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meostasis is altered in heart failure and may play an important role in pathogenesis. p53 has been implicated in heart failure, and although its role in regulating tumorigenesis is well characterized, its activities on cellular metabolism are just beginning to be understood. We investigated the role of p53 and its transcriptional target gene TP53-induced glycolysis and apoptosis regulator (TIGAR) in myocardial energy metabolism under conditions simulating ischemia that can lead to heart failure. Expression of p53 and TIGAR was markedly upregulated after myocardial infarction, and apoptotic myocytes were decreased by 42% in p53-deficient mouse hearts compared with those in wild-type mice. To examine the effect of p53 on energy metabolism, cardiac myocytes were exposed to hypoxia. Hypoxia induced p53 and TIGAR expression in a p53-dependent manner. Knockdown of p53 or TIGAR increased glycolysis with elevated fructose-2,6-bisphosphate levels and reduced myocyte apoptosis. Hypoxic stress decreased phosphocreatine content and the mitochondrial membrane potential of myocytes without changes in ATP content, the effects of which were prevented by the knockdown of TIGAR. Inhibition of glycolysis by 2-deoxyglucose blocked these bioenergetic effects and TIGAR siRNA-mediated prevention of apoptosis, and, in contrast, overexpression of TIGAR reduced glucose utilization and increased apoptosis. Our data demonstrate that p53 and TIGAR inhibit glycolysis in hypoxic myocytes and that inhibition of glycolysis is closely involved in apoptosis, suggesting that p53 and TIGAR are significant mediators of cellular energy homeostasis and cell death under ischemic stress.TP53-induced glycolysis and apoptosis regulator; hypoxia; metabolism; mitochondria; glycolysis DESPITE SIGNIFICANT THERAPEUTIC ADVANCES, heart failure (HF) remains a leading cause of morbidity and mortality (12, 32). Numerous studies (10, 26) have identified altered cardiac energy homeostasis as a consistent feature of HF. Recently, metabolic-based therapies have attracted much interest as a new approach for the treatment of HF. For example, a metabolic modulator, trimetazidine, shifts the energy source from free fatty acid toward predominantly glucose utilization and improves the cardiac function of patients with idiopathic dilated cardiomyopathy (35). Transgenic mice overexpressing glucose transporter (GLUT)-1 have increased glucose uptake, preserved contractile reserve, and resist the development of HF by chronic pressure overload or ischemic injury (17,20). Based on these promising findings, additional insights into the mechanisms regulating cardiac energy metabolism may be helpful for further advancing our treatment regimens.Cardiac myocytes are known to undergo apoptosis in hypoxia and ischemia-reperfusion (6, 34). Reducing apoptotic cell death and the effect of remodeling after myocardial infarction (MI) have been primary goals, as extensive MI causes severe congestive HF (15). p53 regulates apoptosis, DNA repair, cell cycle progression, and senescence in response...

Background-Diabetic cardiomyopathy is characterized by energetic dysregulation caused by glucotoxicity, lipotoxicity, and mitochondrial alterations. p53 and its downstream mitochondrial assembly protein, synthesis of cytochrome c oxidase 2 (SCO2), are important regulators of mitochondrial respiration, whereas the involvement in diabetic cardiomyopathy remains to be determined. Methods and Results-The role of p53 and SCO2 in energy metabolism was examined in both type I (streptozotocin [STZ] administration) and type II diabetic (db/db) mice. Cardiac expressions of p53 and SCO2 in 4-week STZ diabetic mice were upregulated (185% and 152% versus controls, respectively, PϽ0.01), with a marked decrease in cardiac performance. Mitochondrial oxygen consumption was increased (136% versus control, PϽ0.01) in parallel with augmentation of mitochondrial cytochrome c oxidase (complex IV) activity. Reactive oxygen species (ROS)-damaged myocytes and lipid accumulation were increased in association with membrane-localization of fatty acid translocase protein FAT/CD36. Antioxidant tempol reduced the increased expressions of p53 and SCO2 in STZ-diabetic hearts and normalized alterations in mitochondrial oxygen consumption, lipid accumulation, and cardiac dysfunction. Similar results were observed in db/db mice, whereas in p53-deficient or SCO2-deficient diabetic mice, the cardiac and metabolic abnormalities were prevented. Overexpression of SCO2 in cardiac myocytes increased mitochondrial ROS and fatty acid accumulation, whereas knockdown of SCO2 ameliorated them. Conclusions-Myocardial p53/SCO2 signal is activated by diabetes-mediated ROS generation to increase mitochondrial oxygen consumption, resulting in excessive generation of mitochondria-derived ROS and lipid accumulation in association with cardiac dysfunction. (Circ Heart Fail. 2012;5:106-115.)Key Words: cardiomyopathy Ⅲ diabetes mellitus Ⅲ metabolism Ⅲ heart failure Ⅲ free radicals Ⅲ mitochondria D iabetic cardiomyopathy is one of the leading causes of increased morbidity and mortality in the patients with diabetes mellitus. 1,2 Although the pathogenesis of this cardiac contractile dysfunction is still unclear, an involvement of increased reactive oxygen species (ROS) production 3 and altered mitochondrial function 4,5 have been reported. Mitochondrial uncoupling was shown to be a possible mechanism to reduce cardiac efficiency in type 2 diabetes models 6 but not in type 1 diabetes models. 7 Recent study using positron emission tomography in patients with type 1 diabetes mellitus has revealed the Clinical Perspective on p 115increased oxygen consumption and altered fatty acid (FA) metabolism. 8 These human and animal studies have shown that increased oxidative stress correlates with lipid overload, Received February 9, 2011; accepted October 31, 2011. From the Department of Cardiovascular Medicine, Kyoto Prefectural University School of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan (H.N., S.M., E.I.-K., M. Kimata, A.H., M. Katamura, Y.O., M.A., Y.M., K.I....

Aldosterone antagonists have been reported to prevent ventricular remodeling after myocardial infarction (MI) via their action to extracellular matrix (ECM).

Blind needle puncture of the subclavian vein, which is the standard method used for insertion of pacemaker electrodes, causes an increased risk of lead fractures due to entrapment of the lead by the costoclavicular ligament and/or subclavius muscle. The extrathoracic lead insertion technique was developed to prevent such lead fractures. The present study was performed to evaluate the usefulness of extrathoracic subclavian vein puncture under the guidance of both fluoroscopy and venography in the oblique beam projection. Pacemaker leads were implanted in ten patients under the guidance of both fluoroscopy and venography in the ipsilateral anterior oblique projection. The angle of projection was set as large as possible between 35 degrees and 45 degrees . The needle was held parallel to the X-ray angle of incidence and inserted toward the first rib, then withdrawn until the tip entered the subclavian vein. This modified method of pacemaker implantation was successful in all patients, with no complications during the follow-up period ranging from 4 to 19 months. It also prevented pneumothorax and lead entrapment in soft tissue associated with the clavicle that might be caused by the conventional technique.

ulmonary vein varix is a rare abnormality, often presenting as a pulmonary or mediastinal mass on chest roentgenograms, and pulmonary angiography, computed tomography (CT), or magnetic resonance imaging (MRI) is considered necessary for diagnosis. We describe our experience with an unusual case of pulmonary vein varix that was diagnosed noninvasively by echocardiography alone. Case ReportA 47-year-old woman was admitted because of chest discomfort. She did not have a history of cardiovascular disease and the results of physical examination, routine blood tests and electrocardiography were unremarkable. Chest radiography suggested a mediastinal mass inside the left cardiac border in the posteroanterior view ( Fig 1A) and behind the cardiac silhouette in the lateral view (Fig 1B). Two-dimensional transthoracic echocardiography (TTE) was performed. On the parasternal long-axis view, the motion and chamber size of the left ventricle were normal, and there was no enlargement of the left atrial or right ventricular chambers. On the short-axis view and apical 4-chamber view, an echo-free mass was observed outside the posterolateral wall of the left atrium (Fig 2A,B). There was no indentation of the left ventricular wall, suggesting that the mass was an extrapericardial structure. Color Doppler echocardiography detected blood flow from the mass into the left atrium (Fig 2C). Mitral regurgitation was not evident. Transesophageal echocardiography (TEE) more clearly demonstrated dilatation of the pulmonary vein in the proximal left lower lobe with normal intrapulmonary venous connections (Fig 3A,B). The varix communicated with the left atrium. The right pulmonary veins and left upper pulmonary vein were normal. The wall of the varix was Pulmonary vein varix is a rare abnormality, often resembling a pulmonary or mediastinal mass on chest radiographs, and pulmonary angiography has been the mainstay of diagnosis. An unusual case of pulmonary vein varix was clearly defined by echocardiography performed in a 47-year-old woman with chest discomfort who had been found to have an abnormal structure behind the cardiac silhouette on a chest radiograph.

Patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure within a short period during the clinical course. It is essential to predict respiratory deterioration in the short term. We investigated the use of inflammatory markers to predict respiratory distress within three days from their analysis in COVID-19 patients. This retrospective observational study included 81 patients admitted with COVID-19. Patients were divided into two groups according to whether the maximum fraction of inspired oxygen (FiO2) for three days from the blood marker measurements was ≥0.4 (high FiO2 group; HFG) or <0.4 (low FiO2 group; LFG). Interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), white blood cell, D-dimer, and creatinine levels were compared between the two groups. The levels of all markers were significantly higher in HFG patients. Areas under the receiver operating characteristic curve of IL-6, CRP, and LDH had high values of 0.85, 0.82, and 0.81, respectively. The odds ratio of IL-6 which was crude and adjusted for dexamethasone administration initiated before laboratory measurement, showed the high value of 29.1 (5.6–295.6) and 53.9 (4.5–3242.8), respectively. IL-6 can be used as a reliable marker for predicting respiratory illness within three days after assessment.

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