Displaying publications 601 - 620 of 977 in total

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  1. Shah Mohd Shah A, Mohamed Z, Abdullah A, Abdul Malek PM, Saidin N, Maskon O
    Cardiovasc. Pathol., 2007 Nov-Dec;16(6):351-3.
    PMID: 18005874
    A 16-year-old student presented with a 4-week history of progressive shortness of breath, loss of appetite, and occasional blood-tinged sputum. The chest X-ray revealed massive right-sided pleural effusion with cardiomegaly. An echocardiogram revealed a large pericardial mass with massive pericardial effusion. Subsequent computed tomography of the thorax revealed a large heterogeneous mass in the right lung with extension into the pericardium. Lung biopsy revealed primitive neuroectodermal tumor (PNET) with small round blue cells, Homer-Wright rosettes, and CD99 positivity. We discuss pericardial metastases of PNET and its implication in this patient.
    Matched MeSH terms: Heart Neoplasms/complications; Heart Neoplasms/drug therapy; Heart Neoplasms/immunology; Heart Neoplasms/pathology*
  2. Boon CM, Ng MH, Choo YM, Mok SL
    PLoS One, 2013;8(2):e55908.
    PMID: 23409085 DOI: 10.1371/journal.pone.0055908
    Oleic acid has been shown to lower high blood pressure and provide cardiovascular protection. Curiosity arises as to whether super olein (SO), red palm olein (RPO) and palm olein (PO), which have high oleic acid content, are able to prevent the development of hypertension.
    Matched MeSH terms: Heart/anatomy & histology*; Heart/drug effects*; Heart Rate/drug effects
  3. Bonsu KO, Reidpath DD, Kadirvelu A
    Cardiovasc Ther, 2015 Dec;33(6):338-46.
    PMID: 26280110 DOI: 10.1111/1755-5922.12150
    Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF.
    Matched MeSH terms: Heart Failure/blood; Heart Failure/diagnosis; Heart Failure/drug therapy*; Heart Failure/physiopathology
  4. Kruszka P, Addissie YA, McGinn DE, Porras AR, Biggs E, Share M, et al.
    Am J Med Genet A, 2017 Apr;173(4):879-888.
    PMID: 28328118 DOI: 10.1002/ajmg.a.38199
    22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P 
    Matched MeSH terms: Heart Defects, Congenital/diagnosis*; Heart Defects, Congenital/ethnology; Heart Defects, Congenital/genetics; Heart Defects, Congenital/pathology
  5. Ramalingam A, Mohd Fauzi N, Budin SB, Zainalabidin S
    Basic Clin Pharmacol Toxicol, 2021 Feb;128(2):322-333.
    PMID: 32991780 DOI: 10.1111/bcpt.13500
    This study investigated the impact of prolonged nicotine administration on myocardial susceptibility to ischaemia-reperfusion (I/R) injury in a rat model and determined whether nicotine affects mitochondrial reactive oxygen species (ROS) production and permeability transition in rat hearts. Sprague-Dawley rats were administered 0.6 or 1.2 mg/kg nicotine for 28 days, and their hearts were isolated at end-point for assessment of myocardial susceptibility to I/R injury ex vivo. Rat heart mitochondria were also isolated from a subset of rats for analysis of mitochondrial ROS production and permeability transition. Compared to the vehicle controls, rat hearts isolated from nicotine-administered rats exhibited poorer left ventricular function that worsened over the course of I/R. Coronary flow rate was also severely impaired in the nicotine groups at baseline and this worsened after I/R. Nicotine administration significantly increased mitochondrial ROS production and permeability transition relative to the vehicle controls. Interestingly, pre-incubation of isolated mitochondria with ROS scavengers (superoxide dismutase and mitoTEMPO) significantly abolished nicotine-induced increase in mitochondria permeability transition in isolated rat heart mitochondria. Overall, our data showed that prolonged nicotine administration enhances myocardial susceptibility to I/R injury in rats and this is associated with mitochondrial ROS-driven increase in mitochondrial permeability transition.
    Matched MeSH terms: Isolated Heart Preparation; Mitochondria, Heart/drug effects; Mitochondria, Heart/metabolism; Mitochondria, Heart/pathology
  6. Saheb Sharif-Askari N, Sulaiman SA, Saheb Sharif-Askari F, Al Sayed Hussain A, Al-Mulla AA
    Int J Cardiol, 2014 Apr 1;172(3):e491-3.
    PMID: 24462141 DOI: 10.1016/j.ijcard.2014.01.002
    Matched MeSH terms: Heart Failure, Systolic/drug therapy*; Heart Failure, Systolic/epidemiology
  7. Maheshwari S, Animasahun BA, Njokanma OF
    Indian Heart J, 2012 Jan-Feb;64(1):50-3.
    PMID: 22572426 DOI: 10.1016/S0019-4832(12)60011-X
    Factors that have led to the increasing popularity of medical travel include the high cost of healthcare, long wait times for certain procedures, the ease and affordability of international travel, and improvements in both technology and standards of care in many countries.
    Matched MeSH terms: Heart Defects, Congenital/economics; Heart Defects, Congenital/surgery*
  8. Sabarudin A, Md Yusof AK, Tay MF, Ng KH, Sun Z
    Radiat Prot Dosimetry, 2013;153(4):441-7.
    PMID: 22807493 DOI: 10.1093/rpd/ncs127
    This study was conducted to investigate the effectiveness of dose-saving protocols in dual-source computed tomography (CT) coronary angiography compared with invasive coronary angiography (ICA). On 50 patients who underwent coronary CT angiography was performed dual-source CT (DSCT) and compared with ICA procedures. Entrance skin dose (ESD), which was measured at the thyroid gland, and effective dose (E) were assessed for both imaging modalities. The mean ESD measured at the thyroid gland was the highest at 120 kVp, followed by the 100 kVp DSCT and the ICA protocols with 4.0±1.8, 2.7±1.0 and 1.1±1.2 mGy, respectively. The mean E was estimated to be 10.3±2.1, 6.2±2.3 and 5.3±3.4 mSv corresponding to the 120-kVp, 100-kVp DSCT and ICA protocols, respectively. The application of 100 kVp in DSCT coronary angiography is feasible only in patients with a low body mass index of <25 kg m(-2), which leads to a significant dose reduction with the radiation dose being equivalent to that of ICA.
    Matched MeSH terms: Heart/radiation effects; Heart Rate
  9. Yusof AP, Yusoff NH, Suhaimi FW, Coote JH
    Auton Neurosci, 2009 Jun 15;148(1-2):50-4.
    PMID: 19349212 DOI: 10.1016/j.autneu.2009.03.005
    The aim of the present study was to determine if paraventricular-spinal vasopressin neurones participate in the sympatho-inhibitory effects of systemically administered atrial natriuretic peptide (ANP) on renal sympathetic nerve activity (RSNA). Experiments were carried out on male Sprague-Dawley rats anesthetized with 1.3 g/kg urethane. Changes in mean arterial pressure (mm Hg), heart rate (beats per minute) and RSNA (%) were measured following intravenous bolus administration of ANP (250 ng, 500 ng and 5 microg). Intrathecal application of selective V 1a receptor antagonist was performed to test for the involvement of supraspinal vasopressin pathways in mediating the effect on sympathetic outflow evoked by intravenous ANP administration. The results obtained demonstrated that both low and high doses of ANP caused renal sympathoinhibition (250 ng; - 7.5 +/- 1%, 500 ng; - 14.2 +/- 1%, 5 microg; - 16.4 +/- 2%), concomitant with vasodilation and bradycardia. After spinal vasopressin receptor blockade, the inhibitory effects of ANP were prevented and there was a small renal sympatho-excitation (250 ng; + 1.7 +/- 0.2%, 500 ng; + 6.1 +/- 0.03%, 5 microg; + 8.0 +/- 0.03%, P < 0.05). Therefore, the renal sympathetic nerve inhibition elicited by circulating ANP is dependent on the efficacy of a well established supraspinal vasopressin pathway. Since supraspinal vasopressin neurones without exception excite renal sympathetic neurones, it is suggested that ANP elicits this effect by activating cardiac vagal afferents that inhibit the spinally projecting vasopressin neurones at their origin in the paraventricular nucleus of the hypothalamus.
    Matched MeSH terms: Heart Rate/drug effects; Heart Rate/physiology
  10. Murty OP
    Am J Forensic Med Pathol, 2008 Sep;29(3):245-8.
    PMID: 18725781 DOI: 10.1097/PAF.0b013e318183d55f
    Giant cell myocarditis (GCM) is a rare but fatal disease of idiopathic origin. It results in focal necrosis of myocardium. This is a case report of middle aged Malaysian Indian female who died due to cardiac tamponade due to rupture myocardium and tear in the root of aorta. On naked eye examination, it simply resembled as recent as well as old fibrotic areas of myocardial infarction. She was clinically diagnosed as a case of obstructive cardiomyopathy with atrioventricular block, and was on pace maker. There was subendocardial fibrosis and left ventricular transmural infarction in the left ventricle. On histopathology, this was diagnosed as GCM, there were widespread areas of inflammatory cellular infiltration within the myocardium with multinucleated giant cells and granulomas interspersed with lymphocytes. Microscopic field showed up to 10 multinucleated giant cells. In this case, there were focal areas at multiple locations and caused uneven thickness in the left ventricle wall. Idiopathic GCM is very rare and causation of hemopericardium is the unique feature of this case. In this case the direct link of GCM with aortitis and rupture of left ventricle wall resulting in hemopericardium is shown. This case is documented through macroscopic as well as microscopic photographs in H&E, Ziel-Nelson, and GMS staining.
    Matched MeSH terms: Heart Ventricles/injuries; Heart Ventricles/pathology
  11. Seow SC, Chai P, Lee YP, Chan YH, Kwok BW, Yeo TC, et al.
    J. Card. Fail., 2007 Aug;13(6):476-81.
    PMID: 17675062
    Prognostic indicators and mortality in multiethnic Southeast Asian patients with heart failure (HF) may be different.
    Matched MeSH terms: Heart Failure/ethnology; Heart Failure/mortality*
  12. Wee HL, Cheung YB, Li SC, Fong KY, Thumboo J
    PMID: 15644146
    Diabetes mellitus (DM) is an important public health concern, the impact of which is increased by the high prevalence of co-existing chronic medical conditions among subjects with DM. The aims of this study were therefore to (1) evaluate the impact of DM and co-existing chronic medical conditions on health-related quality of life (HRQoL) (which could be additive, synergistic or subtractive); (2) to determine the extent to which the SF-6D (a single-index preference measure) captures the multidimensional information provided by the SF-36 (a profile measure).
    Matched MeSH terms: Heart Diseases/complications; Heart Diseases/ethnology
  13. Aziz NF, Ramalingam A, Latip J, Zainalabidin S
    Life Sci, 2021 Mar 15;269:119080.
    PMID: 33465387 DOI: 10.1016/j.lfs.2021.119080
    S-Allylcysteine (SAC) is an extensively studied natural product which has been proven to confer cardioprotection. This potentiates SAC into many clinical relevance possibilities, hence, the use of it ought to be optimally elucidated. To further confirm this, an ischemia/reperfusion model has been used to determine SAC at 10 mM and 50 mM on cardiac function, cardiac marker, and mitochondrial permeability. Using Langendorff setup, 24 adult male Wistar rats' hearts were isolated to be perfused with Kreb-Henseleit buffer throughout the ischemia/reperfusion method. After 20 min of stabilization, global ischemia was induced by turning off the perfusion for 35 min followed by 60 min of reperfusion with either Kreb-Henseleit buffer or SAC with the dose of 10 mM or 50 mM. The cardiac function was assessed and coronary effluent was collected at different timepoints throughout the experiment for lactate dehydrogenase (LDH) measurement. The harvested hearts were then used to measure glutathione while isolated mitochondria for mPTP analysis. SAC-reperfused hearts were shown to prevent the aggravation of cardiac function after I/R induction. It also dose-dependently upregulated glutathione reductase and glutathione level and these were also accompanied by significant reduction of LDH leakage and preserved mitochondrial permeability. Altogether, SAC dose-dependently was able to recover the post-ischemic cardiac function deterioration alongside with improvement of glutathione metabolism and mitochondrial preservation. These findings highly suggest that SAC when sufficiently supplied to the heart would be able to prevent the deleterious complications after the ischemic insult.
    Matched MeSH terms: Heart/drug effects*; Heart/physiopathology
  14. Chia YC, Ching SM, Lim HM
    J Hypertens, 2017 05;35 Suppl 1:S50-S56.
    PMID: 28350621 DOI: 10.1097/HJH.0000000000001333
    OBJECTIVES: The current study aims to determine the relationship of long-term visit-to-visit variability of SBP to cardiovascular disease (CVD) in a multiethnic primary care setting.
    METHOD: This is a retrospective study of a cohort of 807 hypertensive patients over a period of 10 years. Three-monthly clinic blood pressure readings were used to derive blood pressure variability (BPV), and CVD events were captured from patient records.
    RESULTS: Mean age at baseline was 57.2 ± 9.8 years with 63.3% being women. The BPV and mean SBP over 10 years were 14.7 ± 3.5 and 142 ± 8 mmHg, respectively. Prevalence of cardiovascular event was 13%. In multivariate logistic regression analysis, BPV was the predictor of CVD events, whereas the mean SBP was not independently associated with cardiovascular events in this population. Those with lower SBP and lower BPV had fewer cardiovascular events than those with the same low mean SBP but higher BPV (10.5 versus 12.8%). Similarly those with higher mean SBP but lower BPV also had fewer cardiovascular events than those with the same high mean and higher BPV (11.6 versus 16.7%). Other variables like being men, diabetes and Indian compared with Chinese are more likely to be associated with cardiovascular events.
    CONCLUSION: BPV is associated with an increase in CVD events even in those who have achieved lower mean SBP. Thus, we should prioritize not only control of SBP levels but also BPV to reduce CVD events further.
    Matched MeSH terms: Heart Failure/ethnology; Heart Failure/epidemiology*
  15. Edling CE, Fazmin IT, Chadda KR, Ahmad S, Valli H, Grace AA, et al.
    Biosci Rep, 2019 04 30;39(4).
    PMID: 30914453 DOI: 10.1042/BSR20190127
    Mice deficient in mitochondrial promoter peroxisome proliferator activated receptor-γ co-activator-1β (Pgc-1β-/- ) is a valuable model for metabolic diseases and has been found to present with several pathologies including ventricular arrhythmia. In the present study, our aim was to shed light on the molecular mechanisms behind the observed arrhythmic substrate by studying how the expression of selected genes critical for cardiac function differs in wild-type (WT) compared with Pgc-1β knockout mice and young compared with aged mice. We found that a clear majority of genes are down-regulated in the Pgc-1β-/- ventricular tissue compared with the WT. Although most individual genes are not significantly differentially expressed, a pattern is apparent when the genes are grouped according to their functional properties. Genes encoding proteins relating to ATPase activity, potassium ion channels relating to repolarisation and resting membrane potential, and genes encoding proteins in the cAMP pathway are found to be significantly down-regulated in the Pgc-1β deficient mice. On the contrary, the pacemaker channel genes Hcn3 and Hcn4 are up-regulated in subsets of the Pgc-1β deficient tissue. Furthermore, we found that with age, especially in the Pgc-1β-/- genotype, most genes are up-regulated including genes relating to the resting membrane potential, calcium homeostasis, the cAMP pathway, and most of the tested adrenoceptors. In conclusion, we here demonstrate how a complex pattern of many modest changes at gene level may explain major functional differences of the action potential related to ageing and mitochondrial dysfunction.
    Matched MeSH terms: Heart Ventricles/metabolism*; Heart Ventricles/physiopathology
  16. Leong Abdullah MFI, Tan KL, Narayanan S, Yuvashnee N, Chear NJY, Singh D, et al.
    Clin Toxicol (Phila), 2021 May;59(5):400-408.
    PMID: 32870119 DOI: 10.1080/15563650.2020.1812627
    OBJECTIVES: Little is known about the cardiotoxic effects of kratom (Mitragyna speciosa Korth.), a medicinal plant. This analytical cross-sectional study investigated the prevalence of electrocardiogram (ECG) abnormalities and QTc intervals in regular kratom users compared with non-kratom-using control subjects.

    METHODS: We enrolled regular kratom users and non-kratom-using control subjects from three communities. Demographic data, clinical data, kratom use characteristics, and ECG findings were recorded. The mitragynine content of kratom juice was quantified using a validated gas chromatography-mass spectrometry (GC-MS) method.

    RESULTS: A total of 200 participants (100 kratom users and 100 control subjects) participated in this study. The prevalence of ECG abnormalities in kratom users (28%) did not differ from that of control subjects (32%). Kratom use was not associated with ECG abnormalities, except for significantly higher odds of sinus tachycardia (OR = 8.61, 95% CI = 1.06-70.17, p = 0.035) among kratom users compared with control subjects. The odds of observing borderline QTc intervals were significantly higher for kratom users compared with control subjects, regardless of the age of first use, the duration of use, the daily quantity consumed, and the length of time that had elapsed between last kratom use and ECG assessment. Nevertheless, there were no differences in the odds of having prolonged QTc intervals between kratom users and controls. The estimated average daily intake of mitragynine consumed by kratom users was 434.28 mg.

    CONCLUSION: We found no link between regular kratom use and electrocardiographic abnormalities with an estimated average daily intake of 434.28 mg of mitragynine.

    Matched MeSH terms: Heart Defects, Congenital/chemically induced*; Heart Defects, Congenital/etiology*
  17. Tromp J, Tay WT, Ouwerkerk W, Teng TK, Yap J, MacDonald MR, et al.
    PLoS Med, 2018 03;15(3):e1002541.
    PMID: 29584721 DOI: 10.1371/journal.pmed.1002541
    BACKGROUND: Comorbidities are common in patients with heart failure (HF) and complicate treatment and outcomes. We identified patterns of multimorbidity in Asian patients with HF and their association with patients' quality of life (QoL) and health outcomes.

    METHODS AND FINDINGS: We used data on 6,480 patients with chronic HF (1,204 with preserved ejection fraction) enrolled between 1 October 2012 and 6 October 2016 in the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry. The ASIAN-HF registry is a prospective cohort study, with patients prospectively enrolled from in- and outpatient clinics from 11 Asian regions (Hong Kong, Taiwan, China, Japan, Korea, India, Malaysia, Thailand, Singapore, Indonesia, and Philippines). Latent class analysis was used to identify patterns of multimorbidity. The primary outcome was defined as a composite of all-cause mortality or HF hospitalization within 1 year. To assess differences in QoL, we used the Kansas City Cardiomyopathy Questionnaire. We identified 5 distinct multimorbidity groups: elderly/atrial fibrillation (AF) (N = 1,048; oldest, more AF), metabolic (N = 1,129; obesity, diabetes, hypertension), young (N = 1,759; youngest, low comorbidity rates, non-ischemic etiology), ischemic (N = 1,261; ischemic etiology), and lean diabetic (N = 1,283; diabetic, hypertensive, low prevalence of obesity, high prevalence of chronic kidney disease). Patients in the lean diabetic group had the worst QoL, more severe signs and symptoms of HF, and the highest rate of the primary combined outcome within 1 year (29% versus 11% in the young group) (p for all <0.001). Adjusting for confounders (demographics, New York Heart Association class, and medication) the lean diabetic (hazard ratio [HR] 1.79, 95% CI 1.46-2.22), elderly/AF (HR 1.57, 95% CI 1.26-1.96), ischemic (HR 1.51, 95% CI 1.22-1.88), and metabolic (HR 1.28, 95% CI 1.02-1.60) groups had higher rates of the primary combined outcome compared to the young group. Potential limitations include site selection and participation bias.

    CONCLUSIONS: Among Asian patients with HF, comorbidities naturally clustered in 5 distinct patterns, each differentially impacting patients' QoL and health outcomes. These data underscore the importance of studying multimorbidity in HF and the need for more comprehensive approaches in phenotyping patients with HF and multimorbidity.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT01633398.
    Matched MeSH terms: Heart Failure/complications*; Heart Failure/epidemiology*
  18. Daud ANA, Bergman JEH, Kerstjens-Frederikse WS, van der Vlies P, Hak E, Berger RMF, et al.
    Pharmacogenomics, 2017 Jul;18(10):987-1001.
    PMID: 28639488 DOI: 10.2217/pgs-2017-0036
    AIM: To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors.

    METHODS: We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B.

    RESULTS: Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes.

    CONCLUSION: We identified several polymorphisms that might potentially affect the risk of CHA among exposed fetuses, which warrants further investigation.

    Matched MeSH terms: Heart Defects, Congenital/chemically induced*; Heart Defects, Congenital/genetics
  19. Hafez P, Chowdhury SR, Jose S, Law JX, Ruszymah BHI, Mohd Ramzisham AR, et al.
    Cardiovasc Eng Technol, 2018 09;9(3):529-538.
    PMID: 29948837 DOI: 10.1007/s13239-018-0368-8
    Developing experimental models to study ischemic heart disease is necessary for understanding of biological mechanisms to improve the therapeutic approaches for restoring cardiomyocytes function following injury. The aim of this study was to develop an in vitro hypoxic/re-oxygenation model of ischemia using primary human cardiomyocytes (HCM) and define subsequent cytotoxic effects. HCM were cultured in serum and glucose free medium in hypoxic condition with 1% O2 ranging from 30 min to 12 h. The optimal hypoxic exposure time was determined using Hypoxia Inducible Factor 1α (HIF-1α) as the hypoxic marker. Subsequently, the cells were moved to normoxic condition for 3, 6 and 9 h to replicate the re-oxygenation phase. Optimal period of hypoxic/re-oxygenation was determined based on 50% mitochondrial injury via 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay and cytotoxicity via lactate dehydrogenase (LDH) assay. It was found that the number of cells expressing HIF-1α increased with hypoxic time and 3 h was sufficient to stimulate the expression of this marker in all the cells. Upon re-oxygenation, mitochondrial activity reduced significantly whereas the cytotoxicity increased significantly with time. Six hours of re-oxygenation was optimal to induce reversible cell injury. The injury became irreversible after 9 h as indicated by > 60% LDH leakage compared to the control group cultured in normal condition. Under optimized hypoxic reoxygenation experimental conditions, mesenchymal stem cells formed nanotube with ischemic HCM and facilitated transfer of mitochondria suggesting the feasibility of using this as a model system to study molecular mechanisms of myocardial injury and rescue.
    Matched MeSH terms: Mitochondria, Heart/metabolism; Mitochondria, Heart/pathology
  20. Valli H, Ahmad S, Jiang AY, Smyth R, Jeevaratnam K, Matthews HR, et al.
    Mech Ageing Dev, 2018 01;169:1-9.
    PMID: 29197478 DOI: 10.1016/j.mad.2017.11.016
    INTRODUCTION: Recent studies reported that energetically deficient murine Pgc-1β-/- hearts replicate age-dependent atrial arrhythmic phenotypes associated with their corresponding clinical conditions, implicating action potential (AP) conduction slowing consequent upon reduced AP upstroke rates.

    MATERIALS AND METHODS: We tested a hypothesis implicating Na+ current alterations as a mechanism underlying these electrophysiological phenotypes. We applied loose patch-clamp techniques to intact young and aged, WT and Pgc-1β-/-, atrial cardiomyocyte preparations preserving their in vivo extracellular and intracellular conditions.

    RESULTS AND DISCUSSION: Depolarising steps activated typical voltage-dependent activating and inactivating inward (Na+) currents whose amplitude increased or decreased with the amplitudes of the activating, or preceding inactivating, steps. Maximum values of peak Na+ current were independently influenced by genotype but not age or interacting effects of genotype and age on two-way ANOVA. Neither genotype, nor age, whether independently or interactively, influenced voltages at half-maximal current, or steepness factors, for current activation and inactivation, or time constants for recovery from inactivation following repolarisation. In contrast, delayed outward (K+) currents showed similar activation and rectification properties through all experimental groups. These findings directly demonstrate and implicate reduced Na+ in contrast to unchanged K+ current, as a mechanism for slowed conduction causing atrial arrhythmogenicity in Pgc-1β-/- hearts.

    Matched MeSH terms: Heart Atria/metabolism; Heart Atria/pathology
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