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  1. Izan NF, Salleh SH, Ting CM, Noman F, Sh-Hussain H, Poznanski RR, et al.
    J Integr Neurosci, 2020 Sep 30;19(3):479-487.
    PMID: 33070527 DOI: 10.31083/j.jin.2020.03.222
    The purpose is to estimate the effectiveness of electrocardiograms during resting and active participation by the differentiation between the electrical activity of the heart while standing and sitting in a resting state. The concern is to identify the electrocardiogram parameters that did not show significant changes within these positions. The electrocardiogram parameters can be considered to be a standard marker for medically compromised patients. The electrocardiogram is recorded in the standing and sitting positions focusing on healthy participants using standard electrode placement of lead-I. Combined lead-I patterns (camel-hump or ST-segment prolongation) are usually seen in neurologic injury or hypothermia patients. The pairwise comparisons of a year data are about 454,400 cycles of sitting and 493,470 cycles of standing data. Thus, it is essential to quantify the nature and magnitude of changes seen in the electrocardiogram with a change of posture from sitting to standing in a healthy individual. This makes the findings of electrocardiogram analysis in this paper interesting in which some parameters (i.e., camel-hump patterns in lead-I) are helpful for clinical interpretations and could be suggestive of neurologic injury.
    Matched MeSH terms: Heart/physiology*
  2. Sepantafar M, Maheronnaghsh R, Mohammadi H, Rajabi-Zeleti S, Annabi N, Aghdami N, et al.
    Biotechnol Adv, 2016 Jul-Aug;34(4):362-379.
    PMID: 26976812 DOI: 10.1016/j.biotechadv.2016.03.003
    One of the major problems in the treatment of cardiovascular diseases is the inability of myocardium to self-regenerate. Current therapies are unable to restore the heart's function after myocardial infarction. Myocardial tissue engineering is potentially a key approach to regenerate damaged heart muscle. Myocardial patches are applied surgically, whereas injectable hydrogels provide effective minimally invasive approaches to recover functional myocardium. These hydrogels are easily administered and can be either cell free or loaded with bioactive agents and/or cardiac stem cells, which may apply paracrine effects. The aim of this review is to investigate the advantages and disadvantages of injectable stem cell-laden hydrogels and highlight their potential applications for myocardium repair.
    Matched MeSH terms: Heart/physiology
  3. Baskaran A, Sivalingam N
    Med J Malaysia, 1996 Mar;51(1):64-7.
    PMID: 10967981
    The aim of this study, is to determine whether the fine characteristics of the fetal heart sounds could be used to identify intrauterine growth retarded fetuses. A preliminary evaluation, was conducted to compare these characteristics between intrauterine growth retarded fetuses and normal fetuses in the antenatal period after 36 weeks of gestation. Altogether, 7 IUGR fetuses were compared with 12 normal fetuses. An instrument named the Fetal Frequency Phonocardiogram was designed for this purpose. When connected to a personal computer and with a software programme specially written, the fetal heart sound characteristics were analysed. After detailed analysis, there were 3 significant differences between IUGR and normal fetuses, all of which gave a p-value of < 0.01. The frequency of the first heart sound was significantly higher in the IUGR fetuses compared to normal fetuses. The ratio of the amplitude of the first heart sound over the second heart sound was higher in the IUGR group. Finally, the ratio of the time between the first and second heart sound over the cardiac cycle was shorter in the IUGR fetuses. Fetal heart sound analysis, may provide a simple non-invasive method of detecting and monitoring fetuses at risk in the antenatal period.
    Matched MeSH terms: Fetal Heart/physiology*
  4. Mohd Adib MA, Yusof MF, Ahmad Z, Mohd Hasni NH
    J Integr Bioinform, 2012;9(2):195.
    PMID: 22781711 DOI: 10.2390/biecoll-jib-2012-195
    Echocardiogram is an ultrasound image of the heart that demonstrates the size, motion and composition of cardiac structures and is also used to diagnose various abnormalities of the heart including abnormal chamber size, shape and congenital heart disease. Echocardiography provides important morphological and functional details of the heart. Most of the presented automatic cardiac disease recognition systems that use echocardiograms based on defective anatomical region detection. In this paper we present a simple technique for cardiac geometry detection via echocardiogram images which conquer these borders and exploits cues from cardiac structure. To demonstrate the effectiveness of this technique, we present results for cardiac geometry detection through difference intensity of echocardiogram images. We have developed a simple program code for the prediction of cardiac geometry using difference intensity of echocardiogram images. With this code, users can generate node or point for detection of cardiac geometry as ventricle and atrium in size, shape and location.
    Matched MeSH terms: Heart/physiology*
  5. Bilgen M
    Australas Phys Eng Sci Med, 2010 Dec;33(4):357-66.
    PMID: 21110236 DOI: 10.1007/s13246-010-0039-z
    Homogenous strain analysis (HSA) was developed to evaluate regional cardiac function using tagged cine magnetic resonance images of heart. Current cardiac applications of HSA are however limited in accurately detecting tag intersections within the myocardial wall, producing consistent triangulation of tag cells throughout the image series and achieving optimal spatial resolution due to the large size of the triangles. To address these issues, this article introduces a harmonic phase (HARP) interference method. In principle, as in the standard HARP analysis, the method uses harmonic phases associated with the two of the four fundamental peaks in the spectrum of a tagged image. However, the phase associated with each peak is wrapped when estimated digitally. This article shows that special combination of wrapped phases results in an image with unique intensity pattern that can be exploited to automatically detect tag intersections and to produce reliable triangulation with regularly organized partitioning of the mesh for HSA. In addition, the method offers new opportunities and freedom for evaluating myocardial function when the power and angle of the complex filtered spectra are mathematically modified prior to computing the phase. For example, the triangular elements can be shifted spatially by changing the angle and/or their sizes can be reduced by changing the power. Interference patterns obtained under a variety of power and angle conditions were presented and specific features observed in the results were explained. Together, the advanced processing capabilities increase the power of HSA by making the analysis less prone to errors from human interactions. It also allows strain measurements at higher spatial resolution and multi-scale, thereby improving the display methods for better interpretation of the analysis results.
    Matched MeSH terms: Heart/physiology*
  6. Hasenan SM, Karsani SA, Jubri Z
    Exp Gerontol, 2018 11;113:1-9.
    PMID: 30248357 DOI: 10.1016/j.exger.2018.09.001
    Aging is characterized by progressive decline in biochemical and physiological functions. According to the free radical theory of aging, aging results from oxidative damage due to the accumulation of excess reactive oxygen species (ROS). Mitochondria are the main source of ROS production and are also the main target for ROS. Therefore, a diet high in antioxidant such as honey is potentially able to protect the body from ROS and oxidative damage. Gelam honey is higher in flavonoid content and phenolic compounds compared to other local honey. This study was conducted to determine the effects of gelam honey on age related protein expression changes in cardiac mitochondrial rat. A total of 24 Sprague-Dawley male rats were divided into two groups: the young group (2 months old), and aged group (19 months old). Each group were then subdivided into two groups: control group (force-fed with distilled water), and treatment group (force-fed with gelam honey, 2.5 g/kg), and were treated for 8 months. Comparative proteomic analysis of mitochondria from cardiac tissue was then performed by high performance mass spectrometry (Q-TOF LCMS/MS) followed by validation of selected proteins by Western blotting. Proteins were identified using Spectrum Mill software and were subjected to stringent statistical analysis. A total of 286 proteins were identified in the young control group (YC) and 241 proteins were identified in the young gelam group (YG). In the aged group, a total of 243 proteins were identified in control group (OC), and 271 proteins in gelam group (OG). Comparative proteome profiling identified 69 proteins with different abundance (p 
    Matched MeSH terms: Mitochondria, Heart/physiology*
  7. Singh OP, Howe TA, Malarvili MB
    J Breath Res, 2018 01 04;12(2):026003.
    PMID: 28928295 DOI: 10.1088/1752-7163/aa8dbd
    The development of a human respiration carbon dioxide (CO2) measurement device to evaluate cardiorespiratory status inside and outside a hospital setting has proven to be a challenging area of research over the few last decades. Hence, we report a real-time, user operable CO2 measurement device using an infrared CO2 sensor (Arduino Mega2560) and a thin film transistor (TFT, 3.5″), incorporated with low pass (cut-off frequency, 10 Hz) and moving average (span, 8) filters. The proposed device measures features such as partial end-tidal carbon dioxide (EtCO2), respiratory rate (RR), inspired carbon dioxide (ICO2), and a newly proposed feature-Hjorth activity-that annotates data with the date and time from a real-time clock, and is stored onto a secure digital (SD) card. Further, it was tested on 22 healthy subjects and the performance (reliability, validity and relationship) of each feature was established using (1) an intraclass correlation coefficient (ICC), (2) standard error measurement (SEM), (3) smallest detectable difference (SDD), (4) Bland-Altman plot, and (5) Pearson's correlation (r). The SEM, SDD, and ICC values for inter- and intra-rater reliability were less than 5% and more than 0.8, respectively. Further, the Bland-Altman plot demonstrates that mean differences ± standard deviations for a set limit were 0.30 ± 0.77 mmHg, -0.34 ± 1.41 mmHg and 0.21 ± 0.64 breath per minute (bpm) for CO2, EtCO2 and RR. The findings revealed that the developed device is highly reliable, providing valid measurements for CO2, EtCO2, ICO2 and RR, and can be used in clinical settings for cardiorespiratory assessment. This research also demonstrates that EtCO2 and RR (r, -0.696) are negatively correlated while EtCO2 and activity (r, 0.846) are positively correlated. Thus, simultaneous measurement of these features may possibly assist physicians in understanding the subject's cardiopulmonary status. In future, the proposed device will be tested with asthmatic patients for use as an early screening tool outside a hospital setting.
    Matched MeSH terms: Heart/physiology*
  8. Murray AR, Atkinson L, Mahadi MK, Deuchars SA, Deuchars J
    Auton Neurosci, 2016 08;199:48-53.
    PMID: 27388046 DOI: 10.1016/j.autneu.2016.06.004
    The human ear seems an unlikely candidate for therapies aimed at improving cardiac function, but the ear and the heart share a common connection: the vagus nerve. In recent years there has been increasing interest in the auricular branch of the vagus nerve (ABVN), a unique cutaneous subdivision of the vagus distributed to the external ear. Non-invasive electrical stimulation of this nerve through the skin may offer a simple, cost-effective alternative to the established method of vagus nerve stimulation (VNS), which requires a surgical procedure and has generated mixed results in a number of clinical trials for heart failure. This review discusses the available evidence in support of modulating cardiac activity using this strange auricular nerve.
    Matched MeSH terms: Heart/physiology*
  9. Singh R, Singh HJ, Sirisinghe RG
    Singapore Med J, 1995 Apr;36(2):169-72.
    PMID: 7676261
    Aerobic capacity (VO2max) and lung capacities were measured in 66 healthy females ranging in age from 13 to 49 years. Forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were measured using a dry spirometer and Wrights peak flow meter respectively. Cardiopulmonary parameters were obtained from a progressive ergocycle test to exhaustion. Mean FVC and PEFR obtained were 2.73 +/- 0.07 L and 412 +/- 8.5 L/min respectively. FVC correlated negatively with age in subjects from the 3rd to 5th decade of age (r = 0.38, p < 0.05). Mean VO2max was 43.2 +/- 0.9 ml/kg/min in the 2nd decade compared to 30.3 +/- 0.7 ml/kg/min in the fifth decade. Regression analysis revealed an age related decline in VO2max of 0.45 +/- 0.8 ml/kg/min/year, which was found to be somewhat higher compared to other studies.
    Matched MeSH terms: Heart/physiology*
  10. Duncan MT, Horvath SM
    Singapore Med J, 1988 Aug;29(4):322-6.
    PMID: 3249956
    Cardiorespiratory adjustments to maximal treadmill exercise were studied in young untrained Malaysia men representative of the three major ethnic groups in Malaysia and Singapore. Maximal values for oxygen uptake and cardiac performance were essentially similar In the three groups and were comparable to those reported for other populations.
    Matched MeSH terms: Heart/physiology*
  11. Tay YL, Teah YF, Chong YM, Jamil MFA, Kollert S, Adenan MI, et al.
    Toxicol Appl Pharmacol, 2016 08 15;305:22-39.
    PMID: 27260674 DOI: 10.1016/j.taap.2016.05.022
    Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, IK1, a Kir current mediated by Kir2.1 channel and IKACh, a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC50 value of 1.62μM and 1.15μM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit IKACh current with an IC50 value of 3.32μM but has no significant effects on IK1. Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks.
    Matched MeSH terms: Heart/physiology
  12. Chan BT, Lim E, Chee KH, Abu Osman NA
    Comput Biol Med, 2013 May;43(4):377-85.
    PMID: 23428371 DOI: 10.1016/j.compbiomed.2013.01.013
    The heart is a sophisticated functional organ that plays a crucial role in the blood circulatory system. Hemodynamics within the heart chamber can be indicative of exert cardiac health. Due to the limitations of current cardiac imaging modalities, computational fluid dynamics (CFD) have been widely used for the purposes of cardiac function assessment and heart disease diagnosis, as they provide detailed insights into the cardiac flow field. An understanding of ventricular hemodynamics and pathological severities can be gained through studies that employ the CFD method. In this research the hemodynamics of two common myocardial diseases, dilated cardiomyopathy (DCM) and myocardial infarction (MI) were investigated, during both the filling phase and the whole cardiac cycle, through a prescribed geometry and fluid structure interaction (FSI) approach. The results of the research indicated that early stage disease identification and the improvement of cardiac assisting devices and therapeutic procedures can be facilitated through the use of the CFD method.
    Matched MeSH terms: Heart/physiology
  13. John CM, Khaddaj Mallat R, Mishra RC, George G, Singh V, Turnbull JD, et al.
    Pharmacol Res, 2020 01;151:104539.
    PMID: 31707036 DOI: 10.1016/j.phrs.2019.104539
    Aging represents an independent risk factor for the development of cardiovascular disease, and is associated with complex structural and functional alterations in the vasculature, such as endothelial dysfunction. Small- and intermediate-conductance, Ca2+-activated K+ channels (KCa2.3 and KCa3.1, respectively) are prominently expressed in the vascular endothelium, and pharmacological activators of these channels induce robust vasodilation upon acute exposure in isolated arteries and intact animals. However, the effects of prolonged in vivo administration of such compounds are unknown. In our study, we hypothesized that such treatment would ameliorate aging-related cardiovascular deficits. Aged (∼18 months) male Sprague Dawley rats were treated daily with either vehicle or the KCa channel activator SKA-31 (10 mg/kg, intraperitoneal injection; n = 6/group) for 8 weeks, followed by echocardiography, arterial pressure myography, immune cell and plasma cytokine characterization, and tissue histology. Our results show that SKA-31 administration improved endothelium-dependent vasodilation, reduced agonist-induced vascular contractility, and prevented the aging-associated declines in cardiac ejection fraction, stroke volume and fractional shortening, and further improved the expression of endothelial KCa channels and associated cell signalling components to levels similar to those observed in young male rats (∼5 months at end of study). SKA-31 administration did not promote pro-inflammatory changes in either T cell populations or plasma cytokines/chemokines, and we observed no overt tissue histopathology in heart, kidney, aorta, brain, liver and spleen. SKA-31 treatment in young rats had little to no effect on vascular reactivity, select protein expression, tissue histology, plasma cytokines/chemokines or immune cell properties. Collectively, these data demonstrate that administration of the KCa channel activator SKA-31 improved aging-related cardiovascular function, without adversely affecting the immune system or promoting tissue toxicity.
    Matched MeSH terms: Heart/physiology
  14. Javed E, Faye I, Malik AS, Abdullah JM
    J Neurosci Methods, 2017 11 01;291:150-165.
    PMID: 28842191 DOI: 10.1016/j.jneumeth.2017.08.020
    BACKGROUND: Simultaneous electroencephalography (EEG) and functional magnetic resonance image (fMRI) acquisitions provide better insight into brain dynamics. Some artefacts due to simultaneous acquisition pose a threat to the quality of the data. One such problematic artefact is the ballistocardiogram (BCG) artefact.

    METHODS: We developed a hybrid algorithm that combines features of empirical mode decomposition (EMD) with principal component analysis (PCA) to reduce the BCG artefact. The algorithm does not require extra electrocardiogram (ECG) or electrooculogram (EOG) recordings to extract the BCG artefact.

    RESULTS: The method was tested with both simulated and real EEG data of 11 participants. From the simulated data, the similarity index between the extracted BCG and the simulated BCG showed the effectiveness of the proposed method in BCG removal. On the other hand, real data were recorded with two conditions, i.e. resting state (eyes closed dataset) and task influenced (event-related potentials (ERPs) dataset). Using qualitative (visual inspection) and quantitative (similarity index, improved normalized power spectrum (INPS) ratio, power spectrum, sample entropy (SE)) evaluation parameters, the assessment results showed that the proposed method can efficiently reduce the BCG artefact while preserving the neuronal signals.

    COMPARISON WITH EXISTING METHODS: Compared with conventional methods, namely, average artefact subtraction (AAS), optimal basis set (OBS) and combined independent component analysis and principal component analysis (ICA-PCA), the statistical analyses of the results showed that the proposed method has better performance, and the differences were significant for all quantitative parameters except for the power and sample entropy.

    CONCLUSIONS: The proposed method does not require any reference signal, prior information or assumption to extract the BCG artefact. It will be very useful in circumstances where the reference signal is not available.

    Matched MeSH terms: Heart/physiology
  15. Awang K, Abdullah NH, Hadi AH, Fong YS
    J Biomed Biotechnol, 2012;2012:876458.
    PMID: 22536026 DOI: 10.1155/2012/876458
    The dichloromethane (DCM) extract of Andrographis paniculata Nees was tested for cardiovascular activity. The extract significantly reduced coronary perfusion pressure by up to 24.5 ± 3.0 mm Hg at a 3 mg dose and also reduced heart rate by up to 49.5 ± 11.4 beats/minute at this dose. Five labdane diterpenes, 14-deoxy-12-hydroxyandrographolide (1), 14-deoxy-11,12-didehydroandrographolide (2), 14-deoxyandrographolide (3), andrographolide (4), and neoandrographolide (5), were isolated from the aerial parts of this medicinal plant. Bioassay-guided studies using animal model showed that compounds, (2) and (3) were responsible for the coronary vasodilatation. This study also showed that andrographolide (4), the major labdane diterpene in this plant, has minimal effects on the heart.
    Matched MeSH terms: Heart/physiology
  16. Xin LZ, Govindasamy V, Musa S, Abu Kasim NH
    Med Hypotheses, 2013 Oct;81(4):704-6.
    PMID: 23932760 DOI: 10.1016/j.mehy.2013.07.032
    Dental tissues contains stem cells or progenitors that have high proliferative capacity, are clonogenic in vitro and demonstrate the ability to differentiate to multiple type cells involving neurons, bone, cartilage, fat and smooth muscle. Numerous experiments have demonstrated that the multipotent stem cells are not rejected by immune system and therefore it may be possible to use these cells in allogeneic settings. In addition, these remarkable cells are easily abundantly available couple with less invasive procedure in isolating comparing to bone marrow aspiration. Here we proposed dental stem cells as candidate for cardiac regeneration based on its immature characteristic and propensity towards cardiac lineage via PI3-Kinase/Aktsignalling pathway.
    Matched MeSH terms: Heart/physiology*
  17. Lim E, Chan GS, Dokos S, Ng SC, Latif LA, Vandenberghe S, et al.
    PLoS One, 2013;8(10):e77357.
    PMID: 24204817 DOI: 10.1371/journal.pone.0077357
    A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to [Formula: see text]. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.
    Matched MeSH terms: Heart/physiology*
  18. Lim YC, Budin SB, Othman F, Latip J, Zainalabidin S
    Cardiovasc Toxicol, 2017 Jul;17(3):251-259.
    PMID: 27402292 DOI: 10.1007/s12012-016-9379-6
    Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dtmax, suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca2+channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.
    Matched MeSH terms: Heart/physiology
  19. Jubaidi FF, Zainalabidin S, Mariappan V, Budin SB
    Int J Mol Sci, 2020 Aug 22;21(17).
    PMID: 32842567 DOI: 10.3390/ijms21176043
    As the powerhouse of the cells, mitochondria play a very important role in ensuring that cells continue to function. Mitochondrial dysfunction is one of the main factors contributing to the development of cardiomyopathy in diabetes mellitus. In early development of diabetic cardiomyopathy (DCM), patients present with myocardial fibrosis, dysfunctional remodeling and diastolic dysfunction, which later develop into systolic dysfunction and eventually heart failure. Cardiac mitochondrial dysfunction has been implicated in the development and progression of DCM. Thus, it is important to develop novel therapeutics in order to prevent the progression of DCM, especially by targeting mitochondrial dysfunction. To date, a number of studies have reported the potential of phenolic acids in exerting the cardioprotective effect by combating mitochondrial dysfunction, implicating its potential to be adopted in DCM therapies. Therefore, the aim of this review is to provide a concise overview of mitochondrial dysfunction in the development of DCM and the potential role of phenolic acids in combating cardiac mitochondrial dysfunction. Such information can be used for future development of phenolic acids as means of treating DCM by alleviating the cardiac mitochondrial dysfunction.
    Matched MeSH terms: Mitochondria, Heart/physiology
  20. Valli H, Ahmad S, Sriharan S, Dean LD, Grace AA, Jeevaratnam K, et al.
    Clin Exp Pharmacol Physiol, 2018 03;45(3):278-292.
    PMID: 29027245 DOI: 10.1111/1440-1681.12870
    Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca2+ homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na+ current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na+ currents. Plots of peak current against depolarisation from resting potential gave pretreatment maximum atrial and ventricular currents of -20.23 ± 1.48 (17) and -29.8 ± 2.4 (10) pA/μm2 (mean ± SEM [n]). Challenge by 8-CPT (1 μmol/L) reduced these currents to -11.21 ± 0.91 (12) (P  .05). Assessment of the inactivation that followed by applying subsequent steps to a fixed voltage 100 mV positive to resting potential gave concordant results. Half-maximal inactivation voltages and steepness factors, and time constants for Na+ current recovery from inactivation in double-pulse experiments, were similar through all the pharmacological conditions. Intracellular sharp microelectrode membrane potential recordings in intact Langendorff-perfused preparations demonstrated concordant variations in maximum rates of atrial and ventricular action potential upstroke, (dV/dt)max . We thus demonstrate an acute, reversible, Na+ channel inhibition offering a possible mechanism for previously reported pro-arrhythmic slowing of AP propagation following modifications of Ca2+ homeostasis, complementing earlier findings from chronic alterations in Ca2+ homeostasis in genetically-modified RyR2-P2328S hearts.
    Matched MeSH terms: Heart/physiology
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