Displaying publications 61 - 80 of 114 in total

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  1. Congenital cyanotic heart disease with situs inversus totalis: an autopsy case report
    Dayapala A, Kumar V
    Am J Forensic Med Pathol, 2009 Jun;30(2):171-4.
    PMID: 19465810 DOI: 10.1097/PAF.0b013e3181875a79
    Sudden deaths because of congenital heart diseases are infrequently referred to the forensic pathologist for autopsy. Many of such deaths, if already diagnosed are released directly from the hospital without autopsy. Even forensic pathologists face a few difficulties in performing the autopsy on such infrequent cases, as they are not always updated with the anatomy of anomalies. While dealing with such cases, the concerned forensic pathologist is compelled to refer literature and textbooks again to understand the nature of developmental defects. This is especially so when dealing with cases of situs inversus accompanied by transposition of great arteries and other congenital cardiac abnormalities and variants such as single ventricle, double outlet right ventricle, Taussig-Bing variety etc. In the present case also, situs inversus with transposition of great vessels and other anomalies have been noted and studied.
    Matched MeSH terms: Myocardium/pathology*
  2. Review on CFD simulation in heart with dilated cardiomyopathy and myocardial infarction
    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: Myocardium/pathology
  3. Cardiac sarcoidosis: two cases with autopsy findings
    Wan Muhaizan WM, Swaminathan M, Daud MS
    Malays J Pathol, 2004 Jun;26(1):59-63.
    PMID: 16196153
    Cardiac sarcoidosis is a disease of young adults. In most cases it presents with sudden death, arrhythmias, conduction disorders, heart failure or cardiomyopathy. The authors describe two cases of myocardial involvement by sarcoidosis that lead to death of the patients. Case one was a 26-year-old Indian man who was previously well and presented with sudden death. Autopsy showed nodules of sarcoid granuloma involving the heart, lungs and lymph nodes. Case two was a 47-year-old Indian lady who complained of reduced effort tolerance. Echocardiography showed that she had restrictive hypertrophic cardiomyopathy with heart failure. Seven months after initial presentation, she developed worsening of heart failure and died. Autopsy revealed involvement of the heart, lungs and liver by sarcoidosis.
    Matched MeSH terms: Myocardium/pathology
  4. Microscopical atrial amyloidosis in chronic heart disease
    Looi LM
    Histopathology, 1981 Nov;5(6):615-22.
    PMID: 7319480
    Nineteen out of 121 consecutive cardiac biopsies from 107 patients were found to contain amyloid deposits on routine Congo red screening. Seventeen were left atrial appendages removed during mitral valvotomy for chronic rheumatic mitral valve disease while the remaining two were right atrial appendages excised during surgical repair of atrial septal defects. The distribution of amyloid deposits within the atria and their tinctorial characteristics are described. The high prevalence of atrial amyloidosis observed could not be attributed to generalized or senile amyloidosis. The possibility that this is a distinctive localized form of amyloidosis secondary to chronic heart disease is discussed.
    Matched MeSH terms: Myocardium/pathology*
  5. Fulltext Autopsy findings in 35 cases of leprosy in Malaysia
    Jayalakshmi P, Looi LM, Lim KJ, Rajogopalan K
    Int. J. Lepr. Other Mycobact. Dis., 1987 Sep;55(3):510-4.
    PMID: 3655465
    The findings of autopsies performed on 35 leprosy subjects in the University Hospital, Kuala Lumpur, between January 1981 and December 1985 are presented. This is the first report based on autopsy findings from Malaysia. The patients were elderly subjects with a mean age of 74 years. Sixty-six percent had lepromatous leprosy. None had active skin lesions. The most common cause of death was pyogenic infection, particularly bronchopneumonia. Tuberculosis was noted in 25% of the cases. The other important causes of death included cardiac and renal failure. Renal lesions were evident in 71% of the cases, and the most common pathology was interstitial nephritis. Generalized amyloidosis complicated six (17%) patients.
    Matched MeSH terms: Myocardium/pathology
  6. Studies on the Indonesian Antiaris toxicaria sap
    Fujimoto Y, Suzuki Y, Kanaiwa T, Amiya T, Hoshi K, Fujino S
    J. Pharmacobio-dyn., 1983 Feb;6(2):128-35.
    PMID: 6306201
    The present research is on a milky sap obtained from the Antiaris toxicaria tree (Moraceae) which is called Upas or Ipoh in Indonesia. The crude sap was administered to anesthetized rats, and changes in electrocardiogram (ECG) and systemic blood pressure was observed. Biologically and pharmacologically active components were extracted from the crude sap by means of water-acetone solution. Based on the strength of chemical qualitative detection tests of the sap extract (SE), cardiac glycosides are supposed to be the main components. The SE inhibited the Na+-, K+-ATPase (EC 3.6.1.3) which was partially purified from guinea pig heart muscle. When the SE and, concurrently, authentic ouabain were applied to isolated frog heart muscles, the fall of twitch tension was observed after the increased tension on mechanograms. These facts suggest that the main components of the milky sap are cardiac glycosides, and glycosides affect Na+, K+-ATPase activity of muscle membrane and heart muscle contraction.
    Matched MeSH terms: Myocardium/enzymology
  7. Paper microfluidic device for early diagnosis and prognosis of acute myocardial infarction via quantitative multiplex cardiac biomarker detection
    Lim WY, Thevarajah TM, Goh BT, Khor SM
    Biosens Bioelectron, 2019 Mar 01;128:176-185.
    PMID: 30685097 DOI: 10.1016/j.bios.2018.12.049
    The early detection of acute myocardial infarction (AMI) upon the onset of chest pain symptoms is crucial for patient survival. However, this detection is challenging, particularly without a persistent elevation of ST-segment reflected in an electrocardiogram or in blood tests. A majority of the available point-of-care testing devices allow accurate and rapid diagnosis of AMI. However, AMI diagnosis is reliable only at intermediate and later stages, with myocardial injury (> 6 h) and MI, based on the expression of specific cardiac biomarkers including troponin I or T (cTnI or cTnT), creatine kinase-MB (CK-MB), and myoglobin. Diagnosis at the early myocardial ischemia stage is not possible. To overcome this limitation, a sensitive and rapid microfluidic paper-based device (µPAD) was developed for the simultaneous detection of multiple cardiac biomarkers for the early and late diagnosis of AMI. The glycogen phosphorylase isoenzyme BB (GPBB) was detected during early (within first 4 h) ischemic myocardial injury. On the same µPAD platform, detection of prolonged elevation of levels of cTnT and CK-MB, which are only produced 6 h after the onset of chest pain in human serum, was possible. Sandwich immunoassay performed on the µPAD achieved reproducibility (RSD approximately 10% and intra-and inter-day precision (CV 10-20%, 99th percentile), as well as consistently stable test results for 28 days, with strong correlation (r2= 0.962), using the standard Siemens Centaur XPT Immunoassay system. The present findings indicate the potential of the µPAD platform as a point-of-care device for the early diagnosis and prognosis of AMI.
    Matched MeSH terms: Myocardium/pathology
  8. The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression
    Teah YF, Abduraman MA, Amanah A, Adenan MI, Sulaiman SF, Tan ML
    Food Chem Toxicol, 2017 Sep;107(Pt A):293-301.
    PMID: 28689918 DOI: 10.1016/j.fct.2017.07.011
    Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. 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. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and Ikr blocker.
    Matched MeSH terms: Myocardium/metabolism*
  9. Amyloidosis in Malaysian aborigines (Orang Asli)
    Looi LM, Prathap K
    Pathology, 1979 Oct;11(4):575-82.
    PMID: 93739
    Material from 334 consecutive autopsies on Orang Asli subjects performed in the University Hospital, Kuala Lumpur between May 1967 and June 1978 was examined for amyloidosis. Nine positive cases were found, all in patients above 40 years of age, giving an age-corrected incidence of about 9%. In 6 cases, amyloidosis was probably secondary to tuberculosis. The remaining 3 cases exhibited a pericollagenous distribution characteristic of primary amyloidosis. Involvement of the heart and lungs was prominent. However, there were considerable similarities in the distribution and staining properties of the amyloid in the 2 groups. Though both the heart and kidney were frequently affected, the kidney was the most common organ to give rise to clinical symptoms. Infection probably plays a major contributory role in amyloidosis in the Orang Asli.
    Matched MeSH terms: Myocardium/pathology
  10. Fulltext The protective effects of Mucuna pruriens seed extract against histopathological changes induced by Malayan cobra (Naja sputatrix) venom in rats
    Fung SY, Tan NH, Liew SH, Sim SM, Aguiyi JC
    Trop Biomed, 2009 Apr;26(1):80-4.
    PMID: 19696731
    Seed of Mucuna pruriens (Velvet beans) has been prescribed by traditional medicine practitioners in Nigeria as a prophylactic oral antisnake remedy. In the present studies, we investigated the protective effects of M. pruriens seed extract (MPE) against histopathological changes induced by intravenous injection of Naja sputatrix (Malayan cobra) venom in rats pretreated with the seed extract. Examination by light microscope revealed that the venom induced histopathological changes in heart and blood vessels in liver, but no effect on brain, lung, kidney and spleen. The induced changes were prevented by pretreatment of the rats with MPE. Our results suggest that MPE pretreatment protects rat heart and liver blood vessels against cobra venom-induced damages.
    Matched MeSH terms: Myocardium/pathology*
  11. Methanolic seed extract of Vitis vinifera ameliorates oxidative stress, inflammation and ATPase dysfunction in infarcted and non-infarcted heart of streptozotocin-nicotinamide induced male diabetic rats
    Giribabu N, Roslan J, Rekha SS, Salleh N
    Int J Cardiol, 2016 Nov 01;222:850-65.
    PMID: 27522389 DOI: 10.1016/j.ijcard.2016.07.250
    BACKGROUND: We hypothesized that consumption of Vitis vinifera seed by diabetics could help to ameliorate myocardial damage. Therefore, in this study, we investigated effects of V. vinifera seed methanolic extract (VVSME) on parameters related to myocardial damage in diabetes with or without myocardial infarction (MI).

    METHODS: Streptozotocin-nicotinamide induced diabetic rats received oral VVSME for 28days. MI was induced by intraperitoneal injection of isoproterenol on last two days. Prior to sacrifice, blood was collected and fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid profile and insulin levels were measured. Levels of serum cardiac injury marker (troponin-I and CK-MB) were determined and histopathological changes in the heart were observed following harvesting. Levels of oxidative stress (LPO, SOD, CAT, GPx and RAGE), inflammation (NF-κB, TNF-α, IL-1β and IL-6) and cardiac ATPases (Na(+)/K(+)-ATPase and Ca(2+)-ATPase) were determined in heart homogenates. LC-MS was used to identify constituents in the extracts.

    RESULTS: Consumption of VVSME by diabetic rats with or without MI improved the metabolic profiles while decreased the cardiac injury marker levels with lesser myocardial damage observed. Additionally, VVSME consumption reduced the levels of LPO, RAGE, TNF-α, Iκκβ, NF-κβ, IL-1β and IL-6 while increased the levels of SOD, CAT, GPx, Na(+)/K(+)-ATPase and Ca(2+)-ATPase in the infarcted and non-infarcted heart of diabetic rats (p<0.05). LC-MS analysis revealed 17 major compounds in VVSME which might be responsible for the observed effects.

    CONCLUSIONS: Consumption of VVSME by diabetics helps to ameliorate damage to the infarcted and non-infarcted myocardium by decreasing oxidative stress, inflammation and cardiac ATPases dysfunctions.

    Matched MeSH terms: Myocardium/metabolism
  12. Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats
    Cheah HY, Šarenac O, Arroyo JJ, Vasić M, Lozić M, Glumac S, et al.
    Nanotoxicology, 2017 03;11(2):210-222.
    PMID: 28098511 DOI: 10.1080/17435390.2017.1285071
    Conjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX. Rats implanted with radio-telemetry device were administered intravenously with DOX (5 mg/kg), HPMA-DOX (5 mg DOX equivalent/kg) and HPMA copolymer and subjected to continuous cardiovascular monitoring and echocardiography for 140 days. We found that DOX-treated rats had ruffled fur, reduced body weight (BW) and a low survival rate. Although BP and HR were normal, spectral analysis indicated that their BP and HR variabilities were reduced. All rats exhibited typical signs of cardiotoxicity at histopathology. In contrast, HPMA-DOX rats gained weight over time and survived. Although BP, HR and related variabilities were unaffected, the left ventricular end diastolic volume (EDV) of these rats, as well as of the HPMA copolymer-treated rats, was found increased at the end of observation period. Additionally, HPMA copolymer caused microscopic injury of the heart tissue. All of these suggest the necessity of caution when employing HPMA as carrier for prolonged drug delivery. The current study also indicates the potential of radiotelemetric-spectral-echocardiography approach for improved preclinical cardiovascular risk assessment of polymer-drug conjugate and other nano-sized-drug constructs.
    Matched MeSH terms: Myocardium/pathology
  13. Assessing regional left ventricular thickening dysfunction and dyssynchrony via personalized modeling and 3D wall thickness measurements for acute myocardial infarction
    Khalid A, Lim E, Chan BT, Abdul Aziz YF, Chee KH, Yap HJ, et al.
    J Magn Reson Imaging, 2019 04;49(4):1006-1019.
    PMID: 30211445 DOI: 10.1002/jmri.26302
    BACKGROUND: Existing clinical diagnostic and assessment methods could be improved to facilitate early detection and treatment of cardiac dysfunction associated with acute myocardial infarction (AMI) to reduce morbidity and mortality.

    PURPOSE: To develop 3D personalized left ventricular (LV) models and thickening assessment framework for assessing regional wall thickening dysfunction and dyssynchrony in AMI patients.

    STUDY TYPE: Retrospective study, diagnostic accuracy.

    SUBJECTS: Forty-four subjects consisting of 15 healthy subjects and 29 AMI patients.

    FIELD STRENGTH/SEQUENCE: 1.5T/steady-state free precession cine MRI scans; LGE MRI scans.

    ASSESSMENT: Quantitative thickening measurements across all cardiac phases were correlated and validated against clinical evaluation of infarct transmurality by an experienced cardiac radiologist based on the American Heart Association (AHA) 17-segment model.

    STATISTICAL TEST: Nonparametric 2-k related sample-based Kruskal-Wallis test; Mann-Whitney U-test; Pearson's correlation coefficient.

    RESULTS: Healthy LV wall segments undergo significant wall thickening (P Myocardium with thick infarct (ie, >50% transmurality) underwent remarkable wall thinning during contraction (thickening index [TI] = 1.46 ± 0.26 mm) as opposed to healthy myocardium (TI = 4.01 ± 1.04 mm). For AMI patients, LV that showed signs of thinning were found to be associated with a significantly higher percentage of dyssynchrony as compared with healthy subjects (dyssynchrony index [DI] = 15.0 ± 5.0% vs. 7.5 ± 2.0%, P 

    Matched MeSH terms: Myocardium/pathology
  14. Fulltext Human Wharton's Jelly-Derived Mesenchymal Stem Cells Minimally Improve the Growth Kinetics and Cardiomyocyte Differentiation of Aged Murine Cardiac c-kit Cells in In Vitro without Rejuvenating Effect
    Ng WH, Yong YK, Ramasamy R, Ngalim SH, Lim V, Shaharuddin B, et al.
    Int J Mol Sci, 2019 Nov 06;20(22).
    PMID: 31698679 DOI: 10.3390/ijms20225519
    Cardiac c-kit cells show promise in regenerating an injured heart. While heart disease commonly affects elderly patients, it is unclear if autologous cardiac c-kit cells are functionally competent and applicable to these patients. This study characterised cardiac c-kit cells (CCs) from aged mice and studied the effects of human Wharton's Jelly-derived mesenchymal stem cells (MSCs) on the growth kinetics and cardiac differentiation of aged CCs in vitro. CCs were isolated from 4-week- and 18-month-old C57/BL6N mice and were directly co-cultured with MSCs or separated by transwell insert. Clonogenically expanded aged CCs showed comparable telomere length to young CCs. However, these cells showed lower Gata4, Nkx2.5, and Sox2 gene expressions, with changes of 2.4, 3767.0, and 4.9 folds, respectively. Direct co-culture of both cells increased aged CC migration, which repopulated 54.6 ± 4.4% of the gap area as compared to aged CCs with MSCs in transwell (42.9 ± 2.6%) and CCs without MSCs (44.7 ± 2.5%). Both direct and transwell co-culture improved proliferation in aged CCs by 15.0% and 16.4%, respectively, as traced using carboxyfluorescein succinimidyl ester (CFSE) for three days. These data suggest that MSCs can improve the growth kinetics of aged CCs. CCs retaining intact telomere are present in old hearts and could be obtained based on their self-renewing capability. Although these aged CCs with reduced growth kinetics are improved by MSCs via cell-cell contact, the effect is minimal.
    Matched MeSH terms: Myocardium/cytology*
  15. Altered cardiac tissue and plasma kininogen levels in hypertensive and diabetic rats
    Sharma JN, Kesavarao U, Yusof AP
    Immunopharmacology, 1999 Sep;43(2-3):129-32.
    PMID: 10596843 DOI: 10.1016/s0162-3109(99)00070-3
    The present investigation was aimed at evaluating the cardiac and total plasma kininogen levels, as well as LVWT in hypertensive and diabetic rats. STZ-induced diabetes produced a significant (P < 0.001) rise in mean arterial blood pressure (BP). The LVWT increased (P < 0.001) in SHR with and without diabetes) and diabetic WKYR. The cardiac tissue, as well as total plasma kininogen levels fell significantly (P < 0.001) in diabetic WKYR and SHR with and without diabetes compared to the control WKYR. These findings suggest that reduced kininogen levels may indicate a deficiency in kinin generation in the heart and in the peripheral circulation in diabetic and hypertensive rats. This effect may contribute to the development of LVH.
    Matched MeSH terms: Myocardium/chemistry*
  16. Cardiac kallikrein in hypertensive and normotensive rats with and without diabetes
    Sharma JN, Kesavarao U
    Immunopharmacology, 1996 Jun;33(1-3):341-3.
    PMID: 8856181 DOI: 10.1016/0162-3109(96)00104-x
    This study examined the effects of streptozotocin-induced diabetes on blood pressure and cardiac tissue kallikrein levels in WKYR and SHR. Streptozotocin-induced diabetes caused significant (p < 0.001) increase in SBP and DBP in WKYR and SHR as compared with their respective controls. We also observed that the active cardiac tissue kallikrein levels reduced greatly (p < 0.001) in diabetic WKYR and SHR than the normal rats. These findings suggest for the first time that the cardiac tissue kallikrein formation may have a greater role in the regulation of blood pressure and cardiac function.
    Matched MeSH terms: Myocardium/metabolism*
  17. Left ventricular hypertrophy and its relation to the cardiac kinin-forming system in hypertensive and diabetic rats
    Sharma JN, Uma K, Yusof AP
    Int J Cardiol, 1998 Feb 28;63(3):229-35.
    PMID: 9578349 DOI: 10.1016/s0167-5273(97)00329-x
    We investigated the cardiac tissue kallikrein and kininogen levels, left ventricular wall thickness and mean arterial blood pressure of Wistar Kyoto and spontaneously hypertensive rats with and without streptozotocin-induced diabetes. The mean arterial blood pressure was highly elevated (P<0.001) in Wistar Kyoto diabetic and spontaneously hypertensive diabetic rats as compared with their respective controls. The cardiac tissue kallikrein and kininogen levels were reduced significantly (P<0.001) in diabetic Wistar Kyoto, spontaneously hypertensive and diabetic spontaneously hypertensive compared with Wistar Kyoto control rats. In addition, the left ventricular thickness was found to be increased (P<0.001) in diabetic Wistar Kyoto and spontaneously hypertensive rats in the presence and in the absence of diabetes. Our results indicate that reduced activity of the kinin-forming system may be responsible for inducing left ventricular hypertrophy in the presence of raised mean arterial blood pressure in diabetic and hypertensive rats. Thus, the kinin-forming components might have a protective role against the development of left ventricular hypertrophy. The possible significance of these findings is discussed.
    Matched MeSH terms: Myocardium/chemistry
  18. Protective effects of the standardized extract of Zingiber officinale on myocardium against isoproterenol-induced biochemical and histopathological alterations in rats
    Amran AZ, Jantan I, Dianita R, Buang F
    Pharm Biol, 2015;53(12):1795-802.
    PMID: 25868620 DOI: 10.3109/13880209.2015.1008147
    CONTEXT: Ginger [Zingiber officinale Roscoe. (Zingiberaceae)] has been universally used as a spice as well as for its health benefits.

    OBJECTIVE: The present study evaluates the protective effect of the standardized extract of ginger against isoproterenol (ISO)-induced myocardial infarction (MI) in rats.

    MATERIALS AND METHODS: Wistar rats were pretreated orally with three doses of standardized ginger extract (100, 200, and 400 mg/kg of body weight) or propranolol (5 mg/mL) for 28 d prior to ISO (85 mg/kg) induced MI in two doses on days 29 and 30. The rats were sacrificed 48 h after the first induction; serum and hearts were collected for biochemical and histopathological analysis.

    RESULTS: Gingerols and shogaols were identified and quantitatively analyzed in the extracts using validated reversed phase HPLC methods. Pretreatment with ginger extract at 400 mg/kg showed a significant decrease (p 

    Matched MeSH terms: Myocardium/pathology
  19. Fulltext Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction
    Jasmin NH, Thin MZ, Johnson RD, Jackson LH, Roberts TA, David AL, et al.
    Adv Sci (Weinh), 2021 Jun;8(11):e2003987.
    PMID: 34105284 DOI: 10.1002/advs.202003987
    Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but are challenging to obtain. Here, manganese, a calcium analogue and clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an imaging biomarker of myocardial viability in the first hours after experimental MI. Safe Mn2+ dosing is confirmed by measuring in vitro beating rates, calcium transients, and action potentials in cardiomyocytes, and in vivo heart rates and cardiac contractility in mice. Quantitative T1 mapping-manganese-enhanced MRI (MEMRI) reveals elevated and increasing Mn2+ uptake in viable myocardium remote from the infarct, suggesting MEMRI offers a quantitative biomarker of cardiac inotropy. MEMRI evaluation of infarct size at 1 h, 1 and 14 days after MI quantifies myocardial viability earlier than the current gold-standard technique, late-gadolinium-enhanced MRI. These data, coupled with the re-emergence of clinical Mn2+ -based contrast agents open the possibility of using MEMRI for direct evaluation of myocardial viability early after ischemic onset in patients.
    Matched MeSH terms: Myocardium/pathology
  20. Fulltext DJ-1 protects against cell death following acute cardiac ischemia-reperfusion injury
    Dongworth RK, Mukherjee UA, Hall AR, Astin R, Ong SB, Yao Z, et al.
    Cell Death Dis, 2014 Feb 27;5:e1082.
    PMID: 24577080 DOI: 10.1038/cddis.2014.41
    Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1(L166P) and DJ-1(Cys106A) mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection.
    Matched MeSH terms: Myocardium/metabolism*; Myocardium/ultrastructure
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