Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial infarction is associated with an inflammatory response leading to leukocyte recruitment, healing and formation of a scar. Members of the chemokine superfamily are rapidly induced in the infarcted myocardium and may critically regulate the post-infarction inflammatory response. CXCL8/Interleukin (IL)-8 is upregulated in the infarcted area and may induce neutrophil infiltration. In addition, mononuclear cell chemoattractants, such as the CC chemokines CCL2/Monocyte Chemoattractant Protein (MCP)-1, CCL3/Macrophage Inflammatory Protein (MIP)1alpha, and CCL4/MIP-1beta are expressed in the ischemic area, and may regulate monocyte and lymphocyte recruitment. However, chemokines may have additional effects on healing infarcts beyond their leukotactic properties. The CXC chemokine CXCL10/Interferon-y inducible Protein (IP)-10, a potent angiostatic factor with antifibrotic properties, is induced in the infarct and may prevent premature angiogenesis and fibrous tissue deposition, until the infarct is debrided and provisional matrix necessary to support granulation tissue ingrowth is formed. Chemokine induction in the infarct is transient, suggesting that inhibitory mediators (such as transforming growth Factor (TGF)-beta) may be activated suppressing chemokine synthesis and leading to resolution of inflammation and transition to fibrosis. Brief repetitive ischemia in mice also results in chemokine upregulation followed by suppression of chemokine synthesis and interstitial fibrosis, in the absence of myocardial infarction. Chemokine expression may play a role in the pathogenesis of non-infarctive ischemic cardiomyopathy, where early ischemia-induced chemokine expression may be followed by activation of inhibitory mediators that suppress inflammation, but induce fibrosis.
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PMID:Chemokines in the ischemic myocardium: from inflammation to fibrosis. 1569 6

Imidapril is an angiotensin I converting enzyme inhibitor, a class of drugs with known cardioprotective activity. It is now known that this is due not only to their antihypertensive activity, but also to the fact that they decrease cellular and tissue levels of angiotensin II, a potent vasoconstrictor and inducer of myocardial fibrosis. These mechanisms may explain the good clinical results of this class of drugs in the treatment of coronary artery disease and heart failure, two diseases whose etiopathogenesis is closely related to the activation of the renin-angiotensin-aldosterone system. However, the impact of this class of drugs on cardiac mitochondrial function during acute myocardial ischemia is still largely unknown. With the aim of studying the effect of imidapril on cardiac mitochondrial function during acute ischemia, we used an ex-vivo animal model, perfused in a Langerdorff system and then subjected to ischemia in the presence or absence of imidapril. We evaluated mitochondrial membrane electrical potential, respiratory chain O2 consumption, and rate and amplitude of mitochondrial swelling. We conclude that imidapril did not significantly change oxygen consumption by cardiac mitochondria, as assessed by the rate of respiratory state 3 (the state that corresponds to the active phosphorylation phase). However, imidapril significantly increased transmembrane electrical potential and, in ischemic cardiac mitochondria, was able to prevent the calcium-induced increase in the rate and amplitude of mitochondrial swelling, thus enabling better preservation of mitochondrial membrane structure, with consequent improvement of electrical potential after the phosphorylation cycle. These findings enabled a better understanding of the mechanisms behind the cytoprotection provided by imidapril during ischemic cardiomyopathy, clearly highlighting, at a cellular biology level, the importance of pharmacological modulation of cardiac mitochondrial function during acute ischemia.
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PMID:Impact of imidapril on cardiac mitochondrial function in an ex-vivo animal model of global myocardial ischemia. 1577 66

The effect of valsartan, an angiotensin II-type I receptor blocker, on the mitochondrial function, was studied using an ex vivo animal model (hearts from Wistar rats), perfused in a Langendorff system and then submitted to global acute ischemia. Parameters evaluated were: membrane electrical potential (DeltaPsi, using a tetraphenylphosphonium-TPP+-electrode), oxygen consumption by the respiratory chain (Clark-type O2 electrode), phosphorylation lag phase (time necessary to phosphorylate a fixed amount of ADP) and ATP/ADP ratio (adenine nucleotides quantified by high-pressure liquid chromatography-HPLC). Valsartan acts preferentially in the phosphorylation, increasing ATP/ADP ratios (succinate: 1.6+/-0.4 versus 0.5+/-0.1--P<0.05; ascorbate/N,N,N',N'-tetramethyl-P-phenylenodiamine-TMPD: 1.1+/-0.2 versus 0.4+/-0.1--p<0.05 versus ischemia in the absence of valsartan) and decreasing lag phase (glutamate/malate: 50.0+/-9.6 s versus 127.2+/-19.03 s-84.6+/-16.2% versus 215.3+/-32.2%; P=0.01; succinate: 111.8+/-33.1 s versus 275.73+/-45.99 s-168.2+/-49.8% versus 414.9+/-69.2%; P=0.02 or ascorbate/TMPD: 11.0+/-3.9 s versus 62.4+/-11.63 s-34.9+/-12.4% versus 198.1+/-36.9%; P=0.001 versus ischemia in the absence of valsartan). This enables a higher energy production in hearts submitted to acute ischemia, for which having energy becomes critical to preserve mitochondrial function. These mechanisms allow us to better understand valsartan cytoprotection in ischemic cardiomyopathy.
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PMID:Valsartan improves mitochondrial function in hearts submitted to acute ischemia. 1605 15

As mechanical complications after myocardial infarction in the elderly, we described the therapeutic strategies for postinfarction ventricular septal perforation (PVSP), ischemic cardiomyopathy (ICM), and ischemic mitral regurgitation (IMR). To improve operative results for PVSP in the elderly, it is important to maintain hemodynamics by cardiac support device such as intraaortic balloon pumping, and to perform prompt surgical intervention before cardiogenic shock and multiple organ failure. Infarct exclusion technique is a standard surgery for PVSP. Both ICM and IMR are common disease caused by severe cardiac ischemia and mitral valve (MV) function is related to left ventricular (LV) geometry. We consider total MV-LV geometrical repair by LV restoration surgery, MV repair, and coronary revascularization is essential to improve morphological abnormality in LV and MV even in the elderly. To maximize LV function, septal anterior ventricular exclusion (SAVE) technique for antero-septal myocardial ischemia, apex-sparing Batista operation for lateral ischemia, and undersized mitral annuluoplasty to improve LV sphericity are procedures of choice. However, it is still difficult to save elderly patients with very low cardiac function. Novel treatments such as regenerative medicine by angiogenic cytokines and/or cell transplantation, and advanced medical treatments are waited for this high-risk group.
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PMID:[Mechanical complications of myocardial infarction in elderly patients]. 1609 13

The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with sufficient viable myocardium, patients with predominantly scar tissue should be treated medically. Patients with left ventricular dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischemia but at the same time benefit most from revascularization. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy (SPECT), whether using (201)thallium, (99m)Tc-sestamibi, or (99m)Tc-tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management. Metabolic and perfusion imaging with positron emission tomography (PET) radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularization. New techniques in the nuclear cardiology field, like attenuation corrected SPECT, dual isotope simultaneous acquisition (DISA) SPECT and gated FDG PET are promising and will further improve the detection of myocardial viability. Also the combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and non-invasive coronary angiography to myocardial perfusion imaging and quantification. Evaluation of the clinical role of these creative new possibilities warrants investigation.
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PMID:Imaging techniques in nuclear cardiology for the assessment of myocardial viability. 1637 39

End-stage ischemic cardiomyopathy patients are an ever-increasing group of coronary artery disease patients, often with no options in our current treatment armamentarium. Angiogenesis therapy pre-clinical and phase I clinical trials showed great promise, however, the benefits of single growth factor treatments have not been borne out in the larger phase II randomized trials. The complexity of angiogenesis process and the challenges in creating animal models to replicate and study this process in ischemic adult human myocardium have been major limitations to progress in this field. In addition failure to control for the powerful placebo effect in the clinical trials and inadequate methods of outcomes measures assessment have created difficult to overcome road blocks in establishing the efficacy of angiogenic strategies. Herein we review the challenges of angiogenesis research and development of treatment strategies. We also propose a structured model for further investigations of angiogenic therapies. The adherence to such a regimented approach as proposed here is, in our opinion, the only way to achieve success in angiogenesis approach development to treatment of patients with end-stage cardiac ischemia refractory to other established therapies.
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PMID:Angiogenesis: bench to bedside, have we learned anything? 1650 38

Ischemia and reperfusion (I/R) are characterized by oxidative stress as well as changes in the antioxidant enzymes of the heart. However, little is known about the transcriptional regulation of myocardial antioxidant enzymes in repetitive I/R and hibernating myocardium. In a mouse model of ischemic cardiomyopathy induced by repetitive I/R, we postulated that induction of antioxidant gene expression was dependent on reactive oxygen species (ROS). Repetitive closed-chest I/R (15 min) was performed daily in C57/BL6 mice and in mice overexpressing extracellular superoxide dismutase (EC-SOD). Antioxidant enzyme expression was measured at 3, 5, 7, and 28 days of repetitive I/R as well as 15 and 30 days after discontinuation of I/R. In order to determine whether ROS directly modulates antioxidant gene expression, transcript levels were measured in cardiomyocytes exposed to hydrogen peroxide. Repetitive I/R caused an early and sustained increase in glutathione peroxidase (GPX) transcript levels, while heme oxygenase-1 (HO-1) expression increased only after 7 days of repetitive I/R. Overexpression of EC-SOD prevented the upregulation of GPX and HO-1 transcript levels by repetitive I/R, suggesting that both genes are regulated by ROS. However, while HO-1 transcript levels increased in cardiomyocytes exposed to hydrogen peroxide, oxidative stress failed to induce the expression of GPX implying that ROS regulates GPX transcript levels only indirectly in repetitive I/R. In conclusion, repetitive I/R was associated with an early upregulation of GPX expression as well as a delayed increase of HO-1 transcript levels in the heart. The induction of both antioxidant genes was dependent on ROS, suggesting that alterations in redox balance mediate not only tissue injury but also components of "programmed cell survival" in hibernating myocardium.
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PMID:Induction of antioxidant gene expression in a mouse model of ischemic cardiomyopathy is dependent on reactive oxygen species. 1678 36

Despite treatment with conventional agents, a high proportion of patients with ischemic cardiomyopathy continue to have symptoms. Moreover, a substantial proportion shows progressive contractile dysfunction leading to left ventricular (LV) enlargement and heart failure. Therefore, a need exists for new treatments for ischemic cardiomyopathy that tackle mechanisms other than those already addressed by conventional agents. Emerging evidence suggests that in patients with ischemic cardiomyopathy, LV dysfunction develops as a result of alterations in substrate metabolism, which contribute to contractile dysfunction and the progression of LV remodeling. Trimetazidine, a novel pharmacologic agent that acts on myocardial metabolic pathways, appears to protect the heart from the deleterious effects of ischemia, and it has been shown to enhance LV contractility in patients with stunned or hibernating myocardium. This article reviews recent clinical trials that have assessed the therapeutic role of trimetazidine in patients with ischemic cardiomyopathy. Trimetazidine has been shown to improve symptoms and LV ejection fraction and to have a beneficial effect on the inflammatory profile and endothelial function in these patients. These results suggest that trimetazidine is a useful adjunct to our current armamentarium for the treatment of patients with ischemic cardiomyopathy.
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PMID:Role of trimetazidine in management of ischemic cardiomyopathy. 1693 Dec 2

During acute myocardial infarction, ischemia causes progressive loss of contractile tissue. Subsequently, structural changes lead to left ventricular remodeling finally resulting in the development of heart failure. In addition to an optimal reperfusion and pharmacologinal post-infarction therapy, increased neovascularization and regeneration of cardiomyocytes could reduce or even abolish the ongoing left ventricular remodeling processes within the infarct area. Experimental studies have demonstrated that transplantation of adult progenitor cells leads to increased neovascularization, reduced fibrosis and, therefore, increased left ventricular function after acute myocardial infarction. In contrast to current treatment strategies, progenitor cell therapy offers a new regenerative approach for myocardial tissue. Initial clinical studies have demonstrated, apart from safety and feasibility of intracoronary infusion of adult autologous progenitor cells, a significant improvement of left ventricular function, geometry and vascularization in patients with acute myocardial infarction receiving intracoronary infusion of progenitor cells. However, in patients with chronic ischemic cardiomyopathy, the improvement in contractility is less pronounced. Finally, whether intracoronary infusion of adult progenitor cells can also reduce morbidity and mortality due to heart failure, remains to be investigated.
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PMID:[Regenerative therapy in cardiology: how distant is it from reality?]. 1695 37

Trimetazidine is a new metabolic antiischemic agent, which increases the tolerance of cardiomyocytes to ischemia. The aim of the study was to evaluate the effect of additional trimatazidine therapy in patients with ischemic cardiomyopathy (ICMP) in comparison with standard therapy of cardiac insufficiency. According to the results of the study, trimetazidine improves the clinical status, functional class of cardiac insufficiency, left ventricular ejection fraction, in ICMP patients. Trimetazidine increases physical exercise tolerance according to the results of six-minute walking test. Thus, the optimization of myocardial energetic metabolism may be a promising perspective in the treatment of coronary heart disease with systolic dysfunction.
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PMID:[The effects of trimetazidine on left ventricular function and physical exercise tolerance in patients with ischemic cardiomyopathy]. 1720 Dec 76


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