Strategy For Myocardial Infarction Research Articles

A Plant-Derived Remedy for Repair of Infarcted Heart

BackgroundMyocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration.Methods and FindingsThe present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium.ConclusionsThis study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately.

Why do men and women differ in their risk of myocardial infarction?

Cardiovascular disease is a global problem. To enable more effective prevention strategies for myocardial infarction (MI), the INTERHEART study looked for differences between countries, and between men and women, in risk factors for acute MI.1 It was a case–control study with 15 152 cases of acute MI and 14 820 controls from 262 centres from 52 countries. Information about nine risk factors was collected: smoking, self-reported hypertension and diabetes, measured waist/hip ratio, psychosocial factors, diet, physical activity, alcohol consumption, and measured apolipoprotein B/apolipoprotein A1 ratio.1 In their first report. the INTERHEART investigators concluded that these nine risk factors accounted for most of the risk for acute MI in both sexes, at all ages, and in all regions.1 When all nine risk factors were included in the analysis, the population-attributable risk for men ≤55 years was 93.1% and for women ≤65 years was 96.5%, indicating that most premature MI is preventable.1 The INTERHEART investigators have now extended their analysis of risk factors for MI in men and women.2 They addressed the specific question of why women have their first MI 9–10 years after men by examining whether differences exist between women and men in risk factor distribution across various age categories. The 12 460 cases were 18% fewer than the number in the initail report, and the 14 634 controls were similar in number to those in the initial report. There were some differences in definition of risk factors compared with the initial report and, rather than the different age cut-off points for younger and older men and women in their initial study,1 they used the same age cut-off point of 60 years for both men and … *Corresponding author. Tel: + 61 3 9288 2480, Fax: + 61 3 9416 2676, Email: dcampbell{at}svi.edu.au

Pleiotropic effects of cytokines on acute myocardial infarction: G-CSF as a novel therapy for acute myocardial infarction.

Many cytokines have been reported to be increased in human and animal models with cardiovascular diseases. Myocardial infarction (MI) is accompanied with an inflammatory reaction which induces cardiac dysfunction and remodeling. The inflammatory reaction has been investigated in animal models of MI or myocardial ischemia-reperfusion injury. The mechanisms by which cytokine cascade is activated in the infarcted myocardium have been recently elucidated. Several hematopoietic growth factors including interleukin-3 (IL-3), IL-6, granulocyte-macrophage colony-stimulating factors (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and stem cell factor (SCF) have been reported to be positive regulators of granulopoiesis and act at different stages of myeloid cell development. G-CSF plays a critical role in regulation of proliferation, differentiation, and survival of myeloid progenitor cells. G-CSF also causes a marked increase in the release of hematopoietic stem cells (HSCs) into the peripheral blood circulation, a process termed mobilization. Although cardiac myocytes have been considered as terminally differentiated cells, it has been recently reported that there are many proliferating cardiac myocytes after MI in human heart. After it was demonstrated that bone marrow stem cells (BMSCs) can differentiate into cardiac myocytes, myocardial regeneration has been widely investigated. Recently, G-CSF has been reported to improve cardiac function and reduces mortality after acute MI. Although the mechanism by which G-CSF ameliorates cardiac dysfunction is not fully understood, there is the possibility that G-CSF may regenerate cardiac myocytes and blood vessels through mobilization of BMSCs. In the future, cytokine-mediated regeneration therapy may become to be a novel therapeutic strategy for MI.

Enoxaparin: an update of its clinical use in the management of acute coronary syndromes.

Enoxaparin (enoxaparin sodium) is a low molecular weight heparin (LMWH) indicated for use in the treatment of ischaemic complications of unstable angina and non-Q wave myocardial infarction (MI). Unfractionated heparin (UFH) has for many years represented the standard in anticoagulant therapy for patients with acute coronary syndromes; however, recent studies suggest that enoxaparin is also a viable option for anticoagulant therapy in these patients. The ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events) and the TIMI 11B (Thrombolysis in Myocardial Infarction) studies reported that twice daily enoxaparin was significantly more effective than a continuous infusion of UFH in reducing the composite triple endpoint of death, MI, or recurrent angina or urgent revascularisation. Follow-up of both patient populations showed continued benefit associated with enoxaparin. Enoxaparin has been compared with tinzaparin in the treatment of unstable coronary artery disease using a nonblind study design. There was no difference between treatment groups in the therapeutic endpoints. Three nonblind studies have also compared the effects of enoxaparin and UFH in patients receiving thrombolytic therapy following acute MI. The HART II (Heparin and Aspirin Reperfusion Therapy), the ASSENT 3 (Assessment of the Safety and Efficacy of a New Thrombolytic Regimen) and the ENTIRE-TIMI 23 (Enoxaparin and Tenecteplase with or without glycoprotein IIb/IIIa Inhibitor as Reperfusion strategy in ST Elevation MI - Thrombolysis in Myocardial Infarction) studies have revealed that enoxaparin in combination with alteplase or tenecteplase is at least equivalent (HART II and ENTIRE-TIMI 23), and possibly superior (ASSENT 3) to UFH. Enoxaparin is administered as a twice-daily subcutaneous injection. In contrast, UFH is administered as an intravenous infusion which requires routine monitoring of the activated partial thromboplastin time to ensure adequate levels of anticoagulation are maintained. During the acute phase of the the ESSENCE and TIMI 11B studies, the incidence of major bleeding was similar in patients receiving enoxaparin to that in patients receiving UFH. In contrast, the rates of minor bleeding were higher in patients receiving enoxaparin than in those receiving UFH throughout these studies. Data from the ESSENCE, TIMI 11B and ASSENT 3 studies have prompted calls for those LMWHs which have been shown to be superior to UFH, to be considered as first choice treatment for anticoagulation in unstable coronary syndromes. To date, these suggestions are not reflected in current guidelines which consider UFH and LMWHs equally. Irrespective, the clinical data reported in this review support the use of enoxaparin in the treatment of acute coronary syndromes. These data suggest that enoxaparin shows certain clinical and practical advantages over standard treatment with UFH and represents an important development in the treatment of acute coronary syndromes.

3. Early invasive strategy in myocardial infarction in the elderly

Gottwalles, Y.; Heitz, M.; Katz, O.; Ponchon-Weess, A.; Zimmermann, A.; Gagneur, D.; Paneau, D.; Boulenc, J. M.

3. Early invasive strategy in myocardial infarction in the elderly

3. Early invasive strategy in myocardial infarction in the elderly

Cost analysis of different management strategies for myocardial infarction

Cost analysis of different management strategies for myocardial infarction

Oxidative Injury Induces Influx-Dependent Changes in Intracellular Calcium Homeostasis

Understanding of the mechanisms of cell injury and cell death is fundamental to the understanding of both protection against and initiation of cell injury and cell death. We subjected primary cultures of proximal tubular epithelium (PTE) from adult rats to an exogenous oxidative stress, generated by xanthine/xanthine oxidase (X/XOD), and studied its effect on the concentration of cytosolic ionized calcium ([Ca2+]i) by means of digital imaging fluorescence microscopy (DIFM) using a cytosolic calcium probe, fura-2. Exposure to 25 mU/ml X/XOD caused notable increases in [Ca2+]i detectable within 15 sec and increasing to micromolar levels with time. Experiments with Ca(2+)-free medium containing ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) showed that the increase of [Ca2+]i was due to influx from the extracellular space. Smaller and slower increases in [Ca2+]i were seen after exposure to lower concentrations of X/XOD (5 and 10 mU/ml). PTE injury and killing were assessed by measuring the release of cytosolic lactate dehydrogenase (LDH), exclusion of trypan blue, and observation of morphologic changes. Exposures to the 25 mU/ml concentration of X/XOD caused significant LDH release after 2 hr and correlated with trypan blue staining of exposed cells. Again, lesser concentrations of X/XOD resulted in a slower release of smaller amounts of LDH, and thus delayed trypan blue staining. Cytoplasmic bleb formation was seen by phase microscopy within minutes of exposure to 25 mU/ml, followed by cell rounding, retraction, and disintegration. Transmission electron microscopy revealed a progression of changes characteristic of lethal cell injury, beginning with dilatation of the endoplasmic reticulum, detachment of ribosomes, condensation of mitochondria, and chromatin clumping and terminating with mitochondrial swelling and formation of intramitochondrial flocculent densities. These studies clearly show that notable increases of [Ca2+]i precede both sub-lethal and lethal changes in rat PTE. These results indicate that interventions designed to minimize or to accelerate calcium entry could be of importance in cell preservation or cell killing, respectively, and therefore to therapeutic strategies for myocardial infarction, stroke, or shock in the former instance and for cancers in the latter.