T6 was used by setting the torso phantom equipped with the cardiac, pulmonary, and hepatic components. 201TlCl solution were filled in the left ventricular (LV) myocardium and liver. Each of CF, the low energy high resolution collimator (LEHR), and the low medium energy general purpose collimator (LMEGP) was set on the SPECT equipment. Data acquisitions were made by regarding the center of the phantom as the center of the heart in CF at various acquisition times. Acquired data were reconstructed, and the polar maps were created from the reconstructed images. Coefficient of variation (CV) was calculated as the mean counts determined on the polar maps with their standard deviations. When CF was used, CV was lower at longer acquisition times. CV calculated from the polar maps acquired using CF at 2.83 min of acquisition time was equivalent to CV calculated from those acquired using LEHR in a 180°acquisition range at 20 min of acquisition time.

Correction for the T1 Effect Incorporating Flip Angle Estimated by Kalman Filter in Cardiac-Gated Functional MRI

PubMed Central

Shin, Jaemin; Ahn, Sinyeob; Hu, Xiaoping

2015-01-01

Purpose To develop an improved and generalized technique for correcting T1-related signal fluctuations (T1 effect) in cardiac-gated functional magnetie resonance imaging (fMRI) data with flip angle estimation. Theory and Methods Spatial maps of flip angle and T1 are jointly estimated from cardiac-gated time series using a Kalman filter. These maps are subsequently used for removing the T1 effect in the presence of B1 inhomogeneity. The new technique was compared with a prior technique that uses T1 only while assuming a homogeneous flip angle of 90°. The robustness of the new technique is demonstrated with simulated and experimental data. Results Simulation results revealed that the new method led to increased temporal signal-to-noise ratio across a large range of flip angles, T1s, and stimulus onset asynchrony means compared to the T1 only approach. With the experimental data, the new approach resulted in higher average gray matter temporal signal-to-noise ratio of seven subjects (84 vs. 48). The new approach also led to a higher statistical score of activation in the lateral geniculate nucleus (P < 0.002). Conclusion The new technique is able to remove the T1 effect robustly and is a promising tool for improving the ability to map activation in fMRI, especially in subcortical regions. PMID:23390029

Rapid multislice T1 mapping of mouse myocardium: Application to quantification of manganese uptake in α-Dystrobrevin knockout mice.

PubMed

Jiang, Kai; Li, Wen; Li, Wei; Jiao, Sen; Castel, Laurie; Van Wagoner, David R; Yu, Xin

2015-11-01

The aim of this study was to develop a rapid, multislice cardiac T1 mapping method in mice and to apply the method to quantify manganese (Mn(2+)) uptake in a mouse model with altered Ca(2+) channel activity. An electrocardiography-triggered multislice saturation-recovery Look-Locker method was developed and validated both in vitro and in vivo. A two-dose study was performed to investigate the kinetics of T1 shortening, Mn(2+) relaxivity in myocardium, and the impact of Mn(2+) on cardiac function. The sensitivity of Mn(2+)-enhanced MRI in detecting subtle changes in altered Ca(2+) channel activity was evaluated in a mouse model with α-dystrobrevin knockout. Validation studies showed strong agreement between the current method and an established method. High Mn(2+) dose led to significantly accelerated T1 shortening. Heart rate decreased during Mn(2+) infusion, while ejection ratio increased slightly at the end of imaging protocol. No statistical difference in cardiac function was detected between the two dose groups. Mice with α-dystrobrevin knockout showed enhanced Mn(2+) uptake in vivo. In vitro patch-clamp study showed increased Ca(2+) channel activity. The saturation recovery method provides rapid T1 mapping in mouse hearts, which allowed sensitive detection of subtle changes in Mn(2+) uptake in α-dystrobrevin knockout mice. © 2014 Wiley Periodicals, Inc.

The hemodynamic effects of prolonged respiratory alkalosis in anesthetized newborn piglets.

PubMed

Jundi, K; Barrington, K J; Henderson, C; Allen, R G; Finer, N N

2000-04-01

To test the hypothesis that prolonged alkalosis decreases cardiac output and, furthermore, exacerbates hypoxic pulmonary vasoconstriction, as respiratory alkalosis is frequently induced as a therapy for persistent pulmonary hypertension of the newborn despite a lack of controlled evidence of improved outcomes. Potential adverse effects of prolonged alkalosis have been demonstrated. Two groups (control, n = 6, and hypocapnic alkalosis, n = 6) of 1-3 day old fentanyl-anesthetized, vecuronium-paralyzed piglets were instrumented to measure cardiac index (CI) and mean systemic (MAP) and pulmonary (PAP) arterial pressures. Baseline values were recorded. Alveolar hypoxia was then induced to achieve an arterial oxygen saturation of between 50 and 60% for 15 min. Respiratory alkalosis was then induced, by increasing ventilation to achieve a pH between 7.55-7.60, and was continued for 240 min. Inspired carbon dioxide was used with hyperventilation in the control group to maintain pressure of arterial carbon dioxide (PaCO2) at 35-45 mmHg and pH of 7.35-7.45. Hypoxia was induced again at 15 and 240 min. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated. Prolonged alkalosis led to a significant and progressive fall in mean MAP from 61 (SD 7) mmHg at the start of the study falling to 50 (SD 6.9, p = 0.043), with no effect on CI. Calculated SVR decreased (0.45 SD 0.03 vs 0.36 SD 0.05). There were no statistically significant changes in any of the variables in the control group. Neither acute nor prolonged respiratory alkalosis had a significant effect on hypoxic pulmonary vasoconstriction. Prolonged hyperventilation leads to systemic hypotension, however it does not exacerbate hypoxic pulmonary vasoconstriction.

Estimation of 3-D conduction velocity vector fields from cardiac mapping data.

PubMed

Barnette, A R; Bayly, P V; Zhang, S; Walcott, G P; Ideker, R E; Smith, W M

2000-08-01

A method to estimate three-dimensional (3-D) conduction velocity vector fields in cardiac tissue is presented. The speed and direction of propagation are found from polynomial "surfaces" fitted to space-time (x, y, z, t) coordinates of cardiac activity. The technique is applied to sinus rhythm and paced rhythm mapped with plunge needles at 396-466 sites in the canine myocardium. The method was validated on simulated 3-D plane and spherical waves. For simulated data, conduction velocities were estimated with an accuracy of 1%-2%. In experimental data, estimates of conduction speeds during paced rhythm were slower than those found during normal sinus rhythm. Vector directions were also found to differ between different types of beats. The technique was able to distinguish between premature ventricular contractions and sinus beats and between sinus and paced beats. The proposed approach to computing velocity vector fields provides an automated, physiological, and quantitative description of local electrical activity in 3-D tissue. This method may provide insight into abnormal conduction associated with fatal ventricular arrhythmias.

Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

PubMed Central

Burkhard, Silja Barbara

2018-01-01

Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions. PMID:29400650

Model-based imaging of cardiac electrical function in human atria

NASA Astrophysics Data System (ADS)

Modre, Robert; Tilg, Bernhard; Fischer, Gerald; Hanser, Friedrich; Messnarz, Bernd; Schocke, Michael F. H.; Kremser, Christian; Hintringer, Florian; Roithinger, Franz

2003-05-01

Noninvasive imaging of electrical function in the human atria is attained by the combination of data from electrocardiographic (ECG) mapping and magnetic resonance imaging (MRI). An anatomical computer model of the individual patient is the basis for our computer-aided diagnosis of cardiac arrhythmias. Three patients suffering from Wolff-Parkinson-White syndrome, from paroxymal atrial fibrillation, and from atrial flutter underwent an electrophysiological study. After successful treatment of the cardiac arrhythmia with invasive catheter technique, pacing protocols with stimuli at several anatomical sites (coronary sinus, left and right pulmonary vein, posterior site of the right atrium, right atrial appendage) were performed. Reconstructed activation time (AT) maps were validated with catheter-based electroanatomical data, with invasively determined pacing sites, and with pacing at anatomical markers. The individual complex anatomical model of the atria of each patient in combination with a high-quality mesh optimization enables accurate AT imaging, resulting in a localization error for the estimated pacing sites within 1 cm. Our findings may have implications for imaging of atrial activity in patients with focal arrhythmias.

Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial.

PubMed

Lamontagne, François; Meade, Maureen O; Hébert, Paul C; Asfar, Pierre; Lauzier, François; Seely, Andrew J E; Day, Andrew G; Mehta, Sangeeta; Muscedere, John; Bagshaw, Sean M; Ferguson, Niall D; Cook, Deborah J; Kanji, Salmaan; Turgeon, Alexis F; Herridge, Margaret S; Subramanian, Sanjay; Lacroix, Jacques; Adhikari, Neill K J; Scales, Damon C; Fox-Robichaud, Alison; Skrobik, Yoanna; Whitlock, Richard P; Green, Robert S; Koo, Karen K Y; Tanguay, Teddie; Magder, Sheldon; Heyland, Daren K

2016-04-01

In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock. We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60-65 mmHg) versus a higher (75-80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups. A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95% CI 7-11). In the lower and higher MAP groups, we observed deviations on 12 versus 8% of all days on vasopressors (p = 0.059). Risks of cardiac arrhythmias (20 versus 36%, p = 0.07) and hospital mortality (30 versus 33%, p = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60%, p = 0.03) but not in younger patients. This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy.

Three potential mechanisms for failure of high intensity focused ultrasound ablation in cardiac tissue.

PubMed

Laughner, Jacob I; Sulkin, Matthew S; Wu, Ziqi; Deng, Cheri X; Efimov, Igor R

2012-04-01

High intensity focused ultrasound (HIFU) has been introduced for treatment of cardiac arrhythmias because it offers the ability to create rapid tissue modification in confined volumes without directly contacting the myocardium. In spite of the benefits of HIFU, a number of limitations have been reported, which hindered its clinical adoption. In this study, we used a multimodal approach to evaluate thermal and nonthermal effects of HIFU in cardiac ablation. We designed a computer controlled system capable of simultaneous fluorescence mapping and HIFU ablation. Using this system, linear lesions were created in isolated rabbit atria (n=6), and point lesions were created in the ventricles of whole-heart (n=6) preparations by applying HIFU at clinical doses (4-16 W). Additionally, we evaluate the gap size in ablation lines necessary for conduction in atrial preparations (n=4). The voltage sensitive dye di-4-ANEPPS was used to assess functional damage produced by HIFU. Optical coherence tomography and general histology were used to evaluate lesion extent. Conduction block was achieved in 1 (17%) of 6 atrial preparations with a single ablation line. Following 10 minutes of rest, 0 (0%) of 6 atrial preparations demonstrated sustained conduction block from a single ablation line. Tissue displacement of 1 to 3 mm was observed during HIFU application due to acoustic radiation force along the lesion line. Additionally, excessive acoustic pressure and high temperature from HIFU generated cavitation, causing macroscopic tissue damage. A minimum gap size of 1.5 mm was found to conduct electric activity. This study identified 3 potential mechanisms responsible for the failure of HIFU ablation in cardiac tissues. Both acoustic radiation force and acoustic cavitation, in conjunction with inconsistent thermal deposition, can increase the risk of lesion discontinuity and result in gap sizes that promote ablation failure.

Magnetic Resonance Characterization of Cardiac Adaptation and Myocardial Fibrosis in Pulmonary Hypertension Secondary to Systemic-To-Pulmonary Shunt.

PubMed

Pereda, Daniel; García-Lunar, Inés; Sierra, Federico; Sánchez-Quintana, Damián; Santiago, Evelyn; Ballesteros, Constanza; Encalada, Juan F; Sánchez-González, Javier; Fuster, Valentín; Ibáñez, Borja; García-Álvarez, Ana

2016-09-01

Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR). To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation [n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular end-diastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction. Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation. © 2016 American Heart Association, Inc.

Using geographic information systems to evaluate cardiac arrest survival.

PubMed

Warden, Craig R; Daya, Mohamud; LeGrady, Lara A

2007-01-01

To evaluate cardiac arrest survival using geographical information systems (GIS) methodology. Patient data were obtained from a fire district Utstein-style adult cardiac arrest registry that also included address data. All incident locations were geocoded and fire station first-due areas were mapped by using the new computer-aided dispatch geographic data. Retrospective assignment of first-due versus second-due fire response unit was done by using a GIS "point-in-polygon" algorithm Survival to hospital admission was the primary outcome measure for incidents responded to by first-due versus second-due apparatus controlling for other potential predictors of survival using logistic regression. Cluster analysis was also performed to evaluate potential areas of high or low rates of survival. There were 461 eligible patients with an average age of 67+/-17 years, 63% were male, 53% had a witnessed arrest, bystander cardiopulmonary resuscitation was performed in 38%, bystander automatic external defibrillator (AED) Page: 1 was used in 0.01%, ventricular fibrillation or ventricular tachycardia were the presenting rhythms in 44%, the average response time was 5.5+/-2.1 minutes, and survival to hospital admission was 17%. There was no significant difference in response time between survivors (4.97 minutes) and non-survivors (5.52 minutes), (difference 0.55 minutes, 95%CI -0.08 to 1.18 min). The number of cardiac arrest calls varied from 1 to 49 for each station and the rate of second-due response varied from 0 to 19%. There was a nonsignificant association of survival to hospital admission for the first-due area cohort: odds ratio 0.70, 95% CI 0.38-1.29. GIS is a new methodology for analyzing EMS incident data. It adds a spatial component of analysis to traditional statistical techniques. No spatial difference was found on patient survival in this analysis.

CaMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of catecholaminergic polymorphic ventricular tachycardia

PubMed Central

Di Pasquale, E; Lodola, F; Miragoli, M; Denegri, M; Avelino-Cruz, J E; Buonocore, M; Nakahama, H; Portararo, P; Bloise, R; Napolitano, C; Condorelli, G; Priori, S G

2013-01-01

Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro ‘patient-specific cell-based system' that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac model of CPVT through the generation of iPSC from a CPVT patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene (RyR2) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after β-adrenergic stimulation, resembling the cardiac phenotype of the patients. Furthermore, treatment with KN-93 (2-[N-(2-hydroxyethyl)]-N-(4methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), an antiarrhythmic drug that inhibits Ca2+/calmodulin-dependent serine–threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies. PMID:24113177

External Validation of European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) for Risk Prioritization in an Iranian Population

PubMed Central

Atashi, Alireza; Amini, Shahram; Tashnizi, Mohammad Abbasi; Moeinipour, Ali Asghar; Aazami, Mathias Hossain; Tohidnezhad, Fariba; Ghasemi, Erfan; Eslami, Saeid

2018-01-01

Introduction The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is a prediction model which maps 18 predictors to a 30-day post-operative risk of death concentrating on accurate stratification of candidate patients for cardiac surgery. Objective The objective of this study was to determine the performance of the EuroSCORE II risk-analysis predictions among patients who underwent heart surgeries in one area of Iran. Methods A retrospective cohort study was conducted to collect the required variables for all consecutive patients who underwent heart surgeries at Emam Reza hospital, Northeast Iran between 2014 and 2015. Univariate and multivariate analysis were performed to identify covariates which significantly contribute to higher EuroSCORE II in our population. External validation was performed by comparing the real and expected mortality using area under the receiver operating characteristic curve (AUC) for discrimination assessment. Also, Brier Score and Hosmer-Lemeshow goodness-of-fit test were used to show the overall performance and calibration level, respectively. Results Two thousand five hundred eight one (59.6% males) were included. The observed mortality rate was 3.3%, but EuroSCORE II had a prediction of 4.7%. Although the overall performance was acceptable (Brier score=0.047), the model showed poor discriminatory power by AUC=0.667 (sensitivity=61.90, and specificity=66.24) and calibration (Hosmer-Lemeshow test, P<0.01). Conclusion Our study showed that the EuroSCORE II discrimination power is less than optimal for outcome prediction and less accurate for resource allocation programs. It highlights the need for recalibration of this risk stratification tool aiming to improve post cardiac surgery outcome predictions in Iran. PMID:29617500

A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology.

PubMed

Viventi, Jonathan; Kim, Dae-Hyeong; Moss, Joshua D; Kim, Yun-Soung; Blanco, Justin A; Annetta, Nicholas; Hicks, Andrew; Xiao, Jianliang; Huang, Younggang; Callans, David J; Rogers, John A; Litt, Brian

2010-03-24

In all current implantable medical devices such as pacemakers, deep brain stimulators, and epilepsy treatment devices, each electrode is independently connected to separate control systems. The ability of these devices to sample and stimulate tissues is hindered by this configuration and by the rigid, planar nature of the electronics and the electrode-tissue interfaces. Here, we report the development of a class of mechanically flexible silicon electronics for multiplexed measurement of signals in an intimate, conformal integrated mode on the dynamic, three-dimensional surfaces of soft tissues in the human body. We demonstrate this technology in sensor systems composed of 2016 silicon nanomembrane transistors configured to record electrical activity directly from the curved, wet surface of a beating porcine heart in vivo. The devices sample with simultaneous submillimeter and submillisecond resolution through 288 amplified and multiplexed channels. We use this system to map the spread of spontaneous and paced ventricular depolarization in real time, at high resolution, on the epicardial surface in a porcine animal model. This demonstration is one example of many possible uses of this technology in minimally invasive medical devices.

Heart transplant

MedlinePlus

... Tests of your kidney and liver Tests to evaluate your heart, such as EKG , echocardiogram , and cardiac ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

Assessment of the dose distribution inside a cardiac cath lab using TLD measurements and Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Baptista, M.; Teles, P.; Cardoso, G.; Vaz, P.

2014-11-01

Over the last decade, there was a substantial increase in the number of interventional cardiology procedures worldwide, and the corresponding ionizing radiation doses for both the medical staff and patients became a subject of concern. Interventional procedures in cardiology are normally very complex, resulting in long exposure times. Also, these interventions require the operator to work near the patient and, consequently, close to the primary X-ray beam. Moreover, due to the scattered radiation from the patient and the equipment, the medical staff is also exposed to a non-uniform radiation field that can lead to a significant exposure of sensitive body organs and tissues, such as the eye lens, the thyroid and the extremities. In order to better understand the spatial variation of the dose and dose rate distributions during an interventional cardiology procedure, the dose distribution around a C-arm fluoroscopic system, in operation in a cardiac cath lab at Portuguese Hospital, was estimated using both Monte Carlo (MC) simulations and dosimetric measurements. To model and simulate the cardiac cath lab, including the fluoroscopic equipment used to execute interventional procedures, the state-of-the-art MC radiation transport code MCNPX 2.7.0 was used. Subsequently, Thermo-Luminescent Detector (TLD) measurements were performed, in order to validate and support the simulation results obtained for the cath lab model. The preliminary results presented in this study reveal that the cardiac cath lab model was successfully validated, taking into account the good agreement between MC calculations and TLD measurements. The simulated results for the isodose curves related to the C-arm fluoroscopic system are also consistent with the dosimetric information provided by the equipment manufacturer (Siemens). The adequacy of the implemented computational model used to simulate complex procedures and map dose distributions around the operator and the medical staff is discussed, in view of the optimization principle (and the associated ALARA objective), one of the pillars of the international system of radiological protection.

Effectiveness of the new 'Mobile AED Map' to find and retrieve an AED: A randomised controlled trial.

PubMed

Sakai, Tomohiko; Iwami, Taku; Kitamura, Tetsuhisa; Nishiyama, Chika; Kawamura, Takashi; Kajino, Kentaro; Tanaka, Hiroshi; Marukawa, Seishiro; Tasaki, Osamu; Shiozaki, Tadahiko; Ogura, Hiroshi; Kuwagata, Yasuyuki; Shimazu, Takeshi

2011-01-01

Although early shock with an automated external defibrillator (AED) is one of the several key elements to save out-of-hospital cardiac arrest (OHCA) victims, it is not always easy to find and retrieve a nearby AED in emergency settings. We developed a cell phone web system, the Mobile AED Map, displaying nearby AEDs located anywhere. The simulation trial in the present study aims to compare the time and travel distance required to access an AED and retrieve it with and without the Mobile AED Map. Randomised controlled trial. Two fields where it was estimated to take 2min (120-170m) to access the nearest AED. Participants were randomly assigned to either the Mobile AED Map group or the control group. We provided each participant in both groups with an OHCA scenario, and measured the time and travel distance to find and retrieve a nearby AED. Forty-three volunteers were enrolled and completed the protocol. The time to access and retrieve an AED was not significantly different between the Mobile AED Map group (400±238s) and the control group (407±256s, p=0.92). The travel distance was significantly shorter in the Mobile AED Map group (606m vs. 891m, p=0.019). Trial field conditions affected the results differently. Although the new Mobile AED Map reduced the travel distance to access and retrieve the AED, it failed to shorten the time. Further technological improvements of the system are needed to increase its usefulness in emergency settings (UMIN000002043). Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A systematical analysis of in vivo contact forces on virtual catheter tip/tissue surface contact during cardiac mapping and intervention.

PubMed

Okumura, Yasuo; Johnson, Susan B; Bunch, T Jared; Henz, Benhur D; O'Brien, Christine J; Packer, Douglas L

2008-06-01

While catheter tip/tissue contact has been shown to be an important determinant of ablative lesions in in vitro studies, the impact of contact on the outcomes of mapping and ablation in the intact heart has not been evaluated. Twelve dogs underwent atrial ablation guided by the Senesitrade mark robotic catheter remote control system. After intracardiac ultrasound (ICE) validation of contact force measured by an in-line mechanical sensor, the relationship between contact force and individual lesion formation was established during irrigated-tipped ablation (flow 17 mL/sec) at 15 watts for 30 seconds. Minimal contact by ICE correlated with force of 4.7 +/- 5.8 grams, consistent contact 9.9 +/- 8.6 grams and tissue tenting produced 25.0 +/- 14.0 grams. Conversely, catheter tip/tissue contact by ICE was predicted by contact force. A contact force of 10-20 and > or =20 grams generated full-thickness, larger volume ablative lesions than that created with <10 grams (98 +/- 69 and 89 +/- 70 mm(3) vs 40 +/- 42 mm(3), P < 0.05). Moderate (10 grams) and marked contact (15-20 grams) application produced 1.5 X greater electroanatomic map volumes that were seen with minimal contact (5 grams) (26 +/- 3 cm(3) vs 33 +/- 6, 39 +/- 3 cm(3), P < 0.05). The electroanatomic map/CT merge process was also more distorted when mapping was generated at moderate to marked contact force. This study shows that mapping and ablation using a robotic sheath guidance system are critically dependent on generated force. These findings suggest that ablative lesion size is optimized by the application of 10-20 grams of contact force, although mapping requires lower-force application to avoid image distortions.

Comparison of aortic and carotid baroreflex stimulus-response characteristics in humans

NASA Technical Reports Server (NTRS)

Smith, S. A.; Querry, R. G.; Fadel, P. J.; Weiss, M. W.; Olivencia-Yurvati, A.; Shi, X.; Raven, P. B.

2001-01-01

In order to characterize the stimulus-response relationships of the arterial, aortic, and carotid baroreflexes in mediating cardiac chronotropic function, we measured heart rate (HR) responses elicited by acute changes in mean arterial pressure (MAP) and carotid sinus pressure (CSP) in 11 healthy individuals. Arterial (aortic + carotid) baroreflex control of HR was quantified using ramped changes in MAP induced by bolus injection of phenylephrine (PE) and sodium nitroprusside (SN). To assess aortic-cardiac responses, neck pressure (NP) and suction (NS) were applied during PE and SN administration, respectively, to counter alterations in CSP thereby isolating the aortic baroreflex. Graded levels of NP and NS were delivered to the carotid sinus using a customized neck collar device to assess the carotid-cardiac baroreflex, independent of drug infusion. The operating characteristics of each reflex were determined from the logistic function of the elicited HR response to the induced change in MAP. The arterial pressures at which the threshold was located on the stimulus-response curves determined for the arterial, aortic and carotid baroreflexes were not significantly different (72+/-4, 67+/-3, and 72+/-4 mm Hg, respectively, P > 0.05). Similarly, the MAP at which the saturation of the reflex responses were elicited did not differ among the baroreflex arcs examined (98+/-3, 99+/-2, and 102+/-3 mm Hg, respectively). These data suggest that the baroreceptor populations studied operate over the same range of arterial pressures. This finding indicates each baroreflex functions as both an important anti-hypotensive and anti-hypertensive mechanism. In addition, this investigation describes a model of aortic baroreflex function in normal healthy humans, which may prove useful in identifying the origin of baroreflex dysfunction in disease- and training-induced conditions.

Tracking brain motion during the cardiac cycle using spiral cine-DENSE MRI

PubMed Central

Zhong, Xiaodong; Meyer, Craig H.; Schlesinger, David J.; Sheehan, Jason P.; Epstein, Frederick H.; Larner, James M.; Benedict, Stanley H.; Read, Paul W.; Sheng, Ke; Cai, Jing

2009-01-01

Cardiac-synchronized brain motion is well documented, but the accurate measurement of such motion on the pixel-by-pixel basis has been hampered by the lack of proper imaging technique. In this article, the authors present the implementation of an autotracking spiral cine displacement-encoded stimulation echo (DENSE) magnetic resonance imaging (MRI) technique for the measurement of pulsatile brain motion during the cardiac cycle. Displacement-encoded dynamic MR images of three healthy volunteers were acquired throughout the cardiac cycle using the spiral cine-DENSE pulse sequence gated to the R wave of an electrocardiogram. Pixelwise Lagrangian displacement maps were computed, and 2D displacement as a function of time was determined for selected regions of interests. Different intracranial structures exhibited characteristic motion amplitude, direction, and pattern throughout the cardiac cycle. Time-resolved displacement curves revealed the pathway of pulsatile motion from brain stem to peripheral brain lobes. These preliminary results demonstrated that the spiral cine-DENSE MRI technique can be used to measure cardiac-synchronized pulsatile brain motion on the pixel-by-pixel basis with high temporal∕spatial resolution and sensitivity. PMID:19746774

Role of imaging in evaluation of sudden cardiac death risk in hypertrophic cardiomyopathy.

PubMed

Geske, Jeffrey B; Ommen, Steve R

2015-09-01

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and is associated with sudden cardiac death (SCD) - an uncommon but devastating clinical outcome. This review is designed to assess the role of imaging in established risk factor assessment and its role in emerging SCD risk stratification. Recent publications have highlighted the crucial role of imaging in HCM SCD risk stratification. Left ventricular hypertrophy assessment remains the key imaging determinant of risk. Data continue to emerge on the role of systolic dysfunction, apical aneurysms, left atrial enlargement and left ventricular outflow tract obstruction as markers of risk. Quantitative assessment of delayed myocardial enhancement and T1 mapping on cardiac MRI continue to evolve. Recent multicenter trials have allowed multivariate SCD risk assessment in large HCM cohorts. Given aggregate risk with presence of multiple risk factors, a single parameter should not be used in isolation to determine implantable cardiac defibrillator candidacy. Use of all available imaging data, including cardiac magnetic resonance tissue characterization, allows a comprehensive approach to SCD stratification and implantable cardiac defibrillator decision-making.

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiac allograft gene expression profiling test... Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a) Identification. A cardiac allograft gene expression profiling test system is a device that measures the...

Automated segmentation of cardiac visceral fat in low-dose non-contrast chest CT images

NASA Astrophysics Data System (ADS)

Xie, Yiting; Liang, Mingzhu; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

2015-03-01

Cardiac visceral fat was segmented from low-dose non-contrast chest CT images using a fully automated method. Cardiac visceral fat is defined as the fatty tissues surrounding the heart region, enclosed by the lungs and posterior to the sternum. It is measured by constraining the heart region with an Anatomy Label Map that contains robust segmentations of the lungs and other major organs and estimating the fatty tissue within this region. The algorithm was evaluated on 124 low-dose and 223 standard-dose non-contrast chest CT scans from two public datasets. Based on visual inspection, 343 cases had good cardiac visceral fat segmentation. For quantitative evaluation, manual markings of cardiac visceral fat regions were made in 3 image slices for 45 low-dose scans and the Dice similarity coefficient (DSC) was computed. The automated algorithm achieved an average DSC of 0.93. Cardiac visceral fat volume (CVFV), heart region volume (HRV) and their ratio were computed for each case. The correlation between cardiac visceral fat measurement and coronary artery and aortic calcification was also evaluated. Results indicated the automated algorithm for measuring cardiac visceral fat volume may be an alternative method to the traditional manual assessment of thoracic region fat content in the assessment of cardiovascular disease risk.

The heart, macrocirculation and microcirculation in hypertension: a unifying hypothesis.

PubMed

Struijker Boudier, Harry A J; Cohuet, Géraldine M S; Baumann, Marcus; Safar, Michel E

2003-06-01

Epidemiological studies in the past decade have stressed the importance of both pulse pressure and mean arterial pressure (MAP) as important risk factors in hypertension-related cardiovascular disease. Pulse pressure and MAP are determined by different segments of the cardiovascular system. Pulse pressure is the pulsatile component of the blood pressure curve. It is determined by left ventricular ejection, the cushioning capacity (compliance) of the large arteries, and the timing and intensity of wave reflections from the microcirculation. MAP is the steady component; it is determined by cardiac output and peripheral (micro)vascular resistance. To a large degree, the structural design of the heart and vascular tree determine the pulse pressure and MAP, in addition to the propagation of the pressure wave through the vasculature. Pressure and flow, in contrast, influence the composition and geometry of the heart and vasculature. Hypertensive disease is associated with important structural alterations of the heart, such as hypertrophy and fibrosis, and of the vasculature, such as large artery stiffening, small artery remodelling and microvascular rarefaction. Recent basic research has revealed some of the molecular pathways involved in the remodelling of the cardiovascular system under the influence of physical forces. For correct understanding of the pathophysiology of hypertensive disease, its risks for target-organ damage and its effective treatment, both the pulsatile and steady components of the blood pressure curve must be considered.

A statistical model of false negative and false positive detection of phase singularities.

PubMed

Jacquemet, Vincent

2017-10-01

The complexity of cardiac fibrillation dynamics can be assessed by analyzing the distribution of phase singularities (PSs) observed using mapping systems. Interelectrode distance, however, limits the accuracy of PS detection. To investigate in a theoretical framework the PS false negative and false positive rates in relation to the characteristics of the mapping system and fibrillation dynamics, we propose a statistical model of phase maps with controllable number and locations of PSs. In this model, phase maps are generated from randomly distributed PSs with physiologically-plausible directions of rotation. Noise and distortion of the phase are added. PSs are detected using topological charge contour integrals on regular grids of varying resolutions. Over 100 × 10 6 realizations of the random field process are used to estimate average false negative and false positive rates using a Monte-Carlo approach. The false detection rates are shown to depend on the average distance between neighboring PSs expressed in units of interelectrode distance, following approximately a power law with exponents in the range of 1.14 to 2 for false negatives and around 2.8 for false positives. In the presence of noise or distortion of phase, false detection rates at high resolution tend to a non-zero noise-dependent lower bound. This model provides an easy-to-implement tool for benchmarking PS detection algorithms over a broad range of configurations with multiple PSs.

CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy.

PubMed

Huang, Zhan-Peng; Young Seok, Hee; Zhou, Bin; Chen, Jinghai; Chen, Jian-Fu; Tao, Yazhong; Pu, William T; Wang, Da-Zhi

2012-03-16

Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure and volume overload in the heart cause increased size (hypertrophic growth) of cardiomyocytes. Whereas the regulatory pathways that activate cardiac hypertrophy have been well-established, the molecular events that inhibit or repress cardiac hypertrophy are less known. To identify and investigate novel regulators that modulate cardiac hypertrophy. Here, we report the identification, characterization, and functional examination of a novel cardiac Isl1-interacting protein (CIP). CIP was identified from a bioinformatic search for novel cardiac-expressed genes in mouse embryonic hearts. CIP encodes a nuclear protein without recognizable motifs. Northern blotting, in situ hybridization, and reporter gene tracing demonstrated that CIP is highly expressed in cardiomyocytes of developing and adult hearts. Yeast two-hybrid screening identified Isl1, a LIM/homeodomain transcription factor essential for the specification of cardiac progenitor cells in the second heart field, as a cofactor of CIP. CIP directly interacted with Isl1, and we mapped the domains of these two proteins, which mediate their interaction. We show that CIP represses the transcriptional activity of Isl1 in the activation of the myocyte enhancer factor 2C. The expression of CIP was dramatically reduced in hypertrophic cardiomyocytes. Most importantly, overexpression of CIP repressed agonist-induced cardiomyocyte hypertrophy. Our studies therefore identify CIP as a novel regulator of cardiac hypertrophy.

Photoacoustic characterization of radiofrequency ablation lesions

NASA Astrophysics Data System (ADS)

Bouchard, Richard; Dana, Nicholas; Di Biase, Luigi; Natale, Andrea; Emelianov, Stanislav

2012-02-01

Radiofrequency ablation (RFA) procedures are used to destroy abnormal electrical pathways in the heart that can cause cardiac arrhythmias. Current methods relying on fluoroscopy, echocardiography and electrical conduction mapping are unable to accurately assess ablation lesion size. In an effort to better visualize RFA lesions, photoacoustic (PA) and ultrasonic (US) imaging were utilized to obtain co-registered images of ablated porcine cardiac tissue. The left ventricular free wall of fresh (i.e., never frozen) porcine hearts was harvested within 24 hours of the animals' sacrifice. A THERMOCOOLR Ablation System (Biosense Webster, Inc.) operating at 40 W for 30-60 s was used to induce lesions through the endocardial and epicardial walls of the cardiac samples. Following lesion creation, the ablated tissue samples were placed in 25 °C saline to allow for multi-wavelength PA imaging. Samples were imaged with a VevoR 2100 ultrasound system (VisualSonics, Inc.) using a modified 20-MHz array that could provide laser irradiation to the sample from a pulsed tunable laser (Newport Corp.) to allow for co-registered photoacoustic-ultrasound (PAUS) imaging. PA imaging was conducted from 750-1064 nm, with a surface fluence of approximately 15 mJ/cm2 maintained during imaging. In this preliminary study with PA imaging, the ablated region could be well visualized on the surface of the sample, with contrasts of 6-10 dB achieved at 750 nm. Although imaging penetration depth is a concern, PA imaging shows promise in being able to reliably visualize RF ablation lesions.

Mapping Genetic Variants Associated with Beta-Adrenergic Responses in Inbred Mice

PubMed Central

Hersch, Micha; Peter, Bastian; Kang, Hyun Min; Schüpfer, Fanny; Abriel, Hugues; Pedrazzini, Thierry; Eskin, Eleazar; Beckmann, Jacques S.

2012-01-01

β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS) addressing the values and susceptibility of cardiovascular-related traits to a selective β 1-blocker, Atenolol (ate), and a β-agonist, Isoproterenol (iso). The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA), a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG) values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP) to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10−8). An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10−6). Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD). Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied. PMID:22859963

Influence of menopause status and age on integrated central and peripheral hemodynamic responses to subsystolic cuffing during submaximal exercise

PubMed Central

Gramm, Courtney; Randall, Nicholas R.; Olson, Thomas P.

2016-01-01

Although pathophysiological links between postmenopause and healthy aging remain unclear, both factors are associated with increased blood pressure and sympathetic nerve activity (SNA) in women. Activation of polymodal musculoskeletal neural afferents originating within adventia of venules modulates SNA and blood pressure control during exercise in healthy adults. We hypothesized transient subsystolic regional circulatory occlusion (RCO) during exercise sensitizes these afferents leading to augmented systemic vascular resistance (SVR)-mediated increased mean arterial pressure (MAP) in postmenopause vs. premenopause. Normotensive women in premenopause or postmenopause (n = 14 and 14; ages: 30 ± 9 and 55 ± 7 yr, respectively; P < 0.01) performed: 1) peak exercise testing and 2) fixed-load cycling at 30% peak workload (48 ± 11 and 38 ± 6 W, respectively; P < 0.01), whereby the initial 3 min were control exercise without RCO (CTL), thereafter including 2 min of bilateral-thigh RCO to 20, 40, 60, 80, or 100 mmHg (randomized), with 2 min deflation between RCO. Both MAP (17 ± 4 vs. 4 ± 4%, P = 0.02) and SVR (16 ± 8 vs. −3 ± 8%, P = 0.04) increased at 80 mmHg from CTL in postmenopause vs. premenopause, respectively. However, cardiac index was similar in postmenopause vs. premenopause at 80 mmHg from CTL (1 ± 6 vs. 7 ± 6%, respectively; P = 0.15). There was no continuous effect of aging in MAP (P = 0.12), SVR (P = 0.07), or cardiac index (P = 0.18) models. These data suggest transient locomotor subsystolic RCO sensitizes musculoskeletal afferents, which provoke increased SVR to generate augmented MAP during exercise in postmenopause. These observations provide a novel approach for understanding the age-independent variability in exercise blood pressure control across the normotensive adult pre- to postmenopause spectrum. PMID:27765745

Influence of menopause status and age on integrated central and peripheral hemodynamic responses to subsystolic cuffing during submaximal exercise.

PubMed

Van Iterson, Erik H; Gramm, Courtney; Randall, Nicholas R; Olson, Thomas P

2016-12-01

Although pathophysiological links between postmenopause and healthy aging remain unclear, both factors are associated with increased blood pressure and sympathetic nerve activity (SNA) in women. Activation of polymodal musculoskeletal neural afferents originating within adventia of venules modulates SNA and blood pressure control during exercise in healthy adults. We hypothesized transient subsystolic regional circulatory occlusion (RCO) during exercise sensitizes these afferents leading to augmented systemic vascular resistance (SVR)-mediated increased mean arterial pressure (MAP) in postmenopause vs. premenopause. Normotensive women in premenopause or postmenopause (n = 14 and 14; ages: 30 ± 9 and 55 ± 7 yr, respectively; P < 0.01) performed: 1) peak exercise testing and 2) fixed-load cycling at 30% peak workload (48 ± 11 and 38 ± 6 W, respectively; P < 0.01), whereby the initial 3 min were control exercise without RCO (CTL), thereafter including 2 min of bilateral-thigh RCO to 20, 40, 60, 80, or 100 mmHg (randomized), with 2 min deflation between RCO. Both MAP (17 ± 4 vs. 4 ± 4%, P = 0.02) and SVR (16 ± 8 vs. -3 ± 8%, P = 0.04) increased at 80 mmHg from CTL in postmenopause vs. premenopause, respectively. However, cardiac index was similar in postmenopause vs. premenopause at 80 mmHg from CTL (1 ± 6 vs. 7 ± 6%, respectively; P = 0.15). There was no continuous effect of aging in MAP (P = 0.12), SVR (P = 0.07), or cardiac index (P = 0.18) models. These data suggest transient locomotor subsystolic RCO sensitizes musculoskeletal afferents, which provoke increased SVR to generate augmented MAP during exercise in postmenopause. These observations provide a novel approach for understanding the age-independent variability in exercise blood pressure control across the normotensive adult pre- to postmenopause spectrum. Copyright © 2016 the American Physiological Society.

Differential control over postganglionic neurons in rat cardiac ganglia by NA and DmnX neurons: anatomical evidence.

PubMed

Cheng, Zixi; Zhang, Hong; Guo, Shang Z; Wurster, Robert; Gozal, David

2004-04-01

In previous single-labeling experiments, we showed that neurons in the nucleus ambiguous (NA) and the dorsal moto nucleus of the vagus (DmnX) project to intrinsic cardiac ganglia. Neurons in these two motor nuclei differ significantly in the size of their projection fields, axon caliber, and endings in cardiac ganglia. These differences in NA and DmnX axon cardiac projections raise the question as to whether they target the same, distinct, or overlapping populations of cardiac principal neurons. To address this issue, we examined vagal terminals in cardiac ganglia and trace injection sites in the brain stem using two different anterograde t ace s 1,1-dioleyl-3,3,3,3-tetramethylindocarbocyanine methanesulfonate and 4-[4-(dihexadecylamino)-styryl]-N-methylpyridinium iodide] and confocal microscopy in male Sprague-Dawley rats. We found that 1) NA and DmnX neurons innervate the same cardiac ganglia, but these axons target separate subpopulations of principal neurons and 2) axons arising from neurons in the NA and DmnX in the contralateral sides of the brain stem enter the cardiac ganglionic plexus through separate bundles and preferentially innervate principal neurons near their entry regions, providing topographic mapping of vagal motor neurons in left and right brain stem vagal nuclei. Because the NA and DmnX project to distinct populations of cardiac principal neurons, we propose that they may play different roles in controlling cardiac function.

Proximity to Pediatric Cardiac Surgical Care among Adolescents with Congenital Heart Defects in 11 New York Counties.

PubMed

Sommerhalter, Kristin M; Insaf, Tabassum Z; Akkaya-Hocagil, Tugba; McGarry, Claire E; Farr, Sherry L; Downing, Karrie F; Lui, George K; Zaidi, Ali N; Van Zutphen, Alissa R

2017-11-01

Many individuals with congenital heart defects (CHDs) discontinue cardiac care in adolescence, putting them at risk of adverse health outcomes. Because geographic barriers may contribute to cessation of care, we sought to characterize geographic access to comprehensive cardiac care among adolescents with CHDs. Using a population-based, 11-county surveillance system of CHDs in New York, we characterized proximity to the nearest pediatric cardiac surgical care center among adolescents aged 11 to 19 years with CHDs. Residential addresses were extracted from surveillance records documenting 2008 to 2010 healthcare encounters. Addresses were geocoded using ArcGIS and the New York State Street and Address Maintenance Program, a statewide address point database. One-way drive and public transit time from residence to nearest center were calculated using R packages gmapsdistance and rgeos with the Google Maps Distance Matrix application programming interface. A marginal model was constructed to identify predictors associated with one-way travel time. We identified 2522 adolescents with 3058 corresponding residential addresses and 12 pediatric cardiac surgical care centers. The median drive time from residence to nearest center was 18.3 min, and drive time was 30 min or less for 2475 (80.9%) addresses. Predicted drive time was longest for rural western addresses in high poverty census tracts (68.7 min). Public transit was available for most residences in urban areas but for few in rural areas. We identified areas with geographic barriers to surgical care. Future research is needed to determine how these barriers influence continuity of care among adolescents with CHDs. Birth Defects Research 109:1494-1503, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

In-vitro mapping of E-fields induced near pacemaker leads by simulated MR gradient fields

PubMed Central

2009-01-01

Background Magnetic resonance imaging (MRI) of patients with implanted cardiac pacemakers is generally contraindicated but some clinicians condone scanning certain patients. We assessed the risk of inducing unintended cardiac stimulation by measuring electric fields (E) induced near lead tips by a simulated MRI gradient system. The objectives of this study are to map magnetically induced E near distal tips of leads in a saline tank to determine the spatial distribution and magnitude of E and compare them with E induced by a pacemaker pulse generator (PG). Methods We mapped magnetically induced E with 0.1 mm resolution as close as 1 mm from lead tips. We used probes with two straight electrodes (e.g. wire diameter of 0.2 mm separated by 0.9 mm). We generated magnetic flux density (B) with a Helmholtz coil throughout 0.6% saline in a 24 cm diameter tank with (dB/dt) of 1 T/sec (1 kHz sinusoidal waveform). Separately, we measured E near the tip of leads when connected to a PG set to a unipolar mode. Measurements were non-invasive (not altering the leads or PG under study). Results When scaled to 30 T/s (a clinically relevant value), magnetically-induced E exceeded the E produced by a PG. The magnetically-induced E only occurred when B was coincident with or within 15 msec of implantable pacemaker's pulse. Conclusions Potentially hazardous situations are possible during an MR scan due to gradient fields. Unintended stimulation can be induced via abandoned leads and leads connected to a pulse generator with loss of hermetic seal at the connector. Also, pacemaker-dependent patients can receive drastically altered pacing pulses. PMID:20003479

The hemodynamic effects of methylene blue when administered at the onset of cardiopulmonary bypass.

PubMed

Maslow, Andrew D; Stearns, Gary; Butala, Parag; Batula, Parag; Schwartz, Carl S; Gough, Jeffrey; Singh, Arun K

2006-07-01

Hypotension occurs during cardiopulmonary bypass (CPB), in part because of induction of the inflammatory response, for which nitric oxide and guanylate cyclase play a central role. In this study we examined the hemodynamic effects of methylene blue (MB), an inhibitor of guanylate cyclase, administered during cardiopulmonary bypass (CPB) to patients taking angiotensin-converting enzyme inhibitors. Thirty patients undergoing cardiac surgery were randomized to receive either MB (3 mg/kg) or saline (S) after institution of CPB and cardioplegic arrest. CPB was managed similarly for all study patients. Hemodynamic data were assessed before, during, and after CPB. The use of vasopressors was recorded. All study patients experienced a similar reduction in mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) with the onset of CPB and cardioplegic arrest. MB increased MAP and SVR and this effect lasted for 40 minutes. The saline group demonstrated a persistently reduced MAP and SVR throughout CPB. The saline group received phenylephrine more frequently during CPB, and more norepinephrine after CPB to maintain a desirable MAP. The MB group recorded significantly lower serum lactate levels despite equal or greater MAP and SVR. In conclusion, administration of MB after institution of CPB for patients taking angiotensin-converting enzyme inhibitors increased MAP and SVR and reduced the need for vasopressors. Furthermore, serum lactate levels were lower in MB patients, suggesting more favorable tissue perfusion.

Minimal invasive epicardial lead implantation: optimizing cardiac resynchronization with a new mapping device for epicardial lead placement.

PubMed

Maessen, J G; Phelps, B; Dekker, A L A J; Dijkman, B

2004-05-01

To optimize resynchronization in biventricular pacing with epicardial leads, mapping to determine the best pacing site, is a prerequisite. A port access surgical mapping technique was developed that allowed multiple pace site selection and reproducible lead evaluation and implantation. Pressure-volume loops analysis was used for real time guidance in targeting epicardial lead placement. Even the smallest changes in lead position revealed significantly different functional results. Optimizing the pacing site with this technique allowed functional improvement up to 40% versus random pace site selection.

A priori motion models for four-dimensional reconstruction in gated cardiac SPECT

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

Lalush, D.S.; Tsui, B.M.W.; Cui, Lin

1996-12-31

We investigate the benefit of incorporating a priori assumptions about cardiac motion in a fully four-dimensional (4D) reconstruction algorithm for gated cardiac SPECT. Previous work has shown that non-motion-specific 4D Gibbs priors enforcing smoothing in time and space can control noise while preserving resolution. In this paper, we evaluate methods for incorporating known heart motion in the Gibbs prior model. The new model is derived by assigning motion vectors to each 4D voxel, defining the movement of that volume of activity into the neighboring time frames. Weights for the Gibbs cliques are computed based on these {open_quotes}most likely{close_quotes} motion vectors.more » To evaluate, we employ the mathematical cardiac-torso (MCAT) phantom with a new dynamic heart model that simulates the beating and twisting motion of the heart. Sixteen realistically-simulated gated datasets were generated, with noise simulated to emulate a real Tl-201 gated SPECT study. Reconstructions were performed using several different reconstruction algorithms, all modeling nonuniform attenuation and three-dimensional detector response. These include ML-EM with 4D filtering, 4D MAP-EM without prior motion assumption, and 4D MAP-EM with prior motion assumptions. The prior motion assumptions included both the correct motion model and incorrect models. Results show that reconstructions using the 4D prior model can smooth noise and preserve time-domain resolution more effectively than 4D linear filters. We conclude that modeling of motion in 4D reconstruction algorithms can be a powerful tool for smoothing noise and preserving temporal resolution in gated cardiac studies.« less

Carotid baroreflex responsiveness in heat-stressed humans

NASA Technical Reports Server (NTRS)

Crandall, C. G.

2000-01-01

The effects of whole body heating on human baroreflex function are relatively unknown. The purpose of this project was to identify whether whole body heating reduces the maximal slope of the carotid baroreflex. In 12 subjects, carotid-vasomotor and carotid-cardiac baroreflex responsiveness were assessed in normothermia and during whole body heating. Whole body heating increased sublingual temperature (from 36.4 +/- 0.1 to 37.4 +/- 0.1 degrees C, P < 0.01) and increased heart rate (from 59 +/- 3 to 83 +/- 3 beats/min, P < 0. 01), whereas mean arterial blood pressure (MAP) was slightly decreased (from 88 +/- 2 to 83 +/- 2 mmHg, P < 0.01). Carotid-vasomotor and carotid-cardiac responsiveness were assessed by identifying the maximal gain of MAP and heart rate to R wave-triggered changes in carotid sinus transmural pressure. Whole body heating significantly decreased the responsiveness of the carotid-vasomotor baroreflex (from -0.20 +/- 0.02 to -0.13 +/- 0.02 mmHg/mmHg, P < 0.01) without altering the responsiveness of the carotid-cardiac baroreflex (from -0.40 +/- 0.05 to -0.36 +/- 0.02 beats x min(-1) x mmHg(-1), P = 0.21). Carotid-vasomotor and carotid-cardiac baroreflex curves were shifted downward and upward, respectively, to accommodate the decrease in blood pressure and increase in heart rate that accompanied the heat stress. Moreover, the operating point of the carotid-cardiac baroreflex was shifted closer to threshold (P = 0.02) by the heat stress. Reduced carotid-vasomotor baroreflex responsiveness, coupled with a reduction in the functional reserve for the carotid baroreflex to increase heart rate during a hypotensive challenge, may contribute to increased susceptibility to orthostatic intolerance during a heat stress.

Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

PubMed

Pierce, G L; Harris, S A; Seals, D R; Casey, D P; Barlow, P B; Stauss, H M

2016-09-01

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±s.e.=-5.76±2.01, P=0.01) was the strongest predictor of BRS (model R(2)=0.59, P<0.001). The 8-week-exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=-0.65, P=0.044, adjusted for changes in MAP). Age- and endurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

Estimated Aortic Stiffness is Independently Associated with Cardiac Baroreflex Sensitivity in Humans: Role of Aging and Habitual Endurance Exercise

PubMed Central

Pierce, Gary L.; Harris, Stephen A.; Seals, Douglas R.; Casey, Darren P.; Barlow, Patrick B.; Stauss, Harald M.

2016-01-01

We hypothesized that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease (CVD) risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary; n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique) and estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±SE = −5.76 ± 2.01, P=0.01) was the strongest predictor of BRS (Model R2=0.59, P<0.001). The 8 week exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=−0.65, P=0.044, adjusted for changes in MAP). Age- and endurance exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise. PMID:26911535

SPECT Analysis of Cardiac Perfusion Changes After Whole-Breast/Chest Wall Radiation Therapy With or Without Active Breathing Coordinator: Results of a Randomized Phase 3 Trial

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

Zellars, Richard, E-mail: zellari@jhmi.edu; Bravo, Paco E.; Tryggestad, Erik

2014-03-15

Purpose: Cardiac muscle perfusion, as determined by single-photon emission computed tomography (SPECT), decreases after breast and/or chest wall (BCW) irradiation. The active breathing coordinator (ABC) enables radiation delivery when the BCW is farther from the heart, thereby decreasing cardiac exposure. We hypothesized that ABC would prevent radiation-induced cardiac toxicity and conducted a randomized controlled trial evaluating myocardial perfusion changes after radiation for left-sided breast cancer with or without ABC. Methods and Materials: Stages I to III left breast cancer patients requiring adjuvant radiation therapy (XRT) were randomized to ABC or No-ABC. Myocardial perfusion was evaluated by SPECT scans (before andmore » 6 months after BCW radiation) using 2 methods: (1) fully automated quantitative polar mapping; and (2) semiquantitative visual assessment. The left ventricle was divided into 20 segments for the polar map and 17 segments for the visual method. Segments were grouped by anatomical rings (apical, mid, basal) or by coronary artery distribution. For the visual method, 2 nuclear medicine physicians, blinded to treatment groups, scored each segment's perfusion. Scores were analyzed with nonparametric tests and linear regression. Results: Between 2006 and 2010, 57 patients were enrolled and 43 were available for analysis. The cohorts were well matched. The apical and left anterior descending coronary artery segments had significant decreases in perfusion on SPECT scans in both ABC and No-ABC cohorts. In unadjusted and adjusted analyses, controlling for pretreatment perfusion score, age, and chemotherapy, ABC was not significantly associated with prevention of perfusion deficits. Conclusions: In this randomized controlled trial, ABC does not appear to prevent radiation-induced cardiac perfusion deficits.« less

Biomechanics Simulations Using Cubic Hermite Meshes with Extraordinary Nodes for Isogeometric Cardiac Modeling

PubMed Central

Gonzales, Matthew J.; Sturgeon, Gregory; Segars, W. Paul; McCulloch, Andrew D.

2016-01-01

Cubic Hermite hexahedral finite element meshes have some well-known advantages over linear tetrahedral finite element meshes in biomechanical and anatomic modeling using isogeometric analysis. These include faster convergence rates as well as the ability to easily model rule-based anatomic features such as cardiac fiber directions. However, it is not possible to create closed complex objects with only regular nodes; these objects require the presence of extraordinary nodes (nodes with 3 or >= 5 adjacent elements in 2D) in the mesh. The presence of extraordinary nodes requires new constraints on the derivatives of adjacent elements to maintain continuity. We have developed a new method that uses an ensemble coordinate frame at the nodes and a local-to-global mapping to maintain continuity. In this paper, we make use of this mapping to create cubic Hermite models of the human ventricles and a four-chamber heart. We also extend the methods to the finite element equations to perform biomechanics simulations using these meshes. The new methods are validated using simple test models and applied to anatomically accurate ventricular meshes with valve annuli to simulate complete cardiac cycle simulations. PMID:27182096

Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis

PubMed Central

Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A.; Banypersad, Sanjay M.; Maestrini, Viviana; Barcella, William; Rosmini, Stefania; Bulluck, Heerajnarain; Sayed, Rabya H.; Patel, Ketna; Mamhood, Shameem; Bucciarelli-Ducci, Chiara; Whelan, Carol J.; Herrey, Anna S.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Manisty, Charlotte H.; Schelbert, Eric B.; Kellman, Peter; Gillmore, Julian D.; Hawkins, Philip N.

2015-01-01

Background— The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Methods and Results— Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1–13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3–13.1; P<0.05). Conclusions— There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors. PMID:26362631

Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis.

PubMed

Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A; Banypersad, Sanjay M; Maestrini, Viviana; Barcella, William; Rosmini, Stefania; Bulluck, Heerajnarain; Sayed, Rabya H; Patel, Ketna; Mamhood, Shameem; Bucciarelli-Ducci, Chiara; Whelan, Carol J; Herrey, Anna S; Lachmann, Helen J; Wechalekar, Ashutosh D; Manisty, Charlotte H; Schelbert, Eric B; Kellman, Peter; Gillmore, Julian D; Hawkins, Philip N; Moon, James C

2015-10-20

The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors. © 2015 The Authors.

Anatomical Basis for the Cardiac Interventional Electrophysiologist

PubMed Central

Sánchez-Quintana, Damián; Doblado-Calatrava, Manuel; Cabrera, José Angel; Macías, Yolanda; Saremi, Farhood

2015-01-01

The establishment of radiofrequency catheter ablation techniques as the mainstay in the treatment of tachycardia has renewed new interest in cardiac anatomy. The interventional arrhythmologist has drawn attention not only to the gross anatomic details of the heart but also to architectural and histological characteristics of various cardiac regions that are relevant to the development or recurrence of tachyarrhythmias and procedural related complications of catheter ablation. In this review, therefore, we discuss some anatomic landmarks commonly used in catheter ablations including the terminal crest, sinus node region, Koch's triangle, cavotricuspid isthmus, Eustachian ridge and valve, pulmonary venous orifices, venoatrial junctions, and ventricular outflow tracts. We also discuss the anatomical features of important structures in the vicinity of the atria and pulmonary veins, such as the esophagus and phrenic nerves. This paper provides basic anatomic information to improve understanding of the mapping and ablative procedures for cardiac interventional electrophysiologists. PMID:26665006

Presence and stability of rotors in atrial fibrillation: evidence and therapeutic implications

PubMed Central

Guillem, María S.; Climent, Andreu M.; Rodrigo, Miguel; Fernández-Avilés, Francisco; Atienza, Felipe; Berenfeld, Omer

2016-01-01

Rotor-guided ablation has opened new perspectives into the therapy of atrial fibrillation (AF). Analysis of the spatio-temporal cardiac excitation patterns in the frequency and phase domains has demonstrated the importance of rotors in research models of AF, however, the dynamics and role of rotors in human AF are still controversial. In this review, the current knowledge gained through research models and patient data that support the notion that rotors are key players in AF maintenance is summarized. We report and discuss discrepancies regarding rotor prevalence and stability in various studies, which can be attributed in part to methodological differences among mapping systems. Future research for validation and improvement of current clinical electrophysiology mapping technologies will be crucial for developing mechanistic-based selection and application of the best therapeutic strategy for individual AF patient, being it, pharmaceutical, ablative, or other approach. PMID:26786157

Substrate stiffness-modulated registry phase correlations in cardiomyocytes map structural order to coherent beating

NASA Astrophysics Data System (ADS)

Dasbiswas, K.; Majkut, S.; Discher, D. E.; Safran, Samuel A.

2015-01-01

Recent experiments show that both striation, an indication of the structural registry in muscle fibres, as well as the contractile strains produced by beating cardiac muscle cells can be optimized by substrate stiffness. Here we show theoretically how the substrate rigidity dependence of the registry data can be mapped onto that of the strain measurements. We express the elasticity-mediated structural registry as a phase-order parameter using a statistical physics approach that takes the noise and disorder inherent in biological systems into account. By assuming that structurally registered myofibrils also tend to beat in phase, we explain the observed dependence of both striation and strain measurements of cardiomyocytes on substrate stiffness in a unified manner. The agreement of our ideas with experiment suggests that the correlated beating of heart cells may be limited by the structural order of the myofibrils, which in turn is regulated by their elastic environment.

Echo-Planar Imaging: Magnetic Resonance Imaging in a Fraction of a Second

NASA Astrophysics Data System (ADS)

Stehling, Michael K.; Turner, Robert; Mansfield, Peter

1991-10-01

Progress has recently been made in implementing magnetic resonance imaging (MRI) techniques that can be used to obtain images in a fraction of a second rather than in minutes. Echo-planar imaging (EPI) uses only one nuclear spin excitation per image and lends itself to a variety of critical medical and scientific applications. Among these are evaluation of cardiac function in real time, mapping of water diffusion and temperature in tissue, mapping of organ blood pool and perfusion, functional imaging of the central nervous system, depiction of blood and cerebrospinal fluid flow dynamics, and movie imaging of the mobile fetus in utero. Through shortened patient examination times, higher patient throughput, and lower cost per MRI examination, EPI may become a powerful tool for early diagnosis of some common and potentially treatable diseases such as ischemic heart disease, stroke, and cancer.

Spatiotemporal control to eliminate cardiac alternans using isostable reduction

NASA Astrophysics Data System (ADS)

Wilson, Dan; Moehlis, Jeff

2017-03-01

Cardiac alternans, an arrhythmia characterized by a beat-to-beat alternation of cardiac action potential durations, is widely believed to facilitate the transition from normal cardiac function to ventricular fibrillation and sudden cardiac death. Alternans arises due to an instability of a healthy period-1 rhythm, and most dynamical control strategies either require extensive knowledge of the cardiac system, making experimental validation difficult, or are model independent and sacrifice important information about the specific system under study. Isostable reduction provides an alternative approach, in which the response of a system to external perturbations can be used to reduce the complexity of a cardiac system, making it easier to work with from an analytical perspective while retaining many of its important features. Here, we use isostable reduction strategies to reduce the complexity of partial differential equation models of cardiac systems in order to develop energy optimal strategies for the elimination of alternans. Resulting control strategies require significantly less energy to terminate alternans than comparable strategies and do not require continuous state feedback.

A new algorithm for segmentation of cardiac quiescent phases and cardiac time intervals using seismocardiography

NASA Astrophysics Data System (ADS)

Jafari Tadi, Mojtaba; Koivisto, Tero; Pänkäälä, Mikko; Paasio, Ari; Knuutila, Timo; Teräs, Mika; Hänninen, Pekka

2015-03-01

Systolic time intervals (STI) have significant diagnostic values for a clinical assessment of the left ventricle in adults. This study was conducted to explore the feasibility of using seismocardiography (SCG) to measure the systolic timings of the cardiac cycle accurately. An algorithm was developed for the automatic localization of the cardiac events (e.g. the opening and closing moments of the aortic and mitral valves). Synchronously acquired SCG and electrocardiography (ECG) enabled an accurate beat to beat estimation of the electromechanical systole (QS2), pre-ejection period (PEP) index and left ventricular ejection time (LVET) index. The performance of the algorithm was evaluated on a healthy test group with no evidence of cardiovascular disease (CVD). STI values were corrected based on Weissler's regression method in order to assess the correlation between the heart rate and STIs. One can see from the results that STIs correlate poorly with the heart rate (HR) on this test group. An algorithm was developed to visualize the quiescent phases of the cardiac cycle. A color map displaying the magnitude of SCG accelerations for multiple heartbeats visualizes the average cardiac motions and thereby helps to identify quiescent phases. High correlation between the heart rate and the duration of the cardiac quiescent phases was observed.

Role of Oxygen Free Radicals, Nitric Oxide and Mitochondria in Mediating Cardiac Alterations During Liver Cirrhosis Induced by Thioacetamide.

PubMed

Amirtharaj, G Jayakumar; Natarajan, Sathish Kumar; Pulimood, Anna; Balasubramanian, K A; Venkatraman, Aparna; Ramachandran, Anup

2017-04-01

Thioacetamide (TAA) administration is widely used for induction of liver cirrhosis in rats, where reactive oxygen radicals (ROS) and nitric oxide (NO) participate in development of liver damage. Cardiac dysfunction is an important complication of liver cirrhosis, but the role of ROS or NO in cardiac abnormalities during liver cirrhosis is not well understood. This was investigated in animals after TAA-induced liver cirrhosis and temporal changes in oxidative stress, NO and mitochondrial function in the heart evaluated. TAA induced elevation in cardiac levels of nitrate before development of frank liver cirrhosis, without gross histological alterations. This was accompanied by an early induction of P38 MAP kinase, which is influenced by ROS and plays an important signaling role for induction of iNOS. Increased nitrotyrosine, protein oxidation and lipid peroxidation in the heart and cardiac mitochondria, suggestive of oxidative stress, also preceded frank liver cirrhosis. However, compromised cardiac mitochondrial function with a decrease in respiratory control ratio and increased mitochondrial swelling was seen later, when cirrhosis was evident. In conclusion, TAA induces elevations in ROS and NO in the heart in parallel to early liver damage. This leads to later development of functional deficits in cardiac mitochondria after development of liver cirrhosis.

Comparison between manual and mechanical chest compressions during resuscitation in a pediatric animal model of asphyxial cardiac arrest

PubMed Central

Fernández, Sarah N.; González, Rafael; Solana, María J.; Urbano, Javier; Toledo, Blanca

2017-01-01

Aims Chest compressions (CC) during cardiopulmonary resuscitation are not sufficiently effective in many circumstances. Mechanical CC could be more effective than manual CC, but there are no studies comparing both techniques in children. The objective of this study was to compare the effectiveness of manual and mechanical chest compressions with Thumper device in a pediatric cardiac arrest animal model. Material and methods An experimental model of asphyxial cardiac arrest (CA) in 50 piglets (mean weight 9.6 kg) was used. Animals were randomized to receive either manual CC or mechanical CC using a pediatric piston chest compressions device (Life-Stat®, Michigan Instruments). Mean arterial pressure (MAP), arterial blood gases and end-tidal CO2 (etCO2) values were measured at 3, 9, 18 and 24 minutes after the beginning of resuscitation. Results There were no significant differences in MAP, DAP, arterial blood gases and etCO2 between chest compression techniques during CPR. Survival rate was higher in the manual CC (15 of 30 = 50%) than in the mechanical CC group (3 of 20 = 15%) p = 0.016. In the mechanical CC group there was a non significant higher incidence of haemorrhage through the endotracheal tube (45% vs 20%, p = 0.114). Conclusions In a pediatric animal model of cardiac arrest, mechanical piston chest compressions produced lower survival rates than manual chest compressions, without any differences in hemodynamic and respiratory parameters. PMID:29190801

Slow Pathway Radiofrequency Ablation Using Magnetic Navigation: A Description of Technique and Retrospective Case Analysis.

PubMed

Bhaskaran, Abhishek; Albarri, Maha; Ross, Neil; Al Raisi, Sara; Samanta, Rahul; Roode, Leonette; Nadri, Fazlur; Ng, Jeanette; Thomas, Stuart; Thiagalingam, Aravinda; Kovoor, Pramesh

2017-12-01

The Magnetic Navigation System (MNS) catheter was shown to be stable in the presence of significant cardiac wall motion and delivered more effective lesions compared to manual control. This stability could potentially make AV junctional re-entrant tachycardia (AVNRT) ablation safer. The aim of this study is to describe the method of mapping and ablation of AVNRT with MNS and 3-D electro-anatomical mapping system (CARTO, Biosense Webster, Diamond bar, CA, USA) anatomical mapping, with a view to improve the safety of ablation. The method of precise mapping and ablation with MNS is described. Consecutive AVNRT cases (n=30) from 2012 January to 2015 November, in which magnetic navigation was used, are analysed. Ablation was successful in 27 (90%) out of 30 patients. In three cases, ablation was abandoned due to the proximity of the three-dimensional His image to the potential ablation site. No complications, including AV nodal injury, occurred. The distance from the nearest His position to successful ablation site in both LAO and RAO projections of CARTO images was 26.4±8.8 and 27±7.7mm respectively. Only in two (9%) patients, ablation needed to be extended superior to the plane of coronary sinus ostium, towards the His bundle region, to achieve slow pathway modification. AVNRT ablation with MNS allows for accurate mapping of the AV node and stable ablation at a safe distance, which could help avoid AV nodal injury. We recommend this modality for younger patients with AVNRT. Copyright © 2017. Published by Elsevier B.V.

CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy

PubMed Central

Huang, Zhan-Peng; Seok, Hee Young; Zhou, Bin; Chen, Jinghai; Chen, Jian-Fu; Tao, Yazhong; Pu, William T.; Wang, Da-Zhi

2012-01-01

Rationale Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure and volume overload in the heart cause increased size (hypertrophic growth) of cardiomyocytes. Whereas the regulatory pathways that activate cardiac hypertrophy have been well established, the molecular events that inhibit or repress cardiac hypertrophy are less known. Objective To identify and investigate novel regulators that modulate cardiac hypertrophy. Methods and Results Here, we report the identification, characterization and functional examination of CIP, a novel cardiac Isl1-interacting protein. CIP was identified from a bioinformatic search for novel cardiac-expressed genes in mouse embryonic hearts. CIP encodes a nuclear protein without recognizable motifs. Northern blotting, in situ hybridization and reporter gene tracing demonstrated that CIP is highly expressed in cardiomyocytes of developing and adult hearts. Yeast-two-hybrid screening identified Isl1, a LIM/homeodomain transcription factor essential for the specification of cardiac progenitor cells in the second heart field, as a co-factor of CIP. CIP directly interacted with Isl1 and we mapped the domains of these two proteins which mediate their interaction. We show that CIP represses the transcriptional activity of Isl1 in the activation of the MEF2C enhancer. The expression of CIP was dramatically reduced in hypertrophic cardiomyocytes. Most importantly, overexpression of CIP repressed agonist-induced cardiomyocyte hypertrophy. Conclusions Our studies therefore identify CIP a novel regulator of cardiac hypertrophy. PMID:22343712

Association between increased epicardial adipose tissue volume and coronary plaque composition.

PubMed

Yamashita, Kennosuke; Yamamoto, Myong Hwa; Ebara, Seitarou; Okabe, Toshitaka; Saito, Shigeo; Hoshimoto, Koichi; Yakushiji, Tadayuki; Isomura, Naoei; Araki, Hiroshi; Obara, Chiaki; Ochiai, Masahiko

2014-09-01

To assess the relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in significant coronary stenosis using a 40-MHz intravascular ultrasound (IVUS) imaging system (iMap-IVUS), we analyzed 130 consecutive patients with coronary stenosis who underwent dual-source computed tomography (CT) and cardiac catheterization. Culprit lesions were imaged by iMap-IVUS before stenting. The iMAP-IVUS system classified coronary plaque components as fibrous, lipid, necrotic, or calcified tissue, based on the radiofrequency spectrum. Epicardial adipose tissue was measured as the tissue ranging from -190 to -30 Hounsfield units. EATV, calculated as the sum of the fat areas on short-axis images, was 85.0 ± 34.0 cm(3). There was a positive correlation between EATV and the percentage of necrotic plaque tissue (R (2) = 0.34, P < 0.01), while there was a negative correlation between EATV and the percentage of fibrous tissue (R (2) = 0.24, P < 0.01). Multivariate analysis revealed that an increased low-density lipoprotein cholesterol level (β = 0.15, P = 0.03) and EATV (β = 0.14, P = 0.02) were independently associated with the percentage of necrotic plaque tissue. An increase in EATV was associated with the development of coronary atherosclerosis and, potentially, with the most dangerous type of plaque.

Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

PubMed

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

Microprocessor-controlled hemodynamics: a step towards improved efficiency and safety.

PubMed

Keogh, B E; Jacobs, J; Royston, D; Taylor, K M

1989-02-01

Manual titration of sodium nitroprusside (SNP) is widely used for treatment of hypertension following cardiac surgery. This study compared conventional manual control with control by a research prototype of an automatic infusion module based on a proportional plus integral plus derivative (PID) negative feedback loop. Two groups of coronary artery bypass patients requiring SNP for postoperative hypertension were studied prospectively. In the first group, hypertension was controlled by manual adjustment of the SNP infusion rate, and in the second, the infusion rate was controlled automatically. The actual and desired mean arterial pressures (MAP) over consecutive ten-second epochs were recorded during the period of infusion. The MAP was maintained within 10% of the desired MAP 45.8% of the time in the manual group, compared with 90.0% in the automatic group, and the mean percent error in the automatic group was significantly less than in the manual group (P less than 0.01). It is concluded that adoption of such systems will result in improved patient safety and may facilitate more effective distribution of nursing staff within intensive care units.

Brain perfusion evaluated by regional tissue oxygenation as a possible quality indicator of ongoing cardiopulmonary resuscitation. An experimental porcine cardiac arrest study.

PubMed

Bouček, Tomáš; Mlček, Mikuláš; Krupičková, Petra; Huptych, Michal; Belza, Tomáš; Kittnar, Otomar; Linhart, Aleš; Bělohlávek, Jan

2018-05-01

Relationship between regional tissue oxygenation (rSO 2 ) and microcirculatory changes during cardiac arrest (CA) are still unclear. Therefore, we designed an experimental study to correlate rSO 2 , microcirculation and systemic hemodynamic parameters in a porcine model of CA. Ventricular fibrillation was induced in 24 female pigs (50±3kg) and left for three minutes untreated followed by five minutes of mechanical CPR. Regional and peripheral saturations were assessed by near-infrared spectroscopy, sublingual microcirculation by Sidestream Dark Field technology and continuous hemodynamic parameters, including systemic blood pressure (MAP) and carotid blood flow (CF), during baseline, CA and CPR periods. The Wilcoxon Signed-Rank test, the Friedman test and the partial correlation method were used to compare these parameters. Brain and peripheral rSO 2 showed a gradual decrease during CA and only an increase of brain rSO 2 during mechanical CPR (34.5 to 42.5; p=0.0001), reflected by a rapid decrease of microcirculatory and hemodynamic parameters during CA and a slight increase during CPR. Peripheral rSO 2 was not changed significantly during CPR (38 to 38.5; p=0.09). We only found a moderate correlation of cerebral/peripheral rSO 2 to microcirculatory parameters (PVD: r=0.53/0.46; PPV: r=0.6/0.5 and MFI: r=0.64/0.52) and hemodynamic parameters (MAP: r=0.64/0.71 and CF: 0.71/0.67). Our experimental study confirmed that monitoring brain and peripheral rSO 2 is an easy-to-use method, well reflecting the hemodynamics during CA. However, only brain rSO 2 reflects the CPR efforts and might be used as a potential quality indicator for CPR.

Functional, Anatomical, and Molecular Investigation of the Cardiac Conduction System and Arrhythmogenic Atrioventricular Ring Tissue in the Rat Heart

PubMed Central

Atkinson, Andrew J.; Logantha, Sunil Jit R. J.; Hao, Guoliang; Yanni, Joseph; Fedorenko, Olga; Sinha, Aditi; Gilbert, Stephen H.; Benson, Alan P.; Buckley, David L.; Anderson, Robert H.; Boyett, Mark R.; Dobrzynski, Halina

2013-01-01

Background The cardiac conduction system consists of the sinus node, nodal extensions, atrioventricular (AV) node, penetrating bundle, bundle branches, and Purkinje fibers. Node‐like AV ring tissue also exists at the AV junctions, and the right and left rings unite at the retroaortic node. The study aims were to (1) construct a 3‐dimensional anatomical model of the AV rings and retroaortic node, (2) map electrical activation in the right ring and study its action potential characteristics, and (3) examine gene expression in the right ring and retroaortic node. Methods and Results Three‐dimensional reconstruction (based on magnetic resonance imaging, histology, and immunohistochemistry) showed the extent and organization of the specialized tissues (eg, how the AV rings form the right and left nodal extensions into the AV node). Multiextracellular electrode array and microelectrode mapping of isolated right ring preparations revealed robust spontaneous activity with characteristic diastolic depolarization. Using laser microdissection gene expression measured at the mRNA level (using quantitative PCR) and protein level (using immunohistochemistry and Western blotting) showed that the right ring and retroaortic node, like the sinus node and AV node but, unlike ventricular muscle, had statistically significant higher expression of key transcription factors (including Tbx3, Msx2, and Id2) and ion channels (including HCN4, Cav3.1, Cav3.2, Kv1.5, SK1, Kir3.1, and Kir3.4) and lower expression of other key ion channels (Nav1.5 and Kir2.1). Conclusions The AV rings and retroaortic node possess gene expression profiles similar to that of the AV node. Ion channel expression and electrophysiological recordings show the AV rings could act as ectopic pacemakers and a source of atrial tachycardia. PMID:24356527

Cardiac perioperative complications in noncardiac surgery.

PubMed

Radovanović, Dragana; Kolak, Radmila; Stokić, Aleksandar; Radovanović, Zoran; Jovanović, Gordana

2008-01-01

Anesthesiologists are confronted with an increasing population of patients undergoing noncardiac surgery who are at risk for cardiac complications in the perioperative period. Perioperative cardiac complications are responsible for significant mortality and morbidity. The aim of the present study was to determine the incidence of perioperative (operative and postoperative) cardiac complications and correlations between the incidence of perioperative cardiac complications and type of surgical procedure, age, presence of concurrent deseases. A total of 100 patients with cardiac diseases undergoing noncardiac surgery were included in the prospective study (Group A 50 patients undergoing intraperitoneal surgery and Group B 50 patients undergoing breast and thyroid surgery). The patients were followed up during the perioperative period and after surgery until leaving hospital to assess the occurrence of cardiac events. Cardiac complications (systemic arterial hypertension, systemic arterial hypotension, abnormalities of cardiac conduction and cardiac rhythm, perioperative myocardial ischemia and acute myocardial infarction) occurred in 64% of the patients. One of the 100 patients (1%) had postoperative myocardial infarction which was fatal. Systemic arterial hypertension occured in 57% of patients intraoperatively and 33% postoperatively, abnormalities of cardiac rhythm in 31% of patients intraoperatively and 17% postoperatively, perioperative myocardial ischemia in 23% of patients intraoperatively and 11% of postoperatively. The most often cardiac complications were systemic arterial hypertension, abnormalities of cardiac rhythm and perioperative mvocardial ischemia. Factors independently associated with the incidence of cardiac complications included the type of surgical procedure, advanced age, duration of anaesthesia and surgery, abnormal preoperative electrocardiogram, abnormal preoperative chest radiography and diabetes.

Cardiac surgery during pregnancy: continuous fetal monitoring using umbilical artery Doppler flow velocity indices.

PubMed

Mishra, Manisha; Sawhney, Ravindra; Kumar, Anil; Bapna, Kumar Ramesh; Kohli, Vijay; Wasir, Harpreet; Trehan, Naresh

2014-01-01

The fetal death rate associated with cardiac surgery with cardiopulmonary bypass (CPB) is as high as 9.5-29%. We report continuous monitoring of fetal heart rate and umbilical artery flow-velocity waveforms by transvaginal ultrasonography and their analyses in relation to events of the CPB in two cases in second trimester of pregnancy undergoing mitral valve replacement. Our findings suggest that the transition of circulation from corporeal to extracorporeal is the most important event during surgery; the associated decrease in mean arterial pressure (MAP) at this stage potentially has deleterious effects on the fetus, which get aggravated with the use of vasopressors. We suggest careful management of CPB at this stage, which include partial controlled CPB at initiation and gradual transition to full CPB; this strategy maintains high MAP and avoids the use of vasopressors. Maternal and fetal monitoring can timely recognize the potential problems and provide window for the required treatment.

Single-sensor system for spatially resolved, continuous, and multiparametric optical mapping of cardiac tissue

PubMed Central

Lee, Peter; Bollensdorff, Christian; Quinn, T. Alexander; Wuskell, Joseph P.; Loew, Leslie M.; Kohl, Peter

2011-01-01

Background Simultaneous optical mapping of multiple electrophysiologically relevant parameters in living myocardium is desirable for integrative exploration of mechanisms underlying heart rhythm generation under normal and pathophysiologic conditions. Current multiparametric methods are technically challenging, usually involving multiple sensors and moving parts, which contributes to high logistic and economic thresholds that prevent easy application of the technique. Objective The purpose of this study was to develop a simple, affordable, and effective method for spatially resolved, continuous, simultaneous, and multiparametric optical mapping of the heart, using a single camera. Methods We present a new method to simultaneously monitor multiple parameters using inexpensive off-the-shelf electronic components and no moving parts. The system comprises a single camera, commercially available optical filters, and light-emitting diodes (LEDs), integrated via microcontroller-based electronics for frame-accurate illumination of the tissue. For proof of principle, we illustrate measurement of four parameters, suitable for ratiometric mapping of membrane potential (di-4-ANBDQPQ) and intracellular free calcium (fura-2), in an isolated Langendorff-perfused rat heart during sinus rhythm and ectopy, induced by local electrical or mechanical stimulation. Results The pilot application demonstrates suitability of this imaging approach for heart rhythm research in the isolated heart. In addition, locally induced excitation, whether stimulated electrically or mechanically, gives rise to similar ventricular propagation patterns. Conclusion Combining an affordable camera with suitable optical filters and microprocessor-controlled LEDs, single-sensor multiparametric optical mapping can be practically implemented in a simple yet powerful configuration and applied to heart rhythm research. The moderate system complexity and component cost is destined to lower the threshold to broader application of functional imaging and to ease implementation of more complex optical mapping approaches, such as multiparametric panoramic imaging. A proof-of-principle application confirmed that although electrically and mechanically induced excitation occur by different mechanisms, their electrophysiologic consequences downstream from the point of activation are not dissimilar. PMID:21459161

MO-DE-207A-06: ECG-Gated CT Reconstruction for a C-Arm Inverse Geometry X-Ray System

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

Slagowski, JM; Dunkerley, DAP

2016-06-15

Purpose: To obtain ECG-gated CT images from truncated projection data acquired with a C-arm based inverse geometry fluoroscopy system, for the purpose of cardiac chamber mapping in interventional procedures. Methods: Scanning-beam digital x-ray (SBDX) is an inverse geometry fluoroscopy system with a scanned multisource x-ray tube and a photon-counting detector mounted to a C-arm. In the proposed method, SBDX short-scan rotational acquisition is performed followed by inverse geometry CT (IGCT) reconstruction and segmentation of contrast-enhanced objects. The prior image constrained compressed sensing (PICCS) framework was adapted for IGCT reconstruction to mitigate artifacts arising from data truncation and angular undersampling duemore » to cardiac gating. The performance of the reconstruction algorithm was evaluated in numerical simulations of truncated and non-truncated thorax phantoms containing a dynamic ellipsoid to represent a moving cardiac chamber. The eccentricity of the ellipsoid was varied at frequencies from 1–1.5 Hz. Projection data were retrospectively sorted into 13 cardiac phases. Each phase was reconstructed using IGCT-PICCS, with a nongated gridded FBP (gFBP) prior image. Surface accuracy was determined using Dice similarity coefficient and a histogram of the point distances between the segmented surface and ground truth surface. Results: The gated IGCT-PICCS algorithm improved surface accuracy and reduced streaking and truncation artifacts when compared to nongated gFBP. For the non-truncated thorax with 1.25 Hz motion, 99% of segmented surface points were within 0.3 mm of the 15 mm diameter ground truth ellipse, versus 1.0 mm for gFBP. For the truncated thorax phantom with a 40 mm diameter ellipse, IGCT-PICCS surface accuracy measured 0.3 mm versus 7.8 mm for gFBP. Dice similarity coefficient was 0.99–1.00 (IGCT-PICCS) versus 0.63–0.75 (gFBP) for intensity-based segmentation thresholds ranging from 25–75% maximum contrast. Conclusions: The PICCS algorithm was successfully applied to reconstruct truncated IGCT projection data with angular undersampling resulting from simulated cardiac gating. Research supported by the National Heart, Lung, and Blood Institute of the NIH under award number R01HL084022. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.« less

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

PubMed Central

KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

2008-01-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism. PMID:9277473

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

PubMed

Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

1997-08-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

A Clinical Feasibility Study of Atrial and Ventricular Electromechanical Wave Imaging

PubMed Central

Provost, Jean; Gambhir, Alok; Vest, John; Garan, Hasan; Konofagou, Elisa E.

2014-01-01

Background Cardiac Resynchronization Therapy (CRT) and atrial ablation currently lack a noninvasive imaging modality for reliable treatment planning and monitoring. Electromechanical Wave Imaging (EWI) is an ultrasound-based method that has previously been shown to be capable of noninvasively and transmurally mapping the activation sequence of the heart in animal studies by estimating and imaging the electromechanical wave, i.e., the transient strains occurring in response to the electrical activation, at both very high temporal and spatial resolution. Objective Demonstrate the feasibility of noninvasive transthoracic EWI for mapping the activation sequence during different cardiac rhythms in humans. Methods EWI was performed in CRT patients with a left bundle-branch block (LBBB), during sinus rhythm, left-ventricular pacing, and right-ventricular pacing and in atrial flutter (AFL) patients before intervention and correlated with results from invasive intracardiac electrical mapping studies during intervention. Additionally, the feasibility of single-heartbeat EWI at 2000 frames/s, is demonstrated in humans for the first time in a subject with both AFL and right bundle-branch-block. Results The electromechanical activation maps demonstrated the capability of EWI to localize the pacing sites and characterize the LBBB activation sequence transmurally in CRT patients. In AFL patients, the propagation patterns obtained with EWI were in agreement with results obtained from invasive intracardiac mapping studies. Conclusion Our findings demonstrate the potential capability of EWI to aid in monitoring and follow-up of patients undergoing CRT pacing therapy and atrial ablation with preliminary validation in vivo. PMID:23454060

Voltage-Sensitive Fluorescence of Indocyanine Green in the Heart

PubMed Central

Martišienė, Irma; Mačianskienė, Regina; Treinys, Rimantas; Navalinskas, Antanas; Almanaitytė, Mantė; Karčiauskas, Dainius; Kučinskas, Audrius; Grigalevičiūtė, Ramunė; Zigmantaitė, Vilma; Benetis, Rimantas; Jurevičius, Jonas

2016-01-01

So far, the optical mapping of cardiac electrical signals using voltage-sensitive fluorescent dyes has only been performed in experimental studies because these dyes are not yet approved for clinical use. It was recently reported that the well-known and widely used fluorescent dye indocyanine green (ICG), which has FDA approval, exhibits voltage sensitivity in various tissues, thus raising hopes that electrical activity could be optically mapped in the clinic. The aim of this study was to explore the possibility of using ICG to monitor cardiac electrical activity. Optical mapping experiments were performed on Langendorff rabbit hearts stained with ICG and perfused with electromechanical uncouplers. The residual contraction force and electrical action potentials were recorded simultaneously. Our research confirms that ICG is a voltage-sensitive dye with a dual-component (fast and slow) response to membrane potential changes. The fast component of the optical signal (OS) can have opposite polarities in different parts of the fluorescence spectrum. In contrast, the polarity of the slow component remains the same throughout the entire spectrum. Separating the OS into these components revealed two different voltage-sensitivity mechanisms for ICG. The fast component of the OS appears to be electrochromic in nature, whereas the slow component may arise from the redistribution of the dye molecules within or around the membrane. Both components quite accurately track the time of electrical signal propagation, but only the fast component is suitable for estimating the shape and duration of action potentials. Because ICG has voltage-sensitive properties in the entire heart, we suggest that it can be used to monitor cardiac electrical behavior in the clinic. PMID:26840736

Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

PubMed Central

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

2008-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

Quantitative Analysis of Electro-Anatomical Maps: Application to an Experimental Model of Left Bundle Branch Block/Cardiac Resynchronization Therapy

PubMed Central

Duchateau, Nicolas; Kostantyn Butakov, Constantine Butakoff; Andreu, David; Fernández-Armenta, Juan; Bijnens, Bart; Berruezo, Antonio; Sitges, Marta; Camara, Oscar

2017-01-01

Electro-anatomical maps (EAMs) are commonly acquired in clinical routine for guiding ablation therapies. They provide voltage and activation time information on a 3-D anatomical mesh representation, making them useful for analyzing the electrical activation patterns in specific pathologies. However, the variability between the different acquisitions and anatomies hampers the comparison between different maps. This paper presents two contributions for the analysis of electrical patterns in EAM data from biventricular surfaces of cardiac chambers. The first contribution is an integrated automatic 2-D disk representation (2-D bull’s eye plot) of the left ventricle (LV) and right ventricle (RV) obtained with a quasi-conformal mapping from the 3-D EAM meshes, that allows an analysis of cardiac resynchronization therapy (CRT) lead positioning, interpretation of global (total activation time), and local indices (local activation time (LAT), surrogates of conduction velocity, inter-ventricular, and transmural delays) that characterize changes in the electrical activation pattern. The second contribution is a set of indices derived from the electrical activation: speed maps, computed from LAT values, to study the electrical wave propagation, and histograms of isochrones to analyze regional electrical heterogeneities in the ventricles. We have applied the proposed methods to look for the underlying physiological mechanisms of left bundle branch block (LBBB) and CRT, with the goal of optimizing the therapy by improving CRT response. To better illustrate the benefits of the proposed tools, we created a set of synthetically generated and fully controlled activation patterns, where the proposed representation and indices were validated. Then, the proposed analysis tools are used to analyze EAM data from an experimental swine model of induced LBBB with an implanted CRT device. We have analyzed and compared the electrical activation patterns at baseline, LBBB, and CRT stages in four animals: two without any structural disease and two with an induced infarction. By relating the CRT lead location with electrical dyssynchrony, we evaluated current hypotheses about lead placement in CRT and showed that optimal pacing sites should target the RV lead close to the apex and the LV one distant from it. PMID:29164019

Comparison of yoga and walking-exercise on cardiac time intervals as a measure of cardiac function in elderly with increased pulse pressure.

PubMed

Patil, Satish Gurunathrao; Patil, Shankargouda S; Aithala, Manjunatha R; Das, Kusal Kanti

Arterial aging along with increased blood pressure(BP) has become the major cardiovascular(CV) risk in elderly. The aim of the study was to compare the effects of yoga program and walking-exercise on cardiac function in elderly with increased pulse pressure (PP). An open label, parallel-group randomized controlled study design was adopted. Elderly individuals aged ≥60 years with PP≥60mmHg were recruited for the study. Yoga (study) group (n=30) was assigned for yoga training and walking (exercise) group (n=30) for walking with loosening practices for one hour in the morning for 6days in a week for 3 months. The outcome measures were cardiac time intervals derived from pulse wave analysis and ECG: resting heart rate (RHR), diastolic time(DT), ventricular ejection time(LVET), upstroke time(UT), ejection duration index (ED%), pre-ejection period (PEP), rate pressure product (RPP) and percentage of mean arterial pressure (%MAP). The mean within-yoga group change in RHR(bpm) was 4.41 (p=0.031), PD(ms): -50.29 (p=0.042), DT(ms): -49.04 (p=0.017), ED%: 2.107 (p=0.001), ES(mmHg/ms): 14.62 (p=0.118), ET(ms): -0.66 (p=0.903), UT(ms): -2.54 (p=0.676), PEP(ms): -1.25 (p=0.11) and %MAP: 2.08 (p=0.04). The mean within-control group change in HR (bpm) was 0.35 (p=0.887), PD (ms): 11.15(p=0.717), DT (ms): 11.3 (p=0.706), ED%: -0.101 (p=0.936), ES (mmHg/ms): 0.75 (p=0.926), ET(ms): 2.2 (p=0.721), UT(ms):4.7(p=455), PEP (ms): 2.1(p=0.11), %MAP: 0.65 (p=0.451). A significant difference between-group was found in RHR (p=0.036), PD (p=0.02), ED% (p=0.049), LVET (p=0.048), DT (p=0.02) and RPP (p=0.001). Yoga practice for 3 months showed a significant improvement in diastolic function with a minimal change in systolic function. Yoga is more effective than walking in improving cardiac function in elderly with high PP. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Cardiac conduction system

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... cardiac muscle cells in the walls of the heart that send signals to the heart muscle causing it to contract. The main components ... the cardiac conduction system's electrical activity in the heart.

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure

PubMed Central

Rosa-Garrido, Manuel; Chapski, Douglas J.; Schmitt, Anthony D.; Kimball, Todd H.; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J.; Ren, Shuxun; Wang, Yibin; Ren, Bing

2017-01-01

Background: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. Methods: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload–induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Results: Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. Conclusions: These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. PMID:28802249

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

PubMed

Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M

2017-10-24

Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.

Myocardial ischaemia and the cardiac nervous system.

PubMed

Armour, J A

1999-01-01

The intrinsic cardiac nervous system has been classically considered to contain only parasympathetic efferent postganglionic neurones which receive inputs from medullary parasympathetic efferent preganglionic neurones. In such a view, intrinsic cardiac ganglia act as simple relay stations of parasympathetic efferent neuronal input to the heart, the major autonomic control of the heart purported to reside solely in the brainstem and spinal cord. Data collected over the past two decades indicate that processing occurs within the mammalian intrinsic cardiac nervous system which involves afferent neurones, local circuit neurones (interconnecting neurones) as well as both sympathetic and parasympathetic efferent postganglionic neurones. As such, intrinsic cardiac ganglionic interactions represent the organ component of the hierarchy of intrathoracic nested feedback control loops which provide rapid and appropriate reflex coordination of efferent autonomic neuronal outflow to the heart. In such a concept, the intrinsic cardiac nervous system acts as a distributive processor, integrating parasympathetic and sympathetic efferent centrifugal information to the heart in addition to centripetal information arising from cardiac sensory neurites. A number of neurochemicals have been shown to influence the interneuronal interactions which occur within the intrathoracic cardiac nervous system. For instance, pharmacological interventions that modify beta-adrenergic or angiotensin II receptors affect cardiomyocyte function not only directly, but indirectly by influencing the capacity of intrathoracic neurones to regulate cardiomyocytes. Thus, current pharmacological management of heart disease may influence cardiomyocyte function directly as well as indirectly secondary to modifying the cardiac nervous system. This review presents a brief summary of developing concepts about the role of the cardiac nervous system in regulating the normal heart. In addition, it provides some tentative ideas concerning the importance of this nervous system in cardiac disease states with a view to stimulating further interest in neural control of the heart so that appropriate neurocardiological strategies can be devised for the management of heart disease.

Transcriptional atlas of cardiogenesis maps congenital heart disease interactome.

PubMed

Li, Xing; Martinez-Fernandez, Almudena; Hartjes, Katherine A; Kocher, Jean-Pierre A; Olson, Timothy M; Terzic, Andre; Nelson, Timothy J

2014-07-01

Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, knowledge of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Mapping the dynamic transcriptional landscape of cardiogenesis from a genomic perspective is essential to integrate the knowledge of heart development into translational applications that accelerate disease discovery efforts toward mechanistic-based treatment strategies. Herein, we designed a time-course transcriptome analysis to investigate the genome-wide dynamic expression landscape of innate murine cardiogenesis ranging from embryonic stem cells to adult cardiac structures. This comprehensive analysis generated temporal and spatial expression profiles, revealed stage-specific gene functions, and mapped the dynamic transcriptome of cardiogenesis to curated pathways. Reconciling known genetic underpinnings of CHD, we deconstructed a disease-centric dynamic interactome encoded within this cardiogenic atlas to identify stage-specific developmental disturbances clustered on regulation of epithelial-to-mesenchymal transition (EMT), BMP signaling, NF-AT signaling, TGFb-dependent EMT, and Notch signaling. Collectively, this cardiogenic transcriptional landscape defines the time-dependent expression of cardiac ontogeny and prioritizes regulatory networks at the interface between health and disease. Copyright © 2014 the American Physiological Society.

Haploinsufficiency of TAB2 Causes Congenital Heart Defects in Humans

PubMed Central

Thienpont, Bernard; Zhang, Litu; Postma, Alex V.; Breckpot, Jeroen; Tranchevent, Léon-Charles; Van Loo, Peter; Møllgård, Kjeld; Tommerup, Niels; Bache, Iben; Tümer, Zeynep; van Engelen, Klaartje; Menten, Björn; Mortier, Geert; Waggoner, Darrel; Gewillig, Marc; Moreau, Yves; Devriendt, Koen; Larsen, Lars Allan

2010-01-01

Congenital heart defects (CHDs) are the most common major developmental anomalies and the most frequent cause for perinatal mortality, but their etiology remains often obscure. We identified a locus for CHDs on 6q24-q25. Genotype-phenotype correlations in 12 patients carrying a chromosomal deletion on 6q delineated a critical 850 kb region on 6q25.1 harboring five genes. Bioinformatics prioritization of candidate genes in this locus for a role in CHDs identified the TGF-β-activated kinase 1/MAP3K7 binding protein 2 gene (TAB2) as the top-ranking candidate gene. A role for this candidate gene in cardiac development was further supported by its conserved expression in the developing human and zebrafish heart. Moreover, a critical, dosage-sensitive role during development was demonstrated by the cardiac defects observed upon titrated knockdown of tab2 expression in zebrafish embryos. To definitively confirm the role of this candidate gene in CHDs, we performed mutation analysis of TAB2 in 402 patients with a CHD, which revealed two evolutionarily conserved missense mutations. Finally, a balanced translocation was identified, cosegregating with familial CHD. Mapping of the breakpoints demonstrated that this translocation disrupts TAB2. Taken together, these data clearly demonstrate a role for TAB2 in human cardiac development. PMID:20493459

ENU mutagenesis identifies mice with cardiac fibrosis and hepatic steatosis caused by a mutation in the mitochondrial trifunctional protein beta-subunit.

PubMed

Kao, Hsiao-Jung; Cheng, Ching-Feng; Chen, Yen-Hui; Hung, Shuen-Iu; Huang, Cheng-Chih; Millington, David; Kikuchi, Tateki; Wu, Jer-Yuarn; Chen, Yuan-Tsong

2006-12-15

Using the metabolomics-guided screening coupled to N-ethyl-N-nitrosourea-mediated mutagenesis, we identified mice that exhibited elevated levels of long-chain acylcarnitines. Whole genome homozygosity mapping with 262 SNP markers mapped the disease gene to chromosome 5 where candidate genes Hadha and Hadhb, encoding the mitochondria trifunctional protein (MTP) alpha- and beta-subunits, respectively, are located. Direct sequencing revealed a normal alpha-subunit, but detected a nucleotide T-to-A transversion in exon 14 (c.1210T>A) of beta-subunit (Hadhb) which resulted in a missense mutation of methionine to lysine (M404K). Western blot analysis showed a significant reduction of both the alpha- and beta-subunits, consistent with reduced enzyme activity in both the long-chain 3-hydroxyacyl-CoA dehydrogenase and the long-chain 3-ketoacyl-CoA thiolase activities. These mice had a decreased weight gain and cardiac arrhythmias which manifested from a prolonged PR interval to a complete atrio-ventricular dissociation, and died suddenly between 9 and 16 months of age. Histopathological studies showed multifocal cardiac fibrosis and hepatic steatosis. This mouse model will be useful to further investigate the mechanisms underlying arrhythmogenesis relating to lipotoxic cardiomyopathy and to investigate pathophysiology and treatment strategies for human MTP deficiency.

Diagnostic and Prognostic Value of CMR T1-Mapping in Patients With Heart Failure and Preserved Ejection Fraction.

PubMed

Rommel, Karl-Philipp; Lücke, Christian; Lurz, Philipp

2017-10-01

Heart failure with preserved ejection fraction (HFpEF) presents a major challenge in modern cardiology. Although this syndrome is of increasing prevalence and is associated with unfavorable outcomes, treatment trials have failed to establish effective therapies. Currently, solutions to this dilemma are being investigated, including categorizing and characterizing patients more diversely to individualize treatment. In this regard, new imaging techniques might provide important information. Diastolic dysfunction is a diagnostic and pathophysiological cornerstone in HFpEF and is believed to be caused by systemic inflammation with the development of interstitial myocardial fibrosis and myocardial stiffening. Cardiac magnetic resonance (CMR) T 1 -mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. This review provides an overview of the potential of myocardial tissue characterization with CMR T 1 mapping in HFpEF patients, outlining its diagnostic and prognostic implications and discussing future directions. We conclude that CMR T 1 mapping is potentially an effective tool for patient characterization in large-scale epidemiological, diagnostic, and therapeutic HFpEF trials beyond traditional imaging parameters. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

New insights into differential baroreflex control of heart rate in humans

NASA Technical Reports Server (NTRS)

Fadel, P. J.; Stromstad, M.; Wray, D. W.; Smith, S. A.; Raven, P. B.; Secher, N. H.

2003-01-01

Recent data indicate that bilateral carotid sinus denervation in patients results in a chronic impairment in the rapid reflex control of blood pressure during orthostasis. These findings are inconsistent with previous human experimental investigations indicating a minimal role for the carotid baroreceptor-cardiac reflex in blood pressure control. Therefore, we reexamined arterial baroreflex [carotid (CBR) and aortic baroreflex (ABR)] control of heart rate (HR) using newly developed methodologies. In 10 healthy men, 27 +/- 1 yr old, an abrupt decrease in mean arterial pressure (MAP) was induced nonpharmacologically by releasing a unilateral arterial thigh cuff (300 Torr) after 9 min of resting leg ischemia under two conditions: 1) ABR and CBR deactivation (control) and 2) ABR deactivation. Under control conditions, cuff release decreased MAP by 13 +/- 1 mmHg, whereas HR increased 11 +/- 2 beats/min. During ABR deactivation, neck suction was gradually applied to maintain carotid sinus transmural pressure during the initial 20 s after cuff release (suction). This attenuated the increase in HR (6 +/- 1 beats/min) and caused a greater decrease in MAP (18 +/- 2 mmHg, P < 0.05). Furthermore, estimated cardiac baroreflex responsiveness (DeltaHR/DeltaMAP) was significantly reduced during suction compared with control conditions. These findings suggest that the carotid baroreceptors contribute more importantly to the reflex control of HR than previously reported in healthy individuals.

A diminished aortic-cardiac reflex during hypotension in aerobically fit young men

NASA Technical Reports Server (NTRS)

Shi, X.; Crandall, C. G.; Potts, J. T.; Williamson, J. W.; Foresman, B. H.; Raven, P. B.

1993-01-01

We compared the aortic-cardiac baroreflex sensitivity in eight average fit (AF: VO2max = 44.7 +/- 1.3 ml.kg-1 x min-1) and seven high fit (HF: VO2max = 64.1 +/- 1.7 ml.min-1 x kg-1) healthy young men during hypotension elicited by steady state sodium nitroprusside (SN) infusion. During SN mean arterial pressure (MAP) was similarly decreased in AF (-12.6 +/- 1.0 mm Hg) and HF (-12.1 +/- 1.1 mm Hg). However, the increases in heart rate (HR) were less (P < 0.023) in HF (15 +/- 3 bpm) than AF (25 +/- 1 bpm). When sustained neck suction (NS, -22 +/- 1 torr in AF and -20 +/- 1 torr in HF, P > 0.05) was applied to counteract the decreased carotid sinus transmural pressure during SN, thereby isolating the aortic baroreceptors, the increased HR remained less (P < 0.021) in HF (8 +/- 2 bpm) than AF (16 +/- 2 bpm). During both SN infusion and SN+NS, the calculated gains (i.e., delta HR/delta MAP) were significantly greater in AF (2.1 +/- 0.3 and 1.3 +/- 0.2 bpm.mm Hg-1) than HF (1.2 +/- 0.2 and 0.6 +/- 0.2 bpm.mm Hg-1). However, the estimated carotid-cardiac baroreflex sensitivity (i.e., the gain difference between the stage SN and SN + NS) was not different between AF (0.7 +/- 0.2 bpm.mm Hg-1) and HF (0.6 +/- 0.1 bpm.mm Hg-1). These data indicated that the aortic-cardiac baroreflex sensitivity during hypotension was significantly diminished with endurance exercise training.

Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males.

PubMed

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1997-12-01

Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

Rotors and the Dynamics of Cardiac Fibrillation

PubMed Central

Pandit, Sandeep V.; Jalife, José

2013-01-01

The objective of this article is to present a broad review on the role of cardiac electrical rotors and their accompanying spiral waves in the mechanism of cardiac fibrillation. At the outset, we present a brief historical overview regarding reentry, and then discuss the basic concepts and terminologies pertaining to rotors and their initiation. Thereafter, the intrinsic properties of rotors and spiral waves, including phase singularities, wavefront curvature and dominant frequency maps are discussed. The implications of rotor dynamics for the spatio-temporal organization of fibrillation, independent of the species being studied are touched upon next. The knowledge gained regarding the role of cardiac structure in the initiation and/or maintenance of rotors and the ionic bases of spiral waves in the last two decades, and its significance for drug therapy is reviewed subsequently. We conclude by looking at recent evidence suggesting that rotors are critical in sustaining both atrial and ventricular fibrillation (AF, VF) in the human heart, and its implications for treatment with radio-frequency ablation. PMID:23449547

Ischemic stroke risk reduction following cardiac surgery by carotid compression

NASA Astrophysics Data System (ADS)

Isingoma, Paul

Every year over 500,000 cardiovascular procedures requiring cardiopulmonary bypass (CPB) are performed in the United States. CPB is a technique that temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the body. During CPB, an aortic cross-clamp is used to clamp the aorta and separate the systemic circulation from the outflow of the heart. Unfortunately, these procedures have been found to cause most cerebral emboli, which produce clinical, subclinical and silent neurologic injuries. Many clinical neurologic injuries occur in the postoperative period, with over 20% of the clinical strokes occurring during this period. In this study, we focus on visualizing the flow distribution in the aortic arch, the effect of carotid compression and the influence of compression time and MAP during CPB on reducing cerebral emboli. Experiments are performed with an aortic arch model in a mock cardiovascular system. Fluorescent particles are used to simulate emboli that are released into circulation immediately after carotid compression. The LVAD is used as the pump to produce flow in the system by gradually adjusting the speed to maintain desired clinical conditions. Aortic and proximal branches MAP of 65.0 +/- 5.0 mmHg (normal MAP) or 95.0 +/- 5.0 mmHg (high MAP), aortic flow of 4.0 +/- 0.5 L/min, and all branches flow (left and right carotids, and subclavian arteries) of 10% of the aortic flow. Flow distribution of particles is visualized using LaVision's DaVis imaging software and analyzed using imagej's particle analysis tool to track, count, and record particle properties from the aortic arch. Carotid compression for 10-20 seconds reduces the number of particles entering the carotid arteries by over 73% at normal MAP, and by over 85% at high MAP. A higher MAP resulted in fewer particles entering the branching vessels both at baseline and during occlusion conditions. A compression duration of 20s does not result in greater particle reduction than one of 10s. Our results demonstrate that brief compression of the common carotid arteries during an embolic shower can reduce the number of dangerous emboli by over 85%.

Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis.

PubMed

Muehlenbachs, Atis; Bollweg, Brigid C; Schulz, Thadeus J; Forrester, Joseph D; DeLeon Carnes, Marlene; Molins, Claudia; Ray, Gregory S; Cummings, Peter M; Ritter, Jana M; Blau, Dianna M; Andrew, Thomas A; Prial, Margaret; Ng, Dianna L; Prahlow, Joseph A; Sanders, Jeanine H; Shieh, Wun Ju; Paddock, Christopher D; Schriefer, Martin E; Mead, Paul; Zaki, Sherif R

2016-05-01

Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues. Published by Elsevier Inc.

Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias

PubMed Central

Park, David S.; Cerrone, Marina; Morley, Gregory; Vasquez, Carolina; Fowler, Steven; Liu, Nian; Bernstein, Scott A.; Liu, Fang-Yu; Zhang, Jie; Rogers, Christopher S.; Priori, Silvia G.; Chinitz, Larry A.; Fishman, Glenn I.

2014-01-01

SCN5A encodes the α subunit of the major cardiac sodium channel NaV1.5. Mutations in SCN5A are associated with conduction disease and ventricular fibrillation (VF); however, the mechanisms that link loss of sodium channel function to arrhythmic instability remain unresolved. Here, we generated a large-animal model of a human cardiac sodium channelopathy in pigs, which have cardiac structure and function similar to humans, to better define the arrhythmic substrate. We introduced a nonsense mutation originally identified in a child with Brugada syndrome into the orthologous position (E558X) in the pig SCN5A gene. SCN5AE558X/+ pigs exhibited conduction abnormalities in the absence of cardiac structural defects. Sudden cardiac death was not observed in young pigs; however, Langendorff-perfused SCN5AE558X/+ hearts had an increased propensity for pacing-induced or spontaneous VF initiated by short-coupled ventricular premature beats. Optical mapping during VF showed that activity often began as an organized focal source or broad wavefront on the right ventricular (RV) free wall. Together, the results from this study demonstrate that the SCN5AE558X/+ pig model accurately phenocopies many aspects of human cardiac sodium channelopathy, including conduction slowing and increased susceptibility to ventricular arrhythmias. PMID:25500882

Quantitative evaluation of ischemic myocardial scar tissue by unenhanced T1 mapping using 3.0 Tesla MR scanner

PubMed Central

Okur, Aylin; Kantarcı, Mecit; Kızrak, Yeşim; Yıldız, Sema; Pirimoğlu, Berhan; Karaca, Leyla; Oğul, Hayri; Sevimli, Serdar

2014-01-01

PURPOSE We aimed to use a noninvasive method for quantifying T1 values of chronic myocardial infarction scar by cardiac magnetic resonance imaging (MRI), and determine its diagnostic performance. MATERIALS AND METHODS We performed cardiac MRI on 29 consecutive patients with known coronary artery disease (CAD) on 3.0 Tesla MRI scanner. An unenhanced T1 mapping technique was used to calculate T1 relaxation time of myocardial scar tissue, and its diagnostic performance was evaluated. Chronic scar tissue was identified by delayed contrast-enhancement (DE) MRI and T2-weighted images. Sensitivity, specificity, and accuracy values were calculated for T1 mapping using DE images as the gold standard. RESULTS Four hundred and forty-two segments were analyzed in 26 patients. While myocardial chronic scar was demonstrated in 45 segments on DE images, T1 mapping MRI showed a chronic scar area in 54 segments. T1 relaxation time was higher in chronic scar tissue, compared with remote areas (1314±98 ms vs. 1099±90 ms, P < 0.001). Therefore, increased T1 values were shown in areas of myocardium colocalized with areas of DE and normal signal on T2-weighted images. There was a significant correlation between T1 mapping and DE images in evaluation of myocardial wall injury extent (P < 0.05). We calculated sensitivity, specificity, and accuracy as 95.5%, 97%, and 96%, respectively. CONCLUSION The results of the present study reveal that T1 mapping MRI combined with T2-weighted images might be a feasible imaging modality for detecting chronic myocardial infarction scar tissue. PMID:25010366

High-Speed Real-Time Resting-State fMRI Using Multi-Slab Echo-Volumar Imaging

PubMed Central

Posse, Stefan; Ackley, Elena; Mutihac, Radu; Zhang, Tongsheng; Hummatov, Ruslan; Akhtari, Massoud; Chohan, Muhammad; Fisch, Bruce; Yonas, Howard

2013-01-01

We recently demonstrated that ultra-high-speed real-time fMRI using multi-slab echo-volumar imaging (MEVI) significantly increases sensitivity for mapping task-related activation and resting-state networks (RSNs) compared to echo-planar imaging (Posse et al., 2012). In the present study we characterize the sensitivity of MEVI for mapping RSN connectivity dynamics, comparing independent component analysis (ICA) and a novel seed-based connectivity analysis (SBCA) that combines sliding-window correlation analysis with meta-statistics. This SBCA approach is shown to minimize the effects of confounds, such as movement, and CSF and white matter signal changes, and enables real-time monitoring of RSN dynamics at time scales of tens of seconds. We demonstrate highly sensitive mapping of eloquent cortex in the vicinity of brain tumors and arterio-venous malformations, and detection of abnormal resting-state connectivity in epilepsy. In patients with motor impairment, resting-state fMRI provided focal localization of sensorimotor cortex compared with more diffuse activation in task-based fMRI. The fast acquisition speed of MEVI enabled segregation of cardiac-related signal pulsation using ICA, which revealed distinct regional differences in pulsation amplitude and waveform, elevated signal pulsation in patients with arterio-venous malformations and a trend toward reduced pulsatility in gray matter of patients compared with healthy controls. Mapping cardiac pulsation in cortical gray matter may carry important functional information that distinguishes healthy from diseased tissue vasculature. This novel fMRI methodology is particularly promising for mapping eloquent cortex in patients with neurological disease, having variable degree of cooperation in task-based fMRI. In conclusion, ultra-high-real-time speed fMRI enhances the sensitivity of mapping the dynamics of resting-state connectivity and cerebro-vascular pulsatility for clinical and neuroscience research applications. PMID:23986677

Regional systems of care for out-of-hospital cardiac arrest: A policy statement from the American Heart Association.

PubMed

Nichol, Graham; Aufderheide, Tom P; Eigel, Brian; Neumar, Robert W; Lurie, Keith G; Bufalino, Vincent J; Callaway, Clifton W; Menon, Venugopal; Bass, Robert R; Abella, Benjamin S; Sayre, Michael; Dougherty, Cynthia M; Racht, Edward M; Kleinman, Monica E; O'Connor, Robert E; Reilly, John P; Ossmann, Eric W; Peterson, Eric

2010-02-09

Out-of-hospital cardiac arrest continues to be an important public health problem, with large and important regional variations in outcomes. Survival rates vary widely among patients treated with out-of-hospital cardiac arrest by emergency medical services and among patients transported to the hospital after return of spontaneous circulation. Most regions lack a well-coordinated approach to post-cardiac arrest care. Effective hospital-based interventions for out-of-hospital cardiac arrest exist but are used infrequently. Barriers to implementation of these interventions include lack of knowledge, experience, personnel, resources, and infrastructure. A well-defined relationship between an increased volume of patients or procedures and better outcomes among individual providers and hospitals has been observed for several other clinical disorders. Regional systems of care have improved provider experience and patient outcomes for those with ST-elevation myocardial infarction and life-threatening traumatic injury. This statement describes the rationale for regional systems of care for patients resuscitated from cardiac arrest and the preliminary recommended elements of such systems. Many more people could potentially survive out-of-hospital cardiac arrest if regional systems of cardiac resuscitation were established. A national process is necessary to develop and implement evidence-based guidelines for such systems that must include standards for the categorization, verification, and designation of components of such systems. The time to do so is now.

9 Closed chest compressions reduce survival in a model of haemorrhage-induced traumatic cardiac arrest.

PubMed

Watts, Sarah; Smith, Jason; Gwyther, Robert; Kirkman, Emrys

2017-12-01

Closed chest compressions (CCC) are a key component of resuscitation from medical causes of cardiac arrest, but when haemorrhage, the leading cause of preventable battlefield deaths, is the likely cause there is little evidence to support their use. Resuscitation protocols for traumatic cardiac arrest (TCA) highlight the importance of addressing reversible causes, such as the administration of fluids to treat hypovolaemia. This study evaluated whether CCC were beneficial following haemorrhage-induced TCA and additionally whether resuscitation with blood improved physiological outcomes. The study was conducted with the authority of UK Animals (Scientific Procedures) Act 1986 using 39 terminally anesthetised Large White pigs (35 kg, 29-40 kg) instrumented for invasive physiological monitoring. Following instrumentation and baseline measurements, animals underwent tissue injury (captive bolt to the right thigh) and controlled haemorrhage (30% blood volume). Mean arterial blood pressure (MAP) was maintained at 45 mmHg for 60 min, followed by a further controlled haemorrhage to a MAP of 20 mmHg. As arterial blood and pulse pressures spontaneously deteriorated further over a 5 min period, the randomised resuscitation protocol was initiated as follows: CCC (n=6); IV 0.9% saline (Sal n=8); IV autologous whole blood (WB n=8); IV saline +chest compressions (Sal +CCC n=9); and IV whole blood +chest compressions (WB +CCC n=8). 3×10 ml/kg fluid boluses were administered using the Belmont Rapid Infuser (200 ml/min). CCC were performed using the LUCAS II Chest Compression System.Outcome was attainment of return of spontaneous circulation (ROSC) 15 min post-resuscitation. ROSC was categorised by MAP (MAP ≥50 mmHg=ROSC; MAP >20 <50 mmHg=partial ROSC; MAP ≤20 mmHg=dead).emermed;34/12/A866-a/F1F1F1Figure 1 RESULTS: Outcome was significantly worse in the group that received CCC compared to WB and Sal groups (6/6 dead versus 0/8 and 0/8 respectively) (p<0.0001).A significantly higher number of animals attained ROSC in WB compared to Sal group (6/8 versus 0/8 ROSC and 2/8 versus 8/8 partial ROSC respectively) (p=0.0069).There were some none significant differences between WB and WB+CCC groups (6/8 versus 5/8 ROSC, 2/8 versus 1/8 partial ROSC and 0/8 versus 2/8 dead respectively) (p=0.4411).No animals attained ROSC in the Sal and Sal+CCC groups however significantly more animals died in the Sal+CCC group (0/8 versus 0/9 ROSC, 8/8 versus 2/9 partial ROSC and 0/8 versus 7/9 dead respectively) (p=0.0023). CCC were associated with increased mortality compared to intravenous fluid resuscitation. Resuscitation with whole blood demonstrated the greatest physiological benefit as demonstrated by highest numbers of animals achieving ROSC. © 2017, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

PubMed Central

Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

2016-01-01

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials. PMID:27184924

Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

NASA Astrophysics Data System (ADS)

Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

2016-05-01

Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

Long-term biatrial recordings in post-operative atrial fibrillation.

PubMed

Masè, M; Graffigna, A; Sinelli, S; Pallaoro, G; Nollo, G; Ravelli, F

2010-01-01

Although atrial fibrillation (AF) is a common complication of cardiac surgery, its pathophysiology remains unclear. The study of post-operative AF demands for the recording of cardiac electrical activity in correspondence of AF onset and progression. Long-term recordings in post-surgery patients could provide this information, but, to date, have been limited to surface signals, which precludes a characterization of the arrhythmic triggers and substrate. In this study we demonstrate the feasibility of a continuous long-term recording of atrial electrical activities from the right and left atria in post-surgery patients. Local atrial epicardial electrograms are acquired by positioning temporary pacing wires in the right and left atria at the end of the intervention, while three day recordings are obtained by a digital holter recorder, adapted to epicardial signal features. The capability of the system to map local atrial activity and the possibility to obtain quantitative information on atrial rate and synchronization from the processed epicardial signals are proven in representative examples. The quantitative description of local atrial properties opens new perspective in the investigation of post-surgery AF.

Towards multispectral endoscopic imaging of cardiac lesion assessment and classification for cardiac ablation therapy

NASA Astrophysics Data System (ADS)

Park, Soo Young; Singh-Moon, Rajinder P.; Hendon, Christine P.

2018-02-01

Pulmonary vein (PV) isolation is a critical procedure for the treatment and termination of atrial fibrillation (AF). The success of such treatment depends on the extent of tissue damage, where partial lesions can allow abnormal electrical conduction and risk relapse of AF. Proper evaluation of lesion delivery and ablation line continuity remains challenging with current techniques and in part limit procedural efficacy. A tool for direct visualization of endo-myocardial lesions in vivo could potentially reduce ambiguity in treatment location and extent and improve the overall fidelity of lesion sets. In this work, we introduce a method for wide-field visualization of myocardial tissue including the discernment of ablated and non-ablated regions using an endoscopic multispectral imaging system (EMIS). The system was designed to fit the working channel of most commercial sheathes (<4 Fr) and supported quadruple-wavelength reflectance imaging through a flexible fiber-bundle. A total of 50 endocardial lesions were created and imaged on nine swine hearts, ex vivo in addition to 15 lesions on human LA samples near PV regions. A pixel-wise linear discriminant analysis algorithm was developed to classify regions of ablation treatment based on calibrated EMI maps. Results show good agreement of treatment severity and spatial extent compared to post-hoc tissue vital staining.

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

PubMed Central

Chiam, Elizabeth; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-01-01

Aim The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol‐containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. Methods We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml–1), i.v. mannitol (3.91 g mannitol 100 ml–1) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre‐infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Results Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre‐infusion values (MAP –1.85 mmHg, 95% CI –2.6, –1.1, SBP –0.54 mmHg, 95% CI –1.7, 0.6 and DBP −1.92 mmHg, 95% CI –2.6, –1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP –0.15 mmHg, SBP +1.44 mmHg, DBP −–0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). Conclusions I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri‐operative and critical care setting. PMID:26606263

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.

PubMed

Chiam, Elizabeth; Weinberg, Laurence; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-04-01

The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting. © 2015 The British Pharmacological Society.

Spiral waves characterization: Implications for an automated cardiodynamic tissue characterization.

PubMed

Alagoz, Celal; Cohen, Andrew R; Frisch, Daniel R; Tunç, Birkan; Phatharodom, Saran; Guez, Allon

2018-07-01

Spiral waves are phenomena observed in cardiac tissue especially during fibrillatory activities. Spiral waves are revealed through in-vivo and in-vitro studies using high density mapping that requires special experimental setup. Also, in-silico spiral wave analysis and classification is performed using membrane potentials from entire tissue. In this study, we report a characterization approach that identifies spiral wave behaviors using intracardiac electrogram (EGM) readings obtained with commonly used multipolar diagnostic catheters that perform localized but high-resolution readings. Specifically, the algorithm is designed to distinguish between stationary, meandering, and break-up rotors. The clustering and classification algorithms are tested on simulated data produced using a phenomenological 2D model of cardiac propagation. For EGM measurements, unipolar-bipolar EGM readings from various locations on tissue using two catheter types are modeled. The distance measure between spiral behaviors are assessed using normalized compression distance (NCD), an information theoretical distance. NCD is a universal metric in the sense it is solely based on compressibility of dataset and not requiring feature extraction. We also introduce normalized FFT distance (NFFTD) where compressibility is replaced with a FFT parameter. Overall, outstanding clustering performance was achieved across varying EGM reading configurations. We found that effectiveness in distinguishing was superior in case of NCD than NFFTD. We demonstrated that distinct spiral activity identification on a behaviorally heterogeneous tissue is also possible. This report demonstrates a theoretical validation of clustering and classification approaches that provide an automated mapping from EGM signals to assessment of spiral wave behaviors and hence offers a potential mapping and analysis framework for cardiac tissue wavefront propagation patterns. Copyright © 2018 Elsevier B.V. All rights reserved.

Cytoskeletal role in protection of the failing heart by β-adrenergic blockade

PubMed Central

Cheng, Guangmao; Kasiganesan, Harinath; Baicu, Catalin F.; Wallenborn, J. Grace; Kuppuswamy, Dhandapani

2012-01-01

Formation of a dense microtubule network that impedes cardiac contraction and intracellular transport occurs in severe pressure overload hypertrophy. This process is highly dynamic, since microtubule depolymerization causes striking improvement in contractile function. A molecular etiology for this cytoskeletal alteration has been defined in terms of type 1 and type 2A phosphatase-dependent site-specific dephosphorylation of the predominant myocardial microtubule-associated protein (MAP)4, which then decorates and stabilizes microtubules. This persistent phosphatase activation is dependent upon ongoing upstream activity of p21-activated kinase-1, or Pak1. Because cardiac β-adrenergic activity is markedly and continuously increased in decompensated hypertrophy, and because β-adrenergic activation of cardiac Pak1 and phosphatases has been demonstrated, we asked here whether the highly maladaptive cardiac microtubule phenotype seen in pathological hypertrophy is based on β-adrenergic overdrive and thus could be reversed by β-adrenergic blockade. The data in this study, which were designed to answer this question, show that such is the case; that is, β1- (but not β2-) adrenergic input activates this pathway, which consists of Pak1 activation, increased phosphatase activity, MAP4 dephosphorylation, and thus the stabilization of a dense microtubule network. These data were gathered in a feline model of severe right ventricular (RV) pressure overload hypertrophy in response to tight pulmonary artery banding (PAB) in which a stable, twofold increase in RV mass is reached by 2 wk after pressure overloading. After 2 wk of hypertrophy induction, these PAB cats during the following 2 wk either had no further treatment or had β-adrenergic blockade. The pathological microtubule phenotype and the severe RV cellular contractile dysfunction otherwise seen in this model of RV hypertrophy (PAB No Treatment) was reversed in the treated (PAB β-Blockade) cats. Thus these data provide both a specific etiology and a specific remedy for the abnormal microtubule network found in some forms of pathological cardiac hypertrophy. PMID:22081703

Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest.

PubMed

Elmer, Jonathan; Flickinger, Katharyn L; Anderson, Maighdlin W; Koller, Allison C; Sundermann, Matthew L; Dezfulian, Cameron; Okonkwo, David O; Shutter, Lori A; Salcido, David D; Callaway, Clifton W; Menegazzi, James J

2018-04-18

Brain tissue hypoxia may contribute to preventable secondary brain injury after cardiac arrest. We developed a porcine model of opioid overdose cardiac arrest and post-arrest care including invasive, multimodal neurological monitoring of regional brain physiology. We hypothesized brain tissue hypoxia is common with usual post-arrest care and can be prevented by modifying mean arterial pressure (MAP) and arterial oxygen concentration (PaO 2 ). We induced opioid overdose and cardiac arrest in sixteen swine, attempted resuscitation after 9 min of apnea, and randomized resuscitated animals to three alternating 6-h blocks of standard or titrated care. We invasively monitored physiological parameters including brain tissue oxygen (PbtO 2 ). During standard care blocks, we maintained MAP > 65 mmHg and oxygen saturation 94-98%. During titrated care, we targeted PbtO2 > 20 mmHg. Overall, 10 animals (63%) achieved ROSC after a median of 12.4 min (range 10.8-21.5 min). PbtO 2 was higher during titrated care than standard care blocks (unadjusted β = 0.60, 95% confidence interval (CI) 0.42-0.78, P < 0.001). In an adjusted model controlling for MAP, vasopressors, sedation, and block sequence, PbtO 2 remained higher during titrated care (adjusted β = 0.75, 95%CI 0.43-1.06, P < 0.001). At three predetermined thresholds, brain tissue hypoxia was significantly less common during titrated care blocks (44 vs 2% of the block duration spent below 20 mmHg, P < 0.001; 21 vs 0% below 15 mmHg, P < 0.001; and, 7 vs 0% below 10 mmHg, P = .01). In this model of opioid overdose cardiac arrest, brain tissue hypoxia is common and treatable. Further work will elucidate best strategies and impact of titrated care on functional outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Gene Regulatory Networks in Cardiac Conduction System Development

PubMed Central

Munshi, Nikhil V.

2014-01-01

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Given its critical role in coordinating cardiac performance, a detailed analysis of the molecular mechanisms underlying conduction system formation should inform our understanding of arrhythmia pathophysiology and affect the development of novel therapeutic strategies. Historically, the ability to distinguish cells of the conduction system from neighboring working myocytes presented a major technical challenge for performing comprehensive mechanistic studies. Early lineage tracing experiments suggested that conduction cells derive from cardiomyocyte precursors, and these claims have been substantiated by using more contemporary approaches. However, regional specialization of conduction cells adds an additional layer of complexity to this system, and it appears that different components of the conduction system utilize unique modes of developmental formation. The identification of numerous transcription factors and their downstream target genes involved in regional differentiation of the conduction system has provided insight into how lineage commitment is achieved. Furthermore, by adopting cutting-edge genetic techniques in combination with sophisticated phenotyping capabilities, investigators have made substantial progress in delineating the regulatory networks that orchestrate conduction system formation and their role in cardiac rhythm and physiology. This review describes the connectivity of these gene regulatory networks in cardiac conduction system development and discusses how they provide a foundation for understanding normal and pathological human cardiac rhythms. PMID:22628576

Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

PubMed

Al-Wakeel, Nadya; O h-Ici, Darach; Schmitt, Katharina R; Messroghli, Daniel R; Riesenkampff, Eugénie; Berger, Felix; Kuehne, Titus; Peters, Bjoern

2016-02-01

In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

Real-time magnetic resonance-guided ablation of typical right atrial flutter using a combination of active catheter tracking and passive catheter visualization in man: initial results from a consecutive patient series.

PubMed

Hilbert, Sebastian; Sommer, Philipp; Gutberlet, Matthias; Gaspar, Thomas; Foldyna, Borek; Piorkowski, Christopher; Weiss, Steffen; Lloyd, Thomas; Schnackenburg, Bernhard; Krueger, Sascha; Fleiter, Christian; Paetsch, Ingo; Jahnke, Cosima; Hindricks, Gerhard; Grothoff, Matthias

2016-04-01

Recently cardiac magnetic resonance (CMR) imaging has been found feasible for the visualization of the underlying substrate for cardiac arrhythmias as well as for the visualization of cardiac catheters for diagnostic and ablation procedures. Real-time CMR-guided cavotricuspid isthmus ablation was performed in a series of six patients using a combination of active catheter tracking and catheter visualization using real-time MR imaging. Cardiac magnetic resonance utilizing a 1.5 T system was performed in patients under deep propofol sedation. A three-dimensional-whole-heart sequence with navigator technique and a fast automated segmentation algorithm was used for online segmentation of all cardiac chambers, which were thereafter displayed on a dedicated image guidance platform. In three out of six patients complete isthmus block could be achieved in the MR scanner, two of these patients did not need any additional fluoroscopy. In the first patient technical issues called for a completion of the procedure in a conventional laboratory, in another two patients the isthmus was partially blocked by magnetic resonance imaging (MRI)-guided ablation. The mean procedural time for the MR procedure was 109 ± 58 min. The intubation of the CS was performed within a mean time of 2.75 ± 2.21 min. Total fluoroscopy time for completion of the isthmus block ranged from 0 to 7.5 min. The combination of active catheter tracking and passive real-time visualization in CMR-guided electrophysiologic (EP) studies using advanced interventional hardware and software was safe and enabled efficient navigation, mapping, and ablation. These cases demonstrate significant progress in the development of MR-guided EP procedures. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Computer simulation comparison of tripolar, bipolar, and spline Laplacian electrocadiogram estimators.

PubMed

Chen, T; Besio, W; Dai, W

2009-01-01

A comparison of the performance of the tripolar and bipolar concentric as well as spline Laplacian electrocardiograms (LECGs) and body surface Laplacian mappings (BSLMs) for localizing and imaging the cardiac electrical activation has been investigated based on computer simulation. In the simulation a simplified eccentric heart-torso sphere-cylinder homogeneous volume conductor model were developed. Multiple dipoles with different orientations were used to simulate the underlying cardiac electrical activities. Results show that the tripolar concentric ring electrodes produce the most accurate LECG and BSLM estimation among the three estimators with the best performance in spatial resolution.

Cardiac neuronal hierarchy in health and disease.

PubMed

Armour, J Andrew

2004-08-01

The cardiac neuronal hierarchy can be represented as a redundant control system made up of spatially distributed cell stations comprising afferent, efferent, and interconnecting neurons. Its peripheral and central neurons are in constant communication with one another such that, for the most part, it behaves as a stochastic control system. Neurons distributed throughout this hierarchy interconnect via specific linkages such that each neuronal cell station is involved in temporally dependent cardio-cardiac reflexes that control overlapping, spatially organized cardiac regions. Its function depends primarily, but not exclusively, on inputs arising from afferent neurons transducing the cardiovascular milieu to directly or indirectly (via interconnecting neurons) modify cardiac motor neurons coordinating regional cardiac behavior. As the function of the whole is greater than that of its individual parts, stable cardiac control occurs most of the time in the absence of direct cause and effect. During altered cardiac status, its redundancy normally represents a stabilizing feature. However, in the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change. That, along with any consequent remodeling of the cardiac neuronal hierarchy, alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.

Cardiac tamponade as an initial manifestation of systemic lupus erythematosus.

PubMed

Carrion, Diego M; Carrion, Andres F

2012-06-12

Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment.

Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases nitric oxide production in cirrhotic rats with portal hypertension and ascites.

PubMed Central

López-Talavera, J C; Levitzki, A; Martínez, M; Gazit, A; Esteban, R; Guardia, J

1997-01-01

Tumor necrosis factor-alpha (TNF) causes vasodilatation and a hyperdynamic state by activating nitric oxide (NO) synthesis. Tyrphostins, specific inhibitors of protein tyrosine kinase (PTK), block the signaling events induced by TNF and NO production. A hyperdynamic circulatory syndrome (HCS) is often observed in portal hypertension (PHT). TNF and NO seem to mediate these hemodynamic changes. The aim of this work was to study the effect of PTK inhibition on the systemic and portal hemodynamics, TNF and NO production, in cirrhotic rats with portal hypertension. Rats with liver cirrhosis induced by chronic inhalation of carbon tetrachloride were used. Animals were treated daily with tyrphostin AG 126 (alpha-cyano-(3-hydroxy-4-nitro) cinnamonitrile) or placebo for 5 d. Mean arterial pressure (MAP), heart rate (HR), and portal pressure (PP) were measured by indwelling catheters. Cardiac output (CI) and stroke volume (SV) were estimated by thermodilution, systemic vascular resistance (SVR) was calculated (MAP/CI), and portal systemic shunting (PSS) was quantitated using radioactive microspheres. Serum and mesenteric lymph node (MLN) TNF levels were measured using an immunoassay kit, and serum NOx was determined photometrically by its oxidation products. The AG 126-treated group showed a statistically significant increase in MAP and SVR, and decreases in CI, SV, MLN TNF, and serum NO oxidation products nitrite and nitrate (NOx) in comparison with the placebo-treated rats. No significant differences were noticed in HR, PP, PSS, or serum TNF. Significant correlations were observed between MAP and NOx, MAP and MLN TNF, PSS and NOx, and serum TNF and serum NOx. The HCS observed in PHT seems to be mediated, at least in part, by TNF and NO by the activation of PTKs and their signaling pathways. PTK activity inhibition ameliorates the hyperdynamic abnormalities that characterize animals with cirrhosis and PHT. PMID:9239414

T1 Mapping by Cardiac Magnetic Resonance and Multidimensional Speckle-Tracking Strain by Echocardiography for the Detection of Acute Cellular Rejection in Cardiac Allograft Recipients.

PubMed

Sade, Leyla Elif; Hazirolan, Tuncay; Kozan, Hatice; Ozdemir, Handan; Hayran, Mutlu; Eroglu, Serpil; Pirat, Bahar; Sezgin, Atilla; Muderrisoglu, Haldun

2018-04-14

The aim of this study was to test the hypothesis that echocardiographic strain imaging, by tracking subtle alterations in myocardial function, and cardiac magnetic resonance T1 mapping, by quantifying tissue properties, are useful and complement each other to detect acute cellular rejection in heart transplant recipients. Noninvasive alternatives to endomyocardial biopsy are highly desirable to monitor acute cellular rejection. Surveillance endomyocardial biopsies, catheterizations, and echocardiograms performed serially according to institutional protocol since transplantation were retrospectively reviewed. Sixteen-segment global longitudinal strain (GLS) and circumferential strain were measured before, during, and after the first rejection and at 2 time points for patients without rejection using Velocity Vector Imaging for the first part of the study. The second part, with cardiac magnetic resonance added to the protocol, served to validate previously derived strain cutoffs, examine the progression of strain over time, and to determine the accuracy of strain and T1 measurements to define acute cellular rejection. All tests were performed within 48 h. Median time to first rejection (16 grade 1 rejection, 15 grade ≥2 rejection) was 3 months (interquartile range: 3 to 36 months) in 49 patients. GLS and global circumferential strain worsened significantly during grade 1 rejection and ≥2 rejection and were independent predictors of any rejection. In the second part of the study, T1 time ≥1,090 ms, extracellular volume ≥32%, GLS >-14%, and global circumferential strain ≥-24% had 100% sensitivity and 100% negative predictive value to define grade ≥2 rejection with 70%, 63%, 55%, and 35% positive predictive values, respectively. The combination of GLS >-16% and T1 time ≥1,060 ms defined grade 1 rejection with 91% sensitivity and 92% negative predictive value. After successful treatment, T1 times decreased significantly. T1 mapping and echocardiographic GLS can serve to guide endomyocardial biopsy selectively. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Home C-ABPM for Preventive and Curative Health Care and Transdisciplinary Science

PubMed Central

Halberg, Franz; Cornélissen, Germaine; Otsuka, Kuniaki; Watanabe, Yoshihiko; Singh, Ram B.; Revilla, Miguel; de la Peña, Salvador Sanchez; Gonzalez, Clicerio; Siegelova, Jarmila; Homolka, Pavel; Dusek, Jiri; Zeman, Michal; Singh, RK; Johnson, Dana; Fiser, Bohumil

2011-01-01

The clinical everyday management of blood pressure (BP) and heart rate (HR) can be greatly improved by the mapping of time structures in home ambulatory BP and HR assessment. Thereby, we change focus from the BP and the HR to the dynamics of these variables. This change is achieved by computer-implemented chronomics, the mapping of chronomes, consisting of cyclicities (our concern herein) along with chaos and trends, in the service of cardiologists, general health care providers, the educated public, and transdisciplinary science. We here further illustrate the yield of chronomics in research on long BP and HR series covering years, some several decades long, and on archives of human sudden cardiac death revealing magnetoperiodisms, e.g., “years” longer than a calendar year, i.e., transyears. In this case of cardiac arrest, what we do not see, the 16- to 20-month transyear is prominent, in the absence of any signature of the calendar year, and so can be a cis-half-year of about 5 months. PMID:21966282

Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures

PubMed Central

Wang, Xinchen; Tucker, Nathan R; Rizki, Gizem; Mills, Robert; Krijger, Peter HL; de Wit, Elzo; Subramanian, Vidya; Bartell, Eric; Nguyen, Xinh-Xinh; Ye, Jiangchuan; Leyton-Mange, Jordan; Dolmatova, Elena V; van der Harst, Pim; de Laat, Wouter; Ellinor, Patrick T; Newton-Cheh, Christopher; Milan, David J; Kellis, Manolis; Boyer, Laurie A

2016-01-01

Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes of these sub-threshold loci, demonstrating that most sub-threshold loci have regulatory consequences and that genetic perturbation of nearby genes causes cardiac phenotypes in mouse. Our work provides a general approach for improving the detection of novel loci associated with complex human traits. DOI: http://dx.doi.org/10.7554/eLife.10557.001 PMID:27162171

Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

PubMed Central

Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

2014-01-01

Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

Patterns of gene expression associated with recovery and injury in heat-stressed rats.

PubMed

Stallings, Jonathan D; Ippolito, Danielle L; Rakesh, Vineet; Baer, Christine E; Dennis, William E; Helwig, Bryan G; Jackson, David A; Leon, Lisa R; Lewis, John A; Reifman, Jaques

2014-12-03

The in vivo gene response associated with hyperthermia is poorly understood. Here, we perform a global, multiorgan characterization of the gene response to heat stress using an in vivo conscious rat model. We heated rats until implanted thermal probes indicated a maximal core temperature of 41.8°C (Tc,Max). We then compared transcriptomic profiles of liver, lung, kidney, and heart tissues harvested from groups of experimental animals at Tc,Max, 24 hours, and 48 hours after heat stress to time-matched controls kept at an ambient temperature. Cardiac histopathology at 48 hours supported persistent cardiac injury in three out of six animals. Microarray analysis identified 78 differentially expressed genes common to all four organs at Tc,Max. Self-organizing maps identified gene-specific signatures corresponding to protein-folding disorders in heat-stressed rats with histopathological evidence of cardiac injury at 48 hours. Quantitative proteomics analysis by iTRAQ (isobaric tag for relative and absolute quantitation) demonstrated that differential protein expression most closely matched the transcriptomic profile in heat-injured animals at 48 hours. Calculation of protein supersaturation scores supported an increased propensity of proteins to aggregate for proteins that were found to be changing in abundance at 24 hours and in animals with cardiac injury at 48 hours, suggesting a mechanistic association between protein misfolding and the heat-stress response. Pathway analyses at both the transcript and protein levels supported catastrophic deficits in energetics and cellular metabolism and activation of the unfolded protein response in heat-stressed rats with histopathological evidence of persistent heat injury, providing the basis for a systems-level physiological model of heat illness and recovery.

Retinal nerve fiber layer thickness map and blood flow pulsation measured with SDOCT

NASA Astrophysics Data System (ADS)

Mujat, Mircea; Chan, Raymond C.; Cense, Barry; Pierce, Mark; Park, Hyle; Joo, Chulmin; Chen, Teresa C.; de Boer, Johannes F.

2006-02-01

Spectral-Domain Optical Coherence Tomography (SDOCT) allows for in-vivo video-rate investigation of biomedical tissue depth structure intended for non-invasive optical diagnostics. It has been suggested that OCT can be used for di-agnosis of glaucoma by measuring the thickness of the Retinal Nerve Fiber Layer (RNLF). We present an automated method for determining the RNFL thickness from a 3-D dataset based on edge detection using a deformable spline algo-rithm. The RNFL thickness map is combined with an integrated reflectance map and retinal cross-sectional images to provide the ophthalmologist with a familiar image for interpreting the OCT data. The video-rate capabilities of our SDOCT system allow for mapping the true retinal topography since motion artifacts are significantly reduced as com-pared to slower time-domain systems. Combined with Doppler Velocimetry, SDOCT also provides information on retinal blood flow dynamics. We analyzed the pulsatile nature of the bidirectional flow dynamics in an artery-vein pair for a healthy volunteer at different locations and for different blood vessel diameters. The Doppler phase shift is determined as the phase difference at the same point of adjacent depth profiles, and is integrated over the area delimited by two circles corresponding to the blood vessels location. Its temporal evolution clearly shows the blood flow pulsatile nature, the cardiac cycle, in both artery and vein. The artery is identified as having a stronger variation of the integrated phase shift. We observe that artery pulsation is always easily detectable, while vein pulsation seems to depend on the veins diameter.

Intrinsic cardiac nervous system in tachycardia induced heart failure.

PubMed

Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

2003-11-01

The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to influence cardiodynamics becomes obtunded.

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

PubMed

Louridas, George E; Lourida, Katerina G

2017-02-21

Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

Translational neurocardiology: preclinical models and cardioneural integrative aspects

PubMed Central

Andresen, M. C.; Armour, J. A.; Billman, G. E.; Chen, P.‐S.; Foreman, R. D.; Herring, N.; O'Leary, D. S.; Sabbah, H. N.; Schultz, H. D.; Sunagawa, K.; Zucker, I. H.

2016-01-01

Abstract Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various ‘levels’ become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. PMID:27098459

Cardiac tamponade as an initial manifestation of systemic lupus erythematosus

PubMed Central

Carrion, Diego M; Carrion, Andres F

2012-01-01

Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment. PMID:22693326

ATP-Sensitive K+ Channel Knockout Induces Cardiac Proteome Remodeling Predictive of Heart Disease Susceptibility

PubMed Central

Arrell, D. Kent; Zlatkovic, Jelena; Kane, Garvan C.; Yamada, Satsuki; Terzic, Andre

2010-01-01

Forecasting disease susceptibility requires detection of maladaptive signatures prior to onset of overt symptoms. A case-in-point are cardiac ATP-sensitive K+ (KATP) channelopathies, for which the substrate underlying disease vulnerability remains to be identified. Resolving molecular pathobiology, even for single genetic defects, mandates a systems platform to reliably diagnose disease predisposition. High-throughput proteomic analysis was here integrated with network biology to decode consequences of Kir6.2 KATP channel pore deletion. Differential two-dimensional gel electrophoresis reproducibly resolved > 800 protein species from hearts of asymptomatic wild-type and Kir6.2-knockout counterparts. KATP channel ablation remodeled the cardiac proteome, significantly altering 71 protein spots, from which 102 unique identities were assigned following hybrid linear ion trap quadrupole-Orbitrap tandem mass spectrometry. Ontological annotation stratified the KATP channel-dependent protein cohort into a predominant bioenergetic module (63 resolved identities), with additional focused sets representing signaling molecules (6), oxidoreductases (8), chaperones (6), and proteins involved in catabolism (6), cytostructure (8), and transcription and translation (5). Protein interaction mapping, in conjunction with expression level changes, localized a KATP channel-associated subproteome within a nonstochastic scale-free network. Global assessment of the KATP channel deficient environment verified the primary impact on metabolic pathways and revealed overrepresentation of markers associated with cardiovascular disease. Experimental imposition of graded stress precipitated exaggerated structural and functional myocardial defects in the Kir6.2-knockout, decreasing survivorship and validating the forecast of disease susceptibility. Proteomic cartography thus provides an integral view of molecular remodeling in the heart induced by KATP channel deletion, establishing a systems approach that predicts outcome at a presymptomatic stage. PMID:19673485

System identification of dynamic closed-loop control of total peripheral resistance by arterial and cardiopulmonary baroreceptors

NASA Astrophysics Data System (ADS)

Nikolai Aljuri, A.; Bursac, Nenad; Marini, Robert; Cohen, Richard J.

2001-08-01

Prolonged exposure to microgravity in space flight missions (days) impairs the mechanisms responsible for defense of arterial blood pressure (ABP) and cardiac output (CO) against orthostatic stress in the post-flight period. The mechanisms responsible for the observed orthostatic intolerance are not yet completely understood. Additionally, effective counter measures to attenuate this pathophysiological response are not available. The aim of this study was to investigate the ability of our proposed system identification method to predict closed-loop dynamic changes in TPR induced by changes in mean arterial pressure (MAP) and right atrial pressure (RAP). For this purpose we designed and employed a novel experimental animal model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop control of total peripheral resistance (TPR), and applied system identification to the analysis of beat-to-beat fluctuations in the measured signals.

Out-of-Hospital Cardiac Arrest Resuscitation Systems of Care: A Scientific Statement From the American Heart Association.

PubMed

McCarthy, James J; Carr, Brendan; Sasson, Comilla; Bobrow, Bentley J; Callaway, Clifton W; Neumar, Robert W; Ferrer, Jose Maria E; Garvey, J Lee; Ornato, Joseph P; Gonzales, Louis; Granger, Christopher B; Kleinman, Monica E; Bjerke, Chris; Nichol, Graham

2018-05-22

The American Heart Association previously recommended implementation of cardiac resuscitation systems of care that consist of interconnected community, emergency medical services, and hospital efforts to measure and improve the process of care and outcome for patients with cardiac arrest. In addition, the American Heart Association proposed a national process to develop and implement evidence-based guidelines for cardiac resuscitation systems of care. Significant experience has been gained with implementing these systems, and new evidence has accumulated. This update describes recent advances in the science of cardiac resuscitation systems and evidence of their effectiveness, as well as recent progress in dissemination and implementation throughout the United States. Emphasis is placed on evidence published since the original recommendations (ie, including and since 2010). © 2018 American Heart Association, Inc.

Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

PubMed Central

Hasham, Muneer G.; Baxan, Nicoleta; Stuckey, Daniel J.; Branca, Jane; Perkins, Bryant; Dent, Oliver; Duffy, Ted; Hameed, Tolani S.; Stella, Sarah E.; Bellahcene, Mohammed; Schneider, Michael D.; Harding, Sian E.; Rosenthal, Nadia

2017-01-01

ABSTRACT Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity. PMID:28250051

A Conformal, Bio-interfaced Class of Silicon Electronics for Mapping Cardiac Electrophysiology

PubMed Central

Viventi, Jonathan; Kim, Dae-Hyeong; Moss, Joshua D.; Kim, Yun-Soung; Blanco, Justin A.; Annetta, Nicholas; Hicks, Andrew; Xiao, Jianliang; Huang, Younggang; Callans, David J.; Rogers, John A.; Litt, Brian

2011-01-01

The sophistication and resolution of current implantable medical devices are limited by the need connect each sensor separately to data acquisition systems. The ability of these devices to sample and modulate tissues is further limited by the rigid, planar nature of the electronics and the electrode-tissue interface. Here, we report the development of a class of mechanically flexible silicon electronics for measuring signals in an intimate, conformal integrated mode on the dynamic, three dimensional surfaces of soft tissues in the human body. We illustrate this technology in sensor systems composed of 2016 silicon nanomembrane transistors configured to record electrical activity directly from the curved, wet surface of a beating heart in vivo. The devices sample with simultaneous sub-millimeter and sub-millisecond resolution through 288 amplified and multiplexed channels. We use these systems to map the spread of spontaneous and paced ventricular depolarization in real time, at high resolution, on the epicardial surface in a porcine animal model. This clinical-scale demonstration represents one example of many possible uses of this technology in minimally invasive medical devices. [Conformal electronics and sensors intimately integrated with living tissues enable a new generation of implantable devices capable of addressing important problems in human health.] PMID:20375008

Bolus versus continuous low dose of enalaprilat in congestive heart failure with acute refractory decompensation.

PubMed

Podbregar, M; Voga, G; Horvat, M; Zuran, I; Krivec, B; Skale, R; Pareznik, R

1999-01-01

The first dose of angiotensin-converting enzyme (ACE) inhibitors may trigger a considerable fall of blood pressure in chronic heart failure. The response may be dose-related. To determine hemodynamic and systemic oxygenation effects of low-dose enalaprilat, we administered intravenous enalaprilat (0.004 mg/kg) as bolus (group B) or continuous 1-hour infusion (group C) in 20 patients with congestive heart failure due to ischemic heart disease with acute decompensation refractory to inotropic, vasodilator and diuretic therapy. Hemodynamic and systemic oxygenation variables were recorded at baseline (+0 min), +30, +60, +120, +180, and +360 min after the start of intervention. Mean arterial pressure (MAP) (p < 0. 001), mean pulmonary artery pressure (MPAP) (p < 0.001), pulmonary artery occlusion pressure (PAOP) (p < 0.001), oxygen extraction ratio (ER) (p < 0.026) decreased regardless of enalaprilat application. Compared to group B, there was in group C prolonged decrease of MAP, MPAP, PAOP, ER and increase of pulmonary artery oxyhemoglobin saturation in regard to baseline values. Cardiac index, heart rate, central venous pressure and oxygen consumption index did not change. A low dose of intravenous enalaprilat (0.004 mg/kg) can be used to safely improve hemodynamics and systemic oxygenation in congestive heart failure due to ischemic heart disease with acute refractory decompensation.

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study

PubMed Central

Churilov, Leonid

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting. PMID:29659631

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study.

PubMed

Chiam, Elizabeth; Bellomo, Rinaldo; Churilov, Leonid; Weinberg, Laurence

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting.

Noninvasive imaging of three-dimensional cardiac activation sequence during pacing and ventricular tachycardia.

PubMed

Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

2011-08-01

Imaging cardiac excitation within ventricular myocardium is important in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. This study sought to rigorously assess the imaging performance of a 3-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of 3D intracardiac mapping from up to 216 intramural sites during paced rhythm and norepinephrine (NE)-induced ventricular tachycardia (VT) in the rabbit heart. Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in 13 healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous NE. Computed tomography images were obtained to construct geometry models. The noninvasively imaged activation sequence correlated well with invasively measured counterpart, with a correlation coefficient of 0.72 ± 0.04, and a relative error of 0.30 ± 0.02 averaged over 520 paced beats as well as 73 NE-induced PVCs and VT beats. All PVCs and VT beats initiated in the subendocardium by a nonreentrant mechanism. The averaged distance from the imaged site of initial activation to the pacing site or site of arrhythmias determined from intracardiac mapping was ∼5 mm. For dual-site pacing, the double origins were identified when they were located at contralateral sides of ventricles or at the lateral wall and the apex. 3DCEI can noninvasively delineate important features of focal or multifocal ventricular excitation. It offers the potential to aid in localizing the origins and imaging activation sequences of ventricular arrhythmias, and to provide noninvasive assessment of the underlying arrhythmia mechanisms. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

18-FDG-PET in a patient cohort suspected for cardiac sarcoidosis: Right ventricular uptake is associated with pathological uptake in mediastinal lymph nodes.

PubMed

Tuominen, Heikki; Haarala, Atte; Tikkakoski, Antti; Kähönen, Mika; Nikus, Kjell; Sipilä, Kalle

2018-05-02

In up to 65% of cardiac sarcoidosis patients, the disease is confined to the heart. Diagnosing isolated cardiac sarcoidosis is challenging due to the low sensitivity of endomyocardial biopsy. If cardiac sarcoidosis is part of biopsy-confirmed systemic sarcoidosis, the diagnosis can be based on cardiac imaging studies. We compared the imaging features of patients with isolated cardiac FDG uptake on positron emission tomography with those who had findings indicative of systemic sarcoidosis. 137 consecutive cardiac FDG-PET/CT studies performed on subjects suspected of having cardiac sarcoidosis were retrospectively analyzed. 33 patients had pathological left ventricular FDG uptake, and 12 of these also had pathological right ventricular uptake. 16/33 patients with pathological cardiac uptake had pathological extracardiac uptake. 10/12 patients with both LV- and RV-uptake patterns had extracardiac uptake compared to 6/21 of those with pathological LV uptake without RV uptake. SUVmax values in the myocardium were higher among patients with abnormal extracardiac uptake. The presence of extracardiac uptake was the only imaging-related factor that could predict a biopsy indicative of sarcoidosis. Right ventricular involvement seems to be more common in patients who also have findings suggestive of suspected systemic sarcoidosis, compared with patients with PET findings indicative of isolated cardiac disease.

Localization of cholinergic innervation and neurturin receptors in adult mouse heart and expression of the neurturin gene.

PubMed

Mabe, Abigail M; Hoard, Jennifer L; Duffourc, Michelle M; Hoover, Donald B

2006-10-01

Neurturin (NRTN) is a neurotrophic factor required during development for normal cholinergic innervation of the heart, but whether NRTN continues to function in the adult heart is unknown. We have therefore evaluated NRTN expression in adult mouse heart and the association of NRTN receptors with intracardiac cholinergic neurons and nerve fibers. Mapping the regional distribution and density of cholinergic nerves in mouse heart was an integral part of this goal. Analysis of RNA from adult C57BL/6 mouse hearts demonstrated NRTN expression in atrial and ventricular tissue. Virtually all neurons in the cardiac parasympathetic ganglia exhibited the cholinergic phenotype, and over 90% of these cells contained both components of the NRTN receptor, Ret tyrosine kinase and GDNF family receptor alpha2 (GFRalpha2). Cholinergic nerve fibers, identified by labeling for the high affinity choline transporter, were abundant in the sinus and atrioventricular nodes, ventricular conducting system, interatrial septum, and much of the right atrium, but less abundant in the left atrium. The right ventricular myocardium contained a low density of cholinergic nerves, which were sparse in other regions of the working ventricular myocardium. Some cholinergic nerves were also associated with coronary vessels. GFRalpha2 was present in most cholinergic nerve fibers and in Schwann cells and their processes throughout the heart. Some cholinergic nerve fibers, such as those in the sinus node, also exhibited Ret immunoreactivity. These findings provide the first detailed mapping of cholinergic nerves in mouse heart and suggest that the neurotrophic influence of NRTN on cardiac cholinergic innervation continues in mature animals.

Arm and wrist surface potential mapping for wearable ECG rhythm recording devices: a pilot clinical study

NASA Astrophysics Data System (ADS)

Lynn, W. D.; Escalona, O. J.; McEneaney, D. J.

2013-06-01

This study addresses an important question in the development of a ECG device that enables long term monitoring of cardiac rhythm. This device would utilise edge sensor technologies for dry, non-irritant skin contact suitable for distal limb application and would be supported by embedded ECG denoising processes. Contemporary ECG databases including those provided by MIT-BIH and Physionet are focused on interpretation of cardiac disease and rhythm tracking. The data is recorded using chest leads as in standard clinical practise. For the development of a peripherally located heart rhythm monitor, such data would be of limited use. To provide a useful database adequate for the development of the above mentioned cardiac monitoring device a unipolar body surface potential map from the left arm and wrist was gathered in 37 volunteer patients and characterized in this study. For this, the reference electrode was placed at the wrist. Bipolar far-field electrogram leads were derived and analysed. Factors such as skin variability, 50Hz noise interference, electrode contact noise, motion artifacts and electromyographic noise, presented a challenge. The objective was quantify the signal-to-noise ratio (SNR) at the far-field locations. Preliminary results reveal that an electrogram indicative of the QRS complex can be recorded on the distal portion of the left arm when denoised using signal averaging techniques.

Mapping arginine methylation in the human body and cardiac disease.

PubMed

Onwuli, Donatus O; Rigau-Roca, Laura; Cawthorne, Chris; Beltran-Alvarez, Pedro

2017-01-01

Arginine methylation (ArgMe) is one of the most ubiquitous PTMs, and hundreds of proteins undergo ArgMe in, for example, brain. However, the scope of ArgMe in many tissues, including the heart, is currently underexplored. Here, we aimed to (i) identify proteins undergoing ArgMe in human organs, and (ii) expose the relevance of ArgMe in cardiac disease. The publicly available proteomic data is used to search for ArgMe in 13 human tissues. To induce H9c2 cardiac-like cell hypertrophy glucose is used. The results show that ArgMe is mainly tissue-specific; nevertheless, the authors suggest an embryonic origin of core ArgMe events. In the heart, 103 mostly novel ArgMe sites in 58 nonhistone proteins are found. The authors provide compelling evidence that cardiac protein ArgMe is relevant to cardiomyocyte ontology, and important for proper cardiac function. This is highlighted by the fact that genetic mutations affecting methylated arginine positions are often associated with cardiac disease, including hypertrophic cardiomyopathy. The pilot experimental data suggesting significant changes in ArgMe profiles of H9c2 cells upon induction of cell hypertrophy using glucose is provided. The work calls for in-depth investigation of ArgMe in normal and diseased tissues using methods including clinical proteomics. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

Noninvasive Hemodynamic Measurements During Neurosurgical Procedures in Sitting Position.

PubMed

Schramm, Patrick; Tzanova, Irene; Gööck, Tilman; Hagen, Frank; Schmidtmann, Irene; Engelhard, Kristin; Pestel, Gunther

2017-07-01

Neurosurgical procedures in sitting position need advanced cardiovascular monitoring. Transesophageal echocardiography (TEE) to measure cardiac output (CO)/cardiac index (CI) and stroke volume (SV), and invasive arterial blood pressure measurements for systolic (ABPsys), diastolic (ABPdiast) and mean arterial pressure (MAP) are established monitoring technologies for these kind of procedures. A noninvasive device for continuous monitoring of blood pressure and CO based on a modified Penaz technique (volume-clamp method) was introduced recently. In the present study the noninvasive blood pressure measurements were compared with invasive arterial blood pressure monitoring, and the noninvasive CO monitoring to TEE measurements. Measurements of blood pressure and CO were performed in 35 patients before/after giving a fluid bolus and a change from supine to sitting position, start of surgery, and repositioning from sitting to supine at the end of surgery. Data pairs from the noninvasive device (Nexfin HD) versus arterial line measurements (ABPsys, ABPdiast, MAP) and versus TEE (CO, CI, SV) were compared using Bland-Altman analysis and percentage error. All parameters compared (CO, CI, SV, ABPsys, ABPdiast, MAP) showed a large bias and wide limits of agreement. Percentage error was above 30% for all parameters except ABPsys. The noninvasive device based on a modified Penaz technique cannot replace arterial blood pressure monitoring or TEE in anesthetized patients undergoing neurosurgery in sitting position.

Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis.

PubMed

Swiger, Kristopher J; Friedman, Eitan A; Brittain, Evan L; Tomasek, Kelsey A; Huang, Shi; Su, Yan R; Sawyer, Douglas B; Lenihan, Daniel J

2016-12-01

Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics. Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n = 26); (2) transthyretin (ATTR) cardiac amyloidosis (n = 7); (3) left ventricular hypertrophy (LVH) (n = 45); (4) systolic heart failure (n = 42); and (5) non-cardiac systemic amyloidosis (n = 7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients. HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median = 622, interquartile range (IQR): 299-1228 pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median = 134, IQR: 94-163 pg/mL, p < 0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p = 0.13 and 0.057, respectively). HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

PubMed

Ardell, J L; Andresen, M C; Armour, J A; Billman, G E; Chen, P-S; Foreman, R D; Herring, N; O'Leary, D S; Sabbah, H N; Schultz, H D; Sunagawa, K; Zucker, I H

2016-07-15

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Dynamic three-dimensional phase-contrast technique in MRI: application to complex flow analysis around the artificial heart valve

NASA Astrophysics Data System (ADS)

Kim, Soo Jeong; Lee, Dong Hyuk; Song, Inchang; Kim, Nam Gook; Park, Jae-Hyeung; Kim, JongHyo; Han, Man Chung; Min, Byong Goo

1998-07-01

Phase-contrast (PC) method of magnetic resonance imaging (MRI) has bee used for quantitative measurements of flow velocity and volume flow rate. It is a noninvasive technique which provides an accurate two-dimensional velocity image. Moreover, Phase Contrast Cine magnetic resonance imaging combines the flow dependent contrast of PC-MRI with the ability of cardiac cine imaging to produce images throughout the cardiac cycle. However, the accuracy of the data acquired from the single through-plane velocity encoding can be reduced by the effect of flow direction, because in many practical cases flow directions are not uniform throughout the whole region of interest. In this study, we present dynamic three-dimensional velocity vector mapping method using PC-MRI which can visualize the complex flow pattern through 3D volume rendered images displayed dynamically. The direction of velocity mapping can be selected along any three orthogonal axes. By vector summation, the three maps can be combined to form a velocity vector map that determines the velocity regardless of the flow direction. At the same time, Cine method is used to observe the dynamic change of flow. We performed a phantom study to evaluate the accuracy of the suggested PC-MRI in continuous and pulsatile flow measurement. Pulsatile flow wave form is generated by the ventricular assistant device (VAD), HEMO-PULSA (Biomedlab, Seoul, Korea). We varied flow velocity, pulsatile flow wave form, and pulsing rate. The PC-MRI-derived velocities were compared with Doppler-derived results. The velocities of the two measurements showed a significant linear correlation. Dynamic three-dimensional velocity vector mapping was carried out for two cases. First, we applied to the flow analysis around the artificial heart valve in a flat phantom. We could observe the flow pattern around the valve through the 3-dimensional cine image. Next, it is applied to the complex flow inside the polymer sac that is used as ventricle in totally implantable artificial heart (TAH). As a result we could observe the flow pattern around the valves of the sac, though complex flow can not be detected correctly in the conventional phase contrast method. In addition, we could calculate the cardiac output from TAH sac by quantitative measurement of the volume of flow across the outlet valve.

Prototype development of an electrical impedance based simultaneous respiratory and cardiac monitoring system for gated radiotherapy.

PubMed

Kohli, Kirpal; Liu, Jeff; Schellenberg, Devin; Karvat, Anand; Parameswaran, Ash; Grewal, Parvind; Thomas, Steven

2014-10-14

In radiotherapy, temporary translocations of the internal organs and tumor induced by respiratory and cardiac activities can undesirably lead to significantly lower radiation dose on the targeted tumor but more harmful radiation on surrounding healthy tissues. Respiratory and cardiac gated radiotherapy offers a potential solution for the treatment of tumors located in the upper thorax. The present study focuses on the design and development of simultaneous acquisition of respiratory and cardiac signal using electrical impedance technology for use in dual gated radiotherapy. An electronic circuitry was developed for monitoring the bio-impedance change due to respiratory and cardiac motions and extracting the cardiogenic ECG signal. The system was analyzed in terms of reliability of signal acquisition, time delay, and functionality in a high energy radiation environment. The resulting signal of the system developed was also compared with the output of the commercially available Real-time Position Management™ (RPM) system in both time and frequency domains. The results demonstrate that the bioimpedance-based method can potentially provide reliable tracking of respiratory and cardiac motion in humans, alternative to currently available methods. When compared with the RPM system, the impedance-based system developed in the present study shows similar output pattern but different sensitivities in monitoring different respiratory rates. The tracking of cardiac motion was more susceptible to interference from other sources than respiratory motion but also provided synchronous output compared with the ECG signal extracted. The proposed hardware-based implementation was observed to have a worst-case time delay of approximately 33 ms for respiratory monitoring and 45 ms for cardiac monitoring. No significant effect on the functionality of the system was observed when it was tested in a radiation environment with the electrode lead wires directly exposed to high-energy X-Rays. The developed system capable of rendering quality signals for tracking both respiratory and cardiac motions can potentially provide a solution for simultaneous dual-gated radiotherapy.

Sudden cardiac death and sarcoidosis of the heart in a young patient.

PubMed

Jotterand, Morgane; Grabherr, Silke; Lobrinus, Johannes Alexandre; Michaud, Katarzyna

Sarcoidosis is a granulomatous disease of unknown etiology affecting any organ, microscopically characterized by noncaseating granulomata. Cardiac involvement in sarcoidosis has been reported. It might be symptomatic or not and even revealed by sudden death. Heart conduction system is rarely investigated at autopsy, even in cases of sudden cardiac death. We present a case of a 32-year-old woman who died suddenly. The examination of the heart conduction system revealed a cardiac sarcoidosis that could explain the sudden death. The review of clinical data of the patient revealed some symptoms consistent/in agreement with this hypothesis. Cardiac sarcoidosis remains a diagnostic challenge and can be easily missed, clinically and pathologically. The retrospective analysis of clinical data and autopsy results of fatal and unusual cases might help to better understand sarcoidosis and its clinical presentations. Examination of the cardiac conduction system is crucial in selected cases of sudden cardiac death. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative cardiac SPECT reconstruction with reduced image degradation due to patient anatomy

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

Tsui, B.M.W.; Zhao, X.D.; Gregoriou, G.K.

1994-12-01

Patient anatomy has complicated effects on cardiac SPECT images. The authors investigated reconstruction methods which substantially reduced these effects for improved image quality. A 3D mathematical cardiac-torso (MCAT) phantom which models the anatomical structures in the thorax region were used in the study. The phantom was modified to simulate variations in patient anatomy including regions of natural thinning along the myocardium, body size, diaphragmatic shape, gender, and size and shape of breasts for female patients. Distributions of attenuation coefficients and Tl-201 uptake in different organs in a normal patient were also simulated. Emission projection data were generated from the phantomsmore » including effects of attenuation and detector response. The authors have observed the attenuation-induced artifacts caused by patient anatomy in the conventional FBP reconstructed images. Accurate attenuation compensation using iterative reconstruction algorithms and attenuation maps substantially reduced the image artifacts and improved quantitative accuracy. They conclude that reconstruction methods which accurately compensate for non-uniform attenuation can substantially reduce image degradation caused by variations in patient anatomy in cardiac SPECT.« less

Effects of Early Bedside Cycle Exercise on Intracranial Pressure and Systemic Hemodynamics in Critically Ill Patients in a Neurointensive Care Unit.

PubMed

Thelandersson, Anneli; Nellgård, Bengt; Ricksten, Sven-Erik; Cider, Åsa

2016-12-01

Physiotherapy is an important part of treatment after severe brain injuries and stroke, but its effect on intracranial and systemic hemodynamics is minimally investigated. Therefore, the aim of this study was to assess the effects of an early bedside cycle exercise on intracranial and systemic hemodynamics in critically ill patients when admitted to a neurointensive care unit (NICU). Twenty critically ill patients suffering from brain injuries or stroke were included in this study performed in the NICU at Sahlgrenska University Hospital. One early implemented exercise session was performed using a bedside cycle ergometer for 20 min. Intracranial and hemodynamic variables were measured two times before, three times during, and two times after the bedside cycling exercise. Analyzed variables were intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), heart rate (HR), peripheral oxygen saturation (SpO 2 ), cardiac output (CO), stroke volume (SV), and stroke volume variation (SVV). The cycling intervention was conducted within 7 ± 5 days after admission to the NICU. Cycle exercise increased MAP (p = 0.029) and SV (p = 0.003) significantly. After exercise CO, SV, MAP, and CPP decreased significantly, while no changes in HR, SVV, SpO 2 , or ICP were noted when compared to values obtained during exercise. There were no differences in data obtained before versus after exercise. Early implemented exercise with a bedside cycle ergometer, for patients with severe brain injuries or stroke when admitted to a NICU, is considered to be a clinically safe procedure.

Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium.

PubMed

Matiukas, Arvydas; Mitrea, Bogdan G; Qin, Maochun; Pertsov, Arkady M; Shvedko, Alexander G; Warren, Mark D; Zaitsev, Alexey V; Wuskell, Joseph P; Wei, Mei-de; Watras, James; Loew, Leslie M

2007-11-01

Styryl voltage-sensitive dyes (e.g., di-4-ANEPPS) have been used successfully for optical mapping in cardiac cells and tissues. However, their utility for probing electrical activity deep inside the myocardial wall and in blood-perfused myocardium has been limited because of light scattering and high absorption by endogenous chromophores and hemoglobin at blue-green excitation wavelengths. The purpose of this study was to characterize two new styryl dyes--di-4-ANBDQPQ (JPW-6003) and di-4-ANBDQBS (JPW-6033)--optimized for blood-perfused tissue and intramural optical mapping. Voltage-dependent spectra were recorded in a model lipid bilayer. Optical mapping experiments were conducted in four species (mouse, rat, guinea pig, and pig). Hearts were Langendorff perfused using Tyrode's solution and blood (pig). Dyes were loaded via bolus injection into perfusate. Transillumination experiments were conducted in isolated coronary-perfused pig right ventricular wall preparations. The optimal excitation wavelength in cardiac tissues (650 nm) was >70 nm beyond the absorption maximum of hemoglobin. Voltage sensitivity of both dyes was approximately 10% to 20%. Signal decay half-life due to dye internalization was 80 to 210 minutes, which is 5 to 7 times slower than for di-4-ANEPPS. In transillumination mode, DeltaF/F was as high as 20%. In blood-perfused tissues, DeltaF/F reached 5.5% (1.8 times higher than for di-4-ANEPPS). We have synthesized and characterized two new near-infrared dyes with excitation/emission wavelengths shifted >100 nm to the red. They provide both high voltage sensitivity and 5 to 7 times slower internalization rate compared to conventional dyes. The dyes are optimized for deeper tissue probing and optical mapping of blood-perfused tissue, but they also can be used for conventional applications.

High Resolution Magnetic Images of Planar Wave Fronts Reveal Bidomain Properties of Cardiac Tissue

PubMed Central

Holzer, Jenny R.; Fong, Luis E.; Sidorov, Veniamin Y.; Wikswo, John P.; Baudenbacher, Franz

2004-01-01

We magnetically imaged the magnetic action field and optically imaged the transmembrane potentials generated by planar wavefronts on the surface of the left ventricular wall of Langendorff-perfused isolated rabbit hearts. The magnetic action field images were used to produce a time series of two-dimensional action current maps. Overlaying epifluorescent images allowed us to identify a net current along the wavefront and perpendicular to gradients in the transmembrane potential. This is in contrast to a traditional uniform double-layer model where the net current flows along the gradient in the transmembrane potential. Our findings are supported by numerical simulations that treat cardiac tissue as a bidomain with unequal anisotropies in the intra- and extracellular spaces. Our measurements reveal the anisotropic bidomain nature of cardiac tissue during plane wave propagation. These bidomain effects play an important role in the generation of the whole-heart magnetocardiogram and cannot be ignored. PMID:15377521

Ubiquitous health monitoring and real-time cardiac arrhythmias detection: a case study.

PubMed

Li, Jian; Zhou, Haiying; Zuo, Decheng; Hou, Kun-Mean; De Vaulx, Christophe

2014-01-01

As the symptoms and signs of heart diseases that cause sudden cardiac death, cardiac arrhythmia has attracted great attention. Due to limitations in time and space, traditional approaches to cardiac arrhythmias detection fail to provide a real-time continuous monitoring and testing service applicable in different environmental conditions. Integrated with the latest technologies in ECG (electrocardiograph) analysis and medical care, the pervasive computing technology makes possible the ubiquitous cardiac care services, and thus brings about new technical challenges, especially in the formation of cardiac care architecture and realization of the real-time automatic ECG detection algorithm dedicated to care devices. In this paper, a ubiquitous cardiac care prototype system is presented with its architecture framework well elaborated. This prototype system has been tested and evaluated in all the clinical-/home-/outdoor-care modes with a satisfactory performance in providing real-time continuous cardiac arrhythmias monitoring service unlimitedly adaptable in time and space.

Influence of cardiac nerve status on cardiovascular regulation and cardioprotection

PubMed Central

Kingma, John G; Simard, Denys; Rouleau, Jacques R

2017-01-01

Neural elements of the intrinsic cardiac nervous system transduce sensory inputs from the heart, blood vessels and other organs to ensure adequate cardiac function on a beat-to-beat basis. This inter-organ crosstalk is critical for normal function of the heart and other organs; derangements within the nervous system hierarchy contribute to pathogenesis of organ dysfunction. The role of intact cardiac nerves in development of, as well as protection against, ischemic injury is of current interest since it may involve recruitment of intrinsic cardiac ganglia. For instance, ischemic conditioning, a novel protection strategy against organ injury, and in particular remote conditioning, is likely mediated by activation of neural pathways or by endogenous cytoprotective blood-borne substances that stimulate different signalling pathways. This discovery reinforces the concept that inter-organ communication, and maintenance thereof, is key. As such, greater understanding of mechanisms and elucidation of treatment strategies is imperative to improve clinical outcomes particularly in patients with comorbidities. For instance, autonomic imbalance between sympathetic and parasympathetic nervous system regulation can initiate cardiovascular autonomic neuropathy that compromises cardiac stability and function. Neuromodulation therapies that directly target the intrinsic cardiac nervous system or other elements of the nervous system hierarchy are currently being investigated for treatment of different maladies in animal and human studies. PMID:28706586

Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

PubMed Central

Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

2018-01-01

Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

Composition and distribution of elements and ultrastructural topography of a human cardiac calculus.

PubMed

Cheng, Ching-Li; Chang, Hsiao-Huang; Huang, Pei-Jung; Chu, Yu-Ting; Lin, Shan-Yang

2013-04-01

Trace elements (TEs) may contribute to the formation of calculi or stones or be involved in the aetiopathogenesis of stone diseases. The compositions and spatial distribution of elements from the inner nucleus to outer crust of the cardiac calculus were investigated by energy-dispersive X-ray fluorescence (EDXRF) spectrometer. The surface topograph, distribution map of elements, elemental and chemical compositions were also determined by environmental scanning electron microscope (ESEM)-energy-dispersive X-ray (EDX) analysis. Twenty-five elements were identifiable from 18 positions on the cardiac calculus by EDXRF spectrometer, in which the highest concentrations of toxic TEs (Ni, Pt, Hg, Sn, Pb, W, Au, Al, Si) and higher levels of essential TEs (Ca, Sr, Cr, P) were detected. A moderate positive Pearson's correlation between TEs concentrations of Mg, Ca or P and location differences from centre to periphery in the cardiac calculus was observed. A positive correlation was also found for Ca/Zn and Ca/Cu, indicating the gradual increase of calcium concentration from inner nucleus to outer crust of cardiac calculus. The drop-like nodules/crystals on the surface of petrous part of cardiac calculus were observed from ESEM analysis. ESEM-EDX analysis determined the calculus to be predominantly composed of calcium hydroxyapatite and cholesterol, as indicated by the petrous surface and drop-like nodules/crystals, respectively. This composition was confirmed using a portable Raman analyser. The spatial distribution analysis indicated a gradual increase in Mg, P and Ca concentrations from the inner nucleus to the outer crust of the cardiac calculus. The major chemical compositions of calcium hydroxyapatite and cholesterol were detected on this cardiac calculus.

Space Derived Health Aids (Cardiac Pacemaker)

NASA Technical Reports Server (NTRS)

1981-01-01

St. Jude Medical's Cardiac Rhythm Management Division's (formerly known as Pacesetter Systems, Inc.) pacer is a rechargeable cardiac pacemaker that eliminates the recurring need for surgery to implant a new battery. The Programalith is an advanced cardiac pacing system which permits a physician to reprogram a patient's implanted pacemaker without surgery. System consists of a pacemaker, together with a physician's console containing the programmer and a data printer. Signals are transmitted by wireless telemetry. Two-way communications, originating from spacecraft electrical power systems technology, allows physician to interrogate the pacemaker as to the status of the heart, then to fine tune the device to best suit the patient's needs.

Detection of electrophysiology catheters in noisy fluoroscopy images.

PubMed

Franken, Erik; Rongen, Peter; van Almsick, Markus; ter Haar Romeny, Bart

2006-01-01

Cardiac catheter ablation is a minimally invasive medical procedure to treat patients with heart rhythm disorders. It is useful to know the positions of the catheters and electrodes during the intervention, e.g. for the automatization of cardiac mapping. Our goal is therefore to develop a robust image analysis method that can detect the catheters in X-ray fluoroscopy images. Our method uses steerable tensor voting in combination with a catheter-specific multi-step extraction algorithm. The evaluation on clinical fluoroscopy images shows that especially the extraction of the catheter tip is successful and that the use of tensor voting accounts for a large increase in performance.

Integrating functional and anatomical information to facilitate cardiac resynchronization therapy.

PubMed

Tournoux, Francois B; Manzke, Robert; Chan, Raymond C; Solis, Jorge; Chen-Tournoux, Annabel A; Gérard, Olivier; Nandigam, Veena; Allain, Pascal; Reddy, Vivek; Ruskin, Jeremy N; Weyman, Arthur E; Picard, Michael H; Singh, Jagmeet P

2007-08-01

Multiple imaging modalities are required in patients receiving cardiac resynchronization therapy. We have developed a strategy to integrate echocardiographic and angiographic information to facilitate left ventricle (LV) lead position. Full three-dimensional LV-volumes (3DLVV) and dyssynchrony maps were acquired before and after resynchronization. At the time of device implantation, 3D-rotational coronary venous angiography was performed. 3D-models of the veins were then integrated with the pre- and post-3DLVV. In the case displayed, prior to implantation, the lateral wall was delayed compared to the septum. The LV lead was positioned into the vein over the most delayed region, resulting in improved LV synchrony.

SYSTEMIC IMBALANCE OF ESSENTIAL METALS AND CARDIAC GENE EXPRESSION IN RATS FOLLOWING ACUTE PULMONARY ZINC EXPOSURE

EPA Science Inventory

We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...

External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

PubMed

Hogan, T S

2012-10-01

Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient's cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless electrical activity. Investigation using a variety of animal models of pulseless electrical activity produced by different shock-inducing mechanisms is required to provide an evidence base for resuscitation guidelines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cardiac Dysautonomia in Huntington's Disease.

PubMed

Abildtrup, Mads; Shattock, Michael

2013-01-01

Huntington's disease is a fatal, hereditary, neurodegenerative disorder best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances. Although a disease of the central nervous system, mortality surveys indicate that heart disease is a leading cause of death. The nature of such cardiac abnormalities remains unknown. Clinical findings indicate a high prevalence of autonomic nervous system dysfunction - dysautonomia - which may be a result of pathology of the central autonomic network. Dysautonomia can have profound effects on cardiac health, and pronounced autonomic dysfunction can be associated with neurogenic arrhythmias and sudden cardiac death. Significant advances in the knowledge of neural mechanisms in cardiac disease have recently been made which further aid our understanding of cardiac mortality in Huntington's disease. Even so, despite the evidence of aberrant autonomic activity the potential cardiac consequences of autonomic dysfunction have been somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias have been part of the exclusion criteria in clinical autonomic Huntington's disease research. A comprehensive analysis of cardiac function in Huntington's disease patients is warranted. Further experimental and clinical studies are needed to clarify how the autonomic nervous system is controlled and regulated in higher, central areas of the brain - and how these regions may be altered in neurological pathology, such as Huntington's disease. Ultimately, research will hopefully result in an improvement of management with the aim of preventing early death in Huntington's disease from cardiac causes.

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a...

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a...

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a...

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a...

High Spatial Resolution and Temporally Resolved T2 * Mapping of Normal Human Myocardium at 7.0 Tesla: An Ultrahigh Field Magnetic Resonance Feasibility Study

PubMed Central

Hezel, Fabian; Thalhammer, Christof; Waiczies, Sonia; Schulz-Menger, Jeanette; Niendorf, Thoralf

2012-01-01

Myocardial tissue characterization using T2 * relaxation mapping techniques is an emerging application of (pre)clinical cardiovascular magnetic resonance imaging. The increase in microscopic susceptibility at higher magnetic field strengths renders myocardial T2 * mapping at ultrahigh magnetic fields conceptually appealing. This work demonstrates the feasibility of myocardial T2 * imaging at 7.0 T and examines the applicability of temporally-resolved and high spatial resolution myocardial T2 * mapping. In phantom experiments single cardiac phase and dynamic (CINE) gradient echo imaging techniques provided similar T2 * maps. In vivo studies showed that the peak-to-peak B0 difference following volume selective shimming was reduced to approximately 80 Hz for the four chamber view and mid-ventricular short axis view of the heart and to 65 Hz for the left ventricle. No severe susceptibility artifacts were detected in the septum and in the lateral wall for T2 * weighting ranging from TE = 2.04 ms to TE = 10.2 ms. For TE >7 ms, a susceptibility weighting induced signal void was observed within the anterior and inferior myocardial segments. The longest T2 * values were found for anterior (T2 * = 14.0 ms), anteroseptal (T2 * = 17.2 ms) and inferoseptal (T2 * = 16.5 ms) myocardial segments. Shorter T2 * values were observed for inferior (T2 * = 10.6 ms) and inferolateral (T2 * = 11.4 ms) segments. A significant difference (p = 0.002) in T2 * values was observed between end-diastole and end-systole with T2 * changes of up to approximately 27% over the cardiac cycle which were pronounced in the septum. To conclude, these results underscore the challenges of myocardial T2 * mapping at 7.0 T but demonstrate that these issues can be offset by using tailored shimming techniques and dedicated acquisition schemes. PMID:23251708

Construction and use of a zebrafish heart voltage and calcium optical mapping system, with integrated electrocardiogram and programmable electrical stimulation

PubMed Central

Lin, Eric; Craig, Calvin; Lamothe, Marcel; Sarunic, Marinko V.; Beg, Mirza Faisal

2015-01-01

Zebrafish are increasingly being used as a model of vertebrate cardiology due to mammalian-like cardiac properties in many respects. The size and fecundity of zebrafish make them suitable for large-scale genetic and pharmacological screening. In larger mammalian hearts, optical mapping is often used to investigate the interplay between voltage and calcium dynamics and to investigate their respective roles in arrhythmogenesis. This report outlines the construction of an optical mapping system for use with zebrafish hearts, using the voltage-sensitive dye RH 237 and the calcium indicator dye Rhod-2 using two industrial-level CCD cameras. With the use of economical cameras and a common 532-nm diode laser for excitation, the rate dependence of voltage and calcium dynamics within the atrial and ventricular compartments can be simultaneously determined. At 140 beats/min, the atrial action potential duration was 36 ms and the transient duration was 53 ms. With the use of a programmable electrical stimulator, a shallow rate dependence of 3 and 4 ms per 100 beats/min was observed, respectively. In the ventricle the action potential duration was 109 ms and the transient duration was 124 ms, with a steeper rate dependence of 12 and 16 ms per 100 beats/min. Synchronous electrocardiograms and optical mapping recordings were recorded, in which the P-wave aligns with the atrial voltage peak and R-wave aligns with the ventricular peak. A simple optical pathway and imaging chamber are detailed along with schematics for the in-house construction of the electrocardiogram amplifier and electrical stimulator. Laboratory procedures necessary for zebrafish heart isolation, cannulation, and loading are also presented. PMID:25740339

A Cardiac Early Warning System with Multi Channel SCG and ECG Monitoring for Mobile Health

PubMed Central

Sahoo, Prasan Kumar; Thakkar, Hiren Kumar; Lee, Ming-Yih

2017-01-01

Use of information and communication technology such as smart phone, smart watch, smart glass and portable health monitoring devices for healthcare services has made Mobile Health (mHealth) an emerging research area. Coronary Heart Disease (CHD) is considered as a leading cause of death world wide and an increasing number of people die prematurely due to CHD. Under such circumstances, there is a growing demand for a reliable cardiac monitoring system to catch the intermittent abnormalities and detect critical cardiac behaviors which lead to sudden death. Use of mobile devices to collect Electrocardiography (ECG), Seismocardiography (SCG) data and efficient analysis of those data can monitor a patient’s cardiac activities for early warning. This paper presents a novel cardiac data acquisition method and combined analysis of Electrocardiography (ECG) and multi channel Seismocardiography (SCG) data. An early warning system is implemented to monitor the cardiac activities of a person and accuracy assessment of the early warning system is conducted for the ECG data only. The assessment shows 88% accuracy and effectiveness of our proposed analysis, which implies the viability and applicability of the proposed early warning system. PMID:28353681

A Cardiac Early Warning System with Multi Channel SCG and ECG Monitoring for Mobile Health.

PubMed

Sahoo, Prasan Kumar; Thakkar, Hiren Kumar; Lee, Ming-Yih

2017-03-29

Use of information and communication technology such as smart phone, smart watch, smart glass and portable health monitoring devices for healthcare services has made Mobile Health (mHealth) an emerging research area. Coronary Heart Disease (CHD) is considered as a leading cause of death world wide and an increasing number of people die prematurely due to CHD. Under such circumstances, there is a growing demand for a reliable cardiac monitoring system to catch the intermittent abnormalities and detect critical cardiac behaviors which lead to sudden death. Use of mobile devices to collect Electrocardiography (ECG), Seismocardiography (SCG) data and efficient analysis of those data can monitor a patient's cardiac activities for early warning. This paper presents a novel cardiac data acquisition method and combined analysis of Electrocardiography (ECG) and multi channel Seismocardiography (SCG) data. An early warning system is implemented to monitor the cardiac activities of a person and accuracy assessment of the early warning system is conducted for the ECG data only. The assessment shows 88% accuracy and effectiveness of our proposed analysis, which implies the viability and applicability of the proposed early warning system.

Cardiac dysfunctions following spinal cord injury

PubMed Central

Sandu, AM; Popescu, M; Iacobini, MA; Stoian, R; Neascu, C; Popa, F

2009-01-01

The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1–L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following SCI. Each type of cardiac disturbance requires specific treatment. PMID:20108532

Visualization of bioelectric phenomena.

PubMed

Palmer, T C; Simpson, E V; Kavanagh, K M; Smith, W M

1992-01-01

Biomedical investigators are currently able to acquire and analyze physiological and anatomical data from three-dimensional structures in the body. Often, multiple kinds of data can be recorded simultaneously. The usefulness of this information, either for exploratory viewing or for presentation to others, is limited by the lack of techniques to display it in intuitive, accessible formats. Unfortunately, the complexity of scientific visualization techniques and the inflexibility of commercial packages deter investigators from using sophisticated visualization methods that could provide them added insight into the mechanisms of the phenomena under study. Also, the sheer volume of such data is a problem. High-performance computing resources are often required for storage and processing, in addition to visualization. This chapter describes a novel, language-based interface that allows scientists with basic programming skills to classify and render multivariate volumetric data with a modest investment in software training. The interface facilitates data exploration by enabling experimentation with various algorithms to compute opacity and color from volumetric data. The value of the system is demonstrated using data from cardiac mapping studies, in which multiple electrodes are placed in an on the heart to measure the cardiac electrical activity intrinsic to the heart and its response to external stimulation.

Rapid fusion of 2D X-ray fluoroscopy with 3D multislice CT for image-guided electrophysiology procedures

NASA Astrophysics Data System (ADS)

Zagorchev, Lyubomir; Manzke, Robert; Cury, Ricardo; Reddy, Vivek Y.; Chan, Raymond C.

2007-03-01

Interventional cardiac electrophysiology (EP) procedures are typically performed under X-ray fluoroscopy for visualizing catheters and EP devices relative to other highly-attenuating structures such as the thoracic spine and ribs. These projections do not however contain information about soft-tissue anatomy and there is a recognized need for fusion of conventional fluoroscopy with pre-operatively acquired cardiac multislice computed tomography (MSCT) volumes. Rapid 2D-3D integration in this application would allow for real-time visualization of all catheters present within the thorax in relation to the cardiovascular anatomy visible in MSCT. We present a method for rapid fusion of 2D X-ray fluoroscopy with 3DMSCT that can facilitate EP mapping and interventional procedures by reducing the need for intra-operative contrast injections to visualize heart chambers and specialized systems to track catheters within the cardiovascular anatomy. We use hardware-accelerated ray-casting to compute digitally reconstructed radiographs (DRRs) from the MSCT volume and iteratively optimize the rigid-body pose of the volumetric data to maximize the similarity between the MSCT-derived DRR and the intra-operative X-ray projection data.

Characterization of Glutamatergic Neurons in the Rat Atrial Intrinsic Cardiac Ganglia that Project to the Cardiac Ventricular Wall

PubMed Central

Wang, Ting; Miller, Kenneth E.

2016-01-01

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system. PMID:27167082

Cardiovascular Magnetic Resonance and prognosis in cardiac amyloidosis

PubMed Central

Maceira, Alicia M; Prasad, Sanjay K; Hawkins, Philip N; Roughton, Michael; Pennell, Dudley J

2008-01-01

Background Cardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR) can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE) and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study. Materials and methods The pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE). Results Patients with were followed for a median of 623 days (IQ range 221, 1436), during which 17 (58%) patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis). Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205). Conclusion In cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden. PMID:19032744

Mammalian enabled (Mena) is a critical regulator of cardiac function

PubMed Central

Aguilar, Frédérick; Belmonte, Stephen L.; Ram, Rashmi; Noujaim, Sami F.; Dunaevsky, Olga; Protack, Tricia L.; Jalife, Jose; Todd Massey, H.; Gertler, Frank B.

2011-01-01

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena−/−) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena−/− mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena−/− hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena−/− mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction. PMID:21335464

Mammalian enabled (Mena) is a critical regulator of cardiac function.

PubMed

Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

2011-05-01

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

Reproducibility and Angle Independence of Electromechanical Wave Imaging for the Measurement of Electromechanical Activation during Sinus Rhythm in Healthy Humans.

PubMed

Melki, Lea; Costet, Alexandre; Konofagou, Elisa E

2017-10-01

Electromechanical wave imaging (EWI) is an ultrasound-based technique that can non-invasively map the transmural electromechanical activation in all four cardiac chambers in vivo. The objective of this study was to determine the reproducibility and angle independence of EWI for the assessment of electromechanical activation during normal sinus rhythm (NSR) in healthy humans. Acquisitions were performed transthoracically at 2000 frames/s on seven healthy human hearts in parasternal long-axis, apical four- and two-chamber views. EWI data was collected twice successively in each view in all subjects, while four successive acquisitions were obtained in one case. Activation maps were generated and compared (i) within the same acquisition across consecutive cardiac cycles; (ii) within same view across successive acquisitions; and (iii) within equivalent left-ventricular regions across different views. EWI was capable of characterizing electromechanical activation during NSR and of reliably obtaining similar patterns of activation. For consecutive heart cycles, the average 2-D correlation coefficient between the two isochrones across the seven subjects was 0.9893, with a mean average activation time fluctuation in LV wall segments across acquisitions of 6.19%. A mean activation time variability of 12% was obtained across different views with a measurement bias of only 3.2 ms. These findings indicate that EWI can map the electromechanical activation during NSR in human hearts in transthoracic echocardiography in vivo and results in reproducible and angle-independent activation maps. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Left Ventricular Lead Placement Targeted at the Latest Activated Site Guided by Electrophysiological Mapping in Coronary Sinus Branches Improves Response to Cardiac Resynchronization Therapy.

PubMed

Liang, Yanchun; Yu, Haibo; Zhou, Weiwei; Xu, Guoqing; Sun, Y I; Liu, Rong; Wang, Zulu; Han, Yaling

2015-12-01

Electrophysiological mapping (EPM) in coronary sinus (CS) branches is feasible for guiding LV lead placement to the optimal, latest activated site at cardiac resynchronization therapy (CRT) procedures. However, whether this procedure optimizes the response to CRT has not been demonstrated. This study was to evaluate effects of targeting LV lead at the latest activated site guided by EPM during CRT. Seventy-six consecutive patients with advanced heart failure who were referred for CRT were divided into mapping (MG) and control groups (CG). In MG, the LV lead, also used as a mapping bipolar electrode, was placed at the latest activated site determined by EPM in CS branches. In CG, conventional CRT procedure was performed. Patients were followed for 6 months after CRT. Baseline characteristics were comparable between the 2 groups. In MG (n = 29), EPM was successfully performed in 85 of 91 CS branches during CRT. A LV lead was successfully placed at the latest activated site guided by EPM in 27 (93.1%) patients. Compared with CG (n = 47), MG had a significantly higher rate (86.2% vs. 63.8%, P = 0.039) of response (>15% reduction in LV end-systolic volume) to CRT, a higher percentage of patients with clinical improvement of ≥2 NYHA functional classes (72.4% vs. 44.7%, P = 0.032), and a shorter QRS duration (P = 0.004). LV lead placed at the latest activated site guided by EPM resulted in a significantly greater CRT response, and a shorter QRS duration. © 2015 Wiley Periodicals, Inc.

The potential of multi-slice computed tomography based volumetry for demonstrating reverse remodeling induced by cardiac resynchronization therapy.

PubMed

Langer, Christoph; Schroeder, Janina; Peterschroeder, Andreas; Vaske, Bernhard; Faber, Lothar; Welge, Dirk; Niethammer, Matthias; Lamp, Barbara; Butz, Thomas; Bitter, Thomas; Oldenburg, Olaf; Horstkotte, Dieter

2010-07-01

Multi-slice computed tomography (MSCT) was proved to provide precise cardiac volumetric assessment. Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with heart failure and reduced ejection fraction (HFREF). In HFREF patients we investigated the potential of MSCT based wall motion analysis in order to demonstrate CRT-induced reversed remodeling. Besides six patients with normal cardiac pump function serving as control group seven HFREF patients underwent contrast enhanced MSCT before and after CRT. Short cardiac axis views of the left ventricle (LV) in end-diastole (ED) and end-systole (ES) served for planimetry. Pre- and post-CRT MSCT based volumetry was compared with 2D echo. To demonstrate CRT-induced reverse remodeling, MSCT based multi-segment color-coded polar maps were introduced. With regard to the HFREF patients pre-CRT MSCT based volumetry correlated with 2D echo data for LV-EDV (MSCT 278.3+/-75.0mL vs. echo 274.4+/-85.6mL) r=0.380, p=0.401, LV-ESV (MSCT 226.7+/-75.4mL vs. echo 220.1+/-74.0mL) r=0.323, p=0.479 and LV-EF (MSCT 20.2+/-8.8% vs. echo 20.0+/-11.9%) r=0.617, p=0.143. Post-CRT MSCT correlated well with 2D echo: LV-EDV (MSCT 218.9+/-106.4mL vs. echo 188.7+/-93.1mL) r=0.87, p=0.011, LV-ESV (MSCT 145+/-71.5mL vs. echo 125.6+/-78mL) r=0.84, p=0.018 and LV-EF (MSCT 29.6+/-11.3mL vs. echo 38.6+/-14.6mL) r=0.89, p=0.007. There was a significant increase of the mid-ventricular septum in terms of absolute LV wall thickening of the responders (pre 0.9+/-2.1mm vs. post 3.3+/-2.2mm; p<0.0005). MSCT based volumetry involving multi-segment color-coded polar maps offers wall motion analysis to demonstrate CRT-induced reverse remodeling which needs to be further validated. 2010 Elsevier Ltd. All rights reserved.

Epitope mapping and targeted quantitation of the cardiac biomarker troponin by SID-MRM mass spectrometry.

PubMed

Zhao, Cheng; Trudeau, Beth; Xie, Helen; Prostko, John; Fishpaugh, Jeffrey; Ramsay, Carol

2014-06-01

The absolute quantitation of the targeted protein using MS provides a promising method to evaluate/verify biomarkers used in clinical diagnostics. In this study, a cardiac biomarker, troponin I (TnI), was used as a model protein for method development. The epitope peptide of TnI was characterized by epitope excision followed with LC/MS/MS method and acted as the surrogate peptide for the targeted protein quantitation. The MRM-based MS assay using a stable internal standard that improved the selectivity, specificity, and sensitivity of the protein quantitation. Also, plasma albumin depletion and affinity enrichment of TnI by anti-TnI mAb-coated microparticles reduced the sample complexity, enhanced the dynamic range, and further improved the detecting sensitivity of the targeted protein in the biological matrix. Therefore, quantitation of TnI, a low abundant protein in human plasma, has demonstrated the applicability of the targeted protein quantitation strategy through its epitope peptide determined by epitope mapping method. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reviving the protein quality control system: therapeutic target for cardiac disease in the elderly.

PubMed

Meijering, Roelien A M; Henning, Robert H; Brundel, Bianca J J M

2015-04-01

It has been firmly established that ageing constitutes a principal risk factor for cardiac disease. Currently, the underlying mechanisms of ageing that contribute to the initiation or acceleration of cardiac disease are essentially unresolved. Prevailing theories of ageing center on the loss of cellular protein homeostasis, by either design (genetically) or "wear and tear" (environmentally). Either or both ways, the normal protein homeostasis in the cell is affected, resulting in aberrant and misfolded proteins. Should such misfolded proteins escape the protein quality control (PQC) system, they become proteotoxic and accelerate the loss of cellular integrity. Impairment of PQC plays a prominent role in the pathophysiology of ageing-related neurodegenerative disorders such as Parkinson's, Huntington׳s, and Alzheimer׳s disease. The concept of an impaired PQC driving ageing-related diseases has recently been expanded to cardiac diseases, including atrial fibrillation, cardiac hypertrophy, and cardiomyopathy. In this review, we provide a brief overview of the PQC system in relation to ageing and discuss the emerging concept of the loss of PQC in cardiomyocytes as a trigger for cardiac disease. Finally, we discuss the potential of boosting the PQC system as an innovative therapeutic target to treat cardiac disease in the elderly. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

PubMed

Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

2017-09-01

The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

Remote health monitoring system for detecting cardiac disorders.

PubMed

Bansal, Ayush; Kumar, Sunil; Bajpai, Anurag; Tiwari, Vijay N; Nayak, Mithun; Venkatesan, Shankar; Narayanan, Rangavittal

2015-12-01

Remote health monitoring system with clinical decision support system as a key component could potentially quicken the response of medical specialists to critical health emergencies experienced by their patients. A monitoring system, specifically designed for cardiac care with electrocardiogram (ECG) signal analysis as the core diagnostic technique, could play a vital role in early detection of a wide range of cardiac ailments, from a simple arrhythmia to life threatening conditions such as myocardial infarction. The system that the authors have developed consists of three major components, namely, (a) mobile gateway, deployed on patient's mobile device, that receives 12-lead ECG signals from any ECG sensor, (b) remote server component that hosts algorithms for accurate annotation and analysis of the ECG signal and (c) point of care device of the doctor to receive a diagnostic report from the server based on the analysis of ECG signals. In the present study, their focus has been toward developing a system capable of detecting critical cardiac events well in advance using an advanced remote monitoring system. A system of this kind is expected to have applications ranging from tracking wellness/fitness to detection of symptoms leading to fatal cardiac events.

Three-dimensional self-gated cardiac MR imaging for the evaluation of myocardial infarction in mouse model on a 3T clinical MR system.

PubMed

Zhang, Xiaoyong; Qiu, Bensheng; Wei, Zijun; Yan, Fei; Shi, Caiyun; Su, Shi; Liu, Xin; Ji, Jim X; Xie, Guoxi

2017-01-01

To develop and assess a three-dimensional (3D) self-gated technique for the evaluation of myocardial infarction (MI) in mouse model without the use of external electrocardiogram (ECG) trigger and respiratory motion sensor on a 3T clinical MR system. A 3D T1-weighted GRE sequence with stack-of-stars sampling trajectories was developed and performed on six mice with MIs that were injected with a gadolinium-based contrast agent at a 3T clinical MR system. Respiratory and cardiac self-gating signals were derived from the Cartesian mapping of the k-space center along the partition encoding direction by bandpass filtering in image domain. The data were then realigned according to the predetermined self-gating signals for the following image reconstruction. In order to accelerate the data acquisition, image reconstruction was based on compressed sensing (CS) theory by exploiting temporal sparsity of the reconstructed images. In addition, images were also reconstructed from the same realigned data by conventional regridding method for demonstrating the advantageous of the proposed reconstruction method. Furthermore, the accuracy of detecting MI by the proposed method was assessed using histological analysis as the standard reference. Linear regression and Bland-Altman analysis were used to assess the agreement between the proposed method and the histological analysis. Compared to the conventional regridding method, the proposed CS method reconstructed images with much less streaking artifact, as well as a better contrast-to-noise ratio (CNR) between the blood and myocardium (4.1 ± 2.1 vs. 2.9 ± 1.1, p = 0.031). Linear regression and Bland-Altman analysis demonstrated that excellent correlation was obtained between infarct sizes derived from the proposed method and histology analysis. A 3D T1-weighted self-gating technique for mouse cardiac imaging was developed, which has potential for accurately evaluating MIs in mice at 3T clinical MR system without the use of external ECG trigger and respiratory motion sensor.

Puerarin attenuates severe burn-induced acute myocardial injury in rats.

PubMed

Liu, Sheng; Ren, Hong-Bo; Chen, Xu-Lin; Wang, Fei; Wang, Ren-Su; Zhou, Bo; Wang, Chao; Sun, Ye-Xiang; Wang, Yong-Jie

2015-12-01

Puerarin, the main isoflavone glycoside extracted from the root of Pueraria lobata, is widely prescribed for patients with cardiovascular disorders in China. This study investigates the effect of puerarin on severe burn-induced acute myocardial injury in rats and its underlying mechanisms. Healthy adult Wistar rats were divided into three groups: (1) sham group, sham burn treatment; (2) burn group, third-degree burns over 30% of the total body surface area (TBSA) with lactated Ringer's solution for resuscitation; and (3) burn plus puerarin group, third-degree burns over 30% of TBSA with lactated Ringer's solution containing puerarin for resuscitation. The burned animals were sacrificed at 1, 3, 6, 12, and 24 h after burn injury. Myocardial injury was evaluated by analyzing serum creatine kinase MB fraction (CK-MB) activity and cardiac troponin T (cTNT) level. Changes in cardiomyocyte ultrastructure were also determined using a transmission electron microscope. Tumor necrosis factor (TNF)-α concentration in serum was measured by radioimmunoassay. Cardiac myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to determine neutrophil infiltration and oxidative stress in the heart, respectively. The expression of p38 mitogen-activated protein (MAP) kinase in the heart was determined by Western blot analysis. After the 30% TBSA full-thickness burn injury, serum CK-MB activities and cTnT levels increased markedly, both of which were significantly decreased by the puerarin treatment. The level of serum TNF-α concentration in burn group at each time-point was obviously higher than those in sham group (1.09±0.09 ng/ml), and it reached the peak value at 12 h post burn. Burn trauma also resulted in worsen ultrastructural condition, elevated MPO activity and MDA content in heart tissue, and a significant activation of cardiac p38 MAP kinase. Administration of puerarin improved the ultrastructural changes in cardiomyocytes, decreased TNF-α concentration in serum as well as suppressed cardiac MPO activity and reduced MDA content, and abolished the activation of p38 MAP kinase in heart tissue after severe burn. These results suggest that puerarin attenuates inflammatory responses, reduces neutrophil infiltration and oxidative stress in the heart, and protects against acute myocardial injury induced by severe burn. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Location, variations, and predictors of epicardial fat mapping using multidetector computed tomography to assist epicardial ventricular tachycardia ablation.

PubMed

Sourwine, Mariaileen; Jeudy, Jean; Miller, Brian; Vunnam, Rama; Imanli, Hasan; Mesubi, Olurotimi; Etienne-Mesubi, Martine; See, Vincent; Shorofsky, Stephen; Dickfeld, Timm

2017-10-01

A significant number of ventricular tachycardia circuits are located close to the epicardial surface and are amendable to epicardial ablation. Epicardial fat often interferes with substrate mapping and ablation, though little is known regarding the distribution of fat and its fluctuation with the cardiac cycle. We studied 40 patients who underwent a 64-slice multidetector computed tomography in order to describe patterns of epicardial fat distribution, variation during cardiac cycle, and clinical predictors of epicardial fat. Multiplanar reconstructions were analyzed during systole and diastole in six cross-sections. Epicardial fat thickness was measured across multiple wall segments in each view. Epicardial fat was found to be thicker in areas overlying coronary vasculature (7.8 ± 2.6 mm vs 3.5 ± 0.9 mm, P = 0.001), along with the right ventricular wall (3.9 ± 0.8 mm vs 2.6 ± 0.6 mm, P = 0.001) and the ventricular base (6.1 ± 1.7 mm vs 4.6 ± 1.6 mm, P < 0.01). Epicardial fat thickness increased 27% during systole as compared to diastole (4.9 ± 2.7 mm vs 6.2 ± 3.0 mm, P = 0.04). Variation with cardiac cycle was most evident along the right ventricular wall (3.9 ± 0.8 mm vs 5.0 ± 1.3 mm, P = 0.001) and nonvascular areas (P = 0.001), especially at the ventricular base (3.7 ± 1.1 mm vs 5.3 ± 1.5 mm, P = 0.001). In multivariate logistic regression, we found that age >50 years (P = 0.031) and coronary artery disease (P = 0.023) were statistically correlated with epicardial fat >5-mm thickness and body mass index > 33 (P = 0.052) nearly so. Baseline epicardial fat thickness >5 mm is common in areas typically targeted during epicardial ablation and further increases during the cardiac cycle. Simple clinical characteristics can identify patients with >5 mm epicardial fat in which preprocedural computed tomography imaging and three-dimensional fat map reconstruction may facilitate epicardial ablation. © 2017 Wiley Periodicals, Inc.

Cardiac arrest

MedlinePlus

... it does not necessarily cause death. Sometimes a heart attack can trigger a cardiac arrest, however. Cardiac arrest is caused by a problem with the heart's electrical system, such as: Ventricular fibrillation (VF) . When ...

An adaptive spatio-temporal Gaussian filter for processing cardiac optical mapping data.

PubMed

Pollnow, S; Pilia, N; Schwaderlapp, G; Loewe, A; Dössel, O; Lenis, G

2018-06-04

Optical mapping is widely used as a tool to investigate cardiac electrophysiology in ex vivo preparations. Digital filtering of fluorescence-optical data is an important requirement for robust subsequent data analysis and still a challenge when processing data acquired from thin mammalian myocardium. Therefore, we propose and investigate the use of an adaptive spatio-temporal Gaussian filter for processing optical mapping signals from these kinds of tissue usually having low signal-to-noise ratio (SNR). We demonstrate how filtering parameters can be chosen automatically without additional user input. For systematic comparison of this filter with standard filtering methods from the literature, we generated synthetic signals representing optical recordings from atrial myocardium of a rat heart with varying SNR. Furthermore, all filter methods were applied to experimental data from an ex vivo setup. Our developed filter outperformed the other filter methods regarding local activation time detection at SNRs smaller than 3 dB which are typical noise ratios expected in these signals. At higher SNRs, the proposed filter performed slightly worse than the methods from literature. In conclusion, the proposed adaptive spatio-temporal Gaussian filter is an appropriate tool for investigating fluorescence-optical data with low SNR. The spatio-temporal filter parameters were automatically adapted in contrast to the other investigated filters. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of contact force on voltage mapping: A combined magnetic resonance imaging and electroanatomic mapping study in patients with tetralogy of Fallot.

PubMed

Teijeira-Fernandez, Elvis; Cochet, Hubert; Bourier, Felix; Takigawa, Masateru; Cheniti, Ghassen; Thompson, Nathaniel; Frontera, Antonio; Camaioni, Claudia; Massouille, Gregoire; Jalal, Zakaria; Derval, Nicolas; Iriart, Xavier; Denis, Arnaud; Hocini, Meleze; Haissaguerre, Michel; Jais, Pierre; Thambo, Jean-Benoit; Sacher, Frederic

2018-03-20

Voltage criteria for ventricular mapping have been obtained from small series of patients and prioritizing high specificity. The purpose of this study was to analyse the potential influence of contact force (CF) on voltage mapping and to define voltage cutoff values for right ventricular (RV) scar using the tetralogy of Fallot as a model of transmural RV scar and magnetic resonance imaging (MRI) as reference. Fourteen patients (age 32.6 ± 14.3 years; 5 female) with repaired tetralogy of Fallot underwent high-resolution cardiac MRI (1.25 × 1.25 × 2.5 mm). Scar, defined as pixels with intensity >50% maximum, was mapped over the RV geometry and merged within the CARTO system to RV endocardial voltage maps acquired using a 3.5-mm ablation catheter with CF technology (SmartTouch, Biosense Webster). In total, 2446 points were analyzed, 915 within scars and 1531 in healthy tissue according to MRI. CF correlated to unipolar (ρ = 0.186; P <.001) and bipolar voltage in healthy tissue (ρ = 0.245; P <.001) and in scar tissue. Receiver operating characteristic curve analysis excluding points with very low CF (<5g) identified optimal voltage cutoffs of 5.19 mV for unipolar voltage and 1.76 mV for bipolar voltage, yielding sensitivity/specificity of 0.89/0.85 and 0.9/0.9, respectively. CF is an important factor to be taken into account for voltage mapping. If good CF is applied, unipolar and bipolar voltage cutoffs of 5.19 mV and 1.76 mV are optimal for identifying RV scar on endocardial mapping with the SmartTouch catheter. Data on the diagnostic accuracy of different voltage cutoff values are provided. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Standardized unfold mapping: a technique to permit left atrial regional data display and analysis.

PubMed

Williams, Steven E; Tobon-Gomez, Catalina; Zuluaga, Maria A; Chubb, Henry; Butakoff, Constantine; Karim, Rashed; Ahmed, Elena; Camara, Oscar; Rhode, Kawal S

2017-10-01

Left atrial arrhythmia substrate assessment can involve multiple imaging and electrical modalities, but visual analysis of data on 3D surfaces is time-consuming and suffers from limited reproducibility. Unfold maps (e.g., the left ventricular bull's eye plot) allow 2D visualization, facilitate multimodal data representation, and provide a common reference space for inter-subject comparison. The aim of this work is to develop a method for automatic representation of multimodal information on a left atrial standardized unfold map (LA-SUM). The LA-SUM technique was developed and validated using 18 electroanatomic mapping (EAM) LA geometries before being applied to ten cardiac magnetic resonance/EAM paired geometries. The LA-SUM was defined as an unfold template of an average LA mesh, and registration of clinical data to this mesh facilitated creation of new LA-SUMs by surface parameterization. The LA-SUM represents 24 LA regions on a flattened surface. Intra-observer variability of LA-SUMs for both EAM and CMR datasets was minimal; root-mean square difference of 0.008 ± 0.010 and 0.007 ± 0.005 ms (local activation time maps), 0.068 ± 0.063 gs (force-time integral maps), and 0.031 ± 0.026 (CMR LGE signal intensity maps). Following validation, LA-SUMs were used for automatic quantification of post-ablation scar formation using CMR imaging, demonstrating a weak but significant relationship between ablation force-time integral and scar coverage (R 2  = 0.18, P < 0.0001). The proposed LA-SUM displays an integrated unfold map for multimodal information. The method is applicable to any LA surface, including those derived from imaging and EAM systems. The LA-SUM would facilitate standardization of future research studies involving segmental analysis of the LA.

[Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs.

PubMed

Martins, Luiz Cláudio; Sabha, Maricene; Paganelli, Maria Ondina; Coelho, Otávio Rizzi; Ferreira-Melo, Silvia Elaine; Moreira, Marcos Mello; Cavalho, Adriana Camargo de; Araujo, Sebastião; Moreno Junior, Heitor

2010-01-15

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.

Vasopressin-induced changes in splanchnic blood flow and hepatic and portal venous pressures in liver resection.

PubMed

Bown, L Sand; Ricksten, S-E; Houltz, E; Einarsson, H; Söndergaard, S; Rizell, M; Lundin, S

2016-05-01

To minimize blood loss during hepatic surgery, various methods are used to reduce pressure and flow within the hepato-splanchnic circulation. In this study, the effect of low- to moderate doses of vasopressin, a potent splanchnic vasoconstrictor, on changes in portal and hepatic venous pressures and splanchnic and hepato-splanchnic blood flows were assessed in elective liver resection surgery. Twelve patients were studied. Cardiac output (CO), stroke volume (SV), mean arterial (MAP), central venous (CVP), portal venous (PVP) and hepatic venous pressures (HVP) were measured, intraoperatively, at baseline and during vasopressin infusion at two infusion rates (2.4 and 4.8 U/h). From arterial and venous blood gases, the portal (splanchnic) and hepato-splanchnic blood flow changes were calculated, using Fick's equation. CO, SV, MAP and CVP increased slightly, but significantly, while systemic vascular resistance and heart rate remained unchanged at the highest infusion rate of vasopressin. PVP was not affected by vasopressin, while HVP increased slightly. Vasopressin infusion at 2.4 and 4.8 U/h reduced portal blood flow (-26% and -37%, respectively) and to a lesser extent hepato-splanchnic blood flow (-9% and -14%, respectively). The arterial-portal vein lactate gradient was not significantly affected by vasopressin. Postoperative serum creatinine was not affected by vasopressin. Short-term low to moderate infusion rates of vasopressin induced a splanchnic vasoconstriction without metabolic signs of splanchnic hypoperfusion or subsequent renal impairment. Vasopressin caused a centralization of blood volume and increased cardiac output. Vasopressin does not lower portal or hepatic venous pressures in this clinical setting. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Development and evaluation of a pliable biological valved conduit. Part II: Functional and hemodynamic evaluation.

PubMed

Sung, H W; Witzel, T H; Hata, C; Tu, R; Shen, S H; Lin, D; Noishiki, Y; Tomizawa, Y; Quijano, R C

1993-04-01

Many congenital cardiac malformations may require a valved conduit for the reconstruction of the right ventricular outflow tract. In spite of many endeavors made in the last 25 years, the clinical results of right ventricular outflow tract reconstruction with currently available valved conduits are still not satisfactory. Specific problems encountered clinically include suboptimal hemodynamic performance, conduit kinking or compression, and fibrous peeling from the luminal surface. To address these deficiencies, we undertook the development of a biological valved conduit: a bovine external jugular vein graft with a retained native valve cross-linked with a diglycidyl ether (DE). This study, using a canine model, was to evaluate the functional and hemodynamic performance of this newly developed valved conduit. Three 14 mm conduits, implanted as bypass grafts, right ventricle to pulmonary artery, were evaluated. The evaluation was conducted with a noninvasive color Doppler flow mapping system at pre-implantation, immediately post implantation, one- and three-months post implantation, and prior to retrieval (five-months post implantation). The two-dimensional tomographic inspection of the leaflet motion at various periods post implantation showed that the valvular leaflets in the DE treated conduit was quite pliable. No cardiac failure or valvular dysfunction was observed in any of the studied cases. The color Doppler flow mapping study demonstrated that the valve in the DE treated conduit was competent, with no conduit kinking or compression observed in any of the three cases. The spectral Doppler velocity study evidenced that the transvalvular pressure gradients of the DE treated conduit were minimal as compared to those of the currently available conduits. In conclusion, from the functional and hemodynamic performance points of view, this newly developed valved conduit is superior to those currently available.

3D ultrafast ultrasound imaging in vivo.

PubMed

Provost, Jean; Papadacci, Clement; Arango, Juan Esteban; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

2014-10-07

Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra--and inter-observer variability.

Neurophysiological responses to music and vibroacoustic stimuli in Rett syndrome.

PubMed

Bergström-Isacsson, Märith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

2014-06-01

People with Rett syndrome (RTT) have severe communicative difficulties. They have as well an immature brainstem that implies dysfunction of the autonomic nervous system. Music plays an important role in their life, is often used as a motivating tool in a variety of situations and activities, and caregivers are often clear about people with RTTs favourites. The aim of this study was to investigate physiological and emotional responses related to six different musical stimuli in people with RTT. The study included 29 participants with RTT who were referred to the Swedish Rett Center for medical brainstem assessment during the period 2006-2007. 11 children with a typical developmental pattern were used as comparison. A repeated measures design was used, and physiological data were collected from a neurophysiological brainstem assessment. The continuous dependent variables measured were Cardiac Vagal Tone (CVT), Cardiac Sensitivity to Baroreflex (CSB), Mean Arterial Blood Pressure (MAP) and the Coefficient of Variation of Mean Arterial Blood Pressure (MAP-CV). These parameters were used to categorise brainstem responses as parasympathetic (calming) response, sympathetic (activating) response, arousal (alerting) response and unclear response. The results showed that all participants responded to the musical stimuli, but not always in the expected way. It was noticeable that both people with and without RTT responded with an arousal to all musical stimuli to begin with. Even though the initial expressions sometimes changed after some time due to poor control functions of their brainstem, the present results are consistent with the possibility that the RTT participants' normal responses to music are intact. These findings may explain why music is so important for individuals with RTT throughout life. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cardiac transplant in young female patient diagnosed with diffuse systemic sclerosis.

PubMed

Bennasar, Guillermo; Carlevaris, Leandro; Secco, Anastasia; Romanini, Felix; Mamani, Marta

2016-01-01

Systemic sclerosis (SS) in a multifactorial and systemic, chronic, autoimmune disease that affects the connective tissue. We present this clinical case given the low prevalence of diffuse SS with early and progressive cardiac compromise in a young patient, and treatment with cardiac transplantation. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1-13C]pyruvate.

PubMed

Lau, Angus Z; Miller, Jack J; Tyler, Damian J

2017-05-01

To demonstrate the feasibility of mapping intracellular pH within the in vivo rodent heart. Alterations in cardiac acid-base balance can lead to acute contractile depression and alterations in Ca 2+ signaling. The transient reduction in adenosine triphosphate (ATP) consumption and cardiac contractility may be initially beneficial; however, sustained pH changes can be maladaptive, leading to myocardial damage and electrical arrhythmias. Spectrally selective radiofrequency (RF) pulses were used to excite the HCO3- and CO 2 resonances individually while preserving signal from the injected hyperpolarized [1- 13 C]pyruvate. The large flip angle pulses were placed within a three-dimensional (3D) imaging acquisition, which exploited CA-mediated label exchange between HCO3- and CO 2 . Images at 4.5 × 4.5 × 5 mm 3 resolution were obtained in the in vivo rodent heart. The technique was evaluated in healthy rodents scanned at baseline and during high cardiac workload induced by dobutamine infusion. The intracellular pH was measured to be 7.15 ± 0.04 at baseline, and decreased to 6.90 ± 0.06 following 15 min of continuous β-adrenergic stimulation. Volumetric maps of intracellular pH can be obtained following an injection of hyperpolarized [1- 13 C]pyruvate. The new method is anticipated to enable assessment of stress-inducible ischemia and potential ventricular arrythmogenic substrates within the ischemic heart. Magn Reson Med 77:1810-1817, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Sodium Channel Mutations and Susceptibility to Heart Failure and Atrial Fibrillation

PubMed Central

Olson, Timothy M.; Michels, Virginia V.; Ballew, Jeffrey D.; Reyna, Sandra P.; Karst, Margaret L.; Herron, Kathleen J.; Horton, Steven C.; Rodeheffer, Richard J.; Anderson, Jeffrey L.

2007-01-01

Context Dilated cardiomyopathy (DCM), a genetically heterogeneous disorder, causes heart failure and rhythm disturbances. The majority of identified DCM genes encode structural proteins of the contractile apparatus and cytoskeleton. Recently, genetic defects in calcium and potassium regulation have been discovered in patients with DCM, implicating an alternative disease mechanism. The full spectrum of genetic defects in DCM, however, has not been established. Objectives To identify a novel gene for DCM at a previously mapped locus, define the spectrum of mutations in this gene within a DCM cohort, and determine the frequency of DCM among relatives inheriting a mutation in this gene. Design, Setting, and Participants Refined mapping of a DCM locus on chromosome 3p in a multigenerational family and mutation scanning in 156 unrelated pro-bands with DCM, prospectively identified at the Mayo Clinic between 1987 and 2004. Relatives underwent screening echocardiography and electrocardiography and DNA sample procurement. Main Outcome Measure Correlation of identified mutations with cardiac phenotype. Results Refined locus mapping revealed SCN5A, encoding the cardiac sodium channel, as a candidate gene. Mutation scans identified a missense mutation (D1275N) that cosegregated with an age-dependent, variably expressed phenotype of DCM, atrial fibrillation, impaired automaticity, and conduction delay. In the DCM cohort, additional missense (T220I, R814W, D1595H) and truncation (2550-2551insTG) SCN5A mutations, segregating with cardiac disease or arising de novo, were discovered in unrelated probands. Among individuals with an SCN5A mutation 27% had early features of DCM (mean age at diagnosis, 20.3 years), 38% had DCM (mean age at diagnosis, 47.9 years), and 43% had atrial fibrillation (mean age at diagnosis, 27.8 years). Conclusions Heritable SCN5A defects are associated with susceptibility to early-onset DCM and atrial fibrillation. Similar or even identical mutations may lead to heart failure, arrhythmia, or both. PMID:15671429

[Cardiac tamponade disclosing systemic lupus erythematosus].

PubMed

Nour-Eddine, M; Bennis, A; Soulami, S; Chraibi, N

1996-02-01

Cardiac tamponade secondary to systemic lupus erythematosus is rare and has a very serious prognosis. The authors report a case of cardiac tamponade confirmed by echocardiography, which constituted the presenting sign of systemic lupus erythematosus in a 20-year-old patient, who required emergency pericardial aspiration. The diagnosis of systemic lupus erythematosus was established on the basis of the combination of pericardial involvement, non-erosive arthritis, leukopenia with lymphopenia, presence of LE cells and anti-native DNA antibodies and positive antinuclear antibody titre of 1/2560. The clinical course was favourable in response to 3 months of corticosteroid treatment. The possibility of SLE should be considered in any case of cardiac tamponade in a young patient in which the aetiology is not explained.

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

PubMed

Yu, Ki Jun; Kuzum, Duygu; Hwang, Suk-Won; Kim, Bong Hoon; Juul, Halvor; Kim, Nam Heon; Won, Sang Min; Chiang, Ken; Trumpis, Michael; Richardson, Andrew G; Cheng, Huanyu; Fang, Hui; Thomson, Marissa; Bink, Hank; Talos, Delia; Seo, Kyung Jin; Lee, Hee Nam; Kang, Seung-Kyun; Kim, Jae-Hwan; Lee, Jung Yup; Huang, Younggang; Jensen, Frances E; Dichter, Marc A; Lucas, Timothy H; Viventi, Jonathan; Litt, Brian; Rogers, John A

2016-07-01

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required.

Use of diagnostic information submitted to the United Kingdom Central Cardiac Audit Database: development of categorisation and allocation algorithms.

PubMed

Brown, Kate L; Crowe, Sonya; Pagel, Christina; Bull, Catherine; Muthialu, Nagarajan; Gibbs, John; Cunningham, David; Utley, Martin; Tsang, Victor T; Franklin, Rodney

2013-08-01

To categorise records according to primary cardiac diagnosis in the United Kingdom Central Cardiac Audit Database in order to add this information to a risk adjustment model for paediatric cardiac surgery. Codes from the International Paediatric Congenital Cardiac Code were mapped to recognisable primary cardiac diagnosis groupings, allocated using a hierarchy and less refined diagnosis groups, based on the number of functional ventricles and presence of aortic obstruction. A National Clinical Audit Database. Patients Children undergoing cardiac interventions: the proportions for each diagnosis scheme are presented for 13,551 first patient surgical episodes since 2004. In Scheme 1, the most prevalent diagnoses nationally were ventricular septal defect (13%), patent ductus arteriosus (10.4%), and tetralogy of Fallot (9.5%). In Scheme 2, the prevalence of a biventricular heart without aortic obstruction was 64.2% and with aortic obstruction was 14.1%; the prevalence of a functionally univentricular heart without aortic obstruction was 4.3% and with aortic obstruction was 4.7%; the prevalence of unknown (ambiguous) number of ventricles was 8.4%; and the prevalence of acquired heart disease only was 2.2%. Diagnostic groups added to procedural information: of the 17% of all operations classed as "not a specific procedure", 97.1% had a diagnosis identified in Scheme 1 and 97.2% in Scheme 2. Diagnostic information adds to surgical procedural data when the complexity of case mix is analysed in a national database. These diagnostic categorisation schemes may be used for future investigation of the frequency of conditions and evaluation of long-term outcome over a series of procedures.

Investigation of availability and accessibility of community automated external defibrillators in a territory in Hong Kong.

PubMed

Ho, C L; Lui, C T; Tsui, K L; Kam, C W

2014-10-01

To evaluate the availability and accessibility of community automated external defibrillators in a territory in Hong Kong. Cross-sectional study. Two public hospitals in New Territories West Cluster in Hong Kong. Information about the locations of community automated external defibrillators was obtained from automated external defibrillator suppliers and through community search. Data on locations of out-of-hospital cardiac arrests from August 2010 to September 2013 were obtained from the local cardiac arrest registry of the emergency departments of two hospitals. Sites of both automated external defibrillators and out-of-hospital cardiac arrests were geographically coded and mapped. The number of out-of-hospital cardiac arrests within 100 m of automated external defibrillators per year and the proportion of out-of-hospital cardiac arrests with accessible automated external defibrillators (100 m) were calculated. The number of community automated external defibrillators per 10,000 population and public access defibrillation rate were also calculated and compared with those in other countries. There were a total of 207 community automated external defibrillators in the territory. The number of automated external defibrillators per 10,000 population was 1.942. All facilities with automated external defibrillators in this territory had more than 0.2 out-of-hospital cardiac arrests per automated external defibrillator per year within 100 m. Among all out-of-hospital cardiac arrests, 25.2% could have an automated external defibrillator reachable within 100 m. The public access defibrillation rate was 0.168%. The number and accessibility of community automated external defibrillators in this territory are comparable to those in other developed countries. The placement site of community automated external defibrillators is cost-effective. However, the public access defibrillation rate is low.

Identification of Location Specific Feature Points in a Cardiac Cycle Using a Novel Seismocardiogram Spectrum System.

PubMed

Lin, Wen-Yen; Chou, Wen-Cheng; Chang, Po-Cheng; Chou, Chung-Chuan; Wen, Ming-Shien; Ho, Ming-Yun; Lee, Wen-Chen; Hsieh, Ming-Jer; Lin, Chung-Chih; Tsai, Tsai-Hsuan; Lee, Ming-Yih

2018-03-01

Seismocardiogram (SCG) or mechanocardiography is a noninvasive cardiac diagnostic method; however, previous studies used only a single sensor to detect cardiac mechanical activities that will not be able to identify location-specific feature points in a cardiac cycle corresponding to the four valvular auscultation locations. In this study, a multichannel SCG spectrum measurement system was proposed and examined for cardiac activity monitoring to overcome problems like, position dependency, time delay, and signal attenuation, occurring in traditional single-channel SCG systems. ECG and multichannel SCG signals were simultaneously recorded in 25 healthy subjects. Cardiac echocardiography was conducted at the same time. SCG traces were analyzed and compared with echocardiographic images for feature point identification. Fifteen feature points were identified in the corresponding SCG traces. Among them, six feature points, including left ventricular lateral wall contraction peak velocity, septal wall contraction peak velocity, transaortic peak flow, transpulmonary peak flow, transmitral ventricular relaxation flow, and transmitral atrial contraction flow were identified. These new feature points were not observed in previous studies because the single-channel SCG could not detect the location-specific signals from other locations due to time delay and signal attenuation. As the results, the multichannel SCG spectrum measurement system can record the corresponding cardiac mechanical activities with location-specific SCG signals and six new feature points were identified with the system. This new modality may help clinical diagnoses of valvular heart diseases and heart failure in the future.

The heart as an extravascular target of endothelin-1 in ...

EPA Pesticide Factsheets

Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease and cardiac dysfunction have been explored, though linkage with specific factors or genes remains limited. Given evidence pointing to autocrine/paracrine signaling systems as modulators of cardiac dysfunction, the present review highlights the emerging role of endothelins as mediators of cardiac dysfunction following particulate matter exposure. Endothelin-1 is a small multifunctional protein expressed in the pulmonary and cardiovascular system, known for its ability to constrict blood vessels. Although endothelin-1 can also directly and indirectly (via secondary signaling events) modulate cardiac contractility, heart rate, and rhythm, research on the role of endothelins in the context of air pollution has tended to focus on the vascular effects. The plausibility of endothelin as a mechanism underlying particulate matter-induced cardiac dysfunction is further supported by the therapeutic utility of certain endothelin receptor antagonists. Extravascular effects of endothelin on the heart could better explain one mechanism by which particulate matter exposure may lead to cardiac dysfunction. We propose and support the novel hypothesis that autocrine/paracrine signaling systems, such as endothelins, mediate cardiac

AKAP-scaffolding proteins and regulation of cardiac physiology

PubMed Central

Mauban, JRH; O'Donnell, M; Warrier, S; Manni, S; Bond, M

2009-01-01

A kinase anchoring proteins (AKAPs) compose a growing list of diverse but functionally related proteins defined by their ability to bind to the regulatory subunit of protein kinase A. AKAPs perform an integral role in the spatiotemporal modulation of a multitude of cellular signaling pathways. This review highlights the extensive role of AKAPs in cardiac excitation/contraction coupling and cardiac physiology. The literature shows that particular AKAPs are involved in cardiac Ca2+ influx, release, re-uptake, and myocyte repolarization. Studies have also suggested roles for AKAPs in cardiac remodeling. Transgenic studies show functional effects of AKAPs, not only in the cardiovascular system, but in other organ systems as well. PMID:19364910

Pneumatic antishock garment inflation activates the human sympathetic nervous system by abdominal compression.

PubMed

Garvin, Nathan M; Levine, Benjamin D; Raven, Peter B; Pawelczyk, James A

2014-01-01

Pneumatic antishock garments (PASG) have been proposed to exert their blood pressure-raising effect mechanically, i.e. by increasing venous return and vascular resistance of the lower body. We tested whether, alternatively, PASG inflation activates the sympathetic nervous system. Five men and four women wore PASG while mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), heart rate and stroke volume were measured. One leg bladder (LEG) and the abdominal bladder (ABD) of the trousers were inflated individually and in combination (ABD+LEG), at 60 or 90 mmHg for 3 min. By the end of 3 min of inflation, conditions that included the ABD region caused significant increases in MAP in a dose-dependent fashion (7 ± 2, 8 ± 3, 14 ± 4 and 13 ± 5 mmHg for ABD60, ABD+LEG60, ABD90 and ABD+LEG90, respectively, P < 0.05). Likewise, inflation that included ABD caused significant increases in total MSNA compared with control values [306 ± 70, 426 ± 98 and 247 ± 79 units for ABD60, ABD90 and ABD+LEG90, respectively, P < 0.05 (units = burst frequency × burst amplitude]. There were no changes in MAP or MSNA in the LEG-alone conditions. The ABD inflation also caused a significant decrease in stroke volume (-11 ± 3 and -10 ± 3 ml per beat in ABD90 and ABD+LEG90, respectively, P < 0.05) with no change in cardiac output. Neither cardiopulmonary receptor deactivation nor mechanical effects can account for a slowly developing rise in both sympathetic activity and blood pressure during ABD inflation. Rather, these data provide direct evidence that PASG inflation activates the sympathetic nervous system secondarily to abdominal, but not leg, compression.

RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 6: Post-cardiac arrest care.

PubMed

Smarick, Sean D; Haskins, Steve C; Boller, Manuel; Fletcher, Daniel J

2012-06-01

To systematically examine the evidence for interventions after the return of spontaneous circulation (ROSC) on outcomes from veterinary cardiopulmonary resuscitation and to determine important knowledge gaps. Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical post-cardiac arrest care. Academia, referral practice, and general practice. Fifteen standardized clinical questions important for post-cardiac arrest care were asked and research articles relevant to answering these questions were identified through structured, explicit literature database searches. The majority of these articles report research in species other than dogs or cats or consisted of experimental work in canine cardiac arrest models. Outcome metrics reported in these studies widely varied and ranged from quantification of mechanistic endpoints, such as elaboration of reactive oxygen species, to survival, and functional neurologic outcome. Despite the near complete absence of clinical veterinary studies, the process allowed the formulation of statements for several postcardiac arrest treatments that were either supportive, such as mild therapeutic hypothermia or controlled reoxygenation, or neutral, such as for mannitol administration or seizure prophylaxis. Evidence grading allowed transparency in regards to the strength of these recommendations. Moreover, numerous knowledge gaps emerged that will allow generation of a road map for progress in veterinary post-cardiac arrest care. © Veterinary Emergency and Critical Care Society 2012.

Introduction to the Canadian Cardiovascular Outcomes Research Team's (CCORT) Canadian Cardiovascular Atlas project.

PubMed

Tu, Jack V; Brien, Susan E; Kennedy, Courtney C; Pilote, Louise; Ghali, William A

2003-03-15

The Canadian Cardiovascular Outcomes Research Team's (CCORT) Canadian Cardiovascular Atlas project was developed to provide Canadians with a national report on the state of cardiovascular health and health services in Canada. Written by a group of Canada's leading experts in cardiovascular outcomes research, the CCORT cardiac Atlas will cover a wide variety of topics ranging from cardiac risk factors and cardiac mortality rates to the treatment of patients with acute myocardial infarction and congestive heart failure and the outcomes of invasive cardiac procedures across Canada. Data in the Atlas will be presented at a national, provincial and health region level. The Atlas will be published as a series of 20 articles and chapters in future issues of The Canadian Journal of Cardiology and on CCORT's web site (www.ccort.ca). The journal version of the Atlas chapters will be written for a clinical audience and will include editorials written by invited experts, whereas the web-based version of each chapter will be written for a more general audience and will include additional supplemental information (for example, interactive colour maps and tables) that cannot be included in the journal version. Material from the Journal and the web will eventually be compiled into a book that will be distributed across Canada. This article serves as an introduction to the Atlas project and describes the rationale for and objectives of the CCORT national cardiac Atlas project.

Issues in solid-organ transplantation in children: translational research from bench to bedside

PubMed Central

Lipshultz, Steven E.; Chandar, Jayanthi J.; Rusconi, Paolo G.; Fornoni, Alessia; Abitbol, Carolyn L.; Burke III, George W.; Zilleruelo, Gaston E.; Pham, Si M.; Perez, Elena E.; Karnik, Ruchika; Hunter, Juanita A.; Dauphin, Danielle D.; Wilkinson, James D.

2014-01-01

In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children. PMID:24860861

Primary structure of rat cardiac beta-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: further evidence for a multigene family.

PubMed

Gocayne, J; Robinson, D A; FitzGerald, M G; Chung, F Z; Kerlavage, A R; Lentes, K U; Lai, J; Wang, C D; Fraser, C M; Venter, J C

1987-12-01

Two cDNA clones, lambda RHM-MF and lambda RHB-DAR, encoding the muscarinic cholinergic receptor and the beta-adrenergic receptor, respectively, have been isolated from a rat heart cDNA library. The cDNA clones were characterized by restriction mapping and automated DNA sequence analysis utilizing fluorescent dye primers. The rat heart muscarinic receptor consists of 466 amino acids and has a calculated molecular weight of 51,543. The rat heart beta-adrenergic receptor consists of 418 amino acids and has a calculated molecular weight of 46,890. The two cardiac receptors have substantial amino acid homology (27.2% identity, 50.6% with favored substitutions). The rat cardiac beta receptor has 88.0% homology (92.5% with favored substitutions) with the human brain beta receptor and the rat cardiac muscarinic receptor has 94.6% homology (97.6% with favored substitutions) with the porcine cardiac muscarinic receptor. The muscarinic cholinergic and beta-adrenergic receptors appear to be as conserved as hemoglobin and cytochrome c but less conserved than histones and are clearly members of a multigene family. These data support our hypothesis, based upon biochemical and immunological evidence, that suggests considerable structural homology and evolutionary conservation between adrenergic and muscarinic cholinergic receptors. To our knowledge, this is the first report utilizing automated DNA sequence analysis to determine the structure of a gene.

Patient-specific models of cardiac biomechanics

NASA Astrophysics Data System (ADS)

Krishnamurthy, Adarsh; Villongco, Christopher T.; Chuang, Joyce; Frank, Lawrence R.; Nigam, Vishal; Belezzuoli, Ernest; Stark, Paul; Krummen, David E.; Narayan, Sanjiv; Omens, Jeffrey H.; McCulloch, Andrew D.; Kerckhoffs, Roy C. P.

2013-07-01

Patient-specific models of cardiac function have the potential to improve diagnosis and management of heart disease by integrating medical images with heterogeneous clinical measurements subject to constraints imposed by physical first principles and prior experimental knowledge. We describe new methods for creating three-dimensional patient-specific models of ventricular biomechanics in the failing heart. Three-dimensional bi-ventricular geometry is segmented from cardiac CT images at end-diastole from patients with heart failure. Human myofiber and sheet architecture is modeled using eigenvectors computed from diffusion tensor MR images from an isolated, fixed human organ-donor heart and transformed to the patient-specific geometric model using large deformation diffeomorphic mapping. Semi-automated methods were developed for optimizing the passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Material properties of active cardiac muscle contraction were optimized to match ventricular pressures measured by cardiac catheterization, and parameters of a lumped-parameter closed-loop model of the circulation were estimated with a circulatory adaptation algorithm making use of information derived from echocardiography. These components were then integrated to create a multi-scale model of the patient-specific heart. These methods were tested in five heart failure patients from the San Diego Veteran's Affairs Medical Center who gave informed consent. The simulation results showed good agreement with measured echocardiographic and global functional parameters such as ejection fraction and peak cavity pressures.

Cardiac Effects of Lightning Strikes

PubMed Central

Khan, Sarosh; Ahmad, Mahmood; Fayed, Hossam; Bogle, Richard

2017-01-01

Lightning strikes are a common and leading cause of morbidity and mortality. Multiple organ systems can be involved, though the effects of the electrical current on the cardiovascular system are one of the main modes leading to cardiorespiratory arrest in these patients. Cardiac effects of lightning strikes can be transient or persistent, and include benign or life-threatening arrhythmias, inappropriate therapies from cardiac implantable electronic devices, cardiac ischaemia, myocardial contusion, pericardial disease, aortic injury, as well as cardiomyopathy with associated ventricular failure. Prolonged resuscitation can lead to favourable outcomes especially in young and previously healthy victims. PMID:29018518

Thyroid disease and the cardiovascular system.

PubMed

Danzi, Sara; Klein, Irwin

2014-06-01

Thyroid hormones, specifically triiodothyronine (T3), have significant effects on the heart and cardiovascular system. Hypothyroidism, hyperthyroidism, subclinical thyroid disease, and low T3 syndrome each cause cardiac and cardiovascular abnormalities through both genomic and nongenomic effects on cardiac myocytes and vascular smooth muscle cells. In compromised health, such as occurs in heart disease, alterations in thyroid hormone metabolism may further impair cardiac and cardiovascular function. Diagnosis and treatment of cardiac disease may benefit from including analysis of thyroid hormone status, including serum total T3 levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Reconstruction of phase maps from the configuration of phase singularities in two-dimensional manifolds.

PubMed

Herlin, Antoine; Jacquemet, Vincent

2012-05-01

Phase singularity analysis provides a quantitative description of spiral wave patterns observed in chemical or biological excitable media. The configuration of phase singularities (locations and directions of rotation) is easily derived from phase maps in two-dimensional manifolds. The question arises whether one can construct a phase map with a given configuration of phase singularities. The existence of such a phase map is guaranteed provided that the phase singularity configuration satisfies a certain constraint associated with the topology of the supporting medium. This paper presents a constructive mathematical approach to numerically solve this problem in the plane and on the sphere as well as in more general geometries relevant to atrial anatomy including holes and a septal wall. This tool can notably be used to create initial conditions with a controllable spiral wave configuration for cardiac propagation models and thus help in the design of computer experiments in atrial electrophysiology.

Perioperative optimal blood pressure as determined by ultrasound tagged near infrared spectroscopy and its association with postoperative acute kidney injury in cardiac surgery patients.

PubMed

Hori, Daijiro; Hogue, Charles; Adachi, Hideo; Max, Laura; Price, Joel; Sciortino, Christopher; Zehr, Kenton; Conte, John; Cameron, Duke; Mandal, Kaushik

2016-04-01

Perioperative blood pressure management by targeting individualized optimal blood pressure, determined by cerebral blood flow autoregulation monitoring, may ensure sufficient renal perfusion. The purpose of this study was to evaluate changes in the optimal blood pressure for individual patients, determined during cardiopulmonary bypass (CPB) and during early postoperative period in intensive care unit (ICU). A secondary aim was to examine if excursions below optimal blood pressure in the ICU are associated with risk of cardiac surgery-associated acute kidney injury (CSA-AKI). One hundred and ten patients undergoing cardiac surgery had cerebral blood flow monitored with a novel technology using ultrasound tagged near infrared spectroscopy (UT-NIRS) during CPB and in the first 3 h after surgery in the ICU. The correlation flow index (CFx) was calculated as a moving, linear correlation coefficient between cerebral flow index measured using UT-NIRS and mean arterial pressure (MAP). Optimal blood pressure was defined as the MAP with the lowest CFx. Changes in optimal blood pressure in the perioperative period were observed and the association of blood pressure excursions (magnitude and duration) below the optimal blood pressure [area under the curve (AUC) < OptMAP mmHgxh] with incidence of CSA-AKI (defined using Kidney Disease: Improving Global Outcomes criteria) was examined. Optimal blood pressure during early ICU stay and CPB was correlated (r = 0.46, P < 0.0001), but was significantly higher in the ICU compared with during CPB (75 ± 8.7 vs 71 ± 10.3 mmHg, P = 0.0002). Thirty patients (27.3%) developed CSA-AKI within 48 h after the surgery. AUC < OptMAP was associated with CSA-AKI during CPB [median, 13.27 mmHgxh, interquartile range (IQR), 4.63-20.14 vs median, 6.05 mmHgxh, IQR 3.03-12.40, P = 0.008], and in the ICU (13.72 mmHgxh, IQR 5.09-25.54 vs 5.65 mmHgxh, IQR 1.71-13.07, P = 0.022). Optimal blood pressure during CPB and in the ICU was correlated. Excursions below optimal blood pressure (AUC < OptMAP mmHgXh) during perioperative period are associated with CSA-AKI. Individualized blood pressure management based on cerebral autoregulation monitoring during the perioperative period may help improve CSA-AKI-related outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Perioperative optimal blood pressure as determined by ultrasound tagged near infrared spectroscopy and its association with postoperative acute kidney injury in cardiac surgery patients

PubMed Central

Hori, Daijiro; Hogue, Charles; Adachi, Hideo; Max, Laura; Price, Joel; Sciortino, Christopher; Zehr, Kenton; Conte, John; Cameron, Duke; Mandal, Kaushik

2016-01-01

OBJECTIVES Perioperative blood pressure management by targeting individualized optimal blood pressure, determined by cerebral blood flow autoregulation monitoring, may ensure sufficient renal perfusion. The purpose of this study was to evaluate changes in the optimal blood pressure for individual patients, determined during cardiopulmonary bypass (CPB) and during early postoperative period in intensive care unit (ICU). A secondary aim was to examine if excursions below optimal blood pressure in the ICU are associated with risk of cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS One hundred and ten patients undergoing cardiac surgery had cerebral blood flow monitored with a novel technology using ultrasound tagged near infrared spectroscopy (UT-NIRS) during CPB and in the first 3 h after surgery in the ICU. The correlation flow index (CFx) was calculated as a moving, linear correlation coefficient between cerebral flow index measured using UT-NIRS and mean arterial pressure (MAP). Optimal blood pressure was defined as the MAP with the lowest CFx. Changes in optimal blood pressure in the perioperative period were observed and the association of blood pressure excursions (magnitude and duration) below the optimal blood pressure [area under the curve (AUC) < OptMAP mmHgxh] with incidence of CSA-AKI (defined using Kidney Disease: Improving Global Outcomes criteria) was examined. RESULTS Optimal blood pressure during early ICU stay and CPB was correlated (r = 0.46, P < 0.0001), but was significantly higher in the ICU compared with during CPB (75 ± 8.7 vs 71 ± 10.3 mmHg, P = 0.0002). Thirty patients (27.3%) developed CSA-AKI within 48 h after the surgery. AUC < OptMAP was associated with CSA-AKI during CPB [median, 13.27 mmHgxh, interquartile range (IQR), 4.63–20.14 vs median, 6.05 mmHgxh, IQR 3.03–12.40, P = 0.008], and in the ICU (13.72 mmHgxh, IQR 5.09–25.54 vs 5.65 mmHgxh, IQR 1.71–13.07, P = 0.022). CONCLUSIONS Optimal blood pressure during CPB and in the ICU was correlated. Excursions below optimal blood pressure (AUC < OptMAP mmHgXh) during perioperative period are associated with CSA-AKI. Individualized blood pressure management based on cerebral autoregulation monitoring during the perioperative period may help improve CSA-AKI-related outcomes. PMID:26763042

System identification of dynamic closed-loop control of total peripheral resistance by arterial and cardiopulmonary baroreceptors

NASA Technical Reports Server (NTRS)

Aljuri, A. N.; Bursac, N.; Marini, R.; Cohen, R. J.

2001-01-01

Prolonged exposure to microgravity in space flight missions (days) impairs the mechanisms responsible for defense of arterial blood pressure (ABP) and cardiac output (CO) against orthostatic stress in the post-flight period. The mechanisms responsible for the observed orthostatic intolerance are not yet completely understood. Additionally, effective counter measures to attenuate this pathophysiological response are not available. The aim of this study was to investigate the ability of our proposed system identification method to predict closed-loop dynamic changes in TPR induced by changes in mean arterial pressure (MAP) and right atrial pressure (RAP). For this purpose we designed and employed a novel experimental animal model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop control of total peripheral resistance (TPR), and applied system identification to the analysis of beat-to-beat fluctuations in the measured signals. Grant numbers: NAG5-4989. c 2001. Elsevier Science Ltd. All rights reserved.

A study of reconstruction accuracy for a cardiac SPECT system with multi-segmental collimation

NASA Astrophysics Data System (ADS)

Yu, D.-C.; Chang, W.; Pan, T.-S.

1997-06-01

To improve the geometric efficiency of cardiac SPECT imaging, the authors previously proposed to use a multi-segmental collimation with a cylindrical geometry. The proposed collimator consists of multiple parallel-hole collimators with most of the segments directed toward a small central region, where the patient's heart should be positioned. This technique provides a significantly increased detection efficiency for the central region, but at the expense of reduced efficiency for the surrounding region. The authors have used computer simulations to evaluate the implication of this technique on the accuracy of the reconstructed cardiac images. Two imaging situations were simulated: 1) the heart well placed inside the central region, and 2) the heart shifted and partially outside the central region. A neighboring high-uptake liver was simulated for both imaging situations. The images were reconstructed and corrected for attenuation with ML-EM and OS-FM methods using a complete attenuation map. The results indicate that errors caused by projection truncation are not significant and are not strongly dependent on the activity of the liver when the heart is well positioned within the central region. When the heart is partially outside the central region, hybrid emission data (a combination of high-count projections from the central region and low-count projections from the background region) can be used to restore the activity of the truncated section of the myocardium. However, the variance of the image in the section of the myocardium outside the central region is increased by 2-3 times when 10% of the collimator segments are used to image the background region.

Macaque Cardiac Physiology Is Sensitive to the Valence of Passively Viewed Sensory Stimuli

PubMed Central

Bliss-Moreau, Eliza; Machado, Christopher J.; Amaral, David G.

2013-01-01

Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period) increased and parasympathetic activity (as measured by respiratory sinus arrhythmia) decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals. PMID:23940712

Review: Intracardiac intracellular angiotensin system in diabetes

PubMed Central

Kumar, Rajesh; Yong, Qian Chen; Thomas, Candice M.

2012-01-01

The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of action. These differences may alter treatment strategies that target the RAS in several pathological conditions. Recent work from our laboratory has demonstrated significant upregulation of the cardiac, intracellular RAS in diabetes, which is associated with cardiac dysfunction. Here, we have reviewed evidence supporting an intracellular RAS in different cell types, ANG II's actions in cardiac cells, and its mechanism of action, focusing on the intracellular cardiac RAS in diabetes. We have discussed the significance of an intracellular RAS in cardiac pathophysiology and implications for potential therapies. PMID:22170614

Interplay of cell-cell contacts and RhoA/MRTF-A signaling regulates cardiomyocyte identity.

PubMed

Dorn, Tatjana; Kornherr, Jessica; Parrotta, Elvira I; Zawada, Dorota; Ayetey, Harold; Santamaria, Gianluca; Iop, Laura; Mastantuono, Elisa; Sinnecker, Daniel; Goedel, Alexander; Dirschinger, Ralf J; My, Ilaria; Laue, Svenja; Bozoglu, Tarik; Baarlink, Christian; Ziegler, Tilman; Graf, Elisabeth; Hinkel, Rabea; Cuda, Giovanni; Kääb, Stefan; Grace, Andrew A; Grosse, Robert; Kupatt, Christian; Meitinger, Thomas; Smith, Austin G; Laugwitz, Karl-Ludwig; Moretti, Alessandra

2018-06-15

Cell-cell and cell-matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell-cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA-ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis-inducing signals. We also demonstrate by in vivo fate mapping and clonal analysis of cardiac progenitors that cardiac fat and a subset of cardiac muscle arise from a common precursor expressing Isl1 and Wt1 during heart development, suggesting related mechanisms of determination between the two lineages. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Fusion of 4D echocardiography and cine cardiac magnetic resonance volumes using a salient spatio-temporal analysis

NASA Astrophysics Data System (ADS)

Atehortúa, Angélica; Garreau, Mireille; Romero, Eduardo

2017-11-01

An accurate left (LV) and right ventricular (RV) function quantification is important to support evaluation, diagnosis and prognosis of cardiac pathologies such as the cardiomyopathies. Currently, diagnosis by ultrasound is the most cost-effective examination. However, this modality is highly noisy and operator dependent, hence prone to errors. Therefore, fusion with other cardiac modalities may provide complementary information and improve the analysis of the specific pathologies like cardiomyopathies. This paper proposes an automatic registration between two complementary modalities, 4D echocardiography and Magnetic resonance images, by mapping both modalities to a common space of salience where an optimal registration between them is estimated. The obtained matrix transformation is then applied to the MRI volume which is superimposed to the 4D echocardiography. Manually selected marks in both modalities are used to evaluate the precision of the superimposition. Preliminary results, in three evaluation cases, show the distance between these marked points and the estimated with the transformation is about 2 mm.

Important advances in technology and unique applications related to cardiac magnetic resonance imaging.

PubMed

Ghosn, Mohamad G; Shah, Dipan J

2014-01-01

Cardiac magnetic resonance has become a well-established imaging modality and is considered the gold standard for myocardial tissue viability assessment and ventricular volumes quantification. Recent technological hardware and software advancements in magnetic resonance imaging technology have allowed the development of new methods that can improve clinical cardiovascular diagnosis and prognosis. The advent of a new generation of higher magnetic field scanners can be beneficial to various clinical applications. Also, the development of faster acquisition techniques have allowed mapping of the magnetic relaxation properties T1, T2, and T2* in the myocardium that can be used to quantify myocardial diffuse fibrosis, determine the presence of edema or inflammation, and measure iron within the myocardium, respectively. Another recent major advancement in CMR has been the introduction of three-dimension (3D) phase contrast imaging, also known as 4D flow. The following review discusses key advances in cardiac magnetic resonance technology and their potential to improve clinical cardiovascular diagnosis and outcomes.

Local Multi-Channel RF Surface Coil versus Body RF Coil Transmission for Cardiac Magnetic Resonance at 3 Tesla: Which Configuration Is Winning the Game?

PubMed

Weinberger, Oliver; Winter, Lukas; Dieringer, Matthias A; Els, Antje; Oezerdem, Celal; Rieger, Jan; Kuehne, Andre; Cassara, Antonino M; Pfeiffer, Harald; Wetterling, Friedrich; Niendorf, Thoralf

2016-01-01

The purpose of this study was to demonstrate the feasibility and efficiency of cardiac MR at 3 Tesla using local four-channel RF coil transmission and benchmark it against large volume body RF coil excitation. Electromagnetic field simulations are conducted to detail RF power deposition, transmission field uniformity and efficiency for local and body RF coil transmission. For both excitation regimes transmission field maps are acquired in a human torso phantom. For each transmission regime flip angle distributions and blood-myocardium contrast are examined in a volunteer study of 12 subjects. The feasibility of the local transceiver RF coil array for cardiac chamber quantification at 3 Tesla is demonstrated. Our simulations and experiments demonstrate that cardiac MR at 3 Tesla using four-channel surface RF coil transmission is competitive versus current clinical CMR practice of large volume body RF coil transmission. The efficiency advantage of the 4TX/4RX setup facilitates shorter repetition times governed by local SAR limits versus body RF coil transmission at whole-body SAR limit. No statistically significant difference was found for cardiac chamber quantification derived with body RF coil versus four-channel surface RF coil transmission. Our simulation also show that the body RF coil exceeds local SAR limits by a factor of ~2 when driven at maximum applicable input power to reach the whole-body SAR limit. Pursuing local surface RF coil arrays for transmission in cardiac MR is a conceptually appealing alternative to body RF coil transmission, especially for patients with implants.

Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

PubMed

Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

2017-10-01

Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bar-code medication administration system for anesthetics: effects on documentation and billing.

PubMed

Nolen, Agatha L; Rodes, W Dyer

2008-04-01

The effects of using a new bar-code medication administration (BCMA) system for anesthetics to automate documentation of drug administration by anesthesiologists were studied. From October 1, 2004, to September 15, 2005, all medications administered to patients undergoing cardiac surgery were documented with a BCMA system at a large acute care facility. Drug claims data for 12 targeted anesthetics in diagnosis-related groups (DRGs) 104-111 were analyzed to determine the quantity of drugs charged and the revenue generated. Those data were compared with claims data for a historical case-control group (October 1, 2003, to September 15, 2004, for the same DRGs) for which medication use was documented manually. From October 1, 2005, to October 1, 2006, anesthesiologists for cardiac surgeries either voluntarily used the automated system or completed anesthesia records manually. A total of 870 cardiac surgery cases for which the BCMA system was used were evaluated. There were 961 cardiac surgery cases in the historical control group. The BCMA system increased the quantity of drugs documented per case by 21.7% and drug revenue captured per case by 18.8%. The time needed by operating-room pharmacy staff to process an anesthesia record for billing decreased by eight minutes per case. After two years, anesthesiologists voluntarily used the new technology on 100% of cardiac surgery patients. Implementation of a BCMA system for anesthetic use in cardiac surgery increased the quantity of drugs charged by 21.7% per case and drug revenue per case by 18.8%. Anesthesiologists continued to use the automated system on a voluntary basis after conclusion of the initial study.

Genetic Lineage Tracing of Non-Myocyte Population by Dual Recombinases.

PubMed

Li, Yan; He, Lingjuan; Huang, Xiuzhen; Issa Bhaloo, Shirin; Zhao, Huan; Zhang, Shaohua; Pu, Wenjuan; Tian, Xueying; Li, Yi; Liu, Qiaozhen; Yu, Wei; Zhang, Libo; Liu, Xiuxiu; Liu, Kuo; Tang, Juan; Zhang, Hui; Cai, Dongqing; Adams, Ralf H; Xu, Qingbo; Lui, Kathy O; Zhou, Bin

2018-04-26

Background -Whether the adult mammalian heart harbors cardiac stem cells (CSCs) for regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. The putative myocyte stem cell populations recognized without specific cell markers such as the cardiosphere-derived cells or with markers such as Sca1 + , Bmi1 + , Isl1 + or Abcg2 + CSCs have been reported. Moreover, it remains unclear whether putative CSCs with unknown or unidentified markers exist and give rise to de novo cardiomyocytes in the adult heart. Methods -To address this question without relying on a particular stem cell marker, we developed a new genetic lineage tracing system to label all non-myocyte populations that contain putative CSCs. Using dual lineage tracing system, we assessed if non-myocytes generated any new myocytes during embryonic development, adult homeostasis and after myocardial infarction. Skeletal muscle was also examined after injury for internal control of new myocytes generation from non-myocytes. Results -By this stem cell marker-free and dual recombinases-mediated cell tracking approach, our fate mapping data show that new myocytes arise from non-myocytes in the embryonic heart, but not in the adult heart during homeostasis or after myocardial infarction. As positive control, our lineage tracing system detected new myocytes derived from non-myocytes in the skeletal muscle after injury. Conclusions -This study provides in vivo genetic evidence for non-myocyte to myocyte conversion in embryonic but not adult heart, arguing again the myogenic potential of putative stem cell populations for cardiac regeneration in the adult stage. This study also provides a new genetic strategy to identify endogenous stem cells, if any, in other organ systems for tissue repair and regeneration.

Ubiquitin-proteasome system impairment caused by a missense cardiac myosin-binding protein C mutation and associated with cardiac dysfunction in hypertrophic cardiomyopathy.

PubMed

Bahrudin, Udin; Morisaki, Hiroko; Morisaki, Takayuki; Ninomiya, Haruaki; Higaki, Katsumi; Nanba, Eiji; Igawa, Osamu; Takashima, Seiji; Mizuta, Einosuke; Miake, Junichiro; Yamamoto, Yasutaka; Shirayoshi, Yasuaki; Kitakaze, Masafumi; Carrier, Lucie; Hisatome, Ichiro

2008-12-26

The ubiquitin-proteasome system is responsible for the disappearance of truncated cardiac myosin-binding protein C, and the suppression of its activity contributes to cardiac dysfunction. This study investigated whether missense cardiac myosin-binding protein C gene (MYBPC3) mutation in hypertrophic cardiomyopathy (HCM) leads to destabilization of its protein, causes UPS impairment, and is associated with cardiac dysfunction. Mutations were identified in Japanese HCM patients using denaturing HPLC and sequencing. Heterologous expression was investigated in COS-7 cells as well as neonatal rat cardiac myocytes to examine protein stability and proteasome activity. The cardiac function was measured using echocardiography. Five novel MYBPC3 mutations -- E344K, DeltaK814, Delta2864-2865GC, Q998E, and T1046M -- were identified in this study. Compared with the wild type and other mutations, the E334K protein level was significantly lower, it was degraded faster, it had a higher level of polyubiquination, and increased in cells pretreated with the proteasome inhibitor MG132 (50 microM, 6 h). The electrical charge of its amino acid at position 334 influenced its stability, but E334K did not affect its phosphorylation. The E334K protein reduced cellular 20 S proteasome activity, increased the proapoptotic/antiapoptotic protein ratio, and enhanced apoptosis in transfected Cos-7 cells and neonatal rat cardiac myocytes. Patients carrying the E334K mutation presented significant left ventricular dysfunction and dilation. The conclusion is the missense MYBPC3 mutation E334K destabilizes its protein through UPS and may contribute to cardiac dysfunction in HCM through impairment of the ubiquitin-proteasome system.

The use of the RenalGuard system in cardiac surgery with cardiopulmonary bypass: a first in man prospective, observational, feasibility pilot study

PubMed Central

Giri, Ramesh; Wrigley, Benmjamin; Hennessy, Anne-Marie; Nicholas, Johann; Nevill, Alan

2017-01-01

Objectives As proof of concept, this prospective, observational study assessed the feasibility and early clinical outcomes of performing on-pump cardiac surgery with the RenalGuard system. Background Acute kidney injury (AKI) is reported in up to 30% of patients undergoing cardiac surgery and is a recognised independent predictor of both morbidity and mortality. Forced diuresis with the RenalGuard system reduces the incidence of AKI during percutaneous coronary intervention procedures but its use in cardiac surgery has not been explored. Methods Ten consecutive patients who were at risk of developing AKI during cardiac surgery were selected. The RenalGuard system was used to facilitate forced diuresis using weight-adjusted intravenous furosemide while maintaining neutral fluid balance by matched intravenous fluid replacement. This regimen was initiated preoperatively in all patients and continued for 6–12 hours postoperatively. Serum creatinine, electrolytes and need for renal replacement were documented in all patients. Results The RenalGuard system functioned successfully in all patients and facilitated high perioperative urine outputs, even when patients were placed on cardiopulmonary bypass (CPB). There were no incidences of significant (A) electrolyte imbalance, (B) changes in haemoglobin levels or (C) pulmonary oedema. No patients developed AKI within 36 hours of surgery despite one patient developing cardiac tamponade 8 hours postoperatively and one patient developing paralytic ileus. One patient, however, was ‘electively’ haemofiltered on day 2 after developing acute right ventricular failure. The median intensive care stay was 1.5 (1, 5) days. Conclusion The RenalGuard system can be used successfully in patients undergoing cardiac surgery with CPB and may reduce the incidence of AKI in at-risk patients. Trial registration NCT02974946; Pre-results. PMID:29071091

The use of the RenalGuard system in cardiac surgery with cardiopulmonary bypass: a first in man prospective, observational, feasibility pilot study.

PubMed

Luckraz, Heyman; Giri, Ramesh; Wrigley, Benmjamin; Hennessy, Anne-Marie; Nicholas, Johann; Nevill, Alan

2017-01-01

As proof of concept, this prospective, observational study assessed the feasibility and early clinical outcomes of performing on-pump cardiac surgery with the RenalGuard system. Acute kidney injury (AKI) is reported in up to 30% of patients undergoing cardiac surgery and is a recognised independent predictor of both morbidity and mortality. Forced diuresis with the RenalGuard system reduces the incidence of AKI during percutaneous coronary intervention procedures but its use in cardiac surgery has not been explored. Ten consecutive patients who were at risk of developing AKI during cardiac surgery were selected. The RenalGuard system was used to facilitate forced diuresis using weight-adjusted intravenous furosemide while maintaining neutral fluid balance by matched intravenous fluid replacement. This regimen was initiated preoperatively in all patients and continued for 6-12 hours postoperatively. Serum creatinine, electrolytes and need for renal replacement were documented in all patients. The RenalGuard system functioned successfully in all patients and facilitated high perioperative urine outputs, even when patients were placed on cardiopulmonary bypass (CPB). There were no incidences of significant (A) electrolyte imbalance, (B) changes in haemoglobin levels or (C) pulmonary oedema. No patients developed AKI within 36 hours of surgery despite one patient developing cardiac tamponade 8 hours postoperatively and one patient developing paralytic ileus. One patient, however, was 'electively' haemofiltered on day 2 after developing acute right ventricular failure. The median intensive care stay was 1.5 (1, 5) days. The RenalGuard system can be used successfully in patients undergoing cardiac surgery with CPB and may reduce the incidence of AKI in at-risk patients. NCT02974946; Pre-results.

Distinctive Left Ventricular Activations Associated With ECG Pattern in Heart Failure Patients.

PubMed

Derval, Nicolas; Duchateau, Josselin; Mahida, Saagar; Eschalier, Romain; Sacher, Frederic; Lumens, Joost; Cochet, Hubert; Denis, Arnaud; Pillois, Xavier; Yamashita, Seigo; Komatsu, Yuki; Ploux, Sylvain; Amraoui, Sana; Zemmoura, Adlane; Ritter, Philippe; Hocini, Mélèze; Haissaguerre, Michel; Jaïs, Pierre; Bordachar, Pierre

2017-06-01

In contrast to patients with left bundle branch block (LBBB), heart failure patients with narrow QRS and nonspecific intraventricular conduction delay (NICD) display a relatively limited response to cardiac resynchronization therapy. We sought to compare left ventricular (LV) activation patterns in heart failure patients with narrow QRS and NICD to patients with LBBB using high-density electroanatomic activation maps. Fifty-two heart failure patients (narrow QRS [n=18], LBBB [n=11], NICD [n=23]) underwent 3-dimensional electroanatomic mapping with a high density of mapping points (387±349 LV). Adjunctive scar imaging was available in 37 (71%) patients and was analyzed in relation to activation maps. LBBB patients typically demonstrated (1) a single LV breakthrough at the septum (38±15 ms post-QRS onset); (2) prolonged right-to-left transseptal activation with absence of direct LV Purkinje activity; (3) homogeneous propagation within the LV cavity; and (4) latest activation at the basal lateral LV. In comparison, both NICD and narrow QRS patients demonstrated (1) multiple LV breakthroughs along the posterior or anterior fascicles: narrow QRS versus LBBB, 5±2 versus 1±1; P =0.0004; NICD versus LBBB, 4±2 versus 1±1; P =0.001); (2) evidence of early/pre-QRS LV electrograms with Purkinje potentials; (3) rapid propagation in narrow QRS patients and more heterogeneous propagation in NICD patients; and (4) presence of limited areas of late activation associated with LV scar with high interindividual heterogeneity. In contrast to LBBB patients, narrow QRS and NICD patients are characterized by distinct mechanisms of LV activation, which may predict poor response to cardiac resynchronization therapy. © 2017 American Heart Association, Inc.

Validation of high temporal resolution spiral phase velocity mapping of temporal patterns of left and right coronary artery blood flow against Doppler guidewire.

PubMed

Keegan, Jennifer; Raphael, Claire E; Parker, Kim; Simpson, Robin M; Strain, Stephen; de Silva, Ranil; Di Mario, Carlo; Collinson, Julian; Stables, Rod H; Wage, Ricardo; Drivas, Peter; Sugathapala, Malindie; Prasad, Sanjay K; Firmin, David N

2015-10-02

Temporal patterns of coronary blood flow velocity can provide important information on disease state and are currently assessed invasively using a Doppler guidewire. A non-invasive alternative would be beneficial as it would allow study of a wider patient population and serial scanning. A retrospectively-gated breath-hold spiral phase velocity mapping sequence (TR 19 ms) was developed at 3 Tesla. Velocity maps were acquired in 8 proximal right and 15 proximal left coronary arteries of 18 subjects who had previously had a Doppler guidewire study at the time of coronary angiography. Cardiovascular magnetic resonance (CMR) velocity-time curves were processed semi-automatically and compared with corresponding invasive Doppler data. When corrected for differences in heart rate between the two studies, CMR mean velocity through the cardiac cycle, peak systolic velocity (PSV) and peak diastolic velocity (PDV) were approximately 40 % of the peak Doppler values with a moderate - good linear relationship between the two techniques (R(2): 0.57, 0.64 and 0.79 respectively). CMR values of PDV/PSV showed a strong linear relationship with Doppler values with a slope close to unity (0.89 and 0.90 for right and left arteries respectively). In individual vessels, plots of CMR velocities at all cardiac phases against corresponding Doppler velocities showed a consistent linear relationship between the two with high R(2) values (mean +/-SD: 0.79 +/-.13). High temporal resolution breath-hold spiral phase velocity mapping underestimates absolute values of coronary flow velocity but allows accurate assessment of the temporal patterns of blood flow.

Mapping conduction velocity of early embryonic hearts with a robust fitting algorithm

PubMed Central

Gu, Shi; Wang, Yves T; Ma, Pei; Werdich, Andreas A; Rollins, Andrew M; Jenkins, Michael W

2015-01-01

Cardiac conduction maturation is an important and integral component of heart development. Optical mapping with voltage-sensitive dyes allows sensitive measurements of electrophysiological signals over the entire heart. However, accurate measurements of conduction velocity during early cardiac development is typically hindered by low signal-to-noise ratio (SNR) measurements of action potentials. Here, we present a novel image processing approach based on least squares optimizations, which enables high-resolution, low-noise conduction velocity mapping of smaller tubular hearts. First, the action potential trace measured at each pixel is fit to a curve consisting of two cumulative normal distribution functions. Then, the activation time at each pixel is determined based on the fit, and the spatial gradient of activation time is determined with a two-dimensional (2D) linear fit over a square-shaped window. The size of the window is adaptively enlarged until the gradients can be determined within a preset precision. Finally, the conduction velocity is calculated based on the activation time gradient, and further corrected for three-dimensional (3D) geometry that can be obtained by optical coherence tomography (OCT). We validated the approach using published activation potential traces based on computer simulations. We further validated the method by adding artificially generated noise to the signal to simulate various SNR conditions using a curved simulated image (digital phantom) that resembles a tubular heart. This method proved to be robust, even at very low SNR conditions (SNR = 2-5). We also established an empirical equation to estimate the maximum conduction velocity that can be accurately measured under different conditions (e.g. sampling rate, SNR, and pixel size). Finally, we demonstrated high-resolution conduction velocity maps of the quail embryonic heart at a looping stage of development. PMID:26114034

Mapping for Acute Transvenous Phrenic Nerve Stimulation Study (MAPS Study).

PubMed

Dekker, Lukas R C; Gerritse, Bart; Scheiner, Avram; Kornet, Lilian

2017-03-01

Central sleep apnea syndrome, correlated with the occurrence of heart failure, is characterized by periods of insufficient ventilation during sleep. This acute study in 15 patients aims to map the venous system and determine if diaphragmatic movement can be achieved by phrenic nerve stimulation at various locations within the venous system. Subjects underwent a scheduled catheter ablation procedure. During the procedural waiting time, one multielectrode electrophysiology catheter was subsequently placed at the superior and inferior vena cava and the junctions of the left jugular and left brachiocephalic vein and right jugular and right brachiocephalic vein, for phrenic nerve stimulation (1-2 seconds ON/2-3 seconds OFF, 40 Hz, pulse width 210 μs). Diaphragmatic movement was assessed manually and by a breathing mask. During a follow-up assessment between 2 and 4 weeks postprocedure, occurrence of adverse events was assessed. In all patients diaphragmatic movement was induced at one or more locations using a median threshold of at least 2 V and maximally 7.5 V (i.e., e 3.3 mA, 14.2 mA). The lowest median current to obtain diaphragmatic stimulation without discomfort was found for the right brachiocephalic vein (4.7 mA). In 12/15 patients diaphragmatic movement could be induced without any discomfort, but in three patients hiccups occurred. Diaphragmatic stimulation from the brachiocephalic and caval veins is feasible. Potential side effects should be eliminated by adapting the stimulation pattern. This information could be used to design a catheter, combining cardiac pacing with enhancing diaphragm movement during a sleep apnea episode. © 2017 Wiley Periodicals, Inc.

[Cardiac failure in endocrine diseases].

PubMed

Hashizume, K

1993-05-01

Several endocrine diseases show the symptoms of cardiac failure. Among them, patients with acromegaly show a specific cardiomyopathy which results in a severe left-sided cardiac failure. Hypoparathyroidism also induces cardiac failure, which is resulted from hypocalcemia and low levels of serum parathyroid hormone. In the cases of hypothyroidism, the patients with myxedemal coma show a severe cardiac failure, which is characterized by disturbance of central nervous system, renal function, and cardiac function. In the patients with thyroid crisis (storm), the cardiac failure comes from the great reduction of cardiac output with dehydration. The reduction of circulation volume, observed in the patients with pheochromocytoma easily induces cardiac failure (shock) just after the removal of adrenal tumor. In patients with malignant carcinoid syndrome, right-sided ventricular failure which may be occurred through the actions of biogenic amines is observed.

Hierarchical approaches for systems modeling in cardiac development.

PubMed

Gould, Russell A; Aboulmouna, Lina M; Varner, Jeffrey D; Butcher, Jonathan T

2013-01-01

Ordered cardiac morphogenesis and function are essential for all vertebrate life. The heart begins as a simple contractile tube, but quickly grows and morphs into a multichambered pumping organ complete with valves, while maintaining regulation of blood flow and nutrient distribution. Though not identical, cardiac morphogenesis shares many molecular and morphological processes across vertebrate species. Quantitative data across multiple time and length scales have been gathered through decades of reductionist single variable analyses. These range from detailed molecular signaling pathways at the cellular levels to cardiac function at the tissue/organ levels. However, none of these components act in true isolation from others, and each, in turn, exhibits short- and long-range effects in both time and space. With the absence of a gene, entire signaling cascades and genetic profiles may be shifted, resulting in complex feedback mechanisms. Also taking into account local microenvironmental changes throughout development, it is apparent that a systems level approach is an essential resource to accelerate information generation concerning the functional relationships across multiple length scales (molecular data vs physiological function) and structural development. In this review, we discuss relevant in vivo and in vitro experimental approaches, compare different computational frameworks for systems modeling, and the latest information about systems modeling of cardiac development. Finally, we conclude with some important future directions for cardiac systems modeling. Copyright © 2013 Wiley Periodicals, Inc.

A systematic evaluation of three different cardiac T2-mapping sequences at 1.5 and 3T in healthy volunteers.

PubMed

Baeßler, Bettina; Schaarschmidt, Frank; Stehning, Christian; Schnackenburg, Bernhard; Maintz, David; Bunck, Alexander C

2015-11-01

Previous studies showed that myocardial T2 relaxation times measured by cardiac T2-mapping vary significantly depending on sequence and field strength. Therefore, a systematic comparison of different T2-mapping sequences and the establishment of dedicated T2 reference values is mandatory for diagnostic decision-making. Phantom experiments using gel probes with a range of different T1 and T2 times were performed on a clinical 1.5T and 3T scanner. In addition, 30 healthy volunteers were examined at 1.5 and 3T in immediate succession. In each examination, three different T2-mapping sequences were performed at three short-axis slices: Multi Echo Spin Echo (MESE), T2-prepared balanced SSFP (T2prep), and Gradient Spin Echo with and without fat saturation (GraSEFS/GraSE). Segmented T2-Maps were generated according to the AHA 16-segment model and statistical analysis was performed. Significant intra-individual differences between mean T2 times were observed for all sequences. In general, T2prep resulted in lowest and GraSE in highest T2 times. A significant variation with field strength was observed for mean T2 in phantom as well as in vivo, with higher T2 values at 1.5T compared to 3T, regardless of the sequence used. Segmental T2 values for each sequence at 1.5 and 3T are presented. Despite a careful selection of sequence parameters and volunteers, significant variations of the measured T2 values were observed between field strengths, MR sequences and myocardial segments. Therefore, we present segmental T2 values for each sequence at 1.5 and 3T with the inherent potential to serve as reference values for future studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control.

PubMed

Kember, Guy; Ardell, Jeffrey L; Shivkumar, Kalyanam; Armour, J Andrew

2017-01-01

The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as 'free-floating' in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease.

Guidelines for the Use of Echocardiography in the Evaluation of a Cardiac Source of Embolism.

PubMed

Saric, Muhamed; Armour, Alicia C; Arnaout, M Samir; Chaudhry, Farooq A; Grimm, Richard A; Kronzon, Itzhak; Landeck, Bruce F; Maganti, Kameswari; Michelena, Hector I; Tolstrup, Kirsten

2016-01-01

Embolism from the heart or the thoracic aorta often leads to clinically significant morbidity and mortality due to transient ischemic attack, stroke or occlusion of peripheral arteries. Transthoracic and transesophageal echocardiography are the key diagnostic modalities for evaluation, diagnosis, and management of stroke, systemic and pulmonary embolism. This document provides comprehensive American Society of Echocardiography guidelines on the use of echocardiography for evaluation of cardiac sources of embolism. It describes general mechanisms of stroke and systemic embolism; the specific role of cardiac and aortic sources in stroke, and systemic and pulmonary embolism; the role of echocardiography in evaluation, diagnosis, and management of cardiac and aortic sources of emboli including the incremental value of contrast and 3D echocardiography; and a brief description of alternative imaging techniques and their role in the evaluation of cardiac sources of emboli. Specific guidelines are provided for each category of embolic sources including the left atrium and left atrial appendage, left ventricle, heart valves, cardiac tumors, and thoracic aorta. In addition, there are recommendation regarding pulmonary embolism, and embolism related to cardiovascular surgery and percutaneous procedures. The guidelines also include a dedicated section on cardiac sources of embolism in pediatric populations. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Effects of GABA, Neural Regulation, and Intrinsic Cardiac Factors on Heart Rate Variability in Zebrafish Larvae.

PubMed

Vargas, Rafael Antonio

2017-04-01

Heart rate (HR) is a periodic activity that is variable over time due to intrinsic cardiac factors and extrinsic neural control, largely by the autonomic nervous system. Heart rate variability (HRV) is analyzed by measuring consecutive beat-to-beat intervals. This variability can contain information about the factors regulating cardiac activity under normal and pathological conditions, but the information obtained from such analyses is not yet fully understood. In this article, HRV in zebrafish larvae was evaluated under normal conditions and under the effect of substances that modify intrinsic cardiac activity and cardiac activity modulated by the nervous system. We found that the factors affecting intrinsic activity have negative chronotropic and arrhythmogenic effects at this stage of development, whereas neural modulatory factors have a lesser impact. The results suggest that cardiac activity largely depends on the intrinsic properties of the heart tissue in the early stages of development and, to a lesser extent, in the maturing nervous system. We also report, for the first time, the influence of the neurotransmitter gamma amino butyric acid on HRV. The results demonstrate the larval zebrafish model as a useful tool in the study of intrinsic cardiac activity and its role in heart diseases.

Removal of pinned scroll waves in cardiac tissues by electric fields in a generic model of three-dimensional excitable media.

PubMed

Pan, De-Bei; Gao, Xiang; Feng, Xia; Pan, Jun-Ting; Zhang, Hong

2016-02-24

Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves.

Cardiac Arrest Secondary to Lightning Strike: Case Report and Review of the Literature.

PubMed

Rotariu, Elena L; Manole, Mioara D

2017-08-01

Lightning strike injuries, although less common than electrical injuries, have a higher morbidity rate because of critical alterations of the circulatory system, respiratory system, and central nervous system. Most lightning-related deaths occur immediately after injury because of arrhythmia or respiratory failure. We describe the case of a pediatric patient who experienced cardiorespiratory arrest secondary to a lightning strike, where the Advanced Cardiac Life Support and Basic Life Support chain of survival was well executed, leading to return of spontaneous circulation and intact neurological survival. We review the pathophysiology of lightning injuries, prognostic factors of favorable outcome after cardiac arrest, including bystander cardiopulmonary resuscitation, shockable rhythm, and automatic external defibrillator use, and the importance of temperature management after cardiac arrest.

Rotational X-ray angiography: a method for intra-operative volume imaging of the left-atrium and pulmonary veins for atrial fibrillation ablation guidance

NASA Astrophysics Data System (ADS)

Manzke, R.; Zagorchev, L.; d'Avila, A.; Thiagalingam, A.; Reddy, V. Y.; Chan, R. C.

2007-03-01

Catheter-based ablation in the left atrium and pulmonary veins (LAPV) for treatment of atrial fibrillation in cardiac electrophysiology (EP) are complex and require knowledge of heart chamber anatomy. Electroanatomical mapping (EAM) is typically used to define cardiac structures by combining electromagnetic spatial catheter localization with surface models which interpolate the anatomy between EAM point locations in 3D. Recently, the incorporation of pre-operative volumetric CT or MR data sets has allowed for more detailed maps of LAPV anatomy to be used intra-operatively. Preoperative data sets are however a rough guide since they can be acquired several days to weeks prior to EP intervention. Due to positional and physiological changes, the intra-operative cardiac anatomy can be different from that depicted in the pre-operative data. We present an application of contrast-enhanced rotational X-ray imaging for CT-like reconstruction of 3D LAPV anatomy during the intervention itself. Depending on the heart size a single or two selective contrastenhanced rotational acquisitions are performed and CT-like volumes are reconstructed with 3D filtered back projection. In case of dual injection, the two volumes depicting the left and right portions of the LAPV are registered and fused. The data sets are visualized and segmented intra-procedurally to provide anatomical data and surface models for intervention guidance. Our results from animal and human experiments indicate that the anatomical information from intra-operative CT-like reconstructions compares favorably with preacquired imaging data and can be of sufficient quality for intra-operative guidance.

Evidence for a functional cardiac interaction between losartan and angiotensin-(1–7) receptors revealed by orthostatic tilting test in rats

PubMed Central

Matos de Moura, Marina; Augusto Sousa dos Santos, Robson; Antônio Peliky Fontes, Marco

2005-01-01

Studies have shown that the angiotensin II (Ang II) AT1 receptor antagonist, losartan, accentuates the orthostatic hypotensive response in anesthetized rats, and there is evidence indicating that this effect is not exclusively mediated by AT1 receptors. We investigated whether the pronounced orthostatic cardiovascular response observed in losartan-treated rats involves an interference with angiotensin-(1–7) (Ang-(1–7)) receptors. Urethane-anesthetized rats were submitted to orthostatic stress (90° head-up tilt for 2 min). Intravenous injection of losartan (1 mg kg−1, n=9) significantly accentuated the decrease in mean arterial pressure (MAP) induced by head-up tilt (−33±6% after losartan vs −15±8% control tilt). This effect was accompanied by a significant bradycardia (−8±3% after losartan vs −3±3% control tilt). Another AT1 antagonist, candesartan, did not potentiate the decrease of MAP and did not change the cardiac response induced by head-up tilt. Strikingly, administration of the Ang-(1–7) antagonist, A-779 (10 nmol kg−1, n=5), totally reversed the bradicardiac effect caused by losartan and this effect was accompanied by a tendency towards attenuation of the hypotensive response caused by losartan. These findings indicate that the marked orthostatic cardiovascular response is specific for losartan, and that it may be due, in part, to an interaction of this antagonist with Ang-(1–7) receptors, probably at the cardiac level. PMID:15685215

Can Human Pluripotent Stem Cell-Derived Cardiomyocytes Advance Understanding of Muscular Dystrophies?

PubMed

Kalra, Spandan; Montanaro, Federica; Denning, Chris

2016-08-30

Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mortality. Careful monitoring of cardiac issues is necessary but current management of cardiac involvement does not effectively protect from disease progression and cardiac failure. There is a critical need to gain new knowledge on the diverse molecular underpinnings of cardiac disease in MDs in order to guide cardiac treatment development and assist in reaching a clearer consensus on cardiac disease management in the clinic. Animal models are available for the majority of MDs and have been invaluable tools in probing disease mechanisms and in pre-clinical screens. However, there are recognized genetic, physiological, and structural differences between human and animal hearts that impact disease progression, manifestation, and response to pharmacological interventions. Therefore, there is a need to develop parallel human systems to model cardiac disease in MDs. This review discusses the current status of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) to model cardiac disease, with a focus on Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1). We seek to provide a balanced view of opportunities and limitations offered by this system in elucidating disease mechanisms pertinent to human cardiac physiology and as a platform for treatment development or refinement.

Effects of clinically relevant acute hypercapnic and metabolic acidosis on the cardiovascular system: an experimental porcine study

PubMed Central

2013-01-01

Introduction Hypercapnic acidosis (HCA) that accompanies lung-protective ventilation may be considered permissive (a tolerable side effect), or it may be therapeutic by itself. Cardiovascular effects may contribute to, or limit, the potential therapeutic impact of HCA; therefore, a complex physiological study was performed in healthy pigs to evaluate the systemic and organ-specific circulatory effects of HCA, and to compare them with those of metabolic (eucapnic) acidosis (MAC). Methods In anesthetized, mechanically ventilated and instrumented pigs, HCA was induced by increasing the inspired fraction of CO2 (n = 8) and MAC (n = 8) by the infusion of HCl, to reach an arterial plasma pH of 7.1. In the control group (n = 8), the normal plasma pH was maintained throughout the experiment. Hemodynamic parameters, including regional organ hemodynamics, blood gases, and electrocardiograms, were measured in vivo. Subsequently, isometric contractions and membrane potentials were recorded in vitro in the right ventricular trabeculae. Results HCA affected both the pulmonary (increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR)) and systemic (increase in mean arterial pressure (MAP), decrease in systemic vascular resistance (SVR)) circulations. Although the renal perfusion remained unaffected by any type of acidosis, HCA increased carotid, portal, and, hence, total liver blood flow. MAC influenced the pulmonary circulation only (increase in MPAP and PVR). Both MAC and HCA reduced the stroke volume, which was compensated for by an increase in heart rate to maintain (MAC), or even increase (HCA), the cardiac output. The right ventricular stroke work per minute was increased by both MAC and HCA; however, the left ventricular stroke work was increased by HCA only. In vitro, the trabeculae from the control pigs and pigs with acidosis showed similar contraction force and action-potential duration (APD). Perfusion with an acidic solution decreased the contraction force, whereas APD was not influenced. Conclusions MAC preferentially affects the pulmonary circulation, whereas HCA affects the pulmonary, systemic, and regional circulations. The cardiac contractile function was reduced, but the cardiac output was maintained (MAC), or even increased (HCA). The increased ventricular stroke work per minute revealed an increased work demand placed by acidosis on the heart. PMID:24377654

Multiparametric Imaging of Organ System Interfaces

PubMed Central

Vandoorne, Katrien; Nahrendorf, Matthias

2017-01-01

Cardiovascular diseases are a consequence of genetic and environmental risk factors that together generate arterial wall and cardiac pathologies. Blood vessels connect multiple systems throughout the entire body and allow organs to interact via circulating messengers. These same interactions facilitate nervous and metabolic system influence on cardiovascular health. Multiparametric imaging offers the opportunity to study these interfacing systems’ distinct processes, to quantify their interactions and to explore how these contribute to cardiovascular disease. Noninvasive multiparametric imaging techniques are emerging tools that can further our understanding of this complex and dynamic interplay. PET/MRI and multichannel optical imaging are particularly promising because they can simultaneously sample multiple biomarkers. Preclinical multiparametric diagnostics could help discover clinically relevant biomarker combinations pivotal for understanding cardiovascular disease. Interfacing systems important to cardiovascular disease include the immune, nervous and hematopoietic systems. These systems connect with ‘classical’ cardiovascular organs, like the heart and vasculature, and with the brain. The dynamic interplay between these systems and organs enables processes such as hemostasis, inflammation, angiogenesis, matrix remodeling, metabolism and fibrosis. As the opportunities provided by imaging expand, mapping interconnected systems will help us decipher the complexity of cardiovascular disease and monitor novel therapeutic strategies. PMID:28360260

Educational Preparation, Roles, and Competencies to Guide Career Development for Cardiac Rehabilitation Nurses.

PubMed

Lin, Stella H M; Neubeck, Lis; Gallagher, Robyn

Cardiac rehabilitation is one of the most widely recommended strategies to reduce the burden of cardiovascular disease. The multicomponent nature of cardiac rehabilitation programs requires a multidisciplinary team of healthcare professionals including nurses who are equipped with extensive knowledge and skills. However, there is a lack of a comprehensive, explicit career pathway that contains academic and clinical development to prepare nurses to become cardiac rehabilitation specialists. The aim of this study is to identify the 3 essential components for cardiac rehabilitation professionals: (1) educational preparation, (2) role/responsibility, and (3) competency to inform the framework of career development for cardiac rehabilitation nurses. Through scoping review, 4 stages from the methodological framework of scoping review by Arksey and O'Malley (Int J Soc Methodol. 2005;8:19-32) were used. Some attempts have been made in developing frameworks of career development for cardiac rehabilitation professionals with these 3 components through guidelines/standards and core curriculum development worldwide, among which the United States is the only country with a well-established system including guidelines for cardiac rehabilitation/secondary prevention programs, a position statement in terms of competencies, and certification examination for cardiac rehabilitation professionals. Nevertheless, further development and integration of these efforts, specifically for cardiac rehabilitation nurses, are required. It is vital to raise the awareness of the significant contribution that appropriately educated and trained nurses make in reducing the global burden of cardiovascular disease through cardiac rehabilitation. Therefore, action on establishing a system of comprehensive, clearly defined career development pathway for cardiac rehabilitation nurses worldwide is of immediate priority.

Thicker three-dimensional tissue from a "symbiotic recycling system" combining mammalian cells and algae.

PubMed

Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

2017-01-31

In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro "symbiotic recycling system" composed of mammalian cells and algae.

Hemodynamic Effects of Nitroglycerin Ointment in Emergency Department Patients

PubMed Central

Mumma, Bryn E.; Dhingra, Kapil R.; Kurlinkus, Charley; Diercks, Deborah B.

2014-01-01

Background Nitroglycerin ointment is commonly used in the treatment of emergency department (ED) patients with suspected acute heart failure (AHF) or suspected acute coronary syndrome (ACS), but its hemodynamic effects in this population are not well described. Objectives Our objective was to assess effect of nitroglycerin ointment on mean arterial pressure (MAP) and systemic vascular resistance (SVR) in ED patients receiving nitroglycerin. We hypothesized that nitroglycerin ointment would result in a reduction of MAP and SVR in the acute treatment of patients. Methods We conducted a prospective, observational pilot study in a convenience sample of adult patients from a single ED who were treated with nitroglycerin ointment. Impedance cardiography was used to measure MAP, SVR, cardiac output (CO), stroke volume (SV), and thoracic fluid content (TFC) at baseline and at 30, 60, and 120 minutes following application of nitroglycerin ointment. Mixed effects regression models with random slope and random intercept were used to analyze changes in hemodynamic parameters from baseline to 30, 60, and 120 minutes after adjusting for age, sex, and final ED diagnosis of AHF. Results Sixty-four subjects with mean age 55 years (IQR 48-67) were enrolled; 59% were male. In the adjusted analysis, MAP and TFC decreased following application of nitroglycerin ointment (p=0.001 and p=0.043, respectively). CI, CO, SVR, and SV showed no change (p=0.113, p=0.085, p=0.570, and p=0.076, respectively) over time. Conclusions Among ED patients who are treated with nitroglycerin ointment, MAP and TFC decrease over time. However, other hemodynamic parameters do not change following application of nitroglycerin ointment in these patients. PMID:24698507

3D cardiac μ tissues within a microfluidic device with real-time contractile stress readout

PubMed Central

Aung, Aereas; Bhullar, Ivneet Singh; Theprungsirikul, Jomkuan; Davey, Shruti Krishna; Lim, Han Liang; Chiu, Yu-Jui; Ma, Xuanyi; Dewan, Sukriti; Lo, Yu-Hwa; McCulloch, Andrew; Varghese, Shyni

2015-01-01

We present the development of three-dimensional (3D) cardiac microtissues within a microfluidic device with the ability to quantify real-time contractile stress measurements in situ. Using a 3D patterning technology that allows for the precise spatial distribution of cells within the device, we created an array of 3D cardiac microtissues from neonatal mouse cardiomyocytes. We integrated the 3D micropatterning technology with microfluidics to achieve perfused cell-laden structures. The cells were encapsulated within a degradable gelatin methacrylate hydrogel, which was sandwiched between two polyacrylamide hydrogels. The polyacrylamide hydrogels were used as “stress sensors” to acquire the contractile stresses generated by the beating cardiac cells. The cardiac-specific response of the engineered 3D system was examined by exposing it to epinephrine, an adrenergic neurotransmitter known to increase the magnitude and frequency of cardiac contractions. In response to exogenous epinephrine the engineered cardiac tissues exhibited an increased beating frequency and stress magnitude. Such cost-effective and easy-to-adapt 3D cardiac systems with real-time functional readout could be an attractive technological platform for drug discovery and development. PMID:26588203

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

PubMed

Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

2015-01-01

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts

PubMed Central

Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

2015-01-01

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization. PMID:26251592

C-SPECT - a Clinical Cardiac SPECT/Tct Platform: Design Concepts and Performance Potential

PubMed Central

Chang, Wei; Ordonez, Caesar E.; Liang, Haoning; Li, Yusheng; Liu, Jingai

2013-01-01

Because of scarcity of photons emitted from the heart, clinical cardiac SPECT imaging is mainly limited by photon statistics. The sub-optimal detection efficiency of current SPECT systems not only limits the quality of clinical cardiac SPECT imaging but also makes more advanced potential applications difficult to be realized. We propose a high-performance system platform - C-SPECT, which has its sampling geometry optimized for detection of emitted photons in quality and quantity. The C-SPECT has a stationary C-shaped gantry that surrounds the left-front side of a patient’s thorax. The stationary C-shaped collimator and detector systems in the gantry provide effective and efficient detection and sampling of photon emission. For cardiac imaging, the C-SPECT platform could achieve 2 to 4 times the system geometric efficiency of conventional SPECT systems at the same sampling resolution. This platform also includes an integrated transmission CT for attenuation correction. The ability of C-SPECT systems to perform sequential high-quality emission and transmission imaging could bring cost-effective high-performance to clinical imaging. In addition, a C-SPECT system could provide high detection efficiency to accommodate fast acquisition rate for gated and dynamic cardiac imaging. This paper describes the design concepts and performance potential of C-SPECT, and illustrates how these concepts can be implemented in a basic system. PMID:23885129

21 CFR 870.3535 - Intra-aortic balloon and control system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... syndrome, cardiac and non-cardiac surgery, or complications of heart failure. The special controls for this... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Intra-aortic balloon and control system. 870.3535... balloon and control system. (a) Identification. An intra-aortic balloon and control system is a...

The anatomy of the cardiac veins in mice

PubMed Central

Ciszek, Bogdan; Skubiszewska, Daria; Ratajska, Anna

2007-01-01

Although the cardiac coronary system in mice has been the studied in detail by many research laboratories, knowledge of the cardiac veins remains poor. This is because of the difficulty in marking the venous system with a technique that would allow visualization of these large vessels with thin walls. Here we present the visualization of the coronary venous system by perfusion of latex dye through the right caudal vein. Latex injected intravenously does not penetrate into the capillary system. Murine cardiac veins consist of several principal branches (with large diameters), the distal parts of which are located in the subepicardium. We have described the major branches of the left atrial veins, the vein of the left ventricle, the caudal veins, the vein of the right ventricle and the conal veins forming the conal venous circle or the prepulmonary conal venous arch running around the conus of the right ventricle. The venous system of the heart drains the blood to the coronary sinus (the left cranial caval vein) to the right atrium or to the right cranial caval vein. Systemic veins such as the left cranial caval, the right cranial caval and the caudal vein open to the right atrium. Knowledge of cardiac vein location may help to elucidate abnormal vein patterns in certain genetic malformations. PMID:17553104

Segmented slant hole collimator for stationary cardiac SPECT: Monte Carlo simulations

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

Mao, Yanfei, E-mail: ymao@ucair.med.utah.edu; Yu, Zhicong; Zeng, Gengsheng L.

2015-09-15

Purpose: This work is a preliminary study of a stationary cardiac SPECT system. The goal of this research is to propose a stationary cardiac SPECT system using segmented slant-hole collimators and to perform computer simulations to test the feasibility. Compared to the rotational SPECT, a stationary system has a benefit of acquiring temporally consistent projections. The most challenging issue in building a stationary system is to provide sufficient projection view-angles. Methods: A GATE (GEANT4 application for tomographic emission) Monte Carlo model was developed to simulate a two-detector stationary cardiac SPECT that uses segmented slant-hole collimators. Each detector contains seven segmentedmore » slant-hole sections that slant to a common volume at the rotation center. Consequently, 14 view-angles over 180° were acquired without any gantry rotation. The NCAT phantom was used for data generation and a tailored maximum-likelihood expectation-maximization algorithm was used for image reconstruction. Effects of limited number of view-angles and data truncation were carefully evaluated in the paper. Results: Simulation results indicated that the proposed segmented slant-hole stationary cardiac SPECT system is able to acquire sufficient data for cardiac imaging without a loss of image quality, even when the uptakes in the liver and kidneys are high. Seven views are acquired simultaneously at each detector, leading to 5-fold sensitivity gain over the conventional dual-head system at the same total acquisition time, which in turn increases the signal-to-noise ratio by 19%. The segmented slant-hole SPECT system also showed a good performance in lesion detection. In our prototype system, a short hole-length was used to reduce the dead zone between neighboring collimator segments. The measured sensitivity gain is about 17-fold over the conventional dual-head system. Conclusions: The GATE Monte Carlo simulations confirm the feasibility of the proposed stationary cardiac SPECT system with segmented slant-hole collimators. The proposed collimator consists of combined parallel and slant holes, and the image on the detector is not reduced in size.« less

How Hippo Signaling Pathway Modulates Cardiovascular Development and Diseases.

PubMed

Zhou, Wenyi; Zhao, Mingyi

2018-01-01

Cardiovascular disease remains the leading cause of death around the globe. Cardiac deterioration is associated with irreversible cardiomyocyte loss. Understanding how the cardiovascular system develops and the pathological processes of cardiac disease will contribute to finding novel and preventive therapeutic methods. The canonical Hippo tumor suppressor pathway in mammalian cells is primarily composed of the MST1/2-SAV1-LATS1/2-MOB1-YAP/TAZ cascade. Continuing research on this pathway has identified other factors like RASSF1A, Nf2, MAP4Ks, and NDR1/2, further enriching our knowledge of the Hippo-YAP pathway. YAP, the core effecter of the Hippo pathway, may accumulate in the nucleus and initiate transcriptional activity if the pathway is inhibited. The role of Hippo signaling has been widely investigated in organ development and cancers. A heart of normal size and function which is critical for survival could not be generated without the proper regulation of the Hippo tumor suppressor pathway. Recent research has demonstrated a novel role of Hippo signaling in cardiovascular disease in the context of development, hypertrophy, angiogenesis, regeneration, apoptosis, and autophagy. In this review, we summarize the current knowledge of how Hippo signaling modulates pathological processes in cardiovascular disease and discuss potential molecular therapeutic targets.

Various Regulatory Modes for Circadian Rhythmicity and Sexual Dimorphism in the Non-Neuronal Cardiac Cholinergic System.

PubMed

Oikawa, Shino; Kai, Yuko; Mano, Asuka; Ohata, Hisayuki; Nemoto, Takahiro; Kakinuma, Yoshihiko

2017-08-01

Cardiomyocytes possess a non-neuronal cardiac cholinergic system (NNCCS) regulated by a positive feedback system; however, its other regulatory mechanisms remain to be elucidated, which include the epigenetic control or regulation by the female sex steroid, estrogen. Here, the NNCCS was shown to possess a circadian rhythm; its activity was upregulated in the light-off phase via histone acetyltransferase (HAT) activity and downregulated in the light-on phase. Disrupting the circadian rhythm altered the physiological choline acetyltransferase (ChAT) expression pattern. The NNCCS circadian rhythm may be regulated by miR-345, independently of HAT, causing decreased cardiac ChAT expression. Murine cardiac ChAT expression and ACh contents were increased more in female hearts than in male hearts. This upregulation was downregulated by treatment with the estrogen receptor antagonist tamoxifen, and in contrast, estrogen reciprocally regulated cardiac miR-345 expression. These results suggest that the NNCCS is regulated by the circadian rhythm and is affected by sexual dimorphism.

TU-G-BRA-08: BEST IN PHYSICS (JOINT IMAGING-THERAPY): Hybrid PET-MRI Imaging of Acute Radiation Induced Cardiac Toxicity

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

El-Sherif, O; Xhaferllari, I; Gaede, S

Purpose: To identify the presence of low-dose radiation induced cardiac toxicity in a canine model using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: Research ethics board approval was obtained for a longitudinal imaging study of 5 canines after cardiac irradiation. Animals were imaged at baseline, 1 week post cardiac irradiation, and 1 month post cardiac irradiation using a hybrid PET- MRI system (Biograph mMR, Siemens Healthcare). The imaging protocol was designed to assess acute changes in myocardial perfusion and inflammation. Myocardial perfusion imaging was performed using N13-ammonia tracer followed by a dynamic PET acquisition scan. Amore » compartmental tracer kinetic model was used for absolute perfusion quantification. Myocardial inflammation imaging was performed using F18-fluorodeoxyglucose (FDG) tracer. The standard uptake value (SUV) over a region encompassing the whole heart was used to compare FDG scans. All animals received a simulation CT scan (GE Medical Systems) for radiation treatment planning. Radiation treatment plans were created using the Pinncale3 treatment planning system (Philips Radiation Oncology Systems) and designed to resemble the typical cardiac exposure during left-sided breast cancer radiotherapy. Cardiac irradiations were performed in a single fraction using a TrueBeam linear accelerator (Varian Medical Systems). Results: The delivered dose (mean ± standard deviation) to heart was 1.8±0.2 Gy. Reductions in myocardial stress perfusion relative to baseline were observed in 2 of the 5 animals 1 month post radiation. A global inflammatory response 1 month post radiation was observed in 4 of the 5 animals. The calculated SUV at 1 month post radiation was significantly higher (p=0.05) than the baseline SUV. Conclusion: Low doses of cardiac irradiation (< 2 Gy) may lead to myocardial perfusion defects and a global inflammatory response that can be detectable as early as 1 month post irradiation using hybrid PET-MRI imaging techniques.« less

Essential features of designating out-of-hospital cardiac arrest as a reportable event: a scientific statement from the American Heart Association Emergency Cardiovascular Care Committee; Council on Cardiopulmonary, Perioperative, and Critical Care; Council on Cardiovascular Nursing; Council on Clinical Cardiology; and Quality of Care and Outcomes Research Interdisciplinary Working Group.

PubMed

Nichol, Graham; Rumsfeld, John; Eigel, Brian; Abella, Benjamin S; Labarthe, Darwin; Hong, Yuling; O'Connor, Robert E; Mosesso, Vincent N; Berg, Robert A; Leeper, Barbara Bobbi; Weisfeldt, Myron L

2008-04-29

The 2010 impact goal of the American Heart Association is to reduce death rates from heart disease and stroke by 25% and to lower the prevalence of the leading risk factors by the same proportion. Much of the burden of acute heart disease is initially experienced out of hospital and can be reduced by timely delivery of effective prehospital emergency care. Many patients with an acute myocardial infarction die from cardiac arrest before they reach the hospital. A small proportion of those with cardiac arrest who reach the hospital survive to discharge. Current health surveillance systems cannot determine the burden of acute cardiovascular illness in the prehospital setting nor make progress toward reducing that burden without improved surveillance mechanisms. Accordingly, the goals of this article provide a brief overview of strategies for managing out-of-hospital cardiac arrest. We review existing surveillance systems for monitoring progress in reducing the burden of out-of-hospital cardiac arrest in the United States and make recommendations for filling significant gaps in these systems, including the following: 1. Out-of-hospital cardiac arrests and their outcomes through hospital discharge should be classified as reportable events as part of a heart disease and stroke surveillance system. 2. Data collected on patients' encounters with emergency medical services systems should include descriptions of the performance of cardiopulmonary resuscitation by bystanders and defibrillation by lay responders. 3. National annual reports on key indicators of progress in managing acute cardiovascular events in the out-of-hospital setting should be developed and made publicly available. Potential barriers to action on cardiac arrest include concerns about privacy, methodological challenges, and costs associated with designating cardiac arrest as a reportable event.

Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops.

PubMed

Dekker, A L A J; Phelps, B; Dijkman, B; van der Nagel, T; van der Veen, F H; Geskes, G G; Maessen, J G

2004-06-01

Patients in heart failure with left bundle branch block benefit from cardiac resynchronization therapy. Usually the left ventricular pacing lead is placed by coronary sinus catheterization; however, this procedure is not always successful, and patients may be referred for surgical epicardial lead placement. The objective of this study was to develop a method to guide epicardial lead placement in cardiac resynchronization therapy. Eleven patients in heart failure who were eligible for cardiac resynchronization therapy were referred for surgery because of failed coronary sinus left ventricular lead implantation. Minithoracotomy or thoracoscopy was performed, and a temporary epicardial electrode was used for biventricular pacing at various sites on the left ventricle. Pressure-volume loops with the conductance catheter were used to select the best site for each individual patient. Relative to the baseline situation, biventricular pacing with an optimal left ventricular lead position significantly increased stroke volume (+39%, P =.01), maximal left ventricular pressure derivative (+20%, P =.02), ejection fraction (+30%, P =.007), and stroke work (+66%, P =.006) and reduced end-systolic volume (-6%, P =.04). In contrast, biventricular pacing at a suboptimal site did not significantly change left ventricular function and even worsened it in some cases. To optimize cardiac resynchronization therapy with epicardial leads, mapping to determine the best pace site is a prerequisite. Pressure-volume loops offer real-time guidance for targeting epicardial lead placement during minimal invasive surgery.

Analysis of cardiac interventricular septum motion in different respiratory states

NASA Astrophysics Data System (ADS)

Tautz, Lennart; Feng, Li; Otazo, Ricardo; Hennemuth, Anja; Axel, Leon

2016-03-01

The interaction between the left and right heart ventricles (LV and RV) depends on load and pressure conditions that are affected by cardiac contraction and respiration cycles. A novel MRI sequence, XD-GRASP, allows the acquisition of multi-dimensional, respiration-sorted and cardiac-synchronized free-breathing image data. In these data, effects of the cardiac and respiratory cycles on the LV/RV interaction can be observed independently. To enable the analysis of such data, we developed a semi-automatic exploration workflow. After tracking a cross-sectional line positioned over the heart, over all motion states, the septum and heart wall border locations are detected by analyzing the grey-value profile under the lines. These data are used to quantify septum motion, both in absolute units and as a fraction of the heart size, to compare values for different subjects. In addition to conventional visualization techniques, we used color maps for intuitive exploration of the variable values for this multi-dimensional data set. We acquired short-axis image data of nine healthy volunteers, to analyze the position and the motion of the interventricular septum in different breathing states and different cardiac cycle phases. The results indicate a consistent range of normal septum motion values, and also suggest that respiratory phase-dependent septum motion is greatest near end-diastolic phases. These new methods are a promising tool to assess LV/RV ventricle interaction and the effects of respiration on this interaction.

Primary structure of rat cardiac beta-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: further evidence for a multigene family.

PubMed Central

Gocayne, J; Robinson, D A; FitzGerald, M G; Chung, F Z; Kerlavage, A R; Lentes, K U; Lai, J; Wang, C D; Fraser, C M; Venter, J C

1987-01-01

Two cDNA clones, lambda RHM-MF and lambda RHB-DAR, encoding the muscarinic cholinergic receptor and the beta-adrenergic receptor, respectively, have been isolated from a rat heart cDNA library. The cDNA clones were characterized by restriction mapping and automated DNA sequence analysis utilizing fluorescent dye primers. The rat heart muscarinic receptor consists of 466 amino acids and has a calculated molecular weight of 51,543. The rat heart beta-adrenergic receptor consists of 418 amino acids and has a calculated molecular weight of 46,890. The two cardiac receptors have substantial amino acid homology (27.2% identity, 50.6% with favored substitutions). The rat cardiac beta receptor has 88.0% homology (92.5% with favored substitutions) with the human brain beta receptor and the rat cardiac muscarinic receptor has 94.6% homology (97.6% with favored substitutions) with the porcine cardiac muscarinic receptor. The muscarinic cholinergic and beta-adrenergic receptors appear to be as conserved as hemoglobin and cytochrome c but less conserved than histones and are clearly members of a multigene family. These data support our hypothesis, based upon biochemical and immunological evidence, that suggests considerable structural homology and evolutionary conservation between adrenergic and muscarinic cholinergic receptors. To our knowledge, this is the first report utilizing automated DNA sequence analysis to determine the structure of a gene. Images PMID:2825184

Cardiac presentation of ALK positive anaplastic large cell lymphoma.

PubMed

Lim, Z Y; Grace, R; Salisbury, J R; Creamer, D; Jayaprakasam, A; Ho, A Y L; Devereux, S; Mufti, G J; Pagliuca, A

2005-12-01

Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We report the case of an immunocompetent 29-year-old male who presented with syncope and arrythmias secondary to a ventricular cardiac mass. Transcutaneous cardiac biopsy was non-diagnostic, therefore an open cardiac biopsy was performed from which a provisional diagnosis of a cardiac inflammatory pseudotumour was made. Six months after presentation, he developed several subcutaneous lesions with systemic symptoms. Histological and immunophenotypic review of the initial cardiac biopsy revealed features consistent with a diagnosis of CD30, ALK1 positive anaplastic large cell lymphoma (ALCL). Despite intensive treatment with combination chemotherapy, there was significant progression of disease, and he died 11 months after diagnosis. The overall prognosis of cardiac lymphoma remains poor, which may be due to the often late presentation of the tumour. To our knowledge, this is the first reported case of a cardiac ALK positive ALCL. Although rare, cardiac presentation of ALCL should be added to the list of differential diagnoses of cardiac lymphomas.

Effect of losartan, an angiotensin II type 1 receptor antagonist on cardiac autonomic functions of rats during acute and chronic inhibition of nitric oxide synthesis.

PubMed

Chaswal, M; Das, S; Prasad, J; Katyal, A; Mishra, A K; Fahim, M

2012-01-01

We studied the effect of losartan on baroreflex sensitivity (BRS) and heart rate variability (HRV) of adult Wistar rats during acute and chronic inhibition of nitric oxide synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME). Chronic L-NAME administration (50 mg/kg per day for 7 days, orally through gavage) increased mean arterial pressure (MAP), heart rate but significantly decreased BRS. In addition, a significant fall of standard deviation of normal RR intervals, total spectral power, high frequency spectral power and a rise of low frequency to high frequency (LF: HF) ratio was seen. Acute L-NAME administration (30 mg/kg, i.v. bolus dose) also raised MAP and impaired HRV but it was associated with augmented BRS for bradycardia reflex. Losartan treatment (10 mg/kg, i.v.) in both acute and chronic L-NAME treated rats, decreased MAP but the difference was not significant. On the other hand, losartan administration normalized depressed BRS for bradycardia reflex and significantly reduced LF to HF ratio in chronic L-NAME treated rats. But this improvement was not observed in acute L-NAME group. These results indicate importance of mechanisms other than renin-angiotensin system in the pressor response of both acute as well as chronic L-NAME. However, autonomic dysregulation especially following chronic L-NAME appears to be partly angiotensin dependent.

A Two-dimensional Sixteen Channel Transmit/Receive Coil Array for Cardiac MRI at 7.0 Tesla: Design, Evaluation and Application

PubMed Central

Thalhammer, Christof; Renz, Wolfgang; Winter, Lukas; Hezel, Fabian; Rieger, Jan; Pfeiffer, Harald; Graessl, Andreas; Seifert, Frank; Hoffmann, Werner; von Knobelsdorff-Brenkenhoff, Florian; Tkachenko, Valeriy; Schulz-Menger, Jeanette; Kellman, Peter; Niendorf, Thoralf

2012-01-01

Purpose To design, evaluate and apply a two-dimensional 16 channel transmit/receive coil array tailored for cardiac MRI at 7.0 Tesla. Material and Methods The cardiac coil array consists of 2 sections each using 8 elements arranged in a 2 × 4 array. RF safety was validated by SAR simulations. Cardiac imaging was performed using 2D CINE FLASH imaging, T2* mapping and fat-water separation imaging. The characteristics of the coil array were analyzed including parallel imaging performance, left ventricular chamber quantification and overall image quality. Results RF characteristics were found to be appropriate for all subjects included in the study. The SAR values derived from the simulations fall well in the limits of legal guidelines. The baseline SNR advantage at 7.0 T was put to use to acquire 2D CINE images of the heart with a very high spatial resolution of (1 × 1 × 4) mm3. The proposed coil array supports 1D acceleration factors of up to R=4 without impairing image quality significantly. Conclusions The 16 channel TX/RX coil has the capability to acquire high contrast and high spatial resolution images of the heart at 7.0 Tesla. PMID:22706727

A novel multimedia tool to improve bedside teaching of cardiac auscultation

PubMed Central

Woywodt, A; Herrmann, A; Kielstein, J; Haller, H; Haubitz, M; Purnhagen, H

2004-01-01

Training in cardiac auscultation is a core element of undergraduate teaching but recent studies have documented a remarkable decline in auscultatory skills. Therefore there is an interest in new ways to teach cardiac auscultation. In analogy to phonocardiography, an electronic system for simultaneous auscultation and visualisation of murmurs was sought. For this purpose, an electronic stethoscope was linked to a laptop computer and software created to visualise auscultatory findings. In a preliminary trial in undergraduate students, this approach greatly facilitated teaching. Amalgamating traditional phonocardiography with a multimedia approach, this system represents a novel tool for bedside teaching of cardiac auscultation. PMID:15192171

Neural crest contribution to the cardiovascular system.

PubMed

Brown, Christopher B; Baldwin, H Scott

2006-01-01

Normal cardiovascular development requires complex remodeling of the outflow tract and pharyngeal arch arteries to create the separate pulmonic and systemic circulations. During remodeling, the outflow tract is septated to form the ascending aorta and the pulmonary trunk. The initially symmetrical pharyngeal arch arteries are remodeled to form the aortic arch, subclavian and carotid arteries. Remodeling is mediated by a population of neural crest cells arising between the mid-otic placode and somite four called the cardiac neural crest. Cardiac neural crest cells form smooth muscle and pericytes in the great arteries, and the neurons of cardiac innervation. In addition to the physical contribution of smooth muscle to the cardiovascular system, cardiac neural crest cells also provide signals required for the maintenance and differentiation of the other cell layers in the pharyngeal apparatus. Reciprocal signaling between the cardiac neural crest cells and cardiogenic mesoderm of the secondary heart field is required for elaboration of the conotruncus and disruption in this signaling results in primary myocardial dysfunction. Cardiovascular defects attributed to the cardiac neural crest cells may reflect either cell autonomous defects in the neural crest or defects in signaling between the neural crest and adjacent cell layers.

Factors associated with non-participation in and dropout from cardiac rehabilitation programmes: a systematic review of prospective cohort studies.

PubMed

Resurrección, Davinia Maria; Moreno-Peral, Patricia; Gómez-Herranz, Marta; Rubio-Valera, Maria; Pastor, Luis; Caldas de Almeida, Jose Miguel; Motrico, Emma

2018-06-01

Although evidence exists for the efficacy of cardiac rehabilitation programmes to reduce morbidity and mortality among patients with cardiovascular disease, cardiac rehabilitation programmes are underused. We aimed systematically to review the evidence from prospective cohort studies on factors associated with non-participation in and/or dropping out from cardiac rehabilitation programmes. MedLine, Embase, Scopus, Open Grey and Cochrane Database were searched for relevant publications from inception to February 2018. Search terms included (a) coronary heart disease and other cardiac conditions; (b) cardiac rehabilitation and secondary prevention; and (c) non-participation in and/or dropout. Databases were searched following the PRISMA statement. Study selection, data extraction and the assessment of study quality were performed in duplicate. We selected 43 studies with a total of 63,425 patients from 10 different countries that met the inclusion criteria. Factors associated with non-participation in and dropout from cardiac rehabilitation were grouped into six broad categories: intrapersonal factors, clinical factors, interpersonal factors, logistical factors, cardiac rehabilitation programme factors and health system factors. We found that clinical factors, logistical factors and health system factors were the main factors assessed for non-participation in cardiac rehabilitation. We also found differences between the factors associated with non-participation and dropout. Several factors were determinant for non-participation in and dropout from cardiac rehabilitation. These findings could be useful to clinicians and policymakers for developing interventions aimed at improving participation and completion of cardiac rehabilitation, such as E-health or home-based delivery programmes. International Prospective Register of Systematic Reviews (PROSPERO) identifier: CRD42016032973.

Local Multi-Channel RF Surface Coil versus Body RF Coil Transmission for Cardiac Magnetic Resonance at 3 Tesla: Which Configuration Is Winning the Game?

PubMed Central

Winter, Lukas; Dieringer, Matthias A.; Els, Antje; Oezerdem, Celal; Rieger, Jan; Kuehne, Andre; Cassara, Antonino M.; Pfeiffer, Harald; Wetterling, Friedrich; Niendorf, Thoralf

2016-01-01

Introduction The purpose of this study was to demonstrate the feasibility and efficiency of cardiac MR at 3 Tesla using local four-channel RF coil transmission and benchmark it against large volume body RF coil excitation. Methods Electromagnetic field simulations are conducted to detail RF power deposition, transmission field uniformity and efficiency for local and body RF coil transmission. For both excitation regimes transmission field maps are acquired in a human torso phantom. For each transmission regime flip angle distributions and blood-myocardium contrast are examined in a volunteer study of 12 subjects. The feasibility of the local transceiver RF coil array for cardiac chamber quantification at 3 Tesla is demonstrated. Results Our simulations and experiments demonstrate that cardiac MR at 3 Tesla using four-channel surface RF coil transmission is competitive versus current clinical CMR practice of large volume body RF coil transmission. The efficiency advantage of the 4TX/4RX setup facilitates shorter repetition times governed by local SAR limits versus body RF coil transmission at whole-body SAR limit. No statistically significant difference was found for cardiac chamber quantification derived with body RF coil versus four-channel surface RF coil transmission. Our simulation also show that the body RF coil exceeds local SAR limits by a factor of ~2 when driven at maximum applicable input power to reach the whole-body SAR limit. Conclusion Pursuing local surface RF coil arrays for transmission in cardiac MR is a conceptually appealing alternative to body RF coil transmission, especially for patients with implants. PMID:27598923

Cerebral oxygen saturation and cardiac output during anaesthesia in sitting position for neurosurgical procedures: a prospective observational study.

PubMed

Schramm, P; Tzanova, I; Hagen, F; Berres, M; Closhen, D; Pestel, G; Engelhard, K

2016-10-01

Neurosurgical operations in the dorsal cranium often require the patient to be positioned in a sitting position. This can be associated with decreased cardiac output and cerebral hypoperfusion, and possibly, inadequate cerebral oxygenation. In the present study, cerebral oxygen saturation was measured during neurosurgery in the sitting position and correlated with cardiac output. Perioperative cerebral oxygen saturation was measured continuously with two different monitors, INVOS ® and FORE-SIGHT ® . Cardiac output was measured at eight predefined time points using transoesophageal echocardiography. Forty patients were enrolled, but only 35 (20 female) were eventually operated on in the sitting position. At the first time point, the regional cerebral oxygen saturation measured with INVOS ® was 70 (sd 9)%; thereafter, it increased by 0.0187% min -1 (P<0.01). The cerebral tissue oxygen saturation measured with FORE-SIGHT ® started at 68 (sd 13)% and increased by 0.0142% min -1 (P<0.01). The mean arterial blood pressure did not change. Cardiac output was between 6.3 (sd 1.3) and 7.2 (1.8) litre min -1 at the predefined time points. Cardiac output, but not mean arterial blood pressure, showed a positive and significant correlation with cerebral oxygen saturation. During neurosurgery in the sitting position, the cerebral oxygen saturation slowly increases and, therefore, this position seems to be safe with regard to cerebral oxygen saturation. Cerebral oxygen saturation is stable because of constant CO and MAP, while the influence of CO on cerebral oxygen saturation seems to be more relevant. NCT01275898. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Medial prefrontal cortex TRPV1 channels modulate the baroreflex cardiac activity in rats

PubMed Central

Lagatta, D C; Ferreira‐Junior, N C

2015-01-01

Background and Purpose The ventral portion of the medial prefrontal cortex (vMPFC) comprises the infralimbic (IL), prelimbic (PL) and dorsopenducular (DP) cortices. The IL and PL regions facilitate the baroreceptor reflex arc. This facilitatory effect on the baroreflex is thought to be mediated by vMPFC glutamatergic transmission, through NMDA receptors. The glutamatergic transmission can be modulated by other neurotransmitters, such as the endocannabinoids, which are agonists of the TRPV1 receptor. TRPV1 channels facilitate glutamatergic transmission in the brain. Thus, we hypothesized that TRPV1 receptors in the vMPFC enhance the cardiac baroreflex response. Experimental Approach Stainless steel guide cannulae were bilaterally implanted into the vMPFC of male Wistar rats. Afterwards, a catheter was inserted into the femoral artery, for recording MAP and HR, and into the femoral vein for assessing baroreflex activation. Key Results Microinjections of the TRPV1 receptor antagonists capsazepine and 6‐iodo‐nordihydrocapsaicin (6‐IODO) into the vMPFC reduced the cardiac baroreflex activity in unanaesthetized rats. Capsaicin microinjected into the vMPFC increased the cardiac baroreflex activity in unanaesthetized rats. When an ineffective dose of the TRPV1 receptor antagonist 6‐IODO was used, the capsaicin‐induced increase in the cardiac baroreflex response was abolished. The higher doses of capsaicin administered into the vMPFC after the ineffective dose of 6‐IODO displaced the dose–response curve of the baroreflex parameters to the right, with no alteration in the maximum effect of capsaicin. Conclusions and Implications The results of the present study show that stimulation of the TRPV1 receptors in the vMPFC increases the cardiac baroreceptor reflex response. PMID:26360139

Use of the Frank-Starling mechanism during exercise is linked to exercise-induced changes in arterial load

PubMed Central

Chantler, Paul D.; Melenovsky, Vojtech; Schulman, Steven P.; Gerstenblith, Gary; Becker, Lewis C.; Ferrucci, Luigi; Fleg, Jerome L.; Najjar, Samer S.

2012-01-01

Effective arterial elastance(EA) is a measure of the net arterial load imposed on the heart that integrates the effects of heart rate(HR), peripheral vascular resistance(PVR), and total arterial compliance(TAC) and is a modulator of cardiac performance. To what extent the change in EA during exercise impacts on cardiac performance and aerobic capacity is unknown. We examined EA and its relationship with cardiovascular performance in 352 healthy subjects. Subjects underwent rest and exercise gated scans to measure cardiac volumes and to derive EA[end-systolic pressure/stroke volume index(SV)], PVR[MAP/(SV*HR)], and TAC(SV/pulse pressure). EA varied with exercise intensity: the ΔEA between rest and peak exercise along with its determinants, differed among individuals and ranged from −44% to +149%, and was independent of age and sex. Individuals were separated into 3 groups based on their ΔEAI. Individuals with the largest increase in ΔEA(group 3;ΔEA≥0.98 mmHg.m2/ml) had the smallest reduction in PVR, the greatest reduction in TAC and a similar increase in HR vs. group 1(ΔEA<0.22 mmHg.m2/ml). Furthermore, group 3 had a reduction in end-diastolic volume, and a blunted increase in SV(80%), and cardiac output(27%), during exercise vs. group 1. Despite limitations in the Frank-Starling mechanism and cardiac function, peak aerobic capacity did not differ by group because arterial-venous oxygen difference was greater in group 3 vs. 1. Thus the change in arterial load during exercise has important effects on the Frank-Starling mechanism and cardiac performance but not on exercise capacity. These findings provide interesting insights into the dynamic cardiovascular alterations during exercise. PMID:22003052

Device for rapid quantification of human carotid baroreceptor-cardiac reflex responses

NASA Technical Reports Server (NTRS)

Sprenkle, J. M.; Eckberg, D. L.; Goble, R. L.; Schelhorn, J. J.; Halliday, H. C.

1986-01-01

A new device has been designed, constructed, and evaluated to characterize the human carotid baroreceptor-cardiac reflex response relation rapidly. This system was designed for study of reflex responses of astronauts before, during, and after space travel. The system comprises a new tightly sealing silicon rubber neck chamber, a stepping motor-driven electrodeposited nickel bellows pressure system, capable of delivering sequential R-wave-triggered neck chamber pressure changes between +40 and -65 mmHg, and a microprocessor-based electronics system for control of pressure steps and analysis and display of responses. This new system provokes classic sigmoid baroreceptor-cardiac reflex responses with threshold, linear, and saturation ranges in most human volunteers during one held expiration.

Cardiac ACE2/angiotensin 1–7/Mas receptor axis is activated in thyroid hormone-induced cardiac hypertrophy

PubMed Central

Diniz, Gabriela P.; Senger, Nathalia; Carneiro-Ramos, Marcela S.; Santos, Robson A. S.; Barreto-Chaves, Maria Luiza M.

2015-01-01

Objectives: Thyroid hormone (TH) promotes marked effects on the cardiovascular system, including the development of cardiac hypertrophy. Some studies have demonstrated that the renin–angiotensin system (RAS) is a key mediator of the cardiac growth in response to elevated TH levels. Although some of the main RAS components are changed in cardiac tissue on hyperthyroid state, the potential modulation of the counter regulatory components of the RAS, such as angiotensin-converting enzyme type 2 (ACE2), angiotensin 1–7 (Ang 1–7) levels and Mas receptor induced by hyperthyroidism is unknown. The aim of this study was to investigate the effect of hyperthyroidism on cardiac Ang 1–7, ACE2 and Mas receptor levels. Methods: Hyperthyroidism was induced in Wistar rats by daily intraperitoneal injections of T4 for 14 days. Results: Although plasma Ang 1–7 levels were unchanged by hyperthyroidism, cardiac Ang 1–7 levels were increased in TH-induced cardiac hypertrophy. ACE2 enzymatic activity was significantly increased in hearts from hyperthyroid animals, which may be contributing to the higher Ang 1–7 levels observed in the T4 group. Furthermore, elevated cardiac levels of Ang 1–7 levels were accompanied by increased Mas receptor protein levels. Conclusion: The counter-regulatory components of the RAS are activated in hyperthyroidism and may be contributing to modulate the cardiac hypertrophy in response to TH. PMID:26715125

Cardiovascular function, compliance, and connective tissue remodeling in the turtle, Trachemys scripta, following thermal acclimation

PubMed Central

Keen, Adam N.; Crossley, Dane A.

2016-01-01

Low temperature directly alters cardiovascular physiology in freshwater turtles, causing bradycardia, arterial hypotension, and a reduction in systemic blood pressure. At the same time, blood viscosity and systemic resistance increase, as does sensitivity to cardiac preload (e.g., via the Frank-Starling response). However, the long-term effects of these seasonal responses on the cardiovascular system are unclear. We acclimated red-eared slider turtles to a control temperature (25°C) or to chronic cold (5°C). To differentiate the direct effects of temperature from a cold-induced remodeling response, all measurements were conducted at the control temperature (25°C). In anesthetized turtles, cold acclimation reduced systemic resistance by 1.8-fold and increased systemic blood flow by 1.4-fold, resulting in a 2.3-fold higher right to left (R-L; net systemic) cardiac shunt flow and a 1.8-fold greater shunt fraction. Following a volume load by bolus injection of saline (calculated to increase stroke volume by 5-fold, ∼2.2% of total blood volume), systemic resistance was reduced while pulmonary blood flow and systemic pressure increased. An increased systemic blood flow meant the R-L cardiac shunt was further pronounced. In the isolated ventricle, passive stiffness was increased following cold acclimation with 4.2-fold greater collagen deposition in the myocardium. Histological sections of the major outflow arteries revealed a 1.4-fold higher elastin content in cold-acclimated animals. These results suggest that cold acclimation alters cardiac shunting patterns with an increased R-L shunt flow, achieved through reducing systemic resistance and increasing systemic blood flow. Furthermore, our data suggests that cold-induced cardiac remodeling may reduce the stress of high cardiac preload by increasing compliance of the vasculature and decreasing compliance of the ventricle. Together, these responses could compensate for reduced systolic function at low temperatures in the slider turtle. PMID:27101300

Autonomic control of cardiac function and myocardial oxygen consumption during hypoxic hypoxia.

NASA Technical Reports Server (NTRS)

Erickson, H. H.; Stone, H. L.

1972-01-01

Investigation in 19 conscious dogs of the importance of the sympathetic nervous system in the coronary and cardiac response to altitude (hypoxic) hypoxia. Beta-adrenergic blockade was used to minimize the cardiac effect associated with sympathetic receptors. It is shown that the autonomic nervous system, and particularly the sympathetic nervous system, is responsible for the increase in ventricular function and myocardial oxygen consumption that occurs during hypoxia. Minimizing this response through appropriate conditioning and training may improve the operating efficiency of the heart and reduce the hazard of hypoxia and other environmental stresses, such as acceleration, which are encountered in advanced aircraft systems.

Recurrent myocardial infarction: Mechanisms of free-floating adaptation and autonomic derangement in networked cardiac neural control

PubMed Central

Ardell, Jeffrey L.; Shivkumar, Kalyanam; Armour, J. Andrew

2017-01-01

The cardiac nervous system continuously controls cardiac function whether or not pathology is present. While myocardial infarction typically has a major and catastrophic impact, population studies have shown that longer-term risk for recurrent myocardial infarction and the related potential for sudden cardiac death depends mainly upon standard atherosclerotic variables and autonomic nervous system maladaptations. Investigative neurocardiology has demonstrated that autonomic control of cardiac function includes local circuit neurons for networked control within the peripheral nervous system. The structural and adaptive characteristics of such networked interactions define the dynamics and a new normal for cardiac control that results in the aftermath of recurrent myocardial infarction and/or unstable angina that may or may not precipitate autonomic derangement. These features are explored here via a mathematical model of cardiac regulation. A main observation is that the control environment during pathology is an extrapolation to a setting outside prior experience. Although global bounds guarantee stability, the resulting closed-loop dynamics exhibited while the network adapts during pathology are aptly described as ‘free-floating’ in order to emphasize their dependence upon details of the network structure. The totality of the results provide a mechanistic reasoning that validates the clinical practice of reducing sympathetic efferent neuronal tone while aggressively targeting autonomic derangement in the treatment of ischemic heart disease. PMID:28692680

Removal of pinned scroll waves in cardiac tissues by electric fields in a generic model of three-dimensional excitable media

PubMed Central

Pan, De-Bei; Gao, Xiang; Feng, Xia; Pan, Jun-Ting; Zhang, Hong

2016-01-01

Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves. PMID:26905367

Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia.

PubMed

Hoover, D B; Isaacs, E R; Jacques, F; Hoard, J L; Pagé, P; Armour, J A

2009-12-15

Dysfunction of the intrinsic cardiac nervous system is implicated in the genesis of atrial and ventricular arrhythmias. While this system has been studied extensively in animal models, far less is known about the intrinsic cardiac nervous system of humans. This study was initiated to anatomically identify neurotransmitters associated with the right atrial ganglionated plexus (RAGP) of the human heart. Biopsies of epicardial fat containing a portion of the RAGP were collected from eight patients during cardiothoracic surgery and processed for immunofluorescent detection of specific neuronal markers. Colocalization of markers was evaluated by confocal microscopy. Most intrinsic cardiac neuronal somata displayed immunoreactivity for the cholinergic marker choline acetyltransferase and the nitrergic marker neuronal nitric oxide synthase. A subpopulation of intrinsic cardiac neurons also stained for noradrenergic markers. While most intrinsic cardiac neurons received cholinergic innervation evident as punctate immunostaining for the high affinity choline transporter, some lacked cholinergic inputs. Moreover, peptidergic, nitrergic, and noradrenergic nerves provided substantial innervation of intrinsic cardiac ganglia. These findings demonstrate that the human RAGP has a complex neurochemical anatomy, which includes the presence of a dual cholinergic/nitrergic phenotype for most of its neurons, the presence of noradrenergic markers in a subpopulation of neurons, and innervation by a host of neurochemically distinct nerves. The putative role of multiple neurotransmitters in controlling intrinsic cardiac neurons and mediating efferent signaling to the heart indicates the possibility of novel therapeutic targets for arrhythmia prevention.

Contraindications to Athletic Participation. Cardiac, Respiratory, and Central Nervous System Conditions.

ERIC Educational Resources Information Center

Moeller, James L.

1996-01-01

Discusses contraindications to athletic participation, examining the cardiac, respiratory, and central nervous system conditions that warrant activity disqualification. Provides guidelines about when it is safe for individuals to participate, and discusses the physician's responsibility. (SM)

Role of Methylene Blue in the Maintenance of Postinduction Hemodynamic Status in Patients with Perforation Peritonitis: A Pilot Study.

PubMed

Senthilnathan, Muthapillai; Cherian, Anusha; Balachander, Hemavathi; Maroju, Nanda Kishore

2017-01-01

Methylene blue is an inhibitor of guanylate cyclase and hence prevents vasoplegia mediated by nitric oxide in patients with sepsis. This study aimed to analyze the effect of methylene blue on blood pressure maintenance following induction of anesthesia in patients presenting with peritonitis. Thirty patients diagnosed to have perforation peritonitis were randomized into two groups (Group MB, Group NS). Patients in Group MB were given injection methylene blue 2 mg/kg over 20 min and patients in Group NS were given 50 ml of normal saline over 20 min, before induction. Heart rate, mean arterial pressure (MAP), cardiac output, and systemic vascular resistance (SVR) were recorded every 5 min for 1 h after infusion. Hemodynamic parameters were analyzed using repeated-measures analysis of variance with Bonferroni's test. Blood gas analysis was analyzed using independent Student's t -test, and P < 0.05 was considered statistically significant. MAP was lower at all-time points in Group NS than Group MB; however, it was statistically significant immediately, and 5 min the following induction. MAP fell from 94.8 ± 11.8 mmHg to 89.2 ± 16.0 mmHg immediate postinduction in Group MB and from 92.1 ± 9.8 mmHg to 74.1 ± 12.6 mmHg in Group NS. MAP and SVR were significantly higher in Group MB, 5 min following induction. No adverse events attributable to methylene blue were noted. Methylene blue contributes to the maintenance of postinduction hemodynamic stability in patients with perforation peritonitis.

Cardiac parasympathetic reactivation following exercise: implications for training prescription.

PubMed

Stanley, Jamie; Peake, Jonathan M; Buchheit, Martin

2013-12-01

The objective of exercise training is to initiate desirable physiological adaptations that ultimately enhance physical work capacity. Optimal training prescription requires an individualized approach, with an appropriate balance of training stimulus and recovery and optimal periodization. Recovery from exercise involves integrated physiological responses. The cardiovascular system plays a fundamental role in facilitating many of these responses, including thermoregulation and delivery/removal of nutrients and waste products. As a marker of cardiovascular recovery, cardiac parasympathetic reactivation following a training session is highly individualized. It appears to parallel the acute/intermediate recovery of the thermoregulatory and vascular systems, as described by the supercompensation theory. The physiological mechanisms underlying cardiac parasympathetic reactivation are not completely understood. However, changes in cardiac autonomic activity may provide a proxy measure of the changes in autonomic input into organs and (by default) the blood flow requirements to restore homeostasis. Metaboreflex stimulation (e.g. muscle and blood acidosis) is likely a key determinant of parasympathetic reactivation in the short term (0-90 min post-exercise), whereas baroreflex stimulation (e.g. exercise-induced changes in plasma volume) probably mediates parasympathetic reactivation in the intermediate term (1-48 h post-exercise). Cardiac parasympathetic reactivation does not appear to coincide with the recovery of all physiological systems (e.g. energy stores or the neuromuscular system). However, this may reflect the limited data currently available on parasympathetic reactivation following strength/resistance-based exercise of variable intensity. In this review, we quantitatively analyse post-exercise cardiac parasympathetic reactivation in athletes and healthy individuals following aerobic exercise, with respect to exercise intensity and duration, and fitness/training status. Our results demonstrate that the time required for complete cardiac autonomic recovery after a single aerobic-based training session is up to 24 h following low-intensity exercise, 24-48 h following threshold-intensity exercise and at least 48 h following high-intensity exercise. Based on limited data, exercise duration is unlikely to be the greatest determinant of cardiac parasympathetic reactivation. Cardiac autonomic recovery occurs more rapidly in individuals with greater aerobic fitness. Our data lend support to the concept that in conjunction with daily training logs, data on cardiac parasympathetic activity are useful for individualizing training programmes. In the final sections of this review, we provide recommendations for structuring training microcycles with reference to cardiac parasympathetic recovery kinetics. Ultimately, coaches should structure training programmes tailored to the unique recovery kinetics of each individual.

Parametric methods for characterizing myocardial tissue by magnetic resonance imaging (part 2): T2 mapping.

PubMed

Perea Palazón, R J; Solé Arqués, M; Prat González, S; de Caralt Robira, T M; Cibeira López, M T; Ortiz Pérez, J T

2015-01-01

Cardiac magnetic resonance imaging is considered the reference technique for characterizing myocardial tissue; for example, T2-weighted sequences make it possible to evaluate areas of edema or myocardial inflammation. However, traditional sequences have many limitations and provide only qualitative information. Moreover, traditional sequences depend on the reference to remote myocardium or skeletal muscle, which limits their ability to detect and quantify diffuse myocardial damage. Recently developed magnetic resonance myocardial mapping techniques enable quantitative assessment of parameters indicative of edema. These techniques have proven better than traditional sequences both in acute cardiomyopathy and in acute ischemic heart disease. This article synthesizes current developments in T2 mapping as well as their clinical applications and limitations. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Maternal cardiac metabolism in pregnancy

PubMed Central

Liu, Laura X.; Arany, Zolt

2014-01-01

Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

Differences between physician social networks for cardiac surgery serving communities with high versus low proportions of black residents.

PubMed

Hollingsworth, John M; Funk, Russell J; Garrison, Spencer A; Owen-Smith, Jason; Kaufman, Samuel R; Landon, Bruce E; Birkmeyer, John D

2015-02-01

Compared with white patients, black patients are more likely to undergo cardiac surgery at low-quality hospitals, even when they live closer to high-quality ones. Opportunities for organizational interventions to alleviate this problem remain elusive. To explore physician isolation in communities with high proportions of black residents as a factor contributing to racial disparities in access to high-quality hospitals for cardiac surgery. Using national Medicare data (2008-2011), we mapped physician social networks at hospitals where coronary artery bypass grafting procedures were performed, measuring their degree of connectedness. We then fitted a series of multivariate regression models to examine for associations between physician connectedness and the proportion of black residents in the hospital service area (HSA) served by each network. Measures of physician connectedness (ie, repeat-tie fraction, clustering, and number of external ties). After accounting for regional differences in healthcare capacity, the social networks of physicians practicing in areas with more black residents varied in many important respects from those of HSAs with fewer black residents. Physicians serving HSAs with many black residents had a smaller number of repeated interactions with each other than those in other HSAs (P<0.001). When these physicians did interact, they tended to assemble in smaller groups of highly interconnected colleagues (P<0.001). They also had fewer interactions with physicians outside their immediate geographic area (P=0.048). Physicians in HSAs with many black residents are more isolated than those in HSAs with fewer black residents. This isolation may negatively impact on care coordination and information sharing. As such, planned delivery system reforms that encourage minorities to seek care within their established local networks may further exacerbate existing surgical disparities.

Characterization of glutamatergic neurons in the rat atrial intrinsic cardiac ganglia that project to the cardiac ventricular wall.

PubMed

Wang, Ting; Miller, Kenneth E

2016-08-04

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia (ICG) for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside ICG. In the present study, rat ICG neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) ICG contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial ICG contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT; (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG neurons could help in better understanding the function of the intrinsic cardiac nervous system. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles.

PubMed

Mayra, Azat; Tomimitsu, Hiroyuki; Kubodera, Takayuki; Kobayashi, Masaki; Piao, Wenying; Sunaga, Fumiko; Hirai, Yukihiko; Shimada, Takashi; Mizusawa, Hidehiro; Yokota, Takanori

2011-02-11

Systemic injections of AAV vectors generally transduce to the liver more effectively than to cardiac and skeletal muscles. The short hairpin RNA (shRNA)-expressing AAV9 (shRNA-AAV9) can also reduce target gene expression in the liver, but not enough in cardiac or skeletal muscles. Higher doses of shRNA-AAV9 required for inhibiting target genes in cardiac and skeletal muscles often results in shRNA-related toxicity including microRNA oversaturation that can induce fetal liver failure. In this study, we injected high-dose shRNA-AAV9 to neonates and efficiently silenced genes in cardiac and skeletal muscles without inducing liver toxicity. This is because AAV is most likely diluted or degraded in the liver than in cardiac or skeletal muscle during cell division after birth. We report that this systemically injected shRNA-AAV method does not induce any major side effects, such as liver dysfunction, and the dose of shRNA-AAV is sufficient for gene silencing in skeletal and cardiac muscle tissues. This novel method may be useful for generating gene knockdown in skeletal and cardiac mouse tissues, thus providing mouse models useful for analyzing diseases caused by loss-of-function of target genes. Copyright © 2011 Elsevier Inc. All rights reserved.

Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart

PubMed Central

Levick, Scott P.; Murray, David B.; Janicki, Joseph S.; Brower, Gregory L.

2010-01-01

Chronic activation of the sympathetic nervous system (SNS) is a key component of cardiac hypertrophy and fibrosis. However, previous studies have provided evidence to also implicate inflammatory cells, including mast cells, in the development of cardiac fibrosis. The current study investigated the potential interaction of cardiac mast cells with the SNS. Eight week old male SHR were sympathectomized to establish the effect of the SNS on cardiac mast cell density, myocardial remodeling and cytokine production in the hypertensive heart. Age-matched WKY served as controls. Cardiac fibrosis and hypertension were significantly attenuated and left ventricular mass normalized while cardiac mast cell density was markedly increased in sympathectomized SHR. Sympathectomy normalized myocardial levels of IFN-γ, IL-6 and IL-10, but had no effect on IL-4. The effect of norepinephrine and substance P on isolated cardiac mast cell activation was investigated as potential mechanisms of interaction between the two. Only substance P elicited mast cell degranulation. Substance P was also shown to induce the production of angiotensin II by a mixed population of isolated cardiac inflammatory cells, including mast cells, lymphocytes and macrophages. These results demonstrate the ability of neuropeptides to regulate inflammatory cell function, providing a potential mechanism by which the SNS and afferent nerves may interact with inflammatory cells in the hypertensive heart. PMID:20048196

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials.

PubMed

Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J

2014-01-01

The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models-of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells-to investigate the relative effects of reducing two important voltage-gated Ca currents-the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action.

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

PubMed Central

Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J.

2014-01-01

The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models—of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells—to investigate the relative effects of reducing two important voltage-gated Ca currents—the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action. PMID:25360118

Mineralocorticoid receptor antagonism treats obesity-associated cardiac diastolic dysfunction.

PubMed

Bender, Shawn B; DeMarco, Vincent G; Padilla, Jaume; Jenkins, Nathan T; Habibi, Javad; Garro, Mona; Pulakat, Lakshmi; Aroor, Annayya R; Jaffe, Iris Z; Sowers, James R

2015-05-01

Patients with obesity and diabetes mellitus exhibit a high prevalence of cardiac diastolic dysfunction (DD), an independent predictor of cardiovascular events for which no evidence-based treatment exists. In light of renin-angiotensin-aldosterone system activation in obesity and the cardioprotective action of mineralocorticoid receptor (MR) antagonists in systolic heart failure, we examined the hypothesis that MR blockade with a blood pressure-independent low-dose spironolactone (LSp) would treat obesity-associated DD in the Zucker obese (ZO) rat. Treatment of ZO rats exhibiting established DD with LSp normalized cardiac diastolic function, assessed by echocardiography. This was associated with reduced cardiac fibrosis, but not reduced hypertrophy, and restoration of endothelium-dependent vasodilation of isolated coronary arterioles via a nitric oxide-independent mechanism. Further mechanistic studies revealed that LSp reduced cardiac oxidative stress and improved endothelial insulin signaling, with no change in arteriolar stiffness. Infusion of Sprague-Dawley rats with the MR agonist aldosterone reproduced the DD noted in ZO rats. In addition, improved cardiac function in ZO-LSp rats was associated with attenuated systemic and adipose inflammation and an anti-inflammatory shift in cardiac immune cell mRNAs. Specifically, LSp increased cardiac markers of alternatively activated macrophages and regulatory T cells. ZO-LSp rats had unchanged blood pressure, serum potassium, systemic insulin sensitivity, or obesity-associated kidney injury, assessed by proteinuria. Taken together, these data demonstrate that MR antagonism effectively treats established obesity-related DD via blood pressure-independent mechanisms. These findings help identify a particular population with DD that might benefit from MR antagonist therapy, specifically patients with obesity and insulin resistance. © 2015 American Heart Association, Inc.

The challenge of pediatric cardiac services in the developing world.

PubMed

Hewitson, John; Brink, Johan; Zilla, Peter

2002-10-01

Pediatric cardiac services are too expensive for most developing nations. Problems other than cardiac disease take priority when it comes to budget allocations. Poor health infrastructure and referral systems, malnutrition, and the HIV/AIDS pandemic aggravate the situation, and the increasing economic divide is threatening what services do exist. We highlight how the practice of pediatric cardiac surgery in South Africa compares with first-world standards and outline some of the problems faced by pediatric cardiac services in developing nations. Copyright 2002, Elsevier Science (USA). All rights reserved.

Coupling of a 3D Finite Element Model of Cardiac Ventricular Mechanics to Lumped Systems Models of the Systemic and Pulmonic Circulation

PubMed Central

Kerckhoffs, Roy C. P.; Neal, Maxwell L.; Gu, Quan; Bassingthwaighte, James B.; Omens, Jeff H.; McCulloch, Andrew D.

2010-01-01

In this study we present a novel, robust method to couple finite element (FE) models of cardiac mechanics to systems models of the circulation (CIRC), independent of cardiac phase. For each time step through a cardiac cycle, left and right ventricular pressures were calculated using ventricular compliances from the FE and CIRC models. These pressures served as boundary conditions in the FE and CIRC models. In succeeding steps, pressures were updated to minimize cavity volume error (FE minus CIRC volume) using Newton iterations. Coupling was achieved when a predefined criterion for the volume error was satisfied. Initial conditions for the multi-scale model were obtained by replacing the FE model with a varying elastance model, which takes into account direct ventricular interactions. Applying the coupling, a novel multi-scale model of the canine cardiovascular system was developed. Global hemodynamics and regional mechanics were calculated for multiple beats in two separate simulations with a left ventricular ischemic region and pulmonary artery constriction, respectively. After the interventions, global hemodynamics changed due to direct and indirect ventricular interactions, in agreement with previously published experimental results. The coupling method allows for simulations of multiple cardiac cycles for normal and pathophysiology, encompassing levels from cell to system. PMID:17111210

Contour-Driven Atlas-Based Segmentation

PubMed Central

Wachinger, Christian; Fritscher, Karl; Sharp, Greg; Golland, Polina

2016-01-01

We propose new methods for automatic segmentation of images based on an atlas of manually labeled scans and contours in the image. First, we introduce a Bayesian framework for creating initial label maps from manually annotated training images. Within this framework, we model various registration- and patch-based segmentation techniques by changing the deformation field prior. Second, we perform contour-driven regression on the created label maps to refine the segmentation. Image contours and image parcellations give rise to non-stationary kernel functions that model the relationship between image locations. Setting the kernel to the covariance function in a Gaussian process establishes a distribution over label maps supported by image structures. Maximum a posteriori estimation of the distribution over label maps conditioned on the outcome of the atlas-based segmentation yields the refined segmentation. We evaluate the segmentation in two clinical applications: the segmentation of parotid glands in head and neck CT scans and the segmentation of the left atrium in cardiac MR angiography images. PMID:26068202

Phenol intoxication in a child.

PubMed

Unlü, R Erkin; Alagöz, M Sahin; Uysal, A Caĝri; Orbay, Hakan; Kilinç, Hidir; Tekin, Fatih; Sensöz, Omer; Erk, Gülcan

2004-11-01

Phenol preparations are used in dermatology and plastic surgery for the treatment of acne and during chemical face peeling. At this institution, phenol peeling is used in addition to mechanical dermabrasion for the elimination of subclinical premalignant lesions of patients having xeroderma pigmentosum. As the phenol peel is performed, most surgeons concentrate on skin results, ignoring systemic complications. Local histological changes and systemic toxicity have been seen during applications. Cardiac arrhythmias and even sudden death have been reported. The high incidence of cardiac arrhythmias after topical application of phenol preparations is demonstrated. The case of an 11-year-old boy with a diagnosis of xeroderma pigmentosum who underwent mechanical dermabrasion and chemical peeling with phenol and then developed severe cardiac arrhythmias is reported. A serious systemic toxic effect on cardiac rhythm from cutaneously applied phenol occurred in this case.

78 FR 79300 - Cardiovascular Devices; Reclassification of Intra-Aortic Balloon and Control Systems for Acute...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

... balloon and control system (IABP) devices when indicated for acute coronary syndrome, cardiac and non... and non-cardiac surgery, or complications of heart failure. The special controls for this device are.... FDA-2013-N-0581] Cardiovascular Devices; Reclassification of Intra-Aortic Balloon and Control Systems...

Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation “Memories”

PubMed Central

Tompkins, Joshua D.; Jung, Marc; Chen, Chang-yi; Lin, Ziguang; Ye, Jingjing; Godatha, Swetha; Lizhar, Elizabeth; Wu, Xiwei; Hsu, David; Couture, Larry A.; Riggs, Arthur D.

2016-01-01

The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors. PMID:26981572

Prognostic Value of Late Gadolinium Enhancement CMR in Systemic Amyloidosis.

PubMed

Raina, Sameer; Lensing, Shelly Y; Nairooz, Ramez S; Pothineni, Naga Venkata K; Hakeem, Abdul; Bhatti, Sabha; Pandey, Tarun

2016-11-01

The aim of this study was to access the prognostic implication of late gadolinium enhancement (LGE) in patients with systemic amyloidosis undergoing cardiac magnetic resonance (CMR). Cardiac amyloidosis confers significantly worse prognosis in patients with systemic amyloidosis. CMR imaging has emerged as an attractive noninvasive modality to diagnose cardiac involvement in patients with systemic amyloidosis. We performed a systemic review and meta-analysis to evaluate the prognostic role of LGE-CMR imaging in patients with systemic amyloidosis. Electronic databases MEDLINE, PubMed, Embase, and Cochrane were systematically searched to identify studies evaluating the association between LGE-CMR and prognosis in systemic amyloidosis with cardiac involvement. The present study was designed to systematically review and assess the association between LGE and the primary endpoint of all-cause mortality. A random effects model was used to calculate a pooled odds ratio using inverse-variance weighting. Data were included from 7 studies with a total of 425 patients and a mean follow-up of 25 months. Patients had a weighted average age of 64 years and left ventricular ejection fraction of 59.2%; 67% were male. Endomyocardial biopsy was positive for amyloidosis in 20%, whereas LGE was present in 73% of patients. LGE-positive patients had increased overall mortality compared with those without LGE (pooled odds ratio: 4.96; 95% confidence interval [CI]: 1.90 to 12.93; p = 0.001). For the LGE group, the pooled death rate was 0.07 (95% CI: 0.03 to 0.19) events per year and for the LGE+ group, the rate was 0.25 (95% CI: 0.16 to 0.39 per year; p = 0.001). The proportion of patients with cardiac biopsy within each study ranged from 3% to 68%, and the relationship between LGE status and death did not vary according to cardiac biopsy proportion across studies. LGE on CMR in patients with systemic amyloidosis with known or suspected cardiac amyloidosis is associated with increased risk of all-cause mortality. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Zero-fluoroscopy permanent pacemaker implantation using Ensite NavX system: Clinical viability or fanciful technique?

PubMed

Guo, Ping; Qiu, Jie; Wang, Yan; Chen, Guangzhi; Proietti, Riccardo; Fadhle, Al-Selmi; Zhao, Chunxia; Wen Wang, Dao

2018-02-01

Fluoroscopy is the imaging modality routinely used for cardiac device implantation and electrophysiological procedures. Due to the rising concern regarding the harmful effects of radiation exposure to both the patients and operation staffs, novel 3D mapping systems have been developed and implemented in electrophysiological procedure for the navigation of catheters inside the heart chambers. Their applicability in cardiac device implantation has been rarely reported. Our aim is to evaluate the feasibility and safety of permanent pacemaker implantation without fluoroscopy. From January 2012 to June 2016, six patients (50 ± 15 years, four of six were female, one of who was at the 25th week of gestation) who underwent permanent pacemaker implantation were included (zero-fluoroscopy group). Data from 20 consecutive cases of implantation performed under fluoroscopy guidance were chosen as a control group (fluoroscopy group). Total implantation procedure time for single-chamber pacemaker was 51.3 ± 13.1 minutes in the zero-fluoroscopy group and 42.6 ± 7.4 minutes in the fluoroscopy group (P  =  0.155). The implantation procedural time for a dual-chamber pacemaker was 88.3 ± 19.6 minutes and 67.3 ± 7.6 minutes in the zero-fluoroscopy and fluoroscopy groups (P  =  0.013), respectively. No complications were observed during the procedure and the follow-up in the two groups, and all pacemakers worked with satisfactory parameters. Ensite NavX system can be used as a reliable and safe zero-fluoroscopy approach for the implantation of single- or dual-chamber permanent pacemakers in specific patients, such as pregnant women or in extreme situations when the x-ray machine is not available. © 2017 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals, Inc.

Mapping and predicting mortality from systemic sclerosis.

PubMed

Elhai, Muriel; Meune, Christophe; Boubaya, Marouane; Avouac, Jérôme; Hachulla, Eric; Balbir-Gurman, Alexandra; Riemekasten, Gabriela; Airò, Paolo; Joven, Beatriz; Vettori, Serena; Cozzi, Franco; Ullman, Susanne; Czirják, László; Tikly, Mohammed; Müller-Ladner, Ulf; Caramaschi, Paola; Distler, Oliver; Iannone, Florenzo; Ananieva, Lidia P; Hesselstrand, Roger; Becvar, Radim; Gabrielli, Armando; Damjanov, Nemanja; Salvador, Maria J; Riccieri, Valeria; Mihai, Carina; Szücs, Gabriella; Walker, Ulrich A; Hunzelmann, Nicolas; Martinovic, Duska; Smith, Vanessa; Müller, Carolina de Souza; Montecucco, Carlo Maurizio; Opris, Daniela; Ingegnoli, Francesca; Vlachoyiannopoulos, Panayiotis G; Stamenkovic, Bojana; Rosato, Edoardo; Heitmann, Stefan; Distler, Jörg H W; Zenone, Thierry; Seidel, Matthias; Vacca, Alessandra; Langhe, Ellen De; Novak, Srdan; Cutolo, Maurizio; Mouthon, Luc; Henes, Jörg; Chizzolini, Carlo; Mühlen, Carlos Alberto von; Solanki, Kamal; Rednic, Simona; Stamp, Lisa; Anic, Branimir; Santamaria, Vera Ortiz; De Santis, Maria; Yavuz, Sule; Sifuentes-Giraldo, Walter Alberto; Chatelus, Emmanuel; Stork, Jiri; Laar, Jacob van; Loyo, Esthela; García de la Peña Lefebvre, Paloma; Eyerich, Kilian; Cosentino, Vanesa; Alegre-Sancho, Juan Jose; Kowal-Bielecka, Otylia; Rey, Grégoire; Matucci-Cerinic, Marco; Allanore, Yannick

2017-11-01

To determine the causes of death and risk factors in systemic sclerosis (SSc). Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Systems and methods for remote long standoff biometric identification using microwave cardiac signals

NASA Technical Reports Server (NTRS)

McGrath, William R. (Inventor); Talukder, Ashit (Inventor)

2012-01-01

Systems and methods for remote, long standoff biometric identification using microwave cardiac signals are provided. In one embodiment, the invention relates to a method for remote biometric identification using microwave cardiac signals, the method including generating and directing first microwave energy in a direction of a person, receiving microwave energy reflected from the person, the reflected microwave energy indicative of cardiac characteristics of the person, segmenting a signal indicative of the reflected microwave energy into a waveform including a plurality of heart beats, identifying patterns in the microwave heart beats waveform, and identifying the person based on the identified patterns and a stored microwave heart beats waveform.

Spillover Compensation in the Presence of Respiratory Motion Embedded in SPECT Perfusion Data

NASA Astrophysics Data System (ADS)

Pretorius, P. Hendrik; King, Michael A.

2008-02-01

Spillover from adjacent significant accumulations of extra-cardiac activity decreases diagnostic accuracy of SPECT perfusion imaging in especially the inferior/septal cardiac region. One method of compensating for the spillover at some location outside of a structure is to estimate it as the counts blurred into this location when a template (3D model) of the structure undergoes simulated imaging followed by reconstruction. The objective of this study was to determine what impact uncorrected respiratory motion has on such spillover compensation of extra-cardiac activity in the right coronary artery (RCA) territory, and if it is possible to use manual segmentation to define the extra-cardiac activity template(s) used in spillover correction. Two separate MCAT phantoms (1283 matrices) were simulated to represent the source and attenuation distributions of patients with and without respiratory motion. For each phantom the heart was modeled: 1) with a normal perfusion pattern and 2) with an RCA defect equal to 50% of the normal myocardium count level. After Monte Carlo simulation of 64times64times120 projections with appropriate noise, data were reconstructed using the rescaled block iterative (RBI) algorithm with 30 subsets and 5 iterations with compensation for attenuation, scatter and resolution. A 3D Gaussian post-filter with a sigma of 0.476 cm was used to suppress noise. Manual segmentation of the liver in filtered emission slices was used to create 3D binary templates. The true liver distribution (with and without respiratory motion included) was also used as binary templates. These templates were projected using a ray-driven projector simulating the imaging system with the exclusion of Compton scatter and reconstructed using the same protocol as for the emission data, excluding scatter compensation. Reconstructed templates were scaled using reconstructed emission count levels from the liver, and spillover subtracted outside the template. It was evident from the polar maps that the manually segmented template reconstructions were unable to remove all the spillover originating in the liver from the inferior wall. This was especially noticeable when a perfusion defect is present. Templates based on the true liver distribution appreciably improved spillover correction. Thus the emerging combined SPECT/CT technology may play a vital role in identifying and segmenting extra-cardiac structures more reliably thereby facilitating spillover correction. This study also indicates that compensation for respiratory motion might play an important role in spillover compensation.

The Usefulness and Limitations of Point-of-care Cardiac Troponin Measurement in the Emergency Department.

PubMed

Suzuki, Kenichiro; Komukai, Kimiaki; Nakata, Kotaro; Kan, Renshi; Oi, Yuhei; Muto, Eri; Kashiwagi, Yusuke; Tominaga, Mitsutoshi; Miyanaga, Satoru; Ishikawa, Tetsuya; Okuno, Kenji; Uzura, Masahiko; Yoshimura, Michihiro

2018-02-09

Objective This study was carried out to examine the usefulness of point-of-care (POC) cardiac troponin in diagnosing acute coronary syndrome (ACS) and to understand the limitations of a POC cardiac troponin I/T-based diagnoses. Methods Patients whose cardiac troponin levels were measured in the emergency department using a POC system (AQT System; Radiometer, Tokyo, Japan) between January and December 2016 were retrospectively examined (N=1449). Patients who were < 20 years of age or who were admitted with cardiopulmonary arrest were excluded. The sensitivity and specificity of the POC cardiac troponin levels for the diagnosis of ACS were determined. Result One hundred and twenty of 1449 total patients had ACS (acute myocardial infarction, n=88; unstable angina n=32). On comparing the receiver operating characteristic (ROC) curves, the area under the curve (AUC) values for POC cardiac troponin I and cardiac troponin T were 0.833 and 0.786, respectively. The sensitivity and specificity of POC cardiac troponin I when using the 99th percentile (0.023 ng/mL) as the diagnostic cut-off value were 69.0% and 88.1%, respectively. The sensitivity of POC cardiac troponin I (99th percentile) was higher in the patients sampled > 3 h after symptom onset (83.3%) than in those sampled ≤ 3 h after symptom onset (58.8%, p < 0.01). Conclusion When sampled > 3 h after the onset of symptoms, the POC cardiac troponin I level is considered to be suitable for use in diagnosing ACS. However, when sampled ≤ 3 h after the onset of symptoms, careful interpretation of POC cardiac troponins is therefore required to rule out ACS.

Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis.

PubMed

Treibel, Thomas A; Bandula, Steve; Fontana, Marianna; White, Steven K; Gilbertson, Janet A; Herrey, Anna S; Gillmore, Julian D; Punwani, Shonit; Hawkins, Philip N; Taylor, Stuart A; Moon, James C

2015-01-01

Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). ECVCT and ECVCMR results were well correlated (r(2) = 0.85 vs r(2) = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001). Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat.

PubMed

Matsukawa, Kanji; Ishii, Kei; Asahara, Ryota; Idesako, Mitsuhiro

2016-10-01

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade. Copyright © 2016 the American Physiological Society.

Noninvasive cardiac activation imaging of ventricular arrhythmias during drug-induced QT prolongation in the rabbit heart.

PubMed

Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; Zhou, Zhaoye; He, Bin

2013-10-01

Imaging myocardial activation from noninvasive body surface potentials promises to aid in both cardiovascular research and clinical medicine. To investigate the ability of a noninvasive 3-dimensional cardiac electrical imaging technique for characterizing the activation patterns of dynamically changing ventricular arrhythmias during drug-induced QT prolongation in rabbits. Simultaneous body surface potential mapping and 3-dimensional intracardiac mapping were performed in a closed-chest condition in 8 rabbits. Data analysis was performed on premature ventricular complexes, couplets, and torsades de pointes (TdP) induced during intravenous administration of clofilium and phenylephrine with combinations of various infusion rates. The drug infusion led to a significant increase in the QT interval (from 175 ± 7 to 274 ± 31 ms) and rate-corrected QT interval (from 183 ± 5 to 262 ± 21 ms) during the first dose cycle. All the ectopic beats initiated by a focal activation pattern. The initial beat of TdPs arose at the focal site, whereas the subsequent beats were due to focal activity from different sites or 2 competing focal sites. The imaged results captured the dynamic shift of activation patterns and were in good correlation with the simultaneous measurements, with a correlation coefficient of 0.65 ± 0.02 averaged over 111 ectopic beats. Sites of initial activation were localized to be ~5 mm from the directly measured initiation sites. The 3-dimensional cardiac electrical imaging technique could localize the origin of activation and image activation sequence of TdP during QT prolongation induced by clofilium and phenylephrine in rabbits. It offers the potential to noninvasively investigate the proarrhythmic effects of drug infusion and assess the mechanisms of arrhythmias on a beat-to-beat basis. © 2013 Heart Rhythm Society. All rights reserved.

Application of Cardiac Gating to Improve the Reproducibility of Intravoxel Incoherent Motion Measurements in the Head and Neck.

PubMed

Kang, Koung Mi; Choi, Seung Hong; Kim, Dong Eun; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sun-Won

2017-07-10

To prospectively evaluate whether cardiac gating can improve the reproducibility of intravoxel incoherent motion (IVIM) parameters in the head and neck, we performed IVIM diffusion-weighted imaging (DWI) using 4 b values (4b), 4 b values with cardiac gating (4b gating) and 17 b values (17b). We performed IVIM DWI twice per person on nine healthy volunteers using 4b, 4b gating and 17b and five patients with head and neck masses using 4b gating and 17b. The ADC, perfusion fraction (f), diffusion coefficient (D) and perfusion-related diffusion coefficient (D*) were calculated in the brain, masticator muscle, parotid gland, submandibular gland, tonsil and masses. Intraclass coefficient (ICC), Bland-Altman analysis (BAA) and coefficient of variation (CV) were used to assess short-term test-retest reproducibility. Kruskal-Wallis test and Mann-Whitney test were used to investigate whether 4b, 4b gating or 17b had significant influences on the parameters. For normal tissues and masses, ICC was excellent for all maps except the D* map. All parameters showed the lowest CV in the 4b gating. BAA also revealed the narrowest 95% limits of agreement using 4b gating for all parameters. In the subgroup analysis, almost all parameters in brain, muscle, parotid gland and submandibular gland showed the best reproducibility using 4b gating. In the muscle, parotid gland and submandibular gland, the values of ADC, f and D were not significantly different between among the three methods. 4b gating was more reproducible with respect to measurements of IVIM parameters in comparison with 4b or 17b.

MiRNAs with Apoptosis Regulating Potential Are Differentially Expressed in Chronic Exercise-Induced Physiologically Hypertrophied Hearts

PubMed Central

Ramprasath, Tharmarajan; Kalpana, Krishnan

2015-01-01

Physiological cardiac hypertrophy is an adaptive mechanism, induced during chronic exercise. As it is reversible and not associated with cardiomyocyte death, it is considered as a natural tactic to prevent cardiac dysfunction and failure. Though, different studies revealed the importance of microRNAs (miRNAs) in pathological hypertrophy, their role during physiological hypertrophy is largely unexplored. Hence, this study is aimed at revealing the global expression profile of miRNAs during physiological cardiac hypertrophy. Chronic swimming protocol continuously for eight weeks resulted in induction of physiological hypertrophy in rats and histopathology revealed the absence of tissue damage, apoptosis or fibrosis. Subsequently, the total RNA was isolated and small RNA sequencing was executed. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during physiological hypertrophy. The expression profile of the significantly differentially expressed miRNAs was validated by qPCR. In silico prediction of target genes by miRanda, miRdB and TargetScan and subsequent qPCR analysis unraveled that miRNAs including miR-99b, miR-100, miR-19b, miR-10, miR-208a, miR-133, miR-191a, miR-22, miR-30e and miR-181a are targeting the genes that primarily regulate cell proliferation and cell death. Gene ontology and pathway mapping showed that the differentially expressed miRNAs and their target genes were mapped to apoptosis and cell death pathways principally via PI3K/Akt/mTOR and MAPK signaling. In summary, our data indicates that regulation of these miRNAs with apoptosis regulating potential can be one of the major key factors in determining pathological or physiological hypertrophy by controlling fibrosis, apoptosis and cell death mechanisms. PMID:25793527

Single-Construct Polycistronic Doxycycline-Inducible Vectors Improve Direct Cardiac Reprogramming and Can Be Used to Identify the Critical Timing of Transgene Expression.

PubMed

Umei, Tomohiko C; Yamakawa, Hiroyuki; Muraoka, Naoto; Sadahiro, Taketaro; Isomi, Mari; Haginiwa, Sho; Kojima, Hidenori; Kurotsu, Shota; Tamura, Fumiya; Osakabe, Rina; Tani, Hidenori; Nara, Kaori; Miyoshi, Hiroyuki; Fukuda, Keiichi; Ieda, Masaki

2017-08-19

Direct reprogramming is a promising approach in regenerative medicine. Overexpression of the cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2 (GHMT) directly reprogram fibroblasts into cardiomyocyte-like cells (iCMs). However, the critical timing of transgene expression and the molecular mechanisms for cardiac reprogramming remain unclear. The conventional doxycycline (Dox)-inducible temporal transgene expression systems require simultaneous transduction of two vectors (pLVX-rtTA/pLVX-cDNA) harboring the reverse tetracycline transactivator (rtTA) and the tetracycline response element (TRE)-controlled transgene, respectively, leading to inefficient cardiac reprogramming. Herein, we developed a single-construct-based polycistronic Dox-inducible vector (pDox-cDNA) expressing both the rtTA and TRE-controlled transgenes. Fluorescence activated cell sorting (FACS) analyses, quantitative RT-PCR, and immunostaining revealed that pDox-GMT increased cardiac reprogramming three-fold compared to the conventional pLVX-rtTA/pLVX-GMT. After four weeks, pDox-GMT-induced iCMs expressed multiple cardiac genes, produced sarcomeric structures, and beat spontaneously. Co-transduction of pDox-Hand2 with retroviral pMX-GMT increased cardiac reprogramming three-fold compared to pMX-GMT alone. Temporal Dox administration revealed that Hand2 transgene expression is critical during the first two weeks of cardiac reprogramming. Microarray analyses demonstrated that Hand2 represses cell cycle-promoting genes and enhances cardiac reprogramming. Thus, we have developed an efficient temporal transgene expression system, which could be invaluable in the study of cardiac reprogramming.

Single-Construct Polycistronic Doxycycline-Inducible Vectors Improve Direct Cardiac Reprogramming and Can Be Used to Identify the Critical Timing of Transgene Expression

PubMed Central

Umei, Tomohiko C.; Yamakawa, Hiroyuki; Muraoka, Naoto; Sadahiro, Taketaro; Isomi, Mari; Haginiwa, Sho; Kojima, Hidenori; Kurotsu, Shota; Tamura, Fumiya; Osakabe, Rina; Tani, Hidenori; Nara, Kaori; Miyoshi, Hiroyuki; Fukuda, Keiichi; Ieda, Masaki

2017-01-01

Direct reprogramming is a promising approach in regenerative medicine. Overexpression of the cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2 (GHMT) directly reprogram fibroblasts into cardiomyocyte-like cells (iCMs). However, the critical timing of transgene expression and the molecular mechanisms for cardiac reprogramming remain unclear. The conventional doxycycline (Dox)-inducible temporal transgene expression systems require simultaneous transduction of two vectors (pLVX-rtTA/pLVX-cDNA) harboring the reverse tetracycline transactivator (rtTA) and the tetracycline response element (TRE)-controlled transgene, respectively, leading to inefficient cardiac reprogramming. Herein, we developed a single-construct-based polycistronic Dox-inducible vector (pDox-cDNA) expressing both the rtTA and TRE-controlled transgenes. Fluorescence activated cell sorting (FACS) analyses, quantitative RT-PCR, and immunostaining revealed that pDox-GMT increased cardiac reprogramming three-fold compared to the conventional pLVX-rtTA/pLVX-GMT. After four weeks, pDox-GMT-induced iCMs expressed multiple cardiac genes, produced sarcomeric structures, and beat spontaneously. Co-transduction of pDox-Hand2 with retroviral pMX-GMT increased cardiac reprogramming three-fold compared to pMX-GMT alone. Temporal Dox administration revealed that Hand2 transgene expression is critical during the first two weeks of cardiac reprogramming. Microarray analyses demonstrated that Hand2 represses cell cycle-promoting genes and enhances cardiac reprogramming. Thus, we have developed an efficient temporal transgene expression system, which could be invaluable in the study of cardiac reprogramming. PMID:28825623

[The predictive value of dynamic arterial elastance in arterial pressure response after norepinephrine dosage reduction in patients with septic shock].

PubMed

Liang, F M; Yang, T; Dong, L; Hui, J J; Yan, J

2017-05-01

Objective: To assess whether dynamic arterial elastance(Ea(dyn))can be used to predict the reduction of arterial pressure after decreasing norepinephrine (NE) dosage in patients with septic shock. Methods: A prospective observational cohort study was conducted. Thirty-two patients with septic shock and mechanical ventilationwere enrolledfrom January 2014 to December 2015 in ICU of Wuxi People's Hospital of Nanjing Medical University. Hemodynamic parameters were recorded by pulse contour cardiac output(PiCCO)monitoring technology before and after decreasing norepinephrine dosage. Ea(dyn) was defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV). Mean arterial pressure(MAP) variation was calculated after decreasing the dose of NE. Response was defined as a ≥15% decrease of MAP. AUC was plotted to assess the value of Ea(dyn) in predicting MAP response. Results: A total of 32 patients were enrolled in our study, with 13 responding to NE dose decrease where as the other 19 did not. Ea(dyn) was lower in responders than in nonresponders (0.77±0.13 vs 1.09±0.31, P <0.05). Baseline Ea(dyn) was positively correlated with systolic blood pressure variation, diastolic blood pressure variation, systemic vascular resistance variation and MAP variation( r =0.621, P =0.000; r =0.735, P =0.000; r =0.756, P =0.000; r =0.568, P =0.000 respectively). However, stoke volume variation, baseline level of systemic vascular resistance and NE baseline dose were not correlated with Ea(dyn) baseline value( r =0.264, P =0.076; r =0.078, P =0.545; r =0.002, P =0.987 respectively). Ea(dyn)≤0.97 predicted a decrease of MAP when decreasing NE dose, with an area under the receiver-operating characteristic curve of 0.85.The sensitivity was 100.0% and specificity was 73.7%. Conclusions: In septic shock patients treated with NE, Ea(dyn) is an index to predict the decrease of arterial pressure in response to NE dose reduction.

The second phase in creating the cardiac center for the next generation: beyond structure to process improvement.

PubMed

Woods, J

2001-01-01

The third generation cardiac institute will build on the successes of the past in structuring the service line, re-organizing to assimilate specialist interests, and re-positioning to expand cardiac services into cardiovascular services. To meet the challenges of an increasingly competitive marketplace and complex delivery system, the focus for this new model will shift away from improved structures, and toward improved processes. This shift will require a sound methodology for statistically measuring and sustaining process changes related to the optimization of cardiovascular care. In recent years, GE Medical Systems has successfully applied Six Sigma methodologies to enable cardiac centers to control key clinical and market development processes through its DMADV, DMAIC and Change Acceleration processes. Data indicates Six Sigma is having a positive impact within organizations across the United States, and when appropriately implemented, this approach can serve as a solid foundation for building the next generation cardiac institute.

Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts.

PubMed

Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; Patterson, Natalie L; McMullen, Julie R

2018-01-01

The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation. This includes cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival (heat shock response, ubiquitin-proteasome system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein response, DNA damage response), extracellular matrix, inflammatory response, and organ-to-organ crosstalk. We summarize therapeutic strategies targeting known regulators of exercise-induced protection and the challenges translating findings from bench to bedside. We conclude that technological advancements that allow for in-depth profiling of the genome, transcriptome, proteome and metabolome, combined with animal and human studies, provide new opportunities for comprehensively defining the signaling and regulatory aspects of cell/organelle functions that underpin the protective properties of exercise. This is likely to lead to the identification of novel biomarkers and therapeutic targets for heart disease.

Modern Perspectives on Numerical Modeling of Cardiac Pacemaker Cell

PubMed Central

Maltsev, Victor A.; Yaniv, Yael; Maltsev, Anna V.; Stern, Michael D.; Lakatta, Edward G.

2015-01-01

Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent “coupled-clock” theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies, such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age. PMID:24748434

Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis

PubMed Central

Wu, Mei-ping; Zhang, Yi-shuai; Xu, Xiangbin; Zhou, Qian

2017-01-01

Purpose Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II). Methods Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts. Results We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1). Conclusions Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling. PMID:28321644

Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis.

PubMed

Wu, Mei-Ping; Zhang, Yi-Shuai; Xu, Xiangbin; Zhou, Qian; Li, Jian-Dong; Yan, Chen

2017-04-01

Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II). Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts. We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1). Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling.

International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

PubMed

Mehra, Mandeep R; Crespo-Leiro, Maria G; Dipchand, Anne; Ensminger, Stephan M; Hiemann, Nicola E; Kobashigawa, Jon A; Madsen, Joren; Parameshwar, Jayan; Starling, Randall C; Uber, Patricia A

2010-07-01

The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology.

Early structural changes of the heart after experimental polytrauma and hemorrhagic shock

PubMed Central

Halbgebauer, Rebecca; Eisele, Philipp; Messerer, David A. C.; Weckbach, Sebastian; Schultze, Anke; Braumüller, Sonja; Gebhard, Florian

2017-01-01

Evidence is emerging that systemic inflammation after trauma drives structural and functional impairment of cardiomyocytes and leads to cardiac dysfunction, thus worsening the outcome of polytrauma patients. This study investigates the structural and molecular changes in heart tissue 4 h after multiple injuries with additional hemorrhagic shock using a clinically relevant rodent model of polytrauma. We determined mediators of systemic inflammation (keratinocyte chemoattractant, macrophage chemotactic protein 1), activated complement component C3a and cardiac troponin I in plasma and assessed histological specimen of the mouse heart via standard histomorphology and immunohistochemistry for cellular and subcellular damage and ongoing apoptosis. Further we investigated spatial and quantitative changes of connexin 43 by immunohistochemistry and western blotting. Our results show significantly increased plasma levels of both keratinocyte chemoattractant and cardiac troponin I 4 h after polytrauma and 2 h after induction of hypovolemia. Although we could not detect any morphological changes, immunohistochemical evaluation showed increased level of tissue high-mobility group box 1, which is both a damage-associated molecule and actively released as a danger response signal. Additionally, there was marked lateralization of the cardiac gap-junction protein connexin 43 following combined polytrauma and hemorrhagic shock. These results demonstrate a molecular manifestation of remote injury of cardiac muscle cells in the early phase after polytrauma and hemorrhagic shock with marked disruption of the cardiac gap junction. This disruption of an important component of the electrical conduction system of the heart may lead to arrhythmia and consequently to cardiac dysfunction. PMID:29084268

Statistical coding and decoding of heartbeat intervals.

PubMed

Lucena, Fausto; Barros, Allan Kardec; Príncipe, José C; Ohnishi, Noboru

2011-01-01

The heart integrates neuroregulatory messages into specific bands of frequency, such that the overall amplitude spectrum of the cardiac output reflects the variations of the autonomic nervous system. This modulatory mechanism seems to be well adjusted to the unpredictability of the cardiac demand, maintaining a proper cardiac regulation. A longstanding theory holds that biological organisms facing an ever-changing environment are likely to evolve adaptive mechanisms to extract essential features in order to adjust their behavior. The key question, however, has been to understand how the neural circuitry self-organizes these feature detectors to select behaviorally relevant information. Previous studies in computational perception suggest that a neural population enhances information that is important for survival by minimizing the statistical redundancy of the stimuli. Herein we investigate whether the cardiac system makes use of a redundancy reduction strategy to regulate the cardiac rhythm. Based on a network of neural filters optimized to code heartbeat intervals, we learn a population code that maximizes the information across the neural ensemble. The emerging population code displays filter tuning proprieties whose characteristics explain diverse aspects of the autonomic cardiac regulation, such as the compromise between fast and slow cardiac responses. We show that the filters yield responses that are quantitatively similar to observed heart rate responses during direct sympathetic or parasympathetic nerve stimulation. Our findings suggest that the heart decodes autonomic stimuli according to information theory principles analogous to how perceptual cues are encoded by sensory systems.

Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins

PubMed Central

Yao, Chunxiang; Behring, Jessica B.; Shao, Di; Sverdlov, Aaron L.; Whelan, Stephen A.; Elezaby, Aly; Yin, Xiaoyan; Siwik, Deborah A.; Seta, Francesca; Costello, Catherine E.; Cohen, Richard A.; Matsui, Reiko; Colucci, Wilson S.; McComb, Mark E.; Bachschmid, Markus M.

2015-01-01

Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2), react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat), an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a ‘Tandem Mass Tag’ (TMT) labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg) mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation. PMID:26642319

Predictors of change in sexual activity after cardiac diagnosis: Elements to inform sexual counseling.

PubMed

Mosack, Victoria; Hill, Twyla J; Steinke, Elaine E

2017-06-01

Safely returning to sexual activity after being diagnosed with a cardiac condition is at the core of sexual counseling strategies. To further inform sexual counseling, this study examined changes in sexual activity before and after a cardiac diagnosis. Logistic analysis was used to suggest factors that can contribute to a change in sexual activity among cardiac patients. Reduced frequency in sexual activity after a cardiac diagnosis was influenced by greater sexual concerns and a history of smoking, as well as by education and employment status. These findings suggest that cardiac patients experiencing significant concerns about resuming sexual activity need added support through the mental health system.

Rodent Studies of Cardiovascular Deconditioning

NASA Technical Reports Server (NTRS)

Shoukas, Artin A.

1999-01-01

Changes in blood pressure can occur for two reasons: 1) A decrease in cardiac output resulting from the altered contractility of the heart or through changes in venous filling pressure via the Frank Starling mechanism or; 2) A change in systemic vascular resistance. The observed changes in cardiac output and blood pressure after long term space flight cannot be entirely explained through changes in contractility or heart rate alone. Therefore, alterations in filling pressure mediated through changes in systemic venous capacitance and arterial resistance function may be important determinants of cardiac output and blood pressure after long term space flight. Our laboratory and previous studies have shown the importance of veno-constriction mediated by the carotid sinus baroreceptor reflex system on overall circulatory homeostasis and in the regulation of cardiac output. Our proposed experiments test the overall hypothesis that alterations in venous capacitance function and arterial resistance by the carotid sinus baroreceptor reflex system are an important determinant of the cardiac output and blood pressure response seen in astronauts after returning to earth from long term exposure to microgravity. This hypothesis is important to our overall understanding of circulatory adjustments made during long term space flight. It also provides a framework for investigating counter measures to reduce the incidence of orthostatic hypotension caused by an attenuation of cardiac output. We continue to use hind limb unweighted (HLU) rat model to simulate the patho physiological effects as they relate to cardiovascular deconditioning in microgravity. We have used this model to address the hypothesis that microgravity induced cardiovascular deconditioning results in impaired vascular responses and that these impaired vascular responses result from abnormal alpha-1 AR signaling. The impaired vascular reactivity results in attenuated blood pressure and cardiac output responses to an orthostatic challenge. We have used in vitro vascular reactivity assays to explore abnormalities in vascular responses in vessels from HLU animals and, cardiac output (CO), blood pressure (BP) and heart rate (HR) measurements to characterize changes in hemodynamics following HLU.

Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells in Phenotypic Screening: A Transforming Growth Factor-β Type 1 Receptor Kinase Inhibitor Induces Efficient Cardiac Differentiation.

PubMed

Drowley, Lauren; Koonce, Chad; Peel, Samantha; Jonebring, Anna; Plowright, Alleyn T; Kattman, Steven J; Andersson, Henrik; Anson, Blake; Swanson, Bradley J; Wang, Qing-Dong; Brolen, Gabriella

2016-02-01

Several progenitor cell populations have been reported to exist in hearts that play a role in cardiac turnover and/or repair. Despite the presence of cardiac stem and progenitor cells within the myocardium, functional repair of the heart after injury is inadequate. Identification of the signaling pathways involved in the expansion and differentiation of cardiac progenitor cells (CPCs) will broaden insight into the fundamental mechanisms playing a role in cardiac homeostasis and disease and might provide strategies for in vivo regenerative therapies. To understand and exploit cardiac ontogeny for drug discovery efforts, we developed an in vitro human induced pluripotent stem cell-derived CPC model system using a highly enriched population of KDR(pos)/CKIT(neg)/NKX2.5(pos) CPCs. Using this model system, these CPCs were capable of generating highly enriched cultures of cardiomyocytes under directed differentiation conditions. In order to facilitate the identification of pathways and targets involved in proliferation and differentiation of resident CPCs, we developed phenotypic screening assays. Screening paradigms for therapeutic applications require a robust, scalable, and consistent methodology. In the present study, we have demonstrated the suitability of these cells for medium to high-throughput screens to assess both proliferation and multilineage differentiation. Using this CPC model system and a small directed compound set, we identified activin-like kinase 5 (transforming growth factor-β type 1 receptor kinase) inhibitors as novel and potent inducers of human CPC differentiation to cardiomyocytes. Significance: Cardiac disease is a leading cause of morbidity and mortality, with no treatment available that can result in functional repair. This study demonstrates how differentiation of induced pluripotent stem cells can be used to identify and isolate cell populations of interest that can translate to the adult human heart. Two separate examples of phenotypic screens are discussed, demonstrating the value of this biologically relevant and reproducible technology. In addition, this assay system was able to identify novel and potent inducers of differentiation and proliferation of induced pluripotent stem cell-derived cardiac progenitor cells. ©AlphaMed Press.

Ablation of the Right Cardiac Vagus Nerve Reduces Acetylcholine Content without Changing the Inflammatory Response during Endotoxemia.

PubMed

Plaschke, Konstanze; Do, Thuc Quyen Monica; Uhle, Florian; Brenner, Thorsten; Weigand, Markus A; Kopitz, Jürgen

2018-02-01

Acetylcholine is the main transmitter of the parasympathetic vagus nerve. According to the cholinergic anti-inflammatory pathway (CAP) concept, acetylcholine has been shown to be important for signal transmission within the immune system and also for a variety of other functions throughout the organism. The spleen is thought to play an important role in regulating the CAP. In contrast, the existence of a "non-neuronal cardiac cholinergic system" that influences cardiac innervation during inflammation has been hypothesized, with recent publications introducing the heart instead of the spleen as a possible interface between the immune and nervous systems. To prove this hypothesis, we investigated whether selectively disrupting vagal stimulation of the right ventricle plays an important role in rat CAP regulation during endotoxemia. We performed a selective resection of the right cardiac branch of the Nervus vagus (VGX) with a corresponding sham resection in vehicle-injected and endotoxemic rats. Rats were injected with lipopolysaccharide (LPS, 1 mg/kg body weight, intravenously) and observed for 4 h. Intraoperative blood gas analysis was performed, and hemodynamic parameters were assessed using a left ventricular pressure-volume catheter. Rat hearts and blood were collected, and the expression and concentration of proinflammatory cytokines using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were measured, respectively. Four hours after injection, LPS induced a marked deterioration in rat blood gas parameters such as pH value, potassium, base excess, glucose, and lactate. The mean arterial blood pressure and the end-diastolic volume had decreased significantly. Further, significant increases in blood cholinesterases and in proinflammatory (IL-1β, IL-6, TNF-α) cytokine concentration and gene expression were obtained. Right cardiac vagus nerve resection (VGX) led to a marked decrease in heart acetylcholine concentration and an increase in cardiac acetylcholinesterase activity. Without LPS, VGX changed rat hemodynamic parameters, including heart frequency, cardiac output, and end-diastolic volume. In contrast, VGX during endotoxemia did not significantly change the concentration and expression of proinflammatory cytokines in the heart. In conclusion we demonstrate that right cardiac vagal innervation regulates cardiac acetylcholine content but neither improves nor worsens systemic inflammation.

Measures of Autonomic Nervous System

DTIC Science & Technology

2011-04-01

activation encompass non-invasive tools, which measure cardiac, skin conductance, respiratory , and vascular activity. Choice of tools is dependent upon...digestion, excretion, and cardiac and respiratory activity. The ANS consists of the sympathetic and parasympathetic divisions and acts through a... respiratory cycles. Generally, these two systems should be seen as permanently modulating vital functions to achieve homeostasis. Since both systems are

AMPK attenuates microtubule proliferation in cardiac hypertrophy.

PubMed

Fassett, John T; Hu, Xinli; Xu, Xin; Lu, Zhongbing; Zhang, Ping; Chen, Yingjie; Bache, Robert J

2013-03-01

Cell hypertrophy requires increased protein synthesis and expansion of the cytoskeletal networks that support cell enlargement. AMPK limits anabolic processes, such as protein synthesis, when energy supply is insufficient, but its role in cytoskeletal remodeling is not known. Here, we examined the influence of AMPK in cytoskeletal remodeling during cardiomyocyte hypertrophy, a clinically relevant condition in which cardiomyocytes enlarge but do not divide. In neonatal cardiomyocytes, activation of AMPK with 5-aminoimidazole carboxamide ribonucleotide (AICAR) or expression of constitutively active AMPK (CA-AMPK) attenuated cell area increase by hypertrophic stimuli (phenylephrine). AMPK activation had little effect on intermediate filaments or myofilaments but dramatically reduced microtubule stability, as measured by detyrosinated tubulin levels and cytoskeletal tubulin accumulation. Importantly, low-level AMPK activation limited cell expansion and microtubule growth independent of mTORC1 or protein synthesis repression, identifying a new mechanism by which AMPK regulates cell growth. Mechanistically, AICAR treatment increased Ser-915 phosphorylation of microtubule-associated protein 4 (MAP4), which reduces affinity for tubulin and prevents stabilization of microtubules (MTs). RNAi knockdown of MAP4 confirmed its critical role in cardiomyocyte MT stabilization. In support of a pathophysiological role for AMPK regulation of cardiac microtubules, AMPK α2 KO mice exposed to pressure overload (transverse aortic constriction; TAC) demonstrated reduced MAP4 phosphorylation and increased microtubule accumulation that correlated with the severity of contractile dysfunction. Together, our data identify the microtubule cytoskeleton as a sensitive target of AMPK activity, and the data suggest a novel role for AMPK in limiting accumulation and densification of microtubules that occurs in response to hypertrophic stress.

AMPK attenuates microtubule proliferation in cardiac hypertrophy

PubMed Central

Fassett, John T.; Hu, Xinli; Xu, Xin; Lu, Zhongbing; Zhang, Ping; Chen, Yingjie

2013-01-01

Cell hypertrophy requires increased protein synthesis and expansion of the cytoskeletal networks that support cell enlargement. AMPK limits anabolic processes, such as protein synthesis, when energy supply is insufficient, but its role in cytoskeletal remodeling is not known. Here, we examined the influence of AMPK in cytoskeletal remodeling during cardiomyocyte hypertrophy, a clinically relevant condition in which cardiomyocytes enlarge but do not divide. In neonatal cardiomyocytes, activation of AMPK with 5-aminoimidazole carboxamide ribonucleotide (AICAR) or expression of constitutively active AMPK (CA-AMPK) attenuated cell area increase by hypertrophic stimuli (phenylephrine). AMPK activation had little effect on intermediate filaments or myofilaments but dramatically reduced microtubule stability, as measured by detyrosinated tubulin levels and cytoskeletal tubulin accumulation. Importantly, low-level AMPK activation limited cell expansion and microtubule growth independent of mTORC1 or protein synthesis repression, identifying a new mechanism by which AMPK regulates cell growth. Mechanistically, AICAR treatment increased Ser-915 phosphorylation of microtubule-associated protein 4 (MAP4), which reduces affinity for tubulin and prevents stabilization of microtubules (MTs). RNAi knockdown of MAP4 confirmed its critical role in cardiomyocyte MT stabilization. In support of a pathophysiological role for AMPK regulation of cardiac microtubules, AMPK α2 KO mice exposed to pressure overload (transverse aortic constriction; TAC) demonstrated reduced MAP4 phosphorylation and increased microtubule accumulation that correlated with the severity of contractile dysfunction. Together, our data identify the microtubule cytoskeleton as a sensitive target of AMPK activity, and the data suggest a novel role for AMPK in limiting accumulation and densification of microtubules that occurs in response to hypertrophic stress. PMID:23316058

MR fingerprinting for rapid quantification of myocardial T1 , T2 , and proton spin density.

PubMed

Hamilton, Jesse I; Jiang, Yun; Chen, Yong; Ma, Dan; Lo, Wei-Ching; Griswold, Mark; Seiberlich, Nicole

2017-04-01

To introduce a two-dimensional MR fingerprinting (MRF) technique for quantification of T 1 , T 2 , and M 0 in myocardium. An electrocardiograph-triggered MRF method is introduced for mapping myocardial T 1 , T 2 , and M 0 during a single breath-hold in as short as four heartbeats. The pulse sequence uses variable flip angles, repetition times, inversion recovery times, and T 2 preparation dephasing times. A dictionary of possible signal evolutions is simulated for each scan that incorporates the subject's unique variations in heart rate. Aspects of the sequence design were explored in simulations, and the accuracy and precision of cardiac MRF were assessed in a phantom study. In vivo imaging was performed at 3 Tesla in 11 volunteers to generate native parametric maps. T 1 and T 2 measurements from the proposed cardiac MRF sequence correlated well with standard spin echo measurements in the phantom study (R 2  > 0.99). A Bland-Altman analysis revealed good agreement for myocardial T 1 measurements between MRF and MOLLI (bias 1 ms, 95% limits of agreement -72 to 72 ms) and T 2 measurements between MRF and T 2 -prepared balanced steady-state free precession (bias, -2.6 ms; 95% limits of agreement, -8.5 to 3.3 ms). MRF can provide quantitative single slice T 1 , T 2 , and M 0 maps in the heart within a single breath-hold. Magn Reson Med 77:1446-1458, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Detraining Differentially Preserved Beneficial Effects of Exercise on Hypertension: Effects on Blood Pressure, Cardiac Function, Brain Inflammatory Cytokines and Oxidative Stress

PubMed Central

Agarwal, Deepmala; Dange, Rahul B.; Vila, Jorge; Otamendi, Arturo J.; Francis, Joseph

2012-01-01

Aims This study sought to investigate the effects of physical detraining on blood pressure (BP) and cardiac morphology and function in hypertension, and on pro- and anti-inflammatory cytokines (PICs and AIC) and oxidative stress within the brain of hypertensive rats. Methods and Results Hypertension was induced in male Sprague-Dawley rats by delivering AngiotensinII for 42 days using implanted osmotic minipumps. Rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise (ExT) for 42 days, whereas, detrained groups underwent 28 days of exercise followed by 14 days of detraining. BP and cardiac function were evaluated by radio-telemetry and echocardiography, respectively. At the end, the paraventricular nucleus (PVN) was analyzed by Real-time RT-PCR and Western blot. ExT in AngII-infused rats caused delayed progression of hypertension, reduced cardiac hypertrophy, and improved diastolic function. These results were associated with significantly reduced PICs, increased AIC (interleukin (IL)-10), and attenuated oxidative stress in the PVN. Detraining did not abolish the exercise-induced attenuation in MAP in hypertensive rats; however, detraining failed to completely preserve exercise-mediated improvement in cardiac hypertrophy and function. Additionally, detraining did not reverse exercise-induced improvement in PICs in the PVN of hypertensive rats; however, the improvements in IL-10 were abolished. Conclusion These results indicate that although 2 weeks of detraining is not long enough to completely abolish the beneficial effects of regular exercise, continuing cessation of exercise may lead to detrimental effects. PMID:23285093

Impaired atrioventricular transport in patients with transposition of the great arteries palliated by atrial switch and preserved systolic right ventricular function: A magnetic resonance imaging study.

PubMed

Ladouceur, Magalie; Kachenoura, Nadjia; Soulat, Gilles; Bollache, Emilie; Redheuil, Alban; Azizi, Michel; Delclaux, Christophe; Chatellier, Gilles; Boutouyrie, Pierre; Iserin, Laurence; Bonnet, Damien; Mousseaux, Elie

2017-07-01

We aimed (1) determine if systemic right ventricle filling parameters influence systemic right ventricle stroke volume in adult patients with D-transposition of the great arteries (D-TGA) palliated by atrial switch, using cardiac magnetic resonance imaging and echocardiography, and (2) to study relationship of these diastolic parameters with exercise performance and BNP, in patients with preserved systolic systemic right ventricle function. Single-center, cross-sectional, prospective study. In patients with D-TGA palliated by atrial switch, diastolic dysfunction of the systemic right ventricle may precede systolic dysfunction. Forty-five patients with D-TGA and atrial switch and 45 age and sex-matched healthy subjects underwent cardiac magnetic resonance imaging and echocardiography. Filling flow-rates measured by phase-contrast cardiac magnetic resonance imaging were analyzed using customized software to estimate diastolic parameters and compared with exercise performance. In D-TGA, early filling of systemic right ventricle was impaired with a lower peak filling rate normalized by filling volume (Ef/FV measured by cardiac magnetic resonance imaging) and a higher early filling peak velocity normalized by early peak myocardial velocity (E US /Ea measured by echocardiography) compared with controls (P ≤ .04). Stroke volume of systemic right ventricle showed a direct and significant association with pulmonary venous pathway size (respectively r = 0.50, P < .01). Systemic right atrial area and systemic right ventricle mass/volume index measured by cardiac magnetic resonance imaging, as well as Ef/FV were significantly correlated with exercise performances and BNP (P < .01). All correlations were independent of age, gender, body mass index and blood pressure. Systemic right ventricle pre-load and stroke volume depend mainly on intraatrial pathway function. Moreover, systemic right ventricle remodeling and right atrial dysfunction impair systemic right ventricle filling, leading to BNP increase and exercise limitation. Cardiac magnetic resonance imaging should assess systemic right ventricle filling abnormalities in D-TGA patients. © 2017 Wiley Periodicals, Inc.

Cardiac tissue engineering using perfusion bioreactor systems

PubMed Central

Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana

2009-01-01

This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955