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https://www.readbyqxmd.com/read/28933367/targeting-metabolic-modulation-and-mitochondrial-dysfunction-in-the-treatment-of-heart-failure
#1
REVIEW
Abbey Steggall, Ify R Mordi, Chim C Lang
Despite significant improvements in morbidity and mortality with current evidence-based pharmaceutical-based treatment of heart failure (HF) over the previous decades, the burden of HF remains high. An alternative approach is currently being developed, which targets myocardial energy efficiency and the dysfunction of the cardiac mitochondria. Emerging evidence suggests that the insufficient availability of ATP to the failing myocardium can be attributed to abnormalities in the myocardial utilisation of its substrates rather than an overall lack of substrate availability...
May 10, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28906001/overcoming-interference-of-plasma-phospholipids-using-hybridspe-for-the-determination-of-trimetazidine-by-uplc-ms-ms
#2
Pravin G Vanol, Manish Yadav, Mallika Sanyal, Priyanka A Shah, Pranav S Shrivastav
An improved, precise and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the quantification of trimetazidine, using trimetazidine-d8 as the internal standard (IS). Interference due to plasma phospholipids during sample preparation was overcome by using hybrid solid phase extraction-phospholipid ultra cartridge. The mean extraction recovery of trimetazidine (98.66 %) and trimetazidine-d8 (97.63 %) from spiked plasma was consistent and reproducible...
September 14, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28880025/expert-consensus-document-a-diamond-approach-to-personalized-treatment-of-angina
#3
REVIEW
Roberto Ferrari, Paolo G Camici, Filippo Crea, Nicolas Danchin, Kim Fox, Aldo P Maggioni, Athanasios J Manolis, Mario Marzilli, Giuseppe M C Rosano, José L Lopez-Sendon
In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other...
September 7, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28874022/ex-vivo-administration-of-trimetazidine-improves-post-transplant-lung-function-in-pig-model
#4
Tugba Cosgun, Ilker Iskender, Yoshito Yamada, Stephan Arni, Miriam Lipiski, Koen van Tilburg, Walter Weder, Ilhan Inci
OBJECTIVES: Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. METHODS: Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each)...
July 1, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28843336/the-effect-of-trimetazidine-and-diazoxide-on-immunomodulatory-activity-of-human-embryonic-stem-cell-derived-mesenchymal-stem-cell-secretome
#5
Saeed Jahandideh, Faezeh Maghsood, Nastaran Mohammadi Ghahhari, Majid Lotfinia, Mohammad Mohammadi, Behrooz Johari, Mehdi Kadivar
Comprehensive proteome profiling of the factors secreted by mesenchymal stem cells (MSCs), referred to as secretome, revealed that it consists of cytokines, chemokines, growth factors, extracellular matrix proteins, and components of regeneration, vascularization, and hematopoiesis pathways. Harnessing this MSC secretome for therapeutic applications requires the optimization of production of secretary molecules. A variety of preconditioning methods have been introduced, which subject cells to stimulatory molecules to create the preferred response and stimulate persistent effects...
August 16, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28811386/trimetazidine-protects-retinal-ganglion-cells-from-acute-glaucoma-via-the-nrf2-ho-1-pathway
#6
Peixing Wan, Wenru Su, Yingying Zhang, Zhidong Li, Caibin Deng, Yehong Zhuo
Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive...
September 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28767406/effect-of-trimetazidine-on-preventing-contrast-induced-nephropathy-in-diabetic-patients-with-renal-insufficiency
#7
Ziliang Ye, Haili Lu, Qiang Su, Xinhua Xian, Lang Li
BACKGROUND: Our study sought to assess the effect of trimetazidine (TMZ) on preventing contrast-induced nephropathy (CIN) in diabetic patients with renal insufficiency. MATERIALS AND METHODS: 106 diabetic patients with renal insufficiency who were undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) were enrolled in this study. Standard hydration was administered to both groups (the TMZ group and the control group). In the TMZ group, patients were orally administered TMZ for 48 hours before and 24 hours after CAG and/or PCI...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28761019/effects-of-trimetazidine-on-mitochondrial-respiratory-function-biosynthesis-and-fission-fusion-in-rats-with-acute-myocardial-ischemia
#8
Wen Shi, Wenfeng Shangguan, Yue Zhang, Can Li, Guangping Li
OBJECTIVE: Myocardial ischemia affects mitochondrial functions, leading to ionic imbalance and susceptibility to ventricular fibrillation. Trimetazidine, a metabolic agent, is clinically used in anti-anginal therapy. METHODS: In this study, the rats were orally treated by gavage with trimetazidine 10 mg/kg/d for 7 days, and the effects of trimetazidine on mitochondrial respiratory function, biosynthesis, and fission/fusion in rats with acute myocardial ischemia were evaluated...
July 25, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28739174/inhibition-of-mitochondrial-fission-prevents-hypoxia-induced-metabolic-shift-and-cellular-proliferation-of-pulmonary-arterial-smooth-muscle-cells
#9
Valentina Parra, Roberto Bravo-Sagua, Ignacio Norambuena-Soto, Carolina P Hernández-Fuentes, Andrés G Gómez-Contreras, Hugo E Verdejo, Rosemarie Mellado, Mario Chiong, Sergio Lavandero, Pablo F Castro
Chronic hypoxia exacerbates proliferation of pulmonary arterial smooth muscle cells (PASMC), thereby reducing the lumen of pulmonary arteries. This leads to poor blood oxygenation and cardiac work overload, which are the basis of diseases such as pulmonary artery hypertension (PAH). Recent studies revealed an emerging role of mitochondria in PAH pathogenesis, as key regulators of cell survival and metabolism. In this work, we assessed whether hypoxia-induced mitochondrial fragmentation contributes to the alterations of both PASMC death and proliferation...
July 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28736181/succinate-accumulation-impairs-cardiac-pyruvate-dehydrogenase-activity-through-grp91-dependent-and-independent-signaling-pathways-therapeutic-effects-of-ginsenoside-rb1
#10
Jia Li, Yi-Lin Yang, Lan-Zhu Li, Lei Zhang, Qun Liu, Kang Liu, Ping Li, Baolin Liu, Lian-Wen Qi
Altered mitochondrial oxidation increases vulnerability to cardiac ischemia/reperfusion (I/R) injury in metabolic disorders. However, the metabolic signaling responsible for the dysfunction remains partly unknown. We sought to test whether or not hypoxic succinate accumulation could inhibit pyruvate dehydrogenase (PDH) activity and subsequently aggravate I/R injury. Results showed that saturated fatty acid palmitate stimulation increased fatty acid oxidation and induced hypoxia in cardiomyocytes, leading to succinate accumulation...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28683436/effects-of-trimetazidine-on-pdcd4-nf-%C3%AE%C2%BAb-tnf-%C3%AE-pathway-in-coronary-microembolization
#11
Qiang Su, Lang Li, Jinmin Zhao, Yuhan Sun, Huafeng Yang
BACKGROUND/AIMS: The local inflammatory response caused by coronary microembolization (CME) is the primary cause of progressive cardiac dysfunction. The PDCD4/NF-κB/TNF-α signaling pathway plays a significant role in CME-induced myocardial Inflammation. Trimetazidine (TMZ) reduces myocardial injury, caused by percutaneous coronary intervention, through relieving the CME-induced myocardial systolic dysfunction. Therefore, the present study investigated the role of TMZ pre-treatment in the protection of myocardium after CME and PDCD4/NF-κB/TNF-α in mini pigs...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28648439/modulation-of-myocardial-energetics-an-important-category-of-agents-in-the-multimodal-treatment-of-coronary-artery-disease-and-heart-failure
#12
REVIEW
Jamshed J Dalal, Sundeep Mishra
The combined and relative contribution of glucose and fatty acid oxidation generates myocardial energy, which regulates the cardiac function and efficiency. Any dysregulation in this metabolic homeostasis can adversely affect the function of heart and contribute to cardiac conditions such as angina and heart failure. Metabolic agents ameliorate this internal metabolic anomaly, by shifting the energy production pathway from free fatty acids to glucose, resulting in a better performance of the heart. Metabolic therapy is relatively a new modality, which functions through optimization of cardiac substrate metabolism...
May 2017: Indian Heart Journal
https://www.readbyqxmd.com/read/28632748/trimetazidine-therapy-for-diabetic-mouse-hearts-subjected-to-ex-vivo-acute-heart-failure
#13
Emilene Breedt, Lydia Lacerda, M Faadiel Essop
Acute heart failure (AHF) is the most common primary diagnosis for hospitalized heart diseases in Africa. As increased fatty acid β-oxidation (FAO) during heart failure triggers detrimental effects on the myocardium, we hypothesized that trimetazidine (TMZ) (partial FAO inhibitor) offers cardioprotection under normal and obese-related diabetic conditions. Hearts were isolated from 12-14-week-old obese male and female diabetic (db/db) mice versus lean non-diabetic littermates (db/+) controls. The Langendorff retrograde isolated heart perfusion system was employed to establish an ex vivo AHF model: a) Stabilization phase-Krebs Henseleit buffer (10 mM glucose) at 100 mmHg (25 min); b) Critical Acute Heart Failure (CAHF) phase-(1...
2017: PloS One
https://www.readbyqxmd.com/read/28626744/central-beneficial-effects-of-trimetazidine-on-psychomotor-performance-in-normal-healthy-volunteers
#14
Hayder M Al-Kuraishy, Ali I Al-Gareeb
BACKGROUND: Trimetazidine is a fatty oxidation inhibitor, leading to shifting of energy substrate from fatty acid oxidation toward glucose oxidation that leads to the reduction of oxygen requirement. The aims of the present study were to elucidate the effects of trimetazidine on psychomotor performance and vigilance on normal healthy volunteers. MATERIALS AND METHODS: A total of 234 subjects (age 22-25 years) were recruited in this study. The volunteers were randomizing into two groups with 117 volunteers in each group...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28618759/the-effect-of-trimetazidine-on-renal-oxidative-stress-in-partial-and-complete-ureteral-obstructions-in-a-rat-model
#15
Sema Nur Ayyildiz, Ali Ayyildiz, Erdal Benli, Selma Cirrik, Rüştü Cankon Germiyanoğlu, Tevfik Noyan, Abdullah Çirakoğlu
BACKGROUND/AIM: Renal oxidative stress occurs in ureteral obstructions. The purpose of this study was to investigate the effect of the antioxidant and antiischemic agent trimetazidine (TMZ) on oxidative stress following ureteral obstruction. MATERIALS AND METHODS: Ten groups were established. Sham groups were checked as controls after 1 and 3 weeks. The other 8 groups had partial or complete ureteral obstruction while receiving or not receiving trimetazidine (TMZ) at 5 mg/kg daily and were evaluated after either 1 week or 3 weeks...
June 12, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28612522/-the-mechanisms-of-trimetazidine-alleviating-the-oxidative-stress-in-adipose-derived-mesenchymal-stem-cells
#16
Mao-Han Tang, Yan-Jie Zhang, Yin Liu, Zhi-Guang Su
OBJECTIVES: To investigate the effects of trimetazidine (TMZ) on the oxidative stress injury in adipose-derived mesenchymal stem cells (ADSCs). METHODS: ADSCs derived from adipose tissue of SD rats were characterized by flow cytometry and multiline age differentiation. ADSCs apoptosis was induced by H2O2 in vitro , Dirrerent concentration of TMZ (250 μmol/L, 500 μmol/L) was used to protect ADSCs from apoptosis. The morphological features of apoptotic ADSCs were analyzed by Hoechst 33342, mitochondrial potential and structure was analyzed by JC-1 staining and electron microscope, respectively...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28587952/the-effect-of-trimetazidine-treatment-in-patients-with-type-2-diabetes-undergoing-percutaneous-coronary-intervention-for-acute-myocardial-infarction
#17
Runjun Li, Xiuying Tang, Quanmin Jing, Qingsheng Wang, Meihong Yang, Xiaoyu Han, Jiayu Zhao, Xiangyou Yu
PURPOSE: Trimetazidine (TMZ) improves clinical outcomes in patients with chronic heart failure and stable coronary artery disease. No study has yet evaluated the efficacy of TMZ in type 2 diabetes patients with acute myocardial infarction (AMI) undergoing Percutaneous Coronary Intervention (PCI). We performed this study to evaluate the efficacy TMZ in DM patients with AMI undergoing PCI, such as the effect on reductions in myocardial enzyme, improvements in liver function, modulation of glucose levels, and improvement in cardiac function...
May 23, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28581448/trimetazidine-protects-cardiomyocytes-against-hypoxia-reoxygenation-injury-by-promoting-amp-activated-protein-kinase-dependent-autophagic-flux
#18
Yongkang Zhong, Peiyao Zhong, Shangfei He, Ya Zhang, Lu Tang, Yuanna Ling, Shanshan Fu, Ying Tang, Pingzhen Yang, Tao Luo, Baihe Chen, Aihua Chen, Xianbao Wang
Trimetazidine (TMZ), a metabolic agent, may protect against myocardial ischemia/reperfusion injury. Because of the critical role of autophagy in cardioprotection, we aimed to evaluate whether autophagy was involved in TMZ-induced protection during hypoxia/reoxygenation (H/R). Neonatal rat cardiomyocytes were subjected to H/R injury, and they were divided into 7 groups: control, control+TMZ, control+chloroquine (Cq)/compound C (com C), H/R, H/R+TMZ, H/R+Cq/com C, and H/R+TMZ+Cq/com C. Autophagic flux was primarily assessed by Western blot and tandem fluorescent mRFP-GFP-LC3...
June 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28532702/trimetazidine-in-the-prevention-of-contrast-induced-nephropathy-in-chronic-kidney-disease
#19
Tarek A Ibrahim, Ramzy H El-Mawardy, Ahmed S El-Serafy, Ehab M El-Fekky
BACKGROUND: Contrast induced nephropathy (CIN) may be defined as Acute Renal Failure (ARF) that occurs within 24-72h of exposure to intra-venous or intra-arterial iodinated contrast media that cannot be attributed to other causes. CIN occurs in up to 5% of hospitalized patients with normal renal function prior to injection of contrast media. It occurs more frequently in patients with renal impairment particularly if associated with diabetic nephropathy. Among all procedures utilizing contrast agents for either diagnostic or therapeutic purposes, coronary angiography and percutaneous coronary interventions are associated with the highest rates of CIN...
July 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28457391/cross-talk-between-sirtuin-1-and-high-mobility-box-1-in-steatotic-liver-graft-preservation
#20
M A Zaouali, A Panisello, A Lopez, E Folch, C Castro-Benítez, R Adam, J Roselló-Catafau
BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide +-dependent histone deacetylase that regulates various pathways involved in ischemia-reperfusion injury (IRI). Moreover, high-mobility group box 1 protein (HMGB1) has also been involved in inflammatory processes during IRI. However, the roles of both SIRT1 and HMGB1 in liver preservation is poorly understood. In this communication, we evaluated the potential relationship between SIRT1 and HMGB1 in steatotic and non-steatotic liver grafts preserved in Institute Georges Lopez solution (IGL-1) preservation solution enriched or not enriched with trimetazidine (TMZ)...
May 2017: Transplantation Proceedings
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