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Sample records for myocardial metabolic derangement

  1. [Derangements of mineral metabolism associated with tumors].

    PubMed

    Fukumoto, Seiji

    2014-08-01

    Bone as a hard tissue has several functions such as supporting our body and protecting internal organs. In addition, bone has a pivotal role in the regulation of circulatory mineral concentrations. Therefore, abnormal bone metabolism is sometimes accompanied by deranged serum calcium or phosphate levels as shown in patients with malignancy-associated hypercalcemia (MAH) or tumor-induced osteomalacia (TIO) . Parathyroid hormone-related protein, PTHrP, was cloned as a major humoral factor causing MAH. Similarly, fibroblast growth factor 23, FGF23, was identified as a causative factor for TIO. Therefore, MAH and TIO are not only important in clinical practice but also gave us deep insights into the mechanisms of mineral homeostasis, and bone and cartilage metabolism. PMID:25065866

  2. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements.

    PubMed

    Swithers, Susan E

    2013-09-01

    The negative impact of consuming sugar-sweetened beverages on weight and other health outcomes has been increasingly recognized; therefore, many people have turned to high-intensity sweeteners like aspartame, sucralose, and saccharin as a way to reduce the risk of these consequences. However, accumulating evidence suggests that frequent consumers of these sugar substitutes may also be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease. This paper discusses these findings and considers the hypothesis that consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned responses that normally contribute to glucose and energy homeostasis. Because of this interference, frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing metabolic derangements. PMID:23850261

  3. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements

    PubMed Central

    Swithers, Susan E.

    2013-01-01

    The negative impact of consuming sugar-sweetened beverages on weight and other health outcomes has been increasingly recognized; therefore, many people have turned to high-intensity sweeteners like aspartame, sucralose, and saccharin as a way to reduce the risk of these consequences. However, accumulating evidence suggests that frequent consumers of these sugar substitutes may also be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease. This paper discusses these findings and considers the hypothesis that consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned responses that normally contribute to glucose and energy homeostasis. Because of this interference, frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing metabolic derangements. PMID:23850261

  4. Synthetic cannabinoids: the multi-organ failure and metabolic derangements associated with getting high

    PubMed Central

    Sherpa, Dolkar; Paudel, Bishow M.; Subedi, Bishnu H.; Chow, Robert Dobbin

    2015-01-01

    Synthetic cannabinoids (SC), though not detected with routine urine toxicology screening, can cause severe metabolic derangements and widespread deleterious effects in multiple organ systems. The diversity of effects is related to the wide distribution of cannabinoid receptors in multiple organ systems. Both cannabinoid-receptor-mediated and non-receptor-mediated effects can result in severe cardiovascular, renal, and neurologic manifestations. We report the case of a 45-year-old African American male with ST-elevation myocardial infarction, subarachnoid hemorrhage, reversible cardiomyopathy, acute rhabdomyolysis, and severe metabolic derangement associated with the use of K2, an SC. Though each of these complications has been independently associated with SCs, the combination of these effects in a single patient has not been heretofore reported. This case demonstrates the range and severity of complications associated with the recreational use of SCs. Though now banned in the United States, use of systemic cannabinoids is still prevalent, especially among adolescents. Clinicians should be aware of their continued use and the potential for harm. To prevent delay in diagnosis, tests to screen for these substances should be made more readily available. PMID:26333853

  5. Synthetic cannabinoids: the multi-organ failure and metabolic derangements associated with getting high.

    PubMed

    Sherpa, Dolkar; Paudel, Bishow M; Subedi, Bishnu H; Chow, Robert Dobbin

    2015-01-01

    Synthetic cannabinoids (SC), though not detected with routine urine toxicology screening, can cause severe metabolic derangements and widespread deleterious effects in multiple organ systems. The diversity of effects is related to the wide distribution of cannabinoid receptors in multiple organ systems. Both cannabinoid-receptor-mediated and non-receptor-mediated effects can result in severe cardiovascular, renal, and neurologic manifestations. We report the case of a 45-year-old African American male with ST-elevation myocardial infarction, subarachnoid hemorrhage, reversible cardiomyopathy, acute rhabdomyolysis, and severe metabolic derangement associated with the use of K2, an SC. Though each of these complications has been independently associated with SCs, the combination of these effects in a single patient has not been heretofore reported. This case demonstrates the range and severity of complications associated with the recreational use of SCs. Though now banned in the United States, use of systemic cannabinoids is still prevalent, especially among adolescents. Clinicians should be aware of their continued use and the potential for harm. To prevent delay in diagnosis, tests to screen for these substances should be made more readily available. PMID:26333853

  6. Aging signaling pathways and circadian clock-dependent metabolic derangements

    PubMed Central

    Tevy, Maria Florencia; Giebultowicz, Jadwiga; Pincus, Zachary; Mazzoccoli, Gianluigi; Vinciguerra, Manlio

    2013-01-01

    The circadian clock machinery orchestrates organism metabolism in order to ensure that development, survival and reproduction are attuned to diurnal environmental variations. For unknown reasons, there is a decline in circadian rhythms with age, concomitant with declines in the overall metabolic tissues homeostasis and changes in the feeding behavior of aged organisms. This disruption of the relationship between the clock and the nutrient sensing networks might underlie age-related diseases; overall, greater knowledge of the molecular mediators of and variations in clock networks during lifespan may shed light on the aging process and how it may be delayed. In this review we address the complex links between the circadian clock, metabolic (dys)functions and aging in different model organisms. PMID:23299029

  7. Diurnal variations in myocardial metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasin...

  8. Imaging and Modeling of Myocardial Metabolism

    PubMed Central

    Jamshidi, Neema; Karimi, Afshin; Birgersdotter-Green, Ulrika; Hoh, Carl

    2010-01-01

    Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed. PMID:20559785

  9. [Ischemic myocardial metabolism and antianginal drugs].

    PubMed

    Ichihara, K

    1986-12-01

    The effect of several kinds of antianginal drugs: nitrates, coronary vasodilators, beta-adrenergic blocking agents and calcium entry blocking agents on the myocardial metabolism and myocardial acidosis during ischemia was studied in the dog heart in vivo. Ischemia was induced by ligating the left anterior descending coronary artery. Ischemia accelerated anaerobic metabolism in the myocardium, in which glycogen breakdown, accumulation of glycolytic intermediates, loss of high energy phosphate and tissue acidosis occurred. Nitroglycerin, beta-adrenergic blocking agents such as propranolol, and some calcium entry blocking agents such as diltiazem and flunarizine prevented the myocardial metabolism from shifting to an anaerobic metabolism in spite of ischemia. However, coronary vasodilators and the dihydropyridine type of calcium entry blocking agents were not capable of reducing changes in the myocardial metabolism and myocardial acidosis during ischemia. The author makes a point in the present review that all the drugs which dilate coronary artery are not always effective on the ischemic myocardium. PMID:3549484

  10. Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage.

    PubMed

    Raz, Itamar; Eldor, Roi; Cernea, Simona; Shafrir, Eleazar

    2005-01-01

    We present multiple findings on derangements in lipid metabolism in type 2 diabetes. The increase in the intracellular deposition of triglycerides (TG) in muscles, liver and pancreas in subjects prone to diabetes is well documented and demonstrated to attenuate glucose metabolism by interfering with insulin signaling and insulin secretion. The obesity often associated with type 2 diabetes is mainly central, resulting in the overload of abdominal adipocytes with TG and reducing fat depot capacity to protect other tissues from utilizing a large proportion of dietary fat. In contrast to subcutaneous adipocytes, the central adipocytes exhibit a high rate of basal lipolysis and are highly sensitive to fat mobilizing hormones, but respond poorly to lipolysis restraining insulin. The enlarged visceral adipocytes are flooding the portal circulation with free fatty acids (FFA) at metabolically inappropriate time, when FFA should be oxidized, thus exposing nonadipose tissues to fat excess. This leads to ectopic TG accumulation in muscles, liver and pancreatic beta-cells, resulting in insulin resistance and beta-cell dysfunction. This situation, based on a large number of observations in humans and experimental animals, confirms that peripheral adipose tissue is closely regulated, performing a vital role of buffering fluxes of FFA in the circulation. The central adipose tissues tend to upset this balance by releasing large amounts of FFA. To reduce the excessive fat outflow from the abdominal depots and prevent the ectopic fat deposition it is important to decrease the volume of central fat stores or increase the peripheral fat stores. One possibility is to downregulate the activity of lipoprotein lipase, which is overexpressed in abdominal relatively to subcutaneous fat stores. This can be achieved by gastrointestinal bypass or gastroplasty, which decrease dietary fat absorption, or by direct means that include surgical removal of mesenteric fat. Indirect treatment consists

  11. Deranged Exams

    ERIC Educational Resources Information Center

    Spivey, Michael Z.

    2010-01-01

    This article discusses a triangle of numbers that are related to the derangement numbers. These numbers satisfy a Pascal-like recurrence relation with subtraction instead of addition. We describe how they relate to numbers studied by other authors and use them to generalize Euler's famous recurrence relation for the derangement numbers.

  12. Role of Protein Farnesylation in Burn-Induced Metabolic Derangements and Insulin Resistance in Mouse Skeletal Muscle

    PubMed Central

    Tanaka, Tomokazu; Kramer, Joshua; Yu, Yong-Ming; Fischman, Alan J.; Martyn, J. A. Jeevendra; Tompkins, Ronald G.; Kaneki, Masao

    2015-01-01

    Objective Metabolic derangements, including insulin resistance and hyperlactatemia, are a major complication of major trauma (e.g., burn injury) and affect the prognosis of burn patients. Protein farnesylation, a posttranslational lipid modification of cysteine residues, has been emerging as a potential component of inflammatory response in sepsis. However, farnesylation has not yet been studied in major trauma. To study a role of farnesylation in burn-induced metabolic aberration, we examined the effects of farnesyltransferase (FTase) inhibitor, FTI-277, on burn-induced insulin resistance and metabolic alterations in mouse skeletal muscle. Methods A full thickness burn (30% total body surface area) was produced under anesthesia in male C57BL/6 mice at 8 weeks of age. After the mice were treated with FTI-277 (5 mg/kg/day, IP) or vehicle for 3 days, muscle insulin signaling, metabolic alterations and inflammatory gene expression were evaluated. Results Burn increased FTase expression and farnesylated proteins in mouse muscle compared with sham-burn at 3 days after burn. Simultaneously, insulin-stimulated phosphorylation of insulin receptor (IR), insulin receptor substrate (IRS)-1, Akt and GSK-3β was decreased. Protein expression of PTP-1B (a negative regulator of IR-IRS-1 signaling), PTEN (a negative regulator of Akt-mediated signaling), protein degradation and lactate release by muscle, and plasma lactate levels were increased by burn. Burn-induced impaired insulin signaling and metabolic dysfunction were associated with increased inflammatory gene expression. These burn-induced alterations were reversed or ameliorated by FTI-277. Conclusions Our data demonstrate that burn increased FTase expression and protein farnesylation along with insulin resistance, metabolic alterations and inflammatory response in mouse skeletal muscle, all of which were prevented by FTI-277 treatment. These results indicate that increased protein farnesylation plays a pivotal role in burn

  13. Systemic Metabolic Derangement, Pulmonary Effects, and Insulin Insufficiency following subchronic ozone exposure in rats

    EPA Science Inventory

    Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to in...

  14. Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats.

    PubMed

    Miller, Desinia B; Snow, Samantha J; Henriquez, Andres; Schladweiler, Mette C; Ledbetter, Allen D; Richards, Judy E; Andrews, Debora L; Kodavanti, Urmila P

    2016-09-01

    Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25ppm or 1.00ppm ozone, 5h/day, 3 consecutive days/week (wk) for 13wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13wk or following a 1wk recovery period (13wk+1wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13wk, however, these responses were largely reversible following a 1wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. PMID:27368153

  15. [Energy metabolism and myocardial function in myocardiodystrophy].

    PubMed

    Temirova, K V; Kurlygina, L A; Zavodskaia, I S; Novikova, N A

    1976-09-01

    A total of 92 patients with chronic tonsilitis and cardiovascular changes were subjected to clinical observations, ECG analysis, potassium and nitroglycerine tests, and studies of the lactic acid level and creatinekinase activity as indces of myocardial metabolism. The examinations were conducted prior to and following tonsillectomy. In a majority of patients a correlation was revealed between the degree of ECG changes and the serum lactic acid level, as well as between the ECG improvement and a reduction of the lactic acid level following tonsillectomy. Three stages of tonsillogenic myocardiodystrophy were distinguished. The obtained data indicate the rationale of the used tests for the evaluation of the myocardial meabolism alterations and of the efficacy of treatment of chronic tonsillitis patients. PMID:1011536

  16. Modulation of cardiac metabolism during myocardial ischemia.

    PubMed

    Chagas, Antonio C P; Dourado, Paulo M M; Galvão, Tatiana de Fátima Gonçalves

    2008-01-01

    Metabolic modulation during myocardial ischemia is possible by the use of specific drugs, which may induce a shift from free fatty acid towards predominantly glucose utilization by the myocardium to increase ATP generation per unit oxygen consumption. Three agents (trimetazidine, ranolazine, and perhexiline) have well-documented anti-ischaemic effects. However, perhexiline, the most potent agent currently available, requires plasma-level monitoring to avoid hepato-neuro-toxicity. Besides, the long-term safety of trimetazidine and ranolazine has yet to be established. In addition to their effect in ischemia, the potential use of these drugs in chronic heart failure is gaining recognition as clinical and experimental data are showing the improvement of myocardial function following treatment with several of them, even in the absence of ischemia. Future applications for this line of treatment is promising and deserves additional research. In particular, large, randomised, controlled trials investigating the effects of these agents on mortality and hospitalization rates due to coronary artery disease are needed. PMID:18991673

  17. Role of cardiomyocyte circadian clock in myocardial metabolic adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marked circadian rhythmicities in cardiovascular physiology and pathophysiology exist. The cardiomyocyte circadian clock has recently been linked to circadian rhythms in myocardial gene expression, metabolism, and contractile function. For instance, the cardiomyocyte circadian clock is essential f...

  18. Quantitation of myocardial fatty acid metabolism using PET

    SciTech Connect

    Bergmann, S.R.; Weinheimer, C.J.; Markham, J.; Herrero, P.

    1996-10-01

    Abnormalities of fatty acid metabolism in the heart presage contractile dysfunction and arrhythmias. This study was performed to determine whether myocardial fatty acid metabolism could be quantified noninvasively using PET and 1-{sup 11}C-palmitate. Anesthetized dogs were studied during control conditions; during administration of dobutamine; after oxfenicine; and during infusion of glucose. Dynamic PET data after administration of 1-{sup 11}C-palmitate were fitted to a four-compartment mathematical model. Modeled rates of palmitate utilization correlated closely with directly measured myocardial palmitate and total long-chain fatty acid utilization (r = 0.93 and 0.96, respectively, p < 0.001 for each) over a wide range of arterial fatty acid levels and altered patterns of myocardial substrate use (fatty acid extraction fraction ranging from 1% to 56%, glucose extraction fraction from 1% to 16% and myocardial fatty acid utilization from 1 to 484 nmole/g/min). The percent of fatty acid undergoing oxidation could also be measured. The results demonstrate the ability to quantify myocardial fatty acid utilization with PET. The approach is readily applicable for the determination of fatty acid metabolism noninvasively in patients. 37 refs., 5 figs., 4 tabs.

  19. Circadian rhythms in myocardial metabolism and function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in myocardial function and dysfunction are firmly established in both animal models and humans. For example, the incidence of arrhythmias and sudden cardiac death increases when organisms awaken. Such observations have classically been explained by circadian rhythms in neurohumoral...

  20. Tomoscintigraphic assessment of myocardial metabolic heterogenity

    SciTech Connect

    Roesler, H.; Hess, T.; Weiss, M.; Noelpp, U.; Mueller, G.; Hoeflin, F.; Kinser, J.

    1983-04-01

    I-123-omega-heptadecanoic acid (HDA) was evaluated for myocardial scanning in 59 healthy volunteers and 133 patients, using a 7-pinhole collimator. Early (uptake) and late (retention) images were compared visually. Regional HDA elimination was also followed semiquantitatively based on the calculation of a retention-over-uptake ratio, R(phi), derived from the maximal counts/pixel in 60 midventricular slice sectors. The healthy heart concentrated HDA homogeneously in all segments with no difference between early and late images. The minimal R(phi), taken as representative of that myocardium with the best function, was unchanged after maximal ergometer stress and with dipyramidole-induced hyperperfusion. A circumscribed decreased HDA uptake is the clear-cut criterion for an abnormal finding. HDA tomography of the myocardium had an 86% sensitivity for myocardial infarcts (MIs) up to 4 wk old, and 83% for myocardial scars (MSs). Comparing early and late tomograms, we find a cool-warm sequence more often with acute and subacute MIs. A cool-cool or a cold-cold sequence dominated with MSs. HDA tomoscintigraphy cannot replace TI-201 for the evaluation of regional coronary reserve in coronary heart disease.

  1. Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements.

    PubMed

    Lakeland, Thomas V; Borg, Melissa L; Matzaris, Maria; Abdelkader, Amany; Evans, Roger G; Watt, Matthew J

    2014-06-15

    Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo. PMID:24760990

  2. Loss of Toll-Like Receptor 4 Function Partially Protects against Peripheral and Cardiac Glucose Metabolic Derangements During a Long-Term High-Fat Diet

    PubMed Central

    Jackson, Ellen E.; Rendina-Ruedy, Elisabeth; Smith, Brenda J.; Lacombe, Veronique A.

    2015-01-01

    Diabetes is a chronic inflammatory disease that carries a high risk of cardiovascular disease. However, the pathophysiological link between these disorders is not well known. We hypothesize that TLR4 signaling mediates high fat diet (HFD)-induced peripheral and cardiac glucose metabolic derangements. Mice with a loss-of-function mutation in TLR4 (C3H/HeJ) and age-matched control (C57BL/6) mice were fed either a high-fat diet or normal diet for 16 weeks. Glucose tolerance and plasma insulin were measured. Protein expression of glucose transporters (GLUT), AKT (phosphorylated and total), and proinflammatory cytokines (IL-6, TNF-α and SOCS-3) were quantified in the heart using Western Blotting. Both groups fed a long-term HFD had increased body weight, blood glucose and insulin levels, as well as impaired glucose tolerance compared to mice fed a normal diet. TLR4-mutant mice were partially protected against long-term HFD-induced insulin resistance. In control mice, feeding a HFD decreased cardiac crude membrane GLUT4 protein content, which was partially rescued in TLR4-mutant mice. TLR4-mutant mice fed a HFD also had increased expression of GLUT8, a novel isoform, compared to mice fed a normal diet. GLUT8 content was positively correlated with SOCS-3 and IL-6 expression in the heart. No significant differences in cytokine expression were observed between groups, suggesting a lack of inflammation in the heart following a HFD. Loss of TLR4 function partially restored a healthy metabolic phenotype, suggesting that TLR4 signaling is a key mechanism in HFD-induced peripheral and cardiac insulin resistance. Our data further suggest that TLR4 exerts its detrimental metabolic effects in the myocardium through a cytokine-independent pathway. PMID:26539824

  3. Asparaginase-induced derangements of glutamine metabolism: the pathogenetic basis for some drug-related side-effects.

    PubMed

    Ollenschläger, G; Roth, E; Linkesch, W; Jansen, S; Simmel, A; Mödder, B

    1988-10-01

    Several side-effects of asparaginase therapy have been said to be a consequence of the glutaminase activity of Escherichia coli asparaginase, especially the deleterious influence on the liver function. We report here the drug-induced impairments of asparagine and glutamine metabolism in correlation to concentrations changes of plasma proteins, synthesized in the liver, in patients with acute lymphatic leukaemia. One hour after asparaginase application, plasma glutamine decreased to 5% (0-39%: median, range) of the initial values, with a subsequent rise to concentrations slightly lower than those prior to therapy. During the 14 days of drug application the fasting plasma concentrations of glutamine fell to a median of 63% of the pre-therapeutic levels, indicating a depletion of the glutamine pools. Two days after the end of asparaginase application, in one patient the glutamine concentrations increased to the pre-therapeutic range. Plasma concentrations of fibrinogen and antithrombin III decreased to 46% and 56%, respectively, of the initial values, with a slight increase 2 days after the end of therapy. The changes of plasma protein concentrations followed the course of plasma glutamine and asparagine. From that we deduce that the hepatic synthesis of the plasma proteins might be influenced by asparagine and glutamine depletion as a consequence of the therapy with E. coli asparaginase. PMID:3147904

  4. Altered phosphate metabolism in myocardial infarction: P-31 MR spectroscopy

    SciTech Connect

    Bottomley, P.A.; Herfkens, R.J.; Smith, L.S.; Bashore, T.M.

    1987-12-01

    The high-energy myocardial phosphate metabolism of four patients with acute anterior myocardial infarction after coronary angioplasty and drug therapy was evaluated with cardiac-gated phosphorus magnetic resonance (MR) depth-resolved surface coil spectroscopy (DRESS) 5-9 days after the onset of symptoms. Significant reductions (about threefold) in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratio and elevations in the Pi to adenosine triphosphate (ATP) ratio were observed in endocardially or transmurally derived MR spectra when compared with values from epicardially displaced spectra and values from seven healthy volunteers (P less than .05). High-energy phosphate metabolites and Pi ratios did not vary significantly during the cardiac cycle in healthy volunteers. However, contamination of Pi resonances by phosphomonoester components, including blood 2,3-diphosphoglycerate, precluded accurate spectral quantification of Pi and pH. The results indicate that localized P-31 MR spectroscopy may be used to directly assess cellular energy reserve in clinical myocardial infarction and to evaluate metabolic response to interventions.

  5. Evaluation of myocardial metabolism, with /sup 13/N- and /sup 11/C-labeled amino acids and positron computed tomography

    SciTech Connect

    Henze, E.; Schelbert, H.R.; Barrio, J.R.; Egbert, J.E.; Hansen, H.W.; MacDonald, N.S.; Phelps, M.E.

    1982-08-01

    To evaluate the utility of labeled L-amino acids (AA) for imaging regional myocardial AA metabolism by positron computed tomography (PCT), the myocardial uptake and clearance of Ala,* Glu, Gln, Asp, Leu tagged with /sup 13/N, and of /sup 11/C-tagged Asp, and oxaloacetate (Oxal), were examined in 44 experiments at control, during ischemia, and after transaminase inhibition. The myocardial time-activity curves recorded after intracoronary tracer injection had two clearance phases (an early and a late) for all /sup 13/N AA, and three (early, intermediate, late) for the two /sup 11/C compounds, with significantly different clearance half-times of 18.7 +/- 8.0 (s.d.) sec for the early phase, 141.7 +/- 56.5 sec for the intermediate, and 61.2 +/- 43.5 min for the late phase. The residual fractions ranged from 0.07 to 0.23 in normal myocardium, and consistently increased with ischemia by 0.01-0.07 for /sup 13/N-labeled Ala, Glu, Asp, and Leu, but not for /sup 13/N Gln and /sup 11/C compounds. Transaminase inhibition shortened the half-times of the late phases of /sup 13/N-labeled Ala, Glu, Asp, and Leu; had no effect on t1/2 of /sup 13/N Gln and /sup 11/C Oxal; and resulted in a loss of /sup 11/C CO/sub 2/ production and of the intermediate phase for /sup 11/C Asp. On the PCT images, /sup 13/N activity from labeled Ala and Glu was not decreased in an ischemic segment despite a significant flow reduction, as demonstrated by /sup 13/N NH/sub 3/ imaging and labeled microspheres. From the results, a three-compartment tracer kinetic model is proposed for the noninvasive quantification of Krebscycle activity, protein synthesis, and metabolic derangements related to ischemia.

  6. Protective metabolic effects of propranolol during total myocardial ischemia.

    PubMed

    Veronee, C D; Lewis, W R; Takla, M W; Hull-Ryde, E A; Lowe, J E

    1986-09-01

    Clinical trials have shown an increase in survival in patients treated with beta blockers after infarction. In addition, the majority of patients undergoing myocardial revascularization are also treated preoperatively with beta blockers. It is commonly thought that beta blockers exert their protective effect primarily by decreasing heart rate and subsequent myocardial work. The present study was designed to determine whether beta blockade has any primary protective metabolic effects on globally ischemic myocardium. Thirty-four anesthetized dogs underwent total myocardial ischemia at 37 degrees C. High-energy nucleotide and lactate levels in left ventricular tissue samples were determined at control and at 15 minute intervals as well as at the onset of ischemic contracture in 24 dogs. Seventeen dogs were treated with propranolol before ischemia. The time to ischemic contracture in control dogs was 63.3 +/- 1.4 minutes compared with 75.9 +/- 2.2 minutes in the propranolol-treated group (p less than 0.01). In addition to significantly delaying the onset of ischemic contracture, propranolol also decreased the rate of anaerobic glycolysis during ischemia. Ischemic contracture occurred in the control group with an average adenosine triphosphate level of 1.26 +/- 0.08 mumol compared to 0.91 +/- 0.08 mumol/gm wet weight for the beta blocked group (p less than 0.0025). These are the first data suggesting that the protective effects of beta blockade may be related to a beneficial effect on ischemic myocardial metabolism allowing myocardium to survive with lower levels of adenosine triphosphate. PMID:3018382

  7. Regional myocardial metabolism in patients with acute myocardial infarction assessed by positron emission tomography

    SciTech Connect

    Schwaiger, M.; Brunken, R.; Grover-McKay, M.; Krivokapich, J.; Child, J.; Tillisch, J.H.; Phelps, M.E.; Schelbert, H.R.

    1986-10-01

    Positron emission tomography has been shown to distinguish between reversible and irreversible ischemic tissue injury. Using this technique, 13 patients with acute myocardial infarction were studied within 72 hours of onset of symptoms to evaluate regional blood flow and glucose metabolism with nitrogen (N)-13 ammonia and fluorine (F)-18 deoxyglucose, respectively. Serial noninvasive assessment of wall motion was performed to determine the prognostic value of metabolic indexes for functional tissue recovery. Segmental blood flow and glucose utilization were evaluated using a circumferential profile technique and compared with previously established semiquantitative criteria. Relative N-13 ammonia uptake was depressed in 32 left ventricular segments. Sixteen segments demonstrated a concordant decrease in flow and glucose metabolism. Regional function did not change over time in these segments. In contrast, 16 other segments with reduced blood flow revealed maintained F-18 deoxyglucose uptake consistent with remaining viable tissue. The average wall motion score improved significantly in these segments (p less than 0.01), yet the degree of recovery varied considerably among patients. Coronary anatomy was defined in 9 of 13 patients: patent infarct vessels supplied 8 of 10 segments with F-18 deoxyglucose uptake, while 10 of 13 segments in the territory of an occluded vessel showed concordant decreases in flow and metabolism (p less than 0.01). Thus, positron emission tomography reveals a high incidence of residual tissue viability in ventricular segments with reduced flow and impaired function during the subacute phase of myocardial infarction. Absence of residual tissue metabolism is associated with irreversible injury, while preservation of metabolic activity identifies segments with a variable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Adaptation of Myocardial Substrate Metabolism to a Ketogenic Nutrient Environment*

    PubMed Central

    Wentz, Anna E.; d'Avignon, D. André; Weber, Mary L.; Cotter, David G.; Doherty, Jason M.; Kerns, Robnet; Nagarajan, Rakesh; Reddy, Naveen; Sambandam, Nandakumar; Crawford, Peter A.

    2010-01-01

    Heart muscle is metabolically versatile, converting energy stored in fatty acids, glucose, lactate, amino acids, and ketone bodies. Here, we use mouse models in ketotic nutritional states (24 h of fasting and a very low carbohydrate ketogenic diet) to demonstrate that heart muscle engages a metabolic response that limits ketone body utilization. Pathway reconstruction from microarray data sets, gene expression analysis, protein immunoblotting, and immunohistochemical analysis of myocardial tissue from nutritionally modified mouse models reveal that ketotic states promote transcriptional suppression of the key ketolytic enzyme, succinyl-CoA:3-oxoacid CoA transferase (SCOT; encoded by Oxct1), as well as peroxisome proliferator-activated receptor α-dependent induction of the key ketogenic enzyme HMGCS2. Consistent with reduction of SCOT, NMR profiling demonstrates that maintenance on a ketogenic diet causes a 25% reduction of myocardial 13C enrichment of glutamate when 13C-labeled ketone bodies are delivered in vivo or ex vivo, indicating reduced procession of ketones through oxidative metabolism. Accordingly, unmetabolized substrate concentrations are higher within the hearts of ketogenic diet-fed mice challenged with ketones compared with those of chow-fed controls. Furthermore, reduced ketone body oxidation correlates with failure of ketone bodies to inhibit fatty acid oxidation. These results indicate that ketotic nutrient environments engage mechanisms that curtail ketolytic capacity, controlling the utilization of ketone bodies in ketotic states. PMID:20529848

  9. Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography. [Dogs

    SciTech Connect

    Schelbert, H.R.; Phelps, M.E.

    1980-06-01

    While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (/sup 13/N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique.

  10. Polyamine metabolism in rat myocardial ischemia-reperfusion injury.

    PubMed

    Han, Liping; Xu, Changqing; Guo, Yimin; Li, Hongzhu; Jiang, Chunming; Zhao, Yajun

    2009-02-01

    This study was focused on investigating the involvement of polyamine metabolism in the myocardial ischemia-reperfusion injury (MIRI) in an in vivo rat model. A branch of the descending left coronary artery was occluded for 30 min followed by 2 h, 6 h, 12 h, and 24 h reperfusion. Then the expression of spermidine/spermine N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) and the concentrations of polyamines were assessed. It was found that the expression of SSAT and ODC were upregulated after reperfusion and the concentrations of spermidine and spermine were significantly decreased, while putrescine concentration was significantly increased. The results suggest that MIRI may cause disturbance of polyamine metabolism, and it may play a critical role in MIRI. PMID:18077014

  11. The effect of nifedipine on myocardial perfusion and metabolism in systemic sclerosis. A positron emission tomographic study

    SciTech Connect

    Duboc, D.; Kahan, A.; Maziere, B.; Loc'h, C.; Crouzel, C.; Menkes, C.J.; Amor, B.; Strauch, G.; Guerin, F.; Syrota, A. )

    1991-02-01

    We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9 patients with systemic sclerosis, using positron emission tomography with a perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose (18FDG)). Nifedipine, 20 mg 3 times daily for 1 week, induced a significant increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial uptake, and a significant increase in the myocardial 38K: 18FDG ratio. These results indicate that the increase in myocardial perfusion is associated with modifications in myocardial energy metabolism, which probably result from a beneficial anti-ischemic effect of nifedipine in patients with systemic sclerosis.

  12. Succinate metabolism: a new therapeutic target for myocardial reperfusion injury.

    PubMed

    Pell, Victoria R; Chouchani, Edward T; Frezza, Christian; Murphy, Michael P; Krieg, Thomas

    2016-07-15

    Myocardial ischaemia/reperfusion (IR) injury is a major cause of death worldwide and remains a disease for which current clinical therapies are strikingly deficient. While the production of mitochondrial reactive oxygen species (ROS) is a critical driver of tissue damage upon reperfusion, the precise mechanisms underlying ROS production have remained elusive. More recently, it has been demonstrated that a specific metabolic mechanism occurs during ischaemia that underlies elevated ROS at reperfusion, suggesting a unifying model as to why so many different compounds have been found to be cardioprotective against IR injury. This review will discuss the role of the citric acid cycle intermediate succinate in IR pathology focusing on the mechanism by which this metabolite accumulates during ischaemia and how it can drive ROS production at Complex I via reverse electron transport. We will then examine the potential for manipulating succinate accumulation and metabolism during IR injury in order to protect the heart against IR damage and discuss targets for novel therapeutics designed to reduce reperfusion injury in patients. PMID:27194563

  13. Myocardial Function and Lipid Metabolism in the Chronic Alcoholic Animal

    PubMed Central

    Regan, Timothy J.; Khan, Mohammad I.; Ettinger, Philip O.; Haider, Bunyad; Lyons, Michael M.; Oldewurtel, Henry A.; Weber, Marilyn

    1974-01-01

    In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium. To evaluate myocardial lipid metabolism, [1-14C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced 14CO2 production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [14C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic. Images PMID:4368946

  14. Myocardial imaging and metabolic studies with (17-/sup 123/I)iodoheptadecanoic acid

    SciTech Connect

    Freundlieb, C.; Hoeck, A.; Vyska, K.; Feinendegen, L.E.; Machulla, H.J.; Stoecklin, G.

    1980-11-01

    After intravenous administration of the stearic acid analogue (17-/sup 123/I)iodoheptadecanoic acid (I-123 HA), myocardial metabolism was studied in ten normal individuals, eight patients with coronary artery disease and three patients with congestive heart failure. High-quality images were obtained in sequential scintigraphy of I-123 metabolically bound in myocardial tissue. Infarcted zones as well as ischemic regions are indicated by reduced tracer uptake. Iodine-123 in the blood pool and interstitial space consists mainly of radioiodide that is liberated by fatty-acid metabolism and was corrected for. Using the proposed correction not only are the images improved but the uptake and elimination of the I-123 in the myocardial cells can be followed. The average disappearance half-time of I-123 HA from the myocardium of normal persons was 24 +- 4.7 min. In patients with coronary artery disease significant differences between myocardial regions were observed.

  15. Myocardial Energy Substrate Metabolism in Heart Failure : from Pathways to Therapeutic Targets.

    PubMed

    Fukushima, Arata; Milner, Kenneth; Gupta, Abhishek; Lopaschuk, Gary D

    2015-01-01

    Despite recent advances in therapy, heart failure remains a major cause of mortality and morbidity and is a growing healthcare burden worldwide. Alterations in myocardial energy substrate metabolism are a hallmark of heart failure, and are associated with an energy deficit in the failing heart. Previous studies have shown that a metabolic shift from mitochondrial oxidative metabolism to glycolysis, as well as an uncoupling between glycolysis and glucose oxidation, plays a crucial role in the development of cardiac inefficiency and functional impairment in heart failure. Therefore, optimizing energy substrate utilization, particularly by increasing mitochondrial glucose oxidation, can be a potentially promising approach to decrease the severity of heart failure by improving mechanical cardiac efficiency. One approach to stimulating myocardial glucose oxidation is to inhibit fatty acid oxidation. This review will overview the physiological regulation of both myocardial fatty acid and glucose oxidation in the heart, and will discuss what alterations in myocardial energy substrate metabolism occur in the failing heart. Furthermore, lysine acetylation has been recently identified as a novel post-translational pathway by which mitochondrial enzymes involved in all aspects of cardiac energy metabolism can be regulated. Thus, we will also discuss the effect of acetylation of metabolic enzymes on myocardial energy substrate preference in the settings of heart failure. Finally, we will focus on pharmacological interventions that target enzymes involved in fatty acid uptake, fatty acid oxidation, transcriptional regulation of fatty acid oxidation, and glucose oxidation to treat heart failure. PMID:26166604

  16. Testosterone Replacement Modulates Cardiac Metabolic Remodeling after Myocardial Infarction by Upregulating PPARα

    PubMed Central

    Yang, Jing

    2016-01-01

    Despite the importance of testosterone as a metabolic hormone, its effects on myocardial metabolism in the ischemic heart remain unclear. Myocardial ischemia leads to metabolic remodeling, ultimately resulting in ATP deficiency and cardiac dysfunction. In the present study, the effects of testosterone replacement on the ischemic heart were assessed in a castrated rat myocardial infarction model established by ligating the left anterior descending coronary artery 2 weeks after castration. The results of real-time PCR and Western blot analyses showed that peroxisome proliferator-activated receptor α (PPARα) decreased in the ischemic myocardium of castrated rats, compared with the sham-castration group, and the mRNA expression of genes involved in fatty acid metabolism (the fatty acid translocase CD36, carnitine palmitoyltransferase I, and medium-chain acyl-CoA dehydrogenase) and glucose transporter-4 also decreased. A decline in ATP levels in the castrated rats was accompanied by increased cardiomyocyte apoptosis and fibrosis and impaired cardiac function, compared with the sham-castration group, and these detrimental effects were reversed by testosterone replacement. Taken together, our findings suggest that testosterone can modulate myocardial metabolic remodeling by upregulating PPARα after myocardial infarction, exerting a protective effect on cardiac function. PMID:27413362

  17. Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction.

    PubMed

    Barry, James S; Rozance, Paul J; Brown, Laura D; Anthony, Russell V; Thornburg, Kent L; Hay, William W

    2016-04-01

    Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128-132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P < 0.01), but insulin-stimulated LV myocardial blood flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r(2 )= 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P < 0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic-euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply

  18. Metabolic therapy at the crossroad: how to optimize myocardial substrate utilization?

    PubMed

    Kolwicz, Stephen C; Tian, Rong

    2009-08-01

    There has been growing interest in targeting myocardial substrate metabolism for the therapy of cardiovascular and metabolic diseases. This is largely based on the observation that cardiac metabolism undergoes significant changes during both physiologic and pathologic stresses. In search for an effective therapeutic strategy, recent studies have focused on the functional significance of the substrate switch in the heart during stress conditions, such as cardiac hypertrophy and failure, using both pharmacologic and genetic approaches. The results of these studies indicate that both the capacity and the flexibility of the cardiac metabolic network are essential for normal function; thus, their maintenance should be the primary goal for future metabolic therapy. PMID:20211436

  19. Metabolic Therapy at the Crossroad: How to optimize myocardial substrate utilization?

    PubMed Central

    Kolwicz, Stephen C.; Tian, Rong

    2010-01-01

    There has been growing interest in targeting myocardial substrate metabolism for the therapy of cardiovascular and metabolism diseases. This is largely based on the observation that cardiac metabolism undergoes significant changes during both physiological and pathological stresses. In search for an effective therapeutic strategy, recent studies have focused on the functional significance of the substrate switch in the heart during stress conditions, such as cardiac hypertrophy and failure, using both pharmacological and genetic approaches. The results of these studies indicate that both the capacity and the flexibility of the cardiac metabolic network are essential for normal function; thus, their maintenance should be the primary goal for future metabolic therapy. PMID:20211436

  20. Myocardial depression by ketamine. Haemodynamic and metabolic observations in animals.

    PubMed

    Chamberlain, J H; Seed, R G; Undre, N

    1981-04-01

    This study investigated the effect of ketamine on myocardial function. In dogs the drug was infused directly into the left main coronary artery. The concentration chosen was similar to the peak concentration found following a bolus intravenous injection. A mild depression of inotropic state was found which recovered completely after stopping the infusion. Myocardial depression was confirmed in a guinea pig Langendorff preparation. No changes in high energy phosphates were found in these hearts after 45-60 minutes of perfusion with ketamine in the perfusion medium. This study confirms that myocardial depression occurs with ketamine but suggests that it is unlikely to be of clinical significance. Depletion of high energy phosphates did not seem to be the cause of the depression. PMID:7246986

  1. [Effects of dichloroacetate in the ischemic heart. Analysis of hemodynamics, myocardial energy metabolism and myocardial pH].

    PubMed

    Mizushima, M

    1990-05-01

    The effects of dichloroacetate (DCA), which is known to have a beneficial effect on lactic acidosis, were examined on myocardial acidosis during coronary occlusion in dogs. Ischemia was induced by complete ligation of the left anterior descending coronary artery (LAD) of the open-chest dog heart. DCA 100 mg/kg or 200 mg/kg was administered intravenously 10 or 60 min prior to the occlusion of LAD. DCA did not change the LAD flow, decreased heart rate, increased both systolic and diastolic blood pressures transiently. LAD occlusion significantly increased the ST segment of the epicardial ECG in the saline-treated group. DCA administered prior to the LAD occlusion caused 50% decrease of the elevation in ST segment during ischemia. Ischemia accelerated anaerobic metabolism in the myocardium; the levels of glycogen, adenosine triphosphate (ATP) and creatine phosphate (CP) decreased, and lactate increased during ischemia. Calculated energy charge potential was decreased, and [( G6P] + [F6P])/[FDP] ratio was increased by ischemia. The decreased levels of glycogen, ATP, CP in DCA-treated group were similar to those in saline-treated group during 3 min ischemia. Pretreatment of DCA reduced the accumulation of myocardial lactate by ischemia. There were no differences in variables except myocardial lactate levels between DCA 100 mg/kg and 200 mg/kg. The myocardial lactate levels were lower in both nonischemic and ischemic dogs by DCA 200 mg/kg than DCA 100 mg/kg. DCA did not change either the ATP levels or energy charge potential during both ischemia and reperfusion. LAD occlusion caused a significant decrease of myocardial pH from 7.51 to 6.83 in saline-treated group, while it produced only a small decrease in DCA-treated group from 7.56 to 7.35.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2379912

  2. Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects

    SciTech Connect

    Brunken, R.; Schwaiger, M.; Grover-McKay, M.; Phelps, M.E.; Tillisch, J.; Schelbert, H.R.

    1987-09-01

    Positron emission tomography with /sup 13/N-ammonia and /sup 18/F-2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments with a stress thallium defect in 12 patients. Myocardial infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51 segments studied, 36 had a fixed thallium defect, 11 had a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with a fixed defect and 4 (36%) of the 11 segments with a partially reversible defect exhibited myocardial infarction on study with positron tomography. In contrast, residual myocardial glucose utilization was identified in the majority of segments with a fixed (58%) or a partially reversible (64%) thallium defect. All of the segments with a completely reversible defect appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did not distinguish segments with ischemia from infarction. Thus, positron emission tomography reveals evidence of persistent tissue metabolism in the majority of segments with a fixed or partially resolving stress thallium defect, implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.

  3. Circadian rhythms in myocardial metabolism and contractile function; influence of workload and oleate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple extra-cardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its ...

  4. A “PET” area of interest: myocardial metabolism in human systolic heart failure

    PubMed Central

    Kadkhodayan, Ana; Coggan, Andrew R.; Peterson, Linda R.

    2013-01-01

    Myocardial substrate metabolism provides the energy needed for cardiac contraction and relaxation. The normal adult heart uses predominantly fatty acids (FAs) as its primary fuel source. However, the heart can switch and use glucose (and to a lesser extent, ketones, lactate, as well as endogenous triglycerides and glycogen), depending on the metabolic milieu and superimposed conditions. FAs are not a wholly better fuel than glucose, but they do provide more energy per mole than glucose. Conversely, glucose is the more oxygen-efficient fuel. Studies in animal models of heart failure (HF) fairly consistently demonstrate a shift away from myocardial fatty acid metabolism and towards glucose metabolism. Studies in humans are less consistent. Some show the same metabolic switch away from FA metabolism but not all. This may be due to differences in the etiology of HF, sex-related differences, or other mitigating factors. For example, obesity, insulin resistance, and diabetes are all related to an increased risk of HF and may complicate or contribute to its development. However, these conditions are associated with increased FA metabolism. This review will discuss aspects of human heart metabolism in systolic dysfunction as measured by the noninvasive, quantitative method – positron emission tomography. Continued research in this area is vital if we are to ameliorate HF by manipulating heart metabolism with the aim of increasing energy production and/or efficiency. PMID:23180281

  5. Different effects of interventions suppressing free fatty acid metabolism on myocardial ischemia.

    PubMed

    Kahles, H; Hellige, G; Hunnemann, D H; Junggeburth, J; Kochsiek, K

    1984-06-01

    We studied the effects of different metabolic interventions, which stimulate oxidative myocardial carbohydrate metabolism, on ischemic stress during repeated coronary occlusions of three minutes in open-chest dog hearts. Increase of glucose concentration in plasma and decrease of peripheral lipolysis by glucose-insulin-potassium (n = 6) had no substantial beneficial effects on myocardial damage indicated by hemodynamic, electrocardiographic, and metabolic parameters. Infusion of lactate and pyruvate (10 mM, n = 6) was detrimental. Only activation of pyruvate dehydrogenase by dichloroacetate (n = 6) without influence on plasma osmolality reduced epicardial ST-segment elevations (-42%) and myocardial release of potassium (-36%), phosphate (-58%), and lactate (-39%). Elevations of plasma osmolalities by 10 and 20 mOsm with the metabolically inert mannitol increased ECG changes, functional loss and release of potassium, phosphate, and lactate during ischemia in our model. It is suggested, that the oxygen-saving potency of metabolic interventions can exert univocal beneficial effects in experimental and in clinical conditions only when systemic hyperosmolality and hypervolemia are avoided. PMID:6430618

  6. Pilot Study of Pioglitazone and Exercise Training Effects on Basal Myocardial Substrate Metabolism and Left Ventricular Function in HIV-Positive Individuals with Metabolic Complications

    PubMed Central

    Cade, W. Todd; Reeds, Dominic N.; Overton, E. Turner; Herrero, Pilar; Waggoner, Alan D.; Laciny, Erin; Bopp, Coco; Lassa-Claxton, Sherry; Gropler, Robert J.; Peterson, Linda R.; Yarasheski, Kevin E.

    2014-01-01

    Background Individuals with HIV infection and peripheral metabolic complications have impaired basal myocardial insulin sensitivity that is related to left ventricular (LV) diastolic dysfunction. It is unknown whether interventions shown to be effective in improving peripheral insulin sensitivity can improve basal myocardial insulin sensitivity and diastolic function in people with HIV and peripheral metabolic complications. Objective In a pilot study, we evaluated whether the peroxisome proliferator–activated receptor-gamma (PPAR-γ) agonist pioglitazone or combined endurance and resistance exercise training improves basal myocardial insulin sensitivity and diastolic function in HIV+ adults with peripheral metabolic complications. Design Twenty-four HIV+ adults with metabolic complications including peripheral insulin resistance were randomly assigned to 4 months of pioglitazone (PIO; 30 mg/d) or supervised, progressive endurance and resistance exercise training (EXS; 90–120 min/d, 3 d/wk). Basal myocardial substrate metabolism was quantified by radioisotope tracer methodology and positron emission tomography (PET) imaging, and LV function was measured by echocardiography. Results Twenty participants completed the study. Neither PIO nor EXS resulted in a detectable improvement in basal myocardial insulin sensitivity or diastolic function. Post hoc analyses revealed sample sizes of more than 100 participants are needed to detect significant effects of these interventions on basal myocardial insulin sensitivity and function. Conclusions PIO or EXS alone did not significantly increase basal myocardial insulin sensitivity or LV diastolic function in HIV+ individuals with peripheral metabolic complications. PMID:24334183

  7. The role of CD36 in the regulation of myocardial lipid metabolism.

    PubMed

    Kim, Ty T; Dyck, Jason R B

    2016-10-01

    Since the heart has one of the highest energy requirements of all organs in the body, it requires a constant and plentiful supply of fuel to function properly. Mitochondrial oxidation of lipids provides a major source of ATP for the heart, and the cellular processes that regulate lipid uptake and utilization are important contributors to maintaining proper myocardial energetic status. Although numerous proteins are coordinately regulated in order to ensure proper fatty acid utilization in the cardiomyocyte, a key first step in this process is the entry of fatty acids into the cell. An important protein involved in the transport of fatty acids into the cardiomyocyte is the plasma membrane-associated protein known as fatty acid translocase (FAT; also known as CD36). While multiple proteins are involved in facilitating fatty acid uptake in the heart, CD36 accounts for approximately 50-70% of the total fatty acid taken up in cardiomyocytes. As such, myocardial metabolism of fatty acids may depend upon proper CD36 function. Consistent with this, changes in CD36 levels/function have been implicated in the alteration of myocardial metabolism in the pathophysiology of certain cardiovascular diseases. As such, a better understanding of the role and function of CD36 in the heart may provide important insights for the development of new treatments for specific cardiovascular diseases. Herein, we review the role of CD36 in myocardial lipid metabolism in the healthy heart and describe how CD36-mediated alterations in lipid metabolism may contribute to cardiovascular disease. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26995462

  8. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy.

    PubMed

    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p < 0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p < 0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217. PMID:26798650

  9. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy

    PubMed Central

    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p < 0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p < 0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217. PMID:26798650

  10. In Vivo Metabolic Phenotyping of Myocardial Substrate Metabolism in Rodents: Differential Efficacy of Metformin and Rosiglitazone Monotherapy

    PubMed Central

    Shoghi, Kooresh I.; Finck, Brian N.; Schechtman, Kenneth B.; Sharp, Terry; Herrero, Pilar; Gropler, Robert J.; Welch, Michael J.

    2009-01-01

    Background Cardiovascular disease is the leading cause of death among diabetic patients with alterations in myocardial substrate metabolism being a likely contributor. We aimed to assess noninvasively the efficacy of Metformin and Rosiglitazone monotherapy in normalizing myocardial substrate metabolism in an animal model of type-2 diabetes mellitus. Methods and Results The study utilized 18 male ZDF rats (fa/fa) with 6 rats in each group: an untreated group; a group treated with Metformin (16.6mg/kg/day) and a group treated with Rosiglitazone (4mg/kg). Each rat was scanned at age 14 weeks (baseline) and subsequently at 19 weeks with small animal PET to estimate myocardial glucose utilization (MGU) and myocardial utilization (MFAU), oxidation (MFAO) and esterification (MFAE). Treatment lasted for 5 weeks following baseline imaging. At week 19, rats were sacrificed and hearts extracted for expression analysis of select genes encoding for GLUT transporters and fatty acid transport and oxidation genes. In addition, echocardiography (ECHO) measurements were obtained at week 13 and 18 to characterize cardiac function. Metformin had no significant effect on either MGU or MFAU and MFAO. In contrast, Rosiglitazone tended to enhance MGU and significantly reduced MFAU and MFAO. Rosiglitazone-induced increase in glucose uptake correlated significantly with increased expression of GLUT4 while diminished MFAO correlated significantly with decreased expression of FATP-1 and MCAD. Finally, changes in fractional shortening as a measure of cardiac function were unchanged throughout the study. Conclusions Treatment with Rosiglitazone enhanced glucose utilization and diminished MFAO, thus reversing the metabolic phenotype of the diabetic heart. PMID:19808625

  11. Dichloroacetate attenuates myocardial acidosis and metabolic changes induced by partial occlusion of the coronary artery in dogs.

    PubMed

    Sakai, K; Ichihara, K; Nasa, Y; Kamigaki, M; Abiko, Y

    1990-01-01

    The present study was undertaken to examine whether dichloroacetate, which inhibits pyruvate dehydrogenase kinase and, therefore, increases the activity of pyruvate dehydrogenase, attenuates myocardial acidosis and metabolic changes induced by coronary occlusion. In dogs anesthetized with pentobarbital, the left anterior descending coronary artery was incompletely occluded to reduce the left anterior descending flow to a half to one third of the original flow (partial occlusion) to produce myocardial (regional) ischemia. Partial occlusion was continued for 90 min, and a bolus injection of saline or dichloroacetate was made intravenously 30 min after the onset of occlusion. Partial occlusion decreased myocardial pH significantly. An injection of dichloroacetate (150 mg/kg) increased myocardial pH that had been lowered by partial occlusion. Myocardial metabolites were measured in other dogs. Partial occlusion decreased the myocardial levels of adenosine triphosphate, creatine phosphate and energy charge potential, and increased that of lactate significantly, without affecting the myocardial levels of pyruvate and nonesterified fatty acids. Dichloroacetate attenuated the ischemia-induced changes in the myocardial levels of adenosine triphosphate, creatine phosphate, energy charge potential and lactate. These results indicate that dichloroacetate attenuates the myocardial acidosis and metabolic changes during coronary partial occlusion. PMID:2095718

  12. Myocardial oxidative metabolism and protein synthesis during mechanical circulatory support by extracorporeal membrane oxygenation

    PubMed Central

    Priddy, Colleen M. O′Kelly; Kajimoto, Masaki; Ledee, Dolena R.; Bouchard, Bertrand; Isern, Nancy; Olson, Aaron K.; Rosiers, Christine Des

    2013-01-01

    Extracorporeal membrane oxygenation (ECMO) provides essential mechanical circulatory support necessary for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur, which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative metabolism and protein synthesis. We focused on the amino acid leucine and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart 1) the fractional contribution of leucine (FcLeucine) and pyruvate to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and 2) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 h of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (∼40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining 1) metabolic flexibility indicated by ability to respond to pyruvate and 2) a normal or increased capacity for global protein synthesis. PMID:23203964

  13. Myocardial metabolic, hemodynamic, and electrocardiographic significance of reversible thallium-201 abnormalities in hypertrophic cardiomyopathy

    SciTech Connect

    Cannon, R.O. 3d.; Dilsizian, V.; O'Gara, P.T.; Udelson, J.E.; Schenke, W.H.; Quyyumi, A.; Fananapazir, L.; Bonow, R.O. )

    1991-05-01

    Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. Fifty patients with hypertrophic cardiomyopathy underwent exercise {sup 201}Tl scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more {sup 201}Tl abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial {sup 201}Tl defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible {sup 201}Tl abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing compared with four of 13 patients (31%) with normal {sup 201}Tl scans (p less than 0.01). Eleven patients had apparent cavity dilatation as their only {sup 201}Tl abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal {sup 201}Tl studies (33 +/- 5 versus 21 +/- 10 mm Hg, p less than 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of {sup 201}Tl abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible {sup 201}Tl abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible {sup 201}Tl abnormalities, and 55% had pacing-induced ischemia. Reversible {sup 201}Tl abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium.

  14. [Modifications in myocardial energy metabolism in diabetic patients

    NASA Technical Reports Server (NTRS)

    Grynberg, A.

    2001-01-01

    The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell. Both the trigger and the regulation of cardiac contraction result from membrane activity, and the other major FA function in the myocardium is their role in membrane homeostasis, through the phospholipid synthesis and remodeling pathways. Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes. Experimental data suggest that the 2 metabolic pathways involved in membrane homeostasis may represent therapeutic targets for cytoprotection. The drugs that increase cardiac phospholipid turnover (trimetazidine, ranolazine,...) display anti-ischemic non hemodynamic effect. This effect is based on a redirection of FA utilization towards phospholipid synthesis, which decrease their availability for energy production. A nutritional approach gave also promising results. Besides its anti-arrhythmic effect, the dietary docosahexaenoic acid is able to reduce FA energy consumption and hence oxygen demand. The cardiac metabolic pathways involving FA should be considered as a whole, precariously balanced. The diabetic heart being characterised by

  15. Modeling to link regional myocardial work, metabolism and blood flows

    PubMed Central

    Bassingthwaighte, James B.; Beard, Daniel A; Carlson, Brian E.; Dash, Ranjan K.; Vinnakota, Kalyan

    2012-01-01

    Given the mono-functional, highly coordinated processes of cardiac excitation and contraction, the observations that regional myocardial blood flows, rMBF, are broadly heterogeneous has provoked much attention, but a clear explanation has not emerged. In isolated and in vivo heart studies the total coronary flow is found to be proportional to the rate-pressure product (systolic mean blood pressure times heart rate), a measure of external cardiac work. The same relationship might be expected on a local basis: more work requires more flow. The validity of this expectation has never been demonstrated experimentally. In this article we review the concepts linking cellular excitation and contractile work to cellular energetics and ATP demand, substrate utilization, oxygen demand, vasoregulation, and local blood flow. Mathematical models of these processes are now rather well developed. We propose that the construction of an integrated model encompassing the biophysics, biochemistry and physiology of cardiomyocyte contraction, then combined with a detailed three-dimensional structuring of the fiber bundle and sheet arrangements of the heart as a whole will frame an hypothesis that can be quantitatively evaluated to settle the prime issue: Does local work drive local flow in a predictable fashion that explains the heterogeneity? While in one sense one can feel content that work drives flow is irrefutable, there are no cardiac contractile models that demonstrate the required heterogeneity in local strain-stress-work; quite the contrary, cardiac contraction models have tended toward trying to show that work should be uniform. The object of this review is to argue that uniformity of work does not occur, and is impossible in any case, and that further experimentation and analysis are necessary to test the hypothesis. PMID:22915334

  16. Size of myocardial infarction induced by ischaemia/reperfusion is unaltered in rats with metabolic syndrome.

    PubMed

    Thim, Troels; Bentzon, Jacob F; Kristiansen, Steen B; Simonsen, Ulf; Andersen, Heidi L; Wassermann, Karsten; Falk, Erling

    2006-06-01

    Obesity is associated with metabolic syndrome and increased incidence of and mortality from myocardial infarction. The aim of the present study was to develop an animal model with metabolic syndrome and examine how that influences size of myocardial infarcts induced by occlusion and reperfusion of the left anterior descending coronary artery. Sprague-Dawley rats (n = 105) were fed either LF (low-fat) or MHF (moderately high-fat) diets for 13 weeks before coronary occlusion for 45 min, followed by reperfusion for 60 min. Compared with LF-fed and lean MHF-fed rats, obese MHF-fed rats developed metabolic disturbances similar to those seen in the metabolic syndrome, including being overweight by 24% (compared with lean MHF-fed rats), having 74% more visceral fat (compared with LF-fed rats), 15% higher blood pressure (compared with LF-fed rats), 116% higher plasma insulin (compared with lean MHF-fed rats), 10% higher fasting plasma glucose (compared with LF-fed rats), 35% higher non-fasting plasma glucose (compared with lean MHF-fed rats), 36% higher plasma leptin (compared with lean MHF-fed rats) and a tendency to lower plasma adiponectin and higher plasma non-esterified fatty acids. Infarct size was similar in the three groups of rats (36+/-14, 42+/-18 and 41+/-14% in obese MHF-fed, lean MHF-fed and LF-fed rats respectively). In conclusion, rats fed a MHF diet developed metabolic syndrome, but this did not influence myocardial infarct size. PMID:16448385

  17. Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

    SciTech Connect

    Priddy, MD, Colleen M.; Kajimoto, Masaki; Ledee, Dolena; Bouchard, Bertrand; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-02-01

    Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

  18. Myocardial Reloading After Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    PubMed Central

    Kajimoto, Masaki; O'Kelly Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Isern, Nancy; Olson, Aaron K.; Rosiers, Christine Des; Portman, Michael A.

    2013-01-01

    Background Extracorporeal membrane oxygenation (ECMO) unloads the heart, providing a bridge to recovery in children after myocardial stunning. ECMO also induces stress which can adversely affect the ability to reload or wean the heart from the circuit. Metabolic impairments induced by altered loading and/or stress conditions may impact weaning. However, cardiac substrate and amino acid requirements upon weaning are unknown. We assessed the hypothesis that ventricular reloading with ECMO modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Methods and Results Sixteen immature piglets (7.8 to 15.6 kg) were separated into 2 groups based on ventricular loading status: 8‐hour ECMO (UNLOAD) and postwean from ECMO (RELOAD). We infused into the coronary artery [2‐13C]‐pyruvate as an oxidative substrate and [13C6]‐L‐leucine as an indicator for amino acid oxidation and protein synthesis. Upon RELOAD, each functional parameter, which were decreased substantially by ECMO, recovered to near‐baseline level with the exclusion of minimum dP/dt. Accordingly, myocardial oxygen consumption was also increased, indicating that overall mitochondrial metabolism was reestablished. At the metabolic level, when compared to UNLOAD, RELOAD altered the contribution of various substrates/pathways to tissue pyruvate formation, favoring exogenous pyruvate versus glycolysis, and acetyl‐CoA formation, shifting away from pyruvate decarboxylation to endogenous substrate, presumably fatty acids. Furthermore, there was also a significant increase of tissue concentrations for all CAC intermediates (≈80%), suggesting enhanced anaplerosis, and of fractional protein synthesis rates (>70%). Conclusions RELOAD alters both cytosolic and mitochondrial energy substrate metabolism, while favoring leucine incorporation into protein synthesis rather than oxidation in the CAC. Improved understanding of factors governing these metabolic perturbations may

  19. Myocardial Reloading after Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    SciTech Connect

    Kajimoto, Masaki; Priddy, Colleen M.; Ledee, Dolena; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-08-19

    Extracorporeal membrane oxygenation (ECMO) unloads the heart providing a bridge to recovery in children after myocardial stunning. Mortality after ECMO remains high.Cardiac substrate and amino acid requirements upon weaning are unknown and may impact recovery. We assessed the hypothesis that ventricular reloading modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Fourteen immature piglets (7.8-15.6 kg) were separated into 2 groups based on ventricular loading status: 8 hour-ECMO (UNLOAD) and post-wean from ECMO (RELOAD). We infused [2-13C]-pyruvate as an oxidative substrate and [13C6]-L-leucine, as a tracer of amino acid oxidation and protein synthesis into the coronary artery. RELOAD showed marked elevations in myocardial oxygen consumption above baseline and UNLOAD. Pyruvate uptake was markedly increased though RELOAD decreased pyruvate contribution to oxidative CAC metabolism.RELOAD also increased absolute concentrations of all CAC intermediates, while maintaining or increasing 13C-molar percent enrichment. RELOAD also significantly increased cardiac fractional protein synthesis rates by >70% over UNLOAD. Conclusions: RELOAD produced high energy metabolic requirement and rebound protein synthesis. Relative pyruvate decarboxylation decreased with RELOAD while promoting anaplerotic pyruvate carboxylation and amino acid incorporation into protein rather than to the CAC for oxidation. These perturbations may serve as therapeutic targets to improve contractile function after ECMO.

  20. Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy.

    PubMed

    Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B

    2016-02-01

    Regional myocardial blood flows are markedly heterogeneous. Fractal analysis shows strong near-neighbor correlation. In experiments to distinguish control by vascular anatomy vs. local vasomotion, coronary flows were increased in open-chest dogs by stimulating myocardial metabolism (catecholamines + atropine) with and without adenosine. During control states mean left ventricular (LV) myocardial blood flows (microspheres) were 0.5-1 ml·g(-1)·min(-1) and increased to 2-3 ml·g(-1)·min(-1) with catecholamine infusion and to ∼4 ml·g(-1)·min(-1) with adenosine (Ado). Flow heterogeneity was similar in all states: relative dispersion (RD = SD/mean) was ∼25%, using LV pieces 0.1-0.2% of total. During catecholamine infusion local flows increased in proportion to the mean flows in 45% of the LV, "tracking" closely (increased proportionately to mean flow), while ∼40% trended toward the mean. Near-neighbor regional flows remained strongly spatially correlated, with fractal dimension D near 1.2 (Hurst coefficient 0.8). The spatial patterns remain similar at varied levels of metabolic stimulation inferring metabolic dominance. In contrast, adenosine vasodilation increased flows eightfold times control while destroying correlation with the control state. The Ado-induced spatial patterns differed from control but were self-consistent, inferring that with full vasodilation the relaxed arterial anatomy dominates the distribution. We conclude that vascular anatomy governs flow distributions during adenosine vasodilation but that metabolic vasoregulation dominates in normal physiological states. PMID:26589329

  1. Deoxyglucose method for the estimation of local myocardial glucose metabolism with positron computed tomography

    SciTech Connect

    Ratib, O.; Phelps, M.E.; Huang, S.C.; Henze, E.; Selin, C.E.; Schelbert, H.R.

    1981-01-01

    The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to studies of the heart with positron computed tomography (PCT) and FDG. Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by direct arterial-venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was elevated 5 times the control value or when metabolism was reduced to 10% of normal and MBF increased 5 times normal. Improvements in PCT resolution are required to improve the accuracy of the estimates of the rate constants and the MMRGlc.

  2. Deranged sodium to sudden death

    PubMed Central

    Clancy, Colleen E; Chen-Izu, Ye; Bers, Donald M; Belardinelli, Luiz; Boyden, Penelope A; Csernoch, Laszlo; Despa, Sanda; Fermini, Bernard; Hool, Livia C; Izu, Leighton; Kass, Robert S; Lederer, W Jonathan; Louch, William E; Maack, Christoph; Matiazzi, Alicia; Qu, Zhilin; Rajamani, Sridharan; Rippinger, Crystal M; Sejersted, Ole M; O'Rourke, Brian; Weiss, James N; Varró, András; Zaza, Antonio

    2015-01-01

    In February 2014, a group of scientists convened as part of the University of California Davis Cardiovascular Symposium to bring together experimental and mathematical modelling perspectives and discuss points of consensus and controversy on the topic of sodium in the heart. This paper summarizes the topics of presentation and discussion from the symposium, with a focus on the role of aberrant sodium channels and abnormal sodium homeostasis in cardiac arrhythmias and pharmacotherapy from the subcellular scale to the whole heart. Two following papers focus on Na+ channel structure, function and regulation, and Na+/Ca2+ exchange and Na+/K+ ATPase. The UC Davis Cardiovascular Symposium is a biannual event that aims to bring together leading experts in subfields of cardiovascular biomedicine to focus on topics of importance to the field. The focus on Na+ in the 2014 symposium stemmed from the multitude of recent studies that point to the importance of maintaining Na+ homeostasis in the heart, as disruption of homeostatic processes are increasingly identified in cardiac disease states. Understanding how disruption in cardiac Na+-based processes leads to derangement in multiple cardiac components at the level of the cell and to then connect these perturbations to emergent behaviour in the heart to cause disease is a critical area of research. The ubiquity of disruption of Na+ channels and Na+ homeostasis in cardiac disorders of excitability and mechanics emphasizes the importance of a fundamental understanding of the associated mechanisms and disease processes to ultimately reveal new targets for human therapy. PMID:25772289

  3. Myocardial metabolism of pantothenic acid in chronically diabetic rats.

    PubMed

    Beinlich, C J; Naumovitz, R D; Song, W O; Neely, J R

    1990-03-01

    Transport and metabolism of [3H]pantothenic acid ([3H]Pa) was investigated in hearts from control and streptozotocin-induced diabetic rats. In isolated perfused hearts from control animals, the transport of [3H]Pa was linear over 3 h of perfusion when 11 mM glucose was the only exogenous substrate. The in vitro transport of [3H]Pa by hearts from 48-h diabetic rats was reduced by 65% compared to controls and was linear over 2 h of perfusion with no further accumulation of Pa during the third hour. The defect in transport observed in vitro could be corrected by in vivo treatment with 4 U Lente insulin/day for 2 days. In vitro addition of insulin in the presence of 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate had no effect on [3H]Pa transport in hearts from 48-h diabetic rats during 3 h of perfusion. Accumulation of [3H]Pa was not inhibited by inclusion of 0.7 mM amino acids, 1 mM carnitine, 50 microM mersalic acid or 1 mM panthenol, pantoyllactone or pantoyltaurine. Uptake was inhibited by 1 mM nonanoic, octanoic or heptanoic acid, 0.1 mM biotin or 0.25 mM probenecid, suggesting a requirement for the terminal carboxyl group for transport. Transport of pantothenic acid was reduced in hearts from diabetic rats within 24 h of injection of streptozotocin. In vitro accumulation of [3H]Pa decreased to 10% of control 1 week after streptozotocin injection and then remained at 30% of the control value over 10 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141362

  4. Alterations in myocardial energy metabolism induced by the anti-cancer drug doxorubicin.

    PubMed

    Tokarska-Schlattner, Malgorzata; Wallimann, Theo; Schlattner, Uwe

    2006-09-01

    Doxorubicin and other anthracyclines are among the most potent chemotherapeutic drugs for the treatment of acute leukaemia, lymphomas and different types of solid tumours such as breast, liver and lung cancers. Their clinical use is, however, limited by the risk of severe cardiotoxicity, which can lead to irreversible congestive heart failure. There is increasing evidence that essential components of myocardial energy metabolism are among the highly sensitive and early targets of doxorubicin-induced damage. Here we review doxorubicin-induced detrimental changes in cardiac energetics, with an emphasis on the emerging importance of defects in energy-transferring and -signalling systems, like creatine kinase and AMP-activated protein kinase. PMID:16945832

  5. Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following hypothermic cardioplegia.

    PubMed

    Bomfim, V; Kaijser, L; Bendz, R; Sylvén, C; Olin, C

    1980-01-01

    Cardiac metabolism following hypothermic potassium cardioplegia was studied in 23 patients undergoing isolated aortic valve replacement. All had normal coronary arteries. Cardioplegia was induced by infusing 700-1 000 ml of cold Ringer's acetate containing 20 mekv K+ selectively into the left coronary artery. Simultaneous blood samples were taken from the radial artery, a central vein and from the coronary sinus before and after cardioplegia. The PO2, O2-saturation and content, PCO2, pH, lactate, glucose, potassium, myoglobin, total creatine kinase (CK), its isoenzyme CK-MB, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were assessed. Before bypass lactate was extracted by the heart. During the initial 10 to 20 min after cardioplegia there was a marked release of lactate in the coronary sinus. Myoglobin concentration and CK-MB serum activity peaked during the first 4 hours after the release of the aortic cross-clamping. In order to determine the best indicator of myocardial damage after cardioplegia, duration of extracorporeal circulation (ECC-time), aortic occlusion time (AOT), mean myocardial temperature (MMT) and the product of AOT and MMT, referred to as time-temperature area (TTA), were related to possible indicators of myocardial injury, such as enzyme and myoglobin release. The TTA was the best way of expressing the degree of exposure of the heart to ischaemia. The CK-MB to peak area (CK-MB max area) was the best indicator of the degree of ischaemic injury sustained by the heart during operation. PMID:7375890

  6. Adaptation of myocardial blood flow to increased metabolic demand is not dependent on endothelial vasodilators in the rat heart.

    PubMed Central

    Tiefenbacher, C. P.; Tillmanns, H.; Niroomand, F.; Zimmermann, R.; Kübler, W.

    1997-01-01

    OBJECTIVE: To investigate the role of endothelial vasodilating factors in adaptation of myocardial blood flow to increased metabolic demands. DESIGN: Alterations in the effects of endothelium dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators and the beta 1 receptor agonist dobutamine were studied after inhibition of endothelium derived relaxing factor (EDRF) with L-NG-nitro-arginine methyl ester (L-NAME), prostanoid synthesis with indomethacin, and ATP sensitive potassium channels with glibenclamide. EXPERIMENTAL ANIMALS: Female Wistar rats, in situ perfused heart. MAIN OUTCOME MEASURES: Myocardial blood flow (H2 clearance); systolic fractional thickening (pulsed Doppler); mean arterial blood pressure. RESULTS: L-NAME reduced myocardial blood flow by 58 (12)% (mean (SD), P < 0.001) and systolic thickening fraction (FT) by 36 (9)% (P < 0.05). These effects were significantly reversed by administration of L-arginine but not D-arginine. Pretreatment with L-NAME inhibited the increase in myocardial blood flow caused by acetylcholine (control: +42 (9)%; L-NAME: -29 (7)%, P < 0.001) but did not affect the increase in myocardial blood flow caused by sodium nitroprusside (control: +44 (5)%; L-NAME: +34 (10)%, NS). Pretreatment with L-NAME did not change the effect of dobutamine on myocardial blood flow (+61 (3)%) and FT (+32 (8)%) compared with baseline values (P < 0.001). Neither pretreatment with indomethacin nor with glibenclamide reduced the dobutamine induced increase in myocardial blood flow. CONCLUSIONS: Inhibition of EDRF, prostanoid synthesis, and ATP sensitive potassium channels did not reduce the vasodilator reserve during increased metabolic demands induced by beta 1 adrenergic stimulation. Therefore, adaptation of myocardial blood flow to increased metabolic demands is independent of endothelial relaxing factors in the rat heart. PMID:9068398

  7. Exercise and nutrition in myocardial matrix metabolism, remodeling, regeneration, epigenetics, microcirculation, and muscle.

    PubMed

    Tyagi, Suresh C; Joshua, Irving G

    2014-07-01

    Remodeling and myocardial matrix metabolism contributes to cardiac endothelium-myocyte (perivascular fibrosis), myocyte-myocyte (interstitial fibrosis), and mitochondrion-myocyte (fusion and fission) coupling. Matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases (TIMPs) play differential roles in different tissues and diseases. For example, although present in the heart, MMP-3 is known as stromelysin (i.e., stromal tissue enzyme). Interestingly, TIMP-3 causes apoptosis. Exercise and nutrition are synergistic in the mitigation of diseases: exercise releases exosomes containing miRNAs. Nutrition/vitamins B6 and B12 regulate the metabolism of homocysteine (an epigenetic byproduct of DNA/RNA/protein methylation). Thus, epigenetic silencing is an important therapeutic target. The statistical analysis of cohorts may be less indicative for the treatment of a disease, particularly if the 2 twins are different in terms of responding to the medicine for the same disease, therefore, personalized medicine is the future of therapy. PMID:24959992

  8. Targeting myocardial substrate metabolism in heart failure: potential for new therapies

    PubMed Central

    Ardehali, Hossein; Sabbah, Hani N.; Burke, Michael A.; Sarma, Satyam; Liu, Peter P.; Cleland, John G.F.; Maggioni, Aldo; Fonarow, Gregg C.; Abel, E. Dale; Campia, Umberto; Gheorghiade, Mihai

    2012-01-01

    The incidence and prevalence of heart failure have increased significantly over the past few decades. Available data suggest that patients with heart failure independent of the aetiology have viable but dysfunctional myocardium that is potentially salvageable. Although a great deal of research effort has focused on characterizing the molecular basis of heart failure, cardiac metabolism in this disorder remains an understudied discipline. It is known that many aspects of cardiomyocyte energetics are altered in heart failure. These include a shift from fatty acid to glucose as a preferred substrate and a decline in the levels of ATP. Despite these demonstrated changes, there are currently no approved drugs that target metabolic enzymes or proteins in heart failure. This is partly due to our limited knowledge of the mechanisms and pathways that regulate cardiac metabolism. Better characterization of these pathways may potentially lead to new therapies for heart failure. Targeting myocardial energetics in the viable and potentially salvageable tissue may be particularly effective in the treatment of heart failure. Here, we will review metabolic changes that occur in fatty acid and glucose metabolism and AMP-activated kinase in heart failure. We propose that cardiac energetics should be considered as a potential target for therapy in heart failure and more research should be done in this area. PMID:22253453

  9. Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation

    PubMed Central

    Crawford, Peter A.; Crowley, Jan R.; Sambandam, Nandakumar; Muegge, Brian D.; Costello, Elizabeth K.; Hamady, Micah; Knight, Rob; Gordon, Jeffrey I.

    2009-01-01

    Studies in mice indicate that the gut microbiota promotes energy harvest and storage from components of the diet when these components are plentiful. Here we examine how the microbiota shapes host metabolic and physiologic adaptations to periods of nutrient deprivation. Germ-free (GF) mice and mice who had received a gut microbiota transplant from conventionally raised donors were compared in the fed and fasted states by using functional genomic, biochemical, and physiologic assays. A 24-h fast produces a marked change in gut microbial ecology. Short-chain fatty acids generated from microbial fermentation of available glycans are maintained at higher levels compared with GF controls. During fasting, a microbiota-dependent, Pparα-regulated increase in hepatic ketogenesis occurs, and myocardial metabolism is directed to ketone body utilization. Analyses of heart rate, hydraulic work, and output, mitochondrial morphology, number, and respiration, plus ketone body, fatty acid, and glucose oxidation in isolated perfused working hearts from GF and colonized animals (combined with in vivo assessments of myocardial physiology) revealed that the fasted GF heart is able to sustain its performance by increasing glucose utilization, but heart weight, measured echocardiographically or as wet mass and normalized to tibial length or lean body weight, is significantly reduced in both fasted and fed mice. This myocardial-mass phenotype is completely reversed in GF mice by consumption of a ketogenic diet. Together, these results illustrate benefits provided by the gut microbiota during periods of nutrient deprivation, and emphasize the importance of further exploring the relationship between gut microbes and cardiovascular health. PMID:19549860

  10. The haemodynamic and metabolic effects of tolmesoxide with special reference to impaired myocardial function.

    PubMed Central

    Mackenzie, J. E.; Marshall, R. J.; Parratt, J. R.

    1986-01-01

    The haemodynamic, metabolic and regional blood flow effects of the vasodilator, tolmesoxide (1 mg kg-1 min-1 for 20 min by intravenous infusion) were examined in two groups of greyhound dogs anaesthetized with alpha-chloralose and mechanically ventilated. One group of dogs was thoracotomized and subjected to acute coronary artery occlusion. In these dogs tolmesoxide was infused 2.5 h after occlusion when there was evidence of impaired myocardial function. Tolmesoxide administration resulted in marked systemic hypotension which was associated with myocardial stimulation (increase in heart rate and LVdP/dtmax). These effects were less marked in thoracotomized dogs subjected to coronary artery occlusion. Cardiac stimulation was attenuated by pretreatment with the beta-adrenoceptor antagonist, atenolol. Peripheral resistance and left ventricular end-diastolic pressure (LVEDP) were reduced by tolmesoxide. In spite of the systemic hypotension, the marked reduction in LVEDP resulted in an enhanced subendocardial driving pressure and an increased blood flow to ischaemic regions of the left ventricular wall as measured with Xe133 clearance. Blood flow to normal regions of the left ventricular wall was also increased by tolmesoxide. A metabolic and respiratory acidosis may have contributed to the haemodynamic effects of tolmesoxide. Plasma renin levels were significantly elevated by the drug. Tolmesoxide administration thus resulted in cardiac stimulation, reduced both pre-load and after-load, yet maintained coronary and pulmonary perfusion. This haemodynamic profile of tolmesoxide would explain the beneficial effects obtained with this drug in the treatment of cardiac failure. PMID:3779213

  11. Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis

    PubMed Central

    2011-01-01

    Background In the general population, peripheral metabolic complications (MC) increase the risk for left ventricular dysfunction. Human immunodeficiency virus infection (HIV) and combination anti-retroviral therapy (cART) are associated with MC, left ventricular dysfunction, and a higher incidence of cardiovascular events than the general population. We examined whether myocardial nutrient metabolism and left ventricular dysfunction are related to one another and worse in HIV infected men treated with cART vs. HIV-negative men with or without MC. Methods Prospective, cross-sectional study of myocardial glucose and fatty acid metabolism and left ventricular function in HIV+ and HIV-negative men with and without MC. Myocardial glucose utilization (GLUT), and fatty acid oxidation and utilization rates were quantified using 11C-glucose and 11C-palmitate and myocardial positron emission tomography (PET) imaging in four groups of men: 23 HIV+ men with MC+ (HIV+/MC+, 42 ± 6 yrs), 15 HIV+ men without MC (HIV+/MC-, 41 ± 6 yrs), 9 HIV-negative men with MC (HIV-/MC+, 33 ± 5 yrs), and 22 HIV-negative men without MC (HIV-/MC-, 25 ± 6 yrs). Left ventricular function parameters were quantified using echocardiography. Results Myocardial glucose utilization was similar among groups, however when normalized to fasting plasma insulin concentration (GLUT/INS) was lower (p < 0.01) in men with metabolic complications (HIV+: 9.2 ± 6.2 vs. HIV-: 10.4 ± 8.1 nmol/g/min/μU/mL) than men without metabolic complications (HIV+: 45.0 ± 33.3 vs. HIV-: 60.3 ± 53.0 nmol/g/min/μU/mL). Lower GLUT/INS was associated with lower myocardial relaxation velocity during early diastole (r = 0.39, p < 0.001). Conclusion Men with metabolic complications, irrespective of HIV infection, had lower basal myocardial glucose utilization rates per unit insulin that were related to left ventricular diastolic impairments, indicating that well-controlled HIV infection is not an independent risk factor for

  12. Normalizing the metabolic phenotype after myocardial infarction; impact of subchronic high fat feeding

    PubMed Central

    Berthiaume, Jessica M.; Young, Martin E.; Chen, Xiaoqin; McElfresh, Tracy A.; Yu, Xin; Chandler, Margaret P.

    2012-01-01

    The normal heart relies primarily on the oxidation of fatty acids (FA) for ATP production, whereas during heart failure (HF) glucose utilization increases, implying pathological changes to cardiac energy metabolism. Despite the noted lipotoxic effects of elevating FA, our work has demonstrated a cardioprotective effect of a high fat diet (SAT) when fed after myocardial infarction (MI), as compared to normal chow (NC) fed cohorts. This data has suggested a mechanistic link to energy metabolism. The goal of this study was to determine the impact of SAT on the metabolic phenotype of the heart after MI. Male Wistar rats underwent coronary ligation surgery (MI) and were evaluated after 8 weeks of SAT. Induction of MI was verified by echocardiography. LV function assessed by in vivo hemodynamic measurements revealed improvements in the MI-SAT group as compared to MI-NC. Perfused working hearts revealed a decrease in cardiac work in MI-NC that was improved in MI-SAT. Glucose oxidation was increased and FA oxidation decreased in MINC compared to shams suggesting an alteration in the metabolic profile that was ameliorated by SAT. 31P NMR analysis of Langendorff perfused hearts revealed no differences in PCr:ATP indicating no overt energy deficit in MI groups. Phospho-PDH and PDK4 were increased in MI-SAT, consistent with a shift towards fatty acid oxidation (FAO). Overall, these results support the hypothesis that SAT post-infarction promotes a normal metabolic phenotype that may serve a cardioprotective role in the injured heart. PMID:22542451

  13. Control of intraoperative hypertension with isoflurane in patients with coronary artery disease: effects on regional myocardial blood flow and metabolism.

    PubMed

    Sahlman, L; Milocco, I; Appelgren, L; William-Olsson, G; Ricksten, S E

    1989-02-01

    The effect of isoflurane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anesthesia, to control intraoperative hypertension was investigated. Twenty-two patients with two- or three-vessel coronary artery disease with an ejection fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary hemodynamics, and regional (great cardiac vein, GCVF) myocardial blood flow and myocardial metabolic parameters were measured. In 10 patients, both GCVF and global (coronary sinus, CSF) myocardial blood flows were recorded. Measurements were made 1) after induction of anesthesia but prior to skin incision, 2) during sternotomy, and 3) during isoflurane administration after its use to reduce arterial pressure to the presternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance accompanied by increases in heart rate, pulmonary capillary wedge pressure, (PCWP) regional myocardial oxygen consumption and extraction, GCVF and total coronary vascular resistance. Isoflurane reduced systemic arterial pressure but not PCWP, to presternotomy levels within 6.9 +/- 0.7 minutes at an end-tidal concentration of 1.5 +/- 0.2%. Isoflurane induced a pronounced systemic and coronary vasodilatation and increases in cardiac index, heart rate and regional myocardial oxygen extraction while the GCVF/CSF ratio remained unchanged. While mean regional--MLE% values were not effected by sternotomy, in two patients myocardial lactate production was seen during sternotomy but not during isoflurane. In another two patients, isoflurane induced lactate production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2783640

  14. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.

    PubMed

    Peliciari-Garcia, Rodrigo A; Goel, Mehak; Aristorenas, Jonathan A; Shah, Krishna; He, Lan; Yang, Qinglin; Shalev, Anath; Bailey, Shannon M; Prabhu, Sumanth D; Chatham, John C; Gamble, Karen L; Young, Martin E

    2016-10-01

    A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26721420

  15. Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

    PubMed Central

    Neubauer, S; Horn, M; Naumann, A; Tian, R; Hu, K; Laser, M; Friedrich, J; Gaudron, P; Schnackerz, K; Ingwall, J S

    1995-01-01

    The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress. PMID:7883957

  16. Analysis of respiratory water--a new method for evaluation of myocardial energy metabolism.

    PubMed

    Schwanke, U; Strauss, H; Arnold, G; Schipke, J D

    1996-11-01

    Aerobic ATP synthesis via oxidative phosphorylation causes a proportional production of respiratory water. Thus the amount of respiratory water produced at a given time should be a reliable measure of the current ATP demand of the mammalian myocardium. Respiratory water from isolated rabbit hearts was labeled by using the stable oxygen isotope 18O. The hearts were perfused according to the method of Langendorff (O. Langendorff. Pfluegers Arch. 61: 291-332, 1895) with 18O2-equilibrated Krebs-Henseleit solution. Control hearts were exclusively perfused with carbogen-equilibrated Krebs-Henseleit solution. Myocardial tissue was then lyophilized; the extracted water and samples from the coronary venous effluent were converted to CO2 by using the guanidine hydrochloride technique. The delta 18O values within the CO2 samples were determined by mass spectrometry and related to the standard mean ocean water (SMOW) scale. Compared with control hearts, the 18O-labeled hearts exhibited a significant increase of delta 18O values from tissue water (-47.50 +/- 0.64 vs. -40.35 +/- 2.05% SMOW; P < 0.05). The values were also significantly increased in the coronary venous effluent after a perfusion time of only 50 s (-47.50 +/- 0.64 vs. -43.66 +/- 0.91% SMOW; P < 0.05). Thus this first adaptation of the guanidine hydrochloride technique on microliter samples of myocardial tissue water and coronary venous effluent demonstrates that this method can be used to evaluate both respiratory activity and the kinetics of cardiac metabolic processes. PMID:8941536

  17. Myocardial ischemic-reperfusion injury in a rat model of metabolic syndrome.

    PubMed

    Mozaffari, Mahmood S; Schaffer, Stephen W

    2008-10-01

    Hearts of NaCl-induced hypertensive-glucose intolerant (HGI) rats develop reduced infarcts after ischemia-reperfusion injury (IRI) than their hypertensive (H) counterparts. Because high intake of saturated fat is a major risk factor for ischemic heart disease, we tested the hypothesis that chronic (18 weeks) consumption of a high saturated fat diet increases susceptibility to IRI, an effect more marked in the HGI rats than in the H rats. The fat-fed H (HFAT) rat displayed significantly higher body weight and plasma leptin content compared to the H, HGI, or fat-fed HGI (HGIFAT) rats which all showed similar values. In contrast, plasma triglyceride concentration was significantly higher in the HGIFAT rat than in the other three groups. Plasma insulin concentration was similar in the two H groups but higher than that of the two HGI groups. Compared to the H rat, the HGI rat was markedly glucose intolerant, with fat feeding causing comparable worsening of glucose intolerance in each group. The HGIFAT rats displayed a reduction in baseline myocardial contractility and relaxation and a higher end-diastolic pressure compared to the other three groups. Infarct size was significantly lower in the HGI rats than in the H rats. Although fat feeding did not affect infarct size of the H rat, it worsened that of the HGIFAT rat thereby abrogating the differential that existed between the H and HGI rats. In conclusion, excess fat feeding impairs myocardial function of HGI rats and increases their susceptibility to IRI. These findings are of relevance to the metabolic syndrome that manifests as a cluster of insulin resistance, dyslipidemia, and systemic hypertension. PMID:18719642

  18. Influence of beta-blockers on the myocardial mRNA expressions of circadian clock- and metabolism-related genes.

    PubMed

    Ushijima, Kentarou; Maekawa, Tomohiro; Ishikawa-Kobayashi, Eiko; Ando, Hitoshi; Shiga, Tsuyoshi; Fujimura, Akio

    2013-01-01

    Daily rhythms are regulated by a master clock-system in the suprachiasmatic nucleus and by a peripheral clock-system in each organ. Because norepinephrine is one of the timekeepers for the myocardial circadian clock that influences cardiac metabolism, it is speculated that a beta-blocker may affect the circadian clock and metabolism in heart tissue. In this study, thirty mg/kg/day of propranolol (a lipophilic beta-blocker) or atenolol (a hydrophilic beta-blocker) was given orally to Wistar rats for 4 weeks. The mRNA expressions of Bmal1 and E4BP4 in heart tissue were suppressed by the beta-blockers. However, the mRNA expressions of these clock genes in the suprachiasmatic nucleus were unchanged. Myocardial mRNA expressions of lactate dehydrogenase a and pyruvate dehydrogenase kinase 4 were also suppressed by the beta-blockers. In addition, ATP content in heart tissue was significantly elevated by the beta-blockers throughout 24 hours. The effects of propranolol and atenolol did not differ significantly. This study showed for the first time that a beta-blocker affects myocardial clock gene expression. Propranolol and atenolol increased ATP content in heart tissue throughout 24 hours. The influences of beta-blockers may be negligible on the SCN, and may be independent of lipid solubility on heart tissue. It is well known that these drugs exert a protective effect against myocardial ischemia, which may be mediated by an increase in the preservation of myocardial ATP. PMID:23394803

  19. Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease

    PubMed Central

    Bradley, Jessica M.; Islam, Kazi N.; Polhemus, David J.; Donnarumma, Erminia; Brewster, Luke P.; Tao, Ya-Xiong; Goodchild, Traci T.

    2015-01-01

    Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg·kg−1·day−1 bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation. PMID:25957218

  20. O-GlcNAcylation, Novel Post-Translational Modification Linking Myocardial Metabolism and Cardiomyocyte Circadian Clock*

    PubMed Central

    Durgan, David J.; Pat, Betty M.; Laczy, Boglarka; Bradley, Jerry A.; Tsai, Ju-Yun; Grenett, Maximiliano H.; Ratcliffe, William F.; Brewer, Rachel A.; Nagendran, Jeevan; Villegas-Montoya, Carolina; Zou, Chenhang; Zou, Luyun; Johnson, Russell L.; Dyck, Jason R. B.; Bray, Molly S.; Gamble, Karen L.; Chatham, John C.; Young, Martin E.

    2011-01-01

    The cardiomyocyte circadian clock directly regulates multiple myocardial functions in a time-of-day-dependent manner, including gene expression, metabolism, contractility, and ischemic tolerance. These same biological processes are also directly influenced by modification of proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc). Because the circadian clock and protein O-GlcNAcylation have common regulatory roles in the heart, we hypothesized that a relationship exists between the two. We report that total cardiac protein O-GlcNAc levels exhibit a diurnal variation in mouse hearts, peaking during the active/awake phase. Genetic ablation of the circadian clock specifically in cardiomyocytes in vivo abolishes diurnal variations in cardiac O-GlcNAc levels. These time-of-day-dependent variations appear to be mediated by clock-dependent regulation of O-GlcNAc transferase and O-GlcNAcase protein levels, glucose metabolism/uptake, and glutamine synthesis in an NAD-independent manner. We also identify the clock component Bmal1 as an O-GlcNAc-modified protein. Increasing protein O-GlcNAcylation (through pharmacological inhibition of O-GlcNAcase) results in diminished Per2 protein levels, time-of-day-dependent induction of bmal1 gene expression, and phase advances in the suprachiasmatic nucleus clock. Collectively, these data suggest that the cardiomyocyte circadian clock increases protein O-GlcNAcylation in the heart during the active/awake phase through coordinated regulation of the hexosamine biosynthetic pathway and that protein O-GlcNAcylation in turn influences the timing of the circadian clock. PMID:22069332

  1. Influence of revascularization on myocardial perfusion, metabolism and function evaluated with I-123-IPPA

    SciTech Connect

    Kropp, J.; Krois, M.; Eichhorn, B.; Feske, W.; Likungu, J.; Kirchhoff, P.J.; Luederitz, B.; Biersack, H.J.; Knapp, F.F. Jr.

    1993-10-01

    Patients with coronary artery disease (CAD) were investigated with sequential SPECT-scintigraphy after administration of 200 MBq of 15-(p-[I-123]iodophenyl)pentadecanoic acid (IPPA) at peak submaximal exercise. Twenty patients underwent coronary angioplasty (PTCA) from which 14 had control coronary arteriography (CA) and left ventricular cineventriculography (LVCV). Nineteen pts underwent bypass graft surgery (ACB) and stress sonagraphy. Semi-quantification of uptake (Up related to perfusion) and turnover (Tr) was obtained by segmental comparison of oblique slices. About 90% of the reperfused myocardial segments in the PTCA-group and 76% in the ACB-group showed an improvement of uptake after therapy (RUp). Of these, 50% and 66% exhibited increased turnover (RTr) after PTCA or ACB. Pathologic RTr was highly correlated with regional wall motion abnormalities after therapy in both groups. In the ACB-group presence of improvement of RTr was correlated with improved RWM at rest and stress. IPPA-studies show potential to provide information about changes of perfusion and metabolism after reperfusion and IPPA-turnover is a good predictor of the pattern of contractile function.

  2. Heart Failure and Loss of Metabolic Control

    PubMed Central

    Wang, Zhao V.; Li, Dan L.; Hill, Joseph A.

    2014-01-01

    Heart failure is a leading cause of morbidity and mortality worldwide, currently affecting 5 million Americans. A syndrome defined on clinical terms, heart failure is the end-result of events occurring in multiple heart diseases, including hypertension, myocardial infarction, genetic mutations and diabetes, and metabolic dysregulation is a hallmark feature. Mounting evidence from clinical and preclinical studies suggests strongly that fatty acid uptake and oxidation are adversely affected, especially in end-stage heart failure. Moreover, metabolic flexibility, the heart’s ability to move freely among diverse energy substrates, is impaired in heart failure. Indeed, impairment of the heart’s ability to adapt to its metabolic milieu, and associated metabolic derangement, are important contributing factors in heart failure pathogenesis. Elucidation of molecular mechanisms governing metabolic control in heart failure will provide critical insights into disease initiation and progression, raising the prospect of advances with clinical relevance. PMID:24336014

  3. Comparison between myocardial infarction and diabetes mellitus damage caused angiogenesis or energy metabolism.

    PubMed

    Li, Chao; Lu, Chengzhi; Zhao, Xiangdong; Chen, Xin

    2015-01-01

    This study aims to compare and analyze lactate dehydrogenase (LDH), succinic dehydrogenase (SDH) and differences in capillary density level in the model of myocardial damage which caused by rats diabetes. The Wistar rats were divided into 4 groups, including control, diabetic, myocardial infarction and two diseases combined group. Ligate descending branch of left coronary artery on 1/3 position or inject streptozotocin into abdominal cavity to establish two kinds of disease models. After 6 w, obtain the myocardial tissues to do the vascular density analysis of tissue sections which are stained and cell tissue enzyme. Explore change of relevant index and differences among groups. Results indicated that degree of LDH and SDH decrease in two kinds of disease model. Compared with control group, level of myocardial vascular of myocardial injury group is higher, and diabetic group is higher than non diabetic group. Quantitative result of FFA in mitochondrial suspension of single disease group is higher than that of control group and two diseases combined group. Level of FFA and LDH of two diseases combined group is consistent with control group. In conclusion, after myocardial damage, which is caused by diabetes mellitus or myocardial infarction, degree of local vascularization increases, diabetes mellitus is more obvious. After myocardial damage, process of myocardial mitochondrial glycolysis and oxidative phosphorylation has some obstacles. But these two kinds of diseases all have cardiac muscle cell which can keep generated procedure of aerobic and anaerobic energy to instead the normal function of cardiac muscle. PMID:26885216

  4. Comparison between myocardial infarction and diabetes mellitus damage caused angiogenesis or energy metabolism

    PubMed Central

    Li, Chao; Lu, Chengzhi; Zhao, Xiangdong; Chen, Xin

    2015-01-01

    This study aims to compare and analyze lactate dehydrogenase (LDH), succinic dehydrogenase (SDH) and differences in capillary density level in the model of myocardial damage which caused by rats diabetes. The Wistar rats were divided into 4 groups, including control, diabetic, myocardial infarction and two diseases combined group. Ligate descending branch of left coronary artery on 1/3 position or inject streptozotocin into abdominal cavity to establish two kinds of disease models. After 6 w, obtain the myocardial tissues to do the vascular density analysis of tissue sections which are stained and cell tissue enzyme. Explore change of relevant index and differences among groups. Results indicated that degree of LDH and SDH decrease in two kinds of disease model. Compared with control group, level of myocardial vascular of myocardial injury group is higher, and diabetic group is higher than non diabetic group. Quantitative result of FFA in mitochondrial suspension of single disease group is higher than that of control group and two diseases combined group. Level of FFA and LDH of two diseases combined group is consistent with control group. In conclusion, after myocardial damage, which is caused by diabetes mellitus or myocardial infarction, degree of local vascularization increases, diabetes mellitus is more obvious. After myocardial damage, process of myocardial mitochondrial glycolysis and oxidative phosphorylation has some obstacles. But these two kinds of diseases all have cardiac muscle cell which can keep generated procedure of aerobic and anaerobic energy to instead the normal function of cardiac muscle. PMID:26885216

  5. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction

    PubMed Central

    Thackeray, James T.; Bankstahl, Jens P.; Wang, Yong; Wollert, Kai C.; Bengel, Frank M.

    2016-01-01

    Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid 11C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with 11C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher 11C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0.001). C57Bl/6 mice (n=27) underwent coronary artery ligation or no surgery. Serial 11C-methionine PET was performed 3, 5 and 7d later. MI mice exhibited a perfusion defect in 32-50% of the left ventricle (LV). PET detected increased 11C-methionine accumulation in the infarct territory at 3d (5.9±0.9%ID/g vs 4.7±0.9 in remote myocardium, and 2.6±0.5 in healthy mice; p<0.05 and <0.01 respectively), which declined by d7 post-MI (4.3±0.6 in infarct, 3.4±0.8 in remote; p=0.03 vs 3d, p=0.08 vs healthy). Increased 11C-methionine uptake was associated with macrophage infiltration of damaged myocardium. Treatment with anti-integrin antibodies (anti-CD11a, -CD11b, -CD49d; 100µg) lowered macrophage content by 56% and 11C-methionine uptake by 46% at 3d post-MI. A patient study at 3d after ST-elevation MI and early reperfusion confirmed elevated 11C-methionine uptake in the hypoperfused myocardial region. Targeting of elevated amino acid metabolism in pro-inflammatory M1 macrophages enables PET imaging-derived demarcation of tissue inflammation after MI. 11C-methionine-based molecular imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies. PMID:27570549

  6. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction.

    PubMed

    Thackeray, James T; Bankstahl, Jens P; Wang, Yong; Wollert, Kai C; Bengel, Frank M

    2016-01-01

    Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid (11)C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with (11)C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher (11)C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0.001). C57Bl/6 mice (n=27) underwent coronary artery ligation or no surgery. Serial (11)C-methionine PET was performed 3, 5 and 7d later. MI mice exhibited a perfusion defect in 32-50% of the left ventricle (LV). PET detected increased (11)C-methionine accumulation in the infarct territory at 3d (5.9±0.9%ID/g vs 4.7±0.9 in remote myocardium, and 2.6±0.5 in healthy mice; p<0.05 and <0.01 respectively), which declined by d7 post-MI (4.3±0.6 in infarct, 3.4±0.8 in remote; p=0.03 vs 3d, p=0.08 vs healthy). Increased (11)C-methionine uptake was associated with macrophage infiltration of damaged myocardium. Treatment with anti-integrin antibodies (anti-CD11a, -CD11b, -CD49d; 100µg) lowered macrophage content by 56% and (11)C-methionine uptake by 46% at 3d post-MI. A patient study at 3d after ST-elevation MI and early reperfusion confirmed elevated (11)C-methionine uptake in the hypoperfused myocardial region. Targeting of elevated amino acid metabolism in pro-inflammatory M1 macrophages enables PET imaging-derived demarcation of tissue inflammation after MI. (11)C-methionine-based molecular imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies. PMID:27570549

  7. Myocardial metabolism during exposure to carbon monoxide in the conscious dog.

    NASA Technical Reports Server (NTRS)

    Adams, J. D.; Erickson, H. H.; Stone, H. L.

    1973-01-01

    Investigation of the relationship between coronary flow, heart rate, left ventricular function, and myocardial oxygen consumption at increasing levels of carboxyhemoglobin in conscious dogs. The results demonstrate a linear increase in coronary flow and heart rate as the carboxyhemoglobin increases up to 20%. Myocardial oxygen consumption declined during the same period.

  8. Antioxidant treatment normalizes mitochondrial energetics and myocardial insulin sensitivity independently of changes in systemic metabolic homeostasis in a mouse model of the metabolic syndrome.

    PubMed

    Ilkun, Olesya; Wilde, Nicole; Tuinei, Joseph; Pires, Karla M P; Zhu, Yi; Bugger, Heiko; Soto, Jamie; Wayment, Benjamin; Olsen, Curtis; Litwin, Sheldon E; Abel, E Dale

    2015-08-01

    Cardiac dysfunction in obesity is associated with mitochondrial dysfunction, oxidative stress and altered insulin sensitivity. Whether oxidative stress directly contributes to myocardial insulin resistance remains to be determined. This study tested the hypothesis that ROS scavenging will improve mitochondrial function and insulin sensitivity in the hearts of rodent models with varying degrees of insulin resistance and hyperglycemia. The catalytic antioxidant MnTBAP was administered to the uncoupling protein-diphtheria toxin A (UCP-DTA) mouse model of insulin resistance (IR) and obesity, at early and late time points in the evolution of IR, and to db/db mice with severe obesity and type-two diabetes. Mitochondrial function was measured in saponin-permeabilized cardiac fibers. Aconitase activity and hydrogen peroxide emission were measured in isolated mitochondria. Insulin-stimulated glucose oxidation, glycolysis and fatty acid oxidation rates were measured in isolated working hearts, and 2-deoxyglucose uptake was measured in isolated cardiomyocytes. Four weeks of MnTBAP attenuated glucose intolerance in 13-week-old UCP-DTA mice but was without effect in 24-week-old UCP-DTA mice and in db/db mice. Despite the absence of improvement in the systemic metabolic milieu, MnTBAP reversed cardiac mitochondrial oxidative stress and improved mitochondrial bioenergetics by increasing ATP generation and reducing mitochondrial uncoupling in all models. MnTBAP also improved myocardial insulin mediated glucose metabolism in 13 and 24-week-old UCP-DTA mice. Pharmacological ROS scavenging improves myocardial energy metabolism and insulin responsiveness in obesity and type 2 diabetes via direct effects that might be independent of changes in systemic metabolism. PMID:26004364

  9. An intact small animal model of myocardial ischemia-reperfusion: Characterization of metabolic changes by hyperpolarized 13C MR spectroscopy.

    PubMed

    Yoshihara, Hikari A I; Bastiaansen, Jessica A M; Berthonneche, Corinne; Comment, Arnaud; Schwitter, Juerg

    2015-12-15

    Hyperpolarized carbon-13 magnetic resonance spectroscopy ((13)C MRS) enables the sensitive and noninvasive assessment of the metabolic changes occurring during myocardial ischemia-reperfusion. Ischemia-reperfusion models using hyperpolarized (13)C MRS are established in heart preparations ex vivo and in large animals in vivo, but an in vivo model in small animals would be advantageous to allow the study of reperfusion metabolism with neuroendocrine and inflammatory responses intact with the option to perform a greater number of experiments. A novel intact rat model of ischemia-reperfusion is presented that incorporates hyperpolarized (13)C MRS to characterize reperfusion metabolism. Typically, in an in vivo model, a tissue input function (TIF) is required to account for apparent changes in the metabolism of injected hyperpolarized [1-(13)C]pyruvate resulting from changes in perfusion. Whereas the measurement of a TIF by metabolic imaging is particularly challenging in small animals, the ratios of downstream metabolites can be used as an alternative. The ratio of [(13)C]bicarbonate:[1-(13)C]lactate (RatioBic/Lac) measured within 1-2 min after coronary release decreased vs. baseline in ischemic rats (n = 10, 15-min occlusion, controls: n = 10; P = 0.017 for interaction, 2-way ANOVA). The decrease in oxidative pyruvate metabolism [RatioBic/Lac(Ischemia)/RatioBic/Lac(Baseline)] modestly correlated with area at risk (r = 0.66; P = 0.002). Hyperpolarized (13)C MRS was also used to examine alanine production during ischemia, which is observed in ex vivo models, but no significant change was noted; metrics incorporating [1-(13)C]alanine did not substantially improve the discrimination of ischemic-reperfused myocardium from nonischemic myocardium. This intact rat model, which mimics the human situation of reperfused myocardial infarction, could be highly valuable for the testing of new drugs to treat reperfusion injury, thereby facilitating translational research. PMID

  10. Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

    PubMed

    Mather, K J; Hutchins, G D; Perry, K; Territo, W; Chisholm, R; Acton, A; Glick-Wilson, B; Considine, R V; Moberly, S; DeGrado, T R

    2016-03-15

    Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. PMID:26732686

  11. Impact of the Metabolic Syndrome on the Clinical Outcome of Patients with Acute ST-Elevation Myocardial Infarction

    PubMed Central

    Lee, Min Goo; Ahn, Youngkeun; Chae, Shung Chull; Hur, Seung Ho; Hong, Taek Jong; Kim, Young Jo; Seong, In Whan; Chae, Jei Keon; Rhew, Jay Young; Chae, In Ho; Cho, Myeong Chan; Bae, Jang Ho; Rha, Seung Woon; Kim, Chong Jin; Choi, Donghoon; Jang, Yang Soo; Yoon, Junghan; Chung, Wook Sung; Cho, Jeong Gwan; Seung, Ki Bae; Park, Seung Jung

    2010-01-01

    We sought to determine the prevalence of metabolic syndrome (MS) in patients with acute myocardial infarction and its effect on clinical outcomes. Employing data from the Korea Acute Myocardial Infarction Registry, a total of 1,990 patients suffered from acute ST-elevation myocardial infarction (STEMI) between November 2005 and December 2006 were categorized according to the National Cholesterol Education Program-Adult Treatment Panel III criteria of MS. Primary study outcomes included major adverse cardiac events (MACE) during one-year follow-up. Patients were grouped based on existence of MS: group I: MS (n=1,182, 777 men, 62.8±12.3 yr); group II: Non-MS (n=808, 675 men, 64.2±13.1 yr). Group I showed lower left ventricular ejection fraction (LVEF) (P=0.005). There were no differences between two groups in the coronary angiographic findings except for multivessel involvement (P=0.01). The incidence of in-hospital death was higher in group I than in group II (P=0.047), but the rates of composite MACE during one-year clinical follow-up showed no significant differences. Multivariate analysis showed that low LVEF, old age, MS, low high density lipoprotein cholesterol and multivessel involvement were associated with high in-hospital death rate. In conclusion, MS is an important predictor for in-hospital death in patients with STEMI. PMID:20890426

  12. Influence of glyceryl trinitrate and nifedipine on coronary sinus blood flow and global myocardial metabolism during coronary artery operation.

    PubMed

    van Wezel, H B; Bovill, J G; Koolen, J J; Patrick, M R; Fiolet, J W; van der Stroom, J G

    1986-09-01

    The effects of intravenous infusions of glyceryl trinitrate and nifedipine on systemic haemodynamic function, coronary haemodynamic function, and global myocardial metabolism were compared in two groups of eleven patients with unimpaired left ventricular function undergoing elective coronary artery operation who were anaesthetised with high dose fentanyl. Severe post-sternotomy hypertension developed in three patients in the glyceryl trinitrate group who were resistant to the hypotensive effect of this agent. All patients given nifedipine remained haemodynamically stable. Coronary sinus blood flow and myocardial oxygen consumption increased and coronary vascular resistance decreased after sternotomy in the nifedipine group but not in the glyceryl trinitrate group. There is no satisfactory explanation for the apparently paradoxical increase in myocardial oxygen consumption in the patients given nifedipine. This phenomenon did not appear to be associated with any detrimental effect of left ventricular function. Thus nifedipine was better than glyceryl trinitrate for the control of post-sternotomy hypertension in patients with good left ventricular function. Intravenous nifedipine is not recommended, however, for the intraoperative control of blood pressure in patients with unstable angina or impaired left ventricular function. PMID:3092847

  13. Consistency and derangements in brane tilings

    NASA Astrophysics Data System (ADS)

    Hanany, Amihay; Jejjala, Vishnu; Ramgoolam, Sanjaye; Seong, Rak-Kyeong

    2016-09-01

    Brane tilings describe Lagrangians (vector multiplets, chiral multiplets, and the superpotential) of four-dimensional { N }=1 supersymmetric gauge theories. These theories, written in terms of a bipartite graph on a torus, correspond to worldvolume theories on N D3-branes probing a toric Calabi–Yau threefold singularity. A pair of permutations compactly encapsulates the data necessary to specify a brane tiling. We show that geometric consistency for brane tilings, which ensures that the corresponding quantum field theories are well behaved, imposes constraints on the pair of permutations, restricting certain products constructed from the pair to have no one-cycles. Permutations without one-cycles are known as derangements. We illustrate this formulation of consistency with known brane tilings. Counting formulas for consistent brane tilings with an arbitrary number of chiral bifundamental fields are written down in terms of delta functions over symmetric groups.

  14. Proteomic and metabolomic changes driven by elevating myocardial creatine suggest novel metabolic feedback mechanisms.

    PubMed

    Zervou, Sevasti; Yin, Xiaoke; Nabeebaccus, Adam A; O'Brien, Brett A; Cross, Rebecca L; McAndrew, Debra J; Atkinson, R Andrew; Eykyn, Thomas R; Mayr, Manuel; Neubauer, Stefan; Lygate, Craig A

    2016-08-01

    Mice over-expressing the creatine transporter have elevated myocardial creatine levels [Cr] and are protected against ischaemia/reperfusion injury via improved energy reserve. However, mice with very high [Cr] develop cardiac hypertrophy and dysfunction. To investigate these contrasting effects, we applied a non-biased hypothesis-generating approach to quantify global protein and metabolite changes in the LV of mice stratified for [Cr] levels: wildtype, moderately elevated, and high [Cr] (65-85; 100-135; 160-250 nmol/mg protein, respectively). Male mice received an echocardiogram at 7 weeks of age with tissue harvested at 8 weeks. RV was used for [Cr] quantification by HPLC to select LV tissue for subsequent analysis. Two-dimensional difference in-gel electrophoresis identified differentially expressed proteins, which were manually picked and trypsin digested for nano-LC-MS/MS. Principal component analysis (PCA) showed efficient group separation (ANOVA P ≤ 0.05) and peptide sequences were identified by mouse database (UniProt 201203) using Mascot. A total of 27 unique proteins were found to be differentially expressed between normal and high [Cr], with proteins showing [Cr]-dependent differential expression, chosen for confirmation, e.g. α-crystallin B, a heat shock protein implicated in cardio-protection and myozenin-2, which could contribute to the hypertrophic phenotype. Nuclear magnetic resonance (¹H-NMR at 700 MHz) identified multiple strong correlations between [Cr] and key cardiac metabolites. For example, positive correlations with α-glucose (r² = 0.45; P = 0.002), acetyl-carnitine (r² = 0.50; P = 0.001), glutamine (r² = 0.59; P = 0.0002); and negative correlations with taurine (r² = 0.74; P < 0.0001), fumarate (r² = 0.45; P = 0.003), aspartate (r² = 0.59; P = 0.0002), alanine (r² = 0.66; P < 0.0001) and phosphocholine (r² = 0.60; P = 0.0002). These findings suggest wide-ranging and hitherto unexpected

  15. Association of genetic variants with myocardial infarction in Japanese individuals with or without metabolic syndrome

    PubMed Central

    KAWAMIYA, TOSHIKI; KATO, KIMIHIKO; HORIBE, HIDEKI; YOKOI, KIYOSHI; OGURI, MITSUTOSHI; YOSHIDA, TETSURO; FUJIMAKI, TETSUO; WATANABE, SACHIRO; SATOH, KEI; AOYAGI, YUKITOSHI; NOZAWA, YOSHINORI; MUROHARA, TOYOAKI; YAMADA, YOSHIJI

    2010-01-01

    The etiology of metabolic syndrome (MetS) is highly complex, with both genetic and environmental factors being thought to play an important role. Although MetS has been recognized as a risk factor for myocardial infarction (MI), the genetic risk for MI in individuals with or without MetS has remained uncharacterized. We examined a possible association of genetic variants with MI in individuals with or without MetS separately. The study population comprised 4,424 individuals, including 1,918 individuals with MetS (903 subjects with MI and 1,015 controls) and 2,506 individuals without MetS (499 subjects with MI and 2,007 controls). The 150 polymorphisms examined in the present study were selected by genome-wide association studies of MI and ischemic stroke with the use of Affymetrix GeneChip Human Mapping 500K Array Set. Initial screening by the Chi-square test revealed that the C→T polymorphism (rs1794429) of LRPAP1, the A→G polymorphism (rs12373237) of LAMA3 and the A→G polymorphism (rs3782257) of NCOR2 were significantly (false discovery rate of <0.05) associated with MI for individuals with MetS, and that the C→G polymorphism (rs13051704) of TFF1 was significantly related to MI for individuals without MetS. Subsequent multivariable logistic analysis with adjustment for covariates revealed that rs1794429 of LRPAP1 (recessive model; P=0.0218; odds ratio=0.71) and rs3782257 of NCOR2 (dominant model; P=0.0057; odds ratio=1.94) were significantly associated with MI among individuals with MetS, and that rs13051704 of TFF1 (additive model; P=0.0100; odds ratio=0.55) was significantly associated with MI among individuals without MetS. The genetic variants that confer susceptibility to MI differ between individuals with or without MetS. Stratification of subjects according to the presence or absence of MetS may thus be important for personalized prevention of MI based on genetic information. PMID:22993627

  16. Association of genetic variants with myocardial infarction in Japanese individuals with or without metabolic syndrome.

    PubMed

    Kawamiya, Toshiki; Kato, Kimihiko; Horibe, Hideki; Yokoi, Kiyoshi; Oguri, Mitsutoshi; Yoshida, Tetsuro; Fujimaki, Tetsuo; Watanabe, Sachiro; Satoh, Kei; Aoyagi, Yukitoshi; Nozawa, Yoshinori; Murohara, Toyoaki; Yamada, Yoshiji

    2010-11-01

    The etiology of metabolic syndrome (MetS) is highly complex, with both genetic and environmental factors being thought to play an important role. Although MetS has been recognized as a risk factor for myocardial infarction (MI), the genetic risk for MI in individuals with or without MetS has remained uncharacterized. We examined a possible association of genetic variants with MI in individuals with or without MetS separately. The study population comprised 4,424 individuals, including 1,918 individuals with MetS (903 subjects with MI and 1,015 controls) and 2,506 individuals without MetS (499 subjects with MI and 2,007 controls). The 150 polymorphisms examined in the present study were selected by genome-wide association studies of MI and ischemic stroke with the use of Affymetrix GeneChip Human Mapping 500K Array Set. Initial screening by the Chi-square test revealed that the C→T polymorphism (rs1794429) of LRPAP1, the A→G polymorphism (rs12373237) of LAMA3 and the A→G polymorphism (rs3782257) of NCOR2 were significantly (false discovery rate of <0.05) associated with MI for individuals with MetS, and that the C→G polymorphism (rs13051704) of TFF1 was significantly related to MI for individuals without MetS. Subsequent multivariable logistic analysis with adjustment for covariates revealed that rs1794429 of LRPAP1 (recessive model; P=0.0218; odds ratio=0.71) and rs3782257 of NCOR2 (dominant model; P=0.0057; odds ratio=1.94) were significantly associated with MI among individuals with MetS, and that rs13051704 of TFF1 (additive model; P=0.0100; odds ratio=0.55) was significantly associated with MI among individuals without MetS. The genetic variants that confer susceptibility to MI differ between individuals with or without MetS. Stratification of subjects according to the presence or absence of MetS may thus be important for personalized prevention of MI based on genetic information. PMID:22993627

  17. Metabolic imaging of patients with cardiomyopathy

    SciTech Connect

    Geltman, E.M. )

    1991-09-01

    The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies.

  18. Alcoholic metabolic emergencies.

    PubMed

    Allison, Michael G; McCurdy, Michael T

    2014-05-01

    Ethanol intoxication and ethanol use are associated with a variety of metabolic derangements encountered in the Emergency Department. In this article, the authors discuss alcohol intoxication and its treatment, dispel the myth that alcohol intoxication is associated with hypoglycemia, comment on electrolyte derangements and their management, review alcoholic ketoacidosis, and end with a section on alcoholic encephalopathy. PMID:24766933

  19. Thoracic epidural anesthesia during coronary artery bypass surgery: effects on cardiac sympathetic activity, myocardial blood flow and metabolism, and central hemodynamics.

    PubMed

    Kirnö, K; Friberg, P; Grzegorczyk, A; Milocco, I; Ricksten, S E; Lundin, S

    1994-12-01

    The effects of high thoracic epidural anesthesia (TEA) on cardiac sympathetic nerve activity, myocardial blood flow and metabolism, and central hemodynamics were studied in 20 patients undergoing coronary artery bypass grafting (CABG). In 10 of the patients, TEA (T1-5 block) was used as an adjunct to a standardized fentanyl-nitrous oxide anesthesia. Hemodynamic measurements and blood sampling were performed after induction of anesthesia but prior to skin incision and after sternotomy. Assessment of total and cardiac sympathetic activity was performed by means of the norepinephrine kinetic approach. Prior to surgery, mean arterial pressure (MAP), great cardiac vein flow (GCVF), and regional myocardial oxygen consumption (Reg-MVO2) were lower in the TEA group compared to the control group. During sternotomy there was a pronounced increase in cardiac norepinephrine spillover, MAP, systemic vascular resistance index (SVRI), pulmonary capillary wedge pressure (PCWP), GCVF, and Reg-MVO2 in the control group. These changes were clearly attenuated in the TEA group. None of the patients in the TEA group had metabolic (lactate) or electrocardiographic signs of myocardial ischemia. Three patients in the control group had indices of myocardial ischemia prior to and/or during surgery. We conclude that TEA attenuates the surgically mediated sympathetic stress response to sternotomy, thereby preventing the increase in myocardial oxygen demand in the pre-bypass period without jeopardizing myocardial perfusion. PMID:7978429

  20. Effect of Shen-Fu Injection Pretreatment to Myocardial Metabolism During Untreated Ventricular Fibrillation in a Porcine Model

    PubMed Central

    Yuan, Wei; Wu, Jun-Yuan; Wang, Guo-Xing; Zhang, Qian; Li, Chun-Sheng

    2015-01-01

    Background: Shen-Fu injection (SFI) can attenuate ischemia-reperfusion injury, protect cardiac function, and improve microcirculation during cardiopulmonary resuscitation. We hypothesized that SFI may also have an influence on myocardial metabolism during ventricular fibrillation (VF). In this study, we used SFI pretreatment prior to VF to discuss the changes of myocardial metabolism and catecholamine (CA) levels during untreated VF, trying to provide new evidence to the protection of SFI to myocardium. Methods: Twenty-four pigs were divided into three groups: Saline group (SA group), SFI group, and SHAM operation group (SHAM group). Thirty minutes prior to the induction of VF, the SFI group received 0.24 mg/ml SFI through an intravenous injection; the SA group received an equal amount of sodium chloride solution. The interstitial fluid from the left ventricle (LV) wall was collected through the microdialysis tubes during VF. Adenosine diphosphate (ADP), adenosine triphosphate (ATP), and Na+ -K+ -ATPase and Ca2+ -ATPase enzyme activities were measured after untreated VF. Peak-to-trough VF amplitude and median frequency were analyzed for each of these 5-s intervals. Results: The levels of glucose and glutamate were lower after VF in both the SA and SFI groups, compared with baseline, and the levels in the SFI group were higher than those in the SA group. Compared with baseline, the levels of lactate and the lactate/pyruvate ratio increased after VF in both SA and SFI groups, and the levels in the SFI group were lower than those in the SA group. In both the SA and SFI groups, the levels of dopamine, norepinephrine, and epinephrine increased significantly. There were no statistical differences between the two groups. The content of ATP, ADP, and phosphocreatine in the SFI group was higher than those in the SA group. The activity of LV Na+ -K+ -ATPase was significantly higher in the SFI group than in the SA group. Amplitude mean spectrum area (AMSA) was significantly

  1. Differential effects of octanoate and heptanoate on myocardial metabolism during extracorporeal membrane oxygenation in an infant swine model.

    PubMed

    Kajimoto, Masaki; Ledee, Dolena R; Olson, Aaron K; Isern, Nancy G; Des Rosiers, Christine; Portman, Michael A

    2015-10-01

    Nutritional energy support during extracorporeal membrane oxygenation (ECMO) should promote successful myocardial adaptation and eventual weaning from the ECMO circuit. Fatty acids (FAs) are a major myocardial energy source, and medium-chain FAs (MCFAs) are easily taken up by cell and mitochondria without membrane transporters. Odd-numbered MCFAs supply carbons to the citric acid cycle (CAC) via anaplerotic propionyl-CoA as well as acetyl-CoA, the predominant β-oxidation product for even-numbered MCFA. Theoretically, this anaplerotic pathway enhances carbon entry into the CAC, and provides superior energy state and preservation of protein synthesis. We tested this hypothesis in an immature swine model undergoing ECMO. Fifteen male Yorkshire pigs (26-45 days old) with 8-h ECMO received either normal saline, heptanoate (odd-numbered MCFA), or octanoate (even-numbered MCFA) at 2.3 μmol·kg body wt(-1)·min(-1) as MCFAs systemically during ECMO (n = 5/group). The 13-carbon ((13)C)-labeled substrates ([2-(13)C]lactate, [5,6,7-(13)C3]heptanoate, and [U-(13)C6]leucine) were systemically infused as metabolic markers for the final 60 min before left ventricular tissue extraction. Extracted tissues were analyzed for the (13)C-labeled and absolute concentrations of metabolites by nuclear magnetic resonance and gas chromatography-mass spectrometry. Octanoate produced markedly higher myocardial citrate concentration, and led to a higher [ATP]-to-[ADP] ratio compared with other groups. Unexpectedly, octanoate and heptanoate increased the flux of propionyl-CoA relative to acetyl-CoA into the CAC compared with control. MCFAs promoted increases in leucine oxidation, but were not associated with a difference in protein synthesis rate. In conclusion, octanoate provides energetic advantages to the heart over heptanoate. PMID:26232235

  2. Differential Effects Of Octanoate And Heptanoate On Myocardial Metabolism During Extracorporeal Membrane Oxygenation In An Infant Swine Model

    SciTech Connect

    Kajimoto, Masaki; Ledee, Dolena R.; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2015-10-01

    Background: Nutritional energy support during extracorporeal membrane oxygenation (ECMO) should promote successful myocardial adaptation and eventual weaning from the ECMO circuit. Fatty acids (FAs) are a major myocardial energy source, and medium-chain FAs (MCFAs) are easily taken up by cell and mitochondria without membrane transporters. Oddnumbered MCFAs supply carbons to the citric acid cycle (CAC) via anaplerotic propionyl-CoA as well as acetyl-CoA, the predominant betaoxidation product for even-numbered MCFA. Theoretically, this anaplerotic pathway enhances carbon entry into the CAC, and provides superior energy state and preservation of protein synthesis. We tested this hypothesis in an immature swine model undergoing ECMO. Methods: Fifteen male Yorkshire pigs (26-45 days old) with 8-hour ECMO were received either normal saline, heptanoate (odd-numbered MCFA) or octanoate (even-numbered MCFA) at 2.3 μmol/kg body wt/min as MCFAs systemically during ECMO (n = 5 per group). The 13-Carbon (13C)-labeled substrates ([2-13C]lactate, [5,6,7-13C3]heptanoate and [U-13C6]leucine) were systemically infused as metabolic markers for the final 60 minutes before left ventricular tissue extraction. Extracted tissues were analyzed for the 13C-labeled and absolute concentrations of metabolites by nuclear magnetic resonance and gas chromatography-mass spectrometry. Results: Octanoate produced markedly higher myocardial citrate concentration, and led to a higher [ATP]/[ADP] ratio compared with other http://mc.manuscriptcentral.com/jpen Journal of Parenteral and Enteral Nutrition For Peer Review groups. Unexpectedly, octanoate increased the flux of propionyl-CoA relative to acetyl-CoA into the CAC as well as heptanoate. MCFAs promoted increases in leucine oxidation, but were not associated with a difference in fractional protein synthesis rate. Conclusion: Octanoate provides energetic advantages to the heart over heptanoate, while preserving protein synthesis.

  3. Temporal changes in phosphatidylserine expression and glucose metabolism after myocardial infarction: an in vivo imaging study in mice.

    PubMed

    Lehner, Sebastian; Todica, Andrei; Brunner, Stefan; Uebleis, Christopher; Wang, Hao; Wängler, Carmen; Herbach, Nadja; Herrler, Tanja; Böning, Guido; Laubender, Rüdiger Paul; Cumming, Paul; Schirrmacher, Ralf; Franz, Wolfgang; Hacker, Marcus

    2012-01-01

    Positron emission tomography (PET) for in vivo monitoring of phosphatidylserine externalization and glucose metabolism can potentially provide early predictors of outcome of cardioprotective therapies after myocardial infarction. We performed serial [⁶⁸Ga]annexin A5 PET (annexin-PET) and [¹⁸F]fluorodeoxyglucose PET (FDG-PET) after myocardial infarction to determine the time of peak phosphatidylserine externalization in relation to impaired glucose metabolism in infracted tissue. Annexin- and FDG-PET recordings were obtained in female (C57BL6/N) mice on days 1 to 4 after ligation of the left anterior descending (LAD) artery. [⁶⁸Ga]annexin A5 uptake (%ID/g) in the LAD artery territory increased from 1.7 ± 1.1 on day 1 to 5.0 ± 3.3 on day 2 and then declined to 2.0 ± 1.4 on day 3 (p  =  .047 vs day 2) and 1.6 ± 1.4 on day 4 (p  =  .014 vs day 2). These results matched apoptosis rates as estimated by autoradiography and fluorescein staining. FDG uptake (%ID/g) declined from 28 ± 14 on day 1 to 14 ± 3.5 on day 4 (p < .0001 vs day 1). Whereas FDG-PET revealed continuous loss of cell viability after permanent LAD artery occlusion, annexin-PET indicated peak phosphatidylserine expression at day 2, which might be the optimal time point for therapy monitoring. PMID:23084247

  4. Alcohol Deranges Hepatic Lipid Metabolism via Altered Transcriptional Regulation.

    PubMed Central

    Crabb, David W.

    2004-01-01

    Alcohol has classically been thought to cause fatty liver by way of altered redox potential in the liver, which inhibits fatty acid oxidation. Additional effects appear to play a role both in impairing fat oxidation and stimulating lipogenesis. Alcohol reduces the DNA binding and transcription-activating properties of peroxisome proliferator-activated receptor alpha (PPARalpha), both in cultured cells and in mice fed alcohol. Treatment of alcohol-fed mice with a PPARalpha agonist reverses fatty liver despite continued alcohol consumption. Alcohol also activates sterol response element- binding protein 1 (SREBP-1), inducing a battery of lipogenic enzymes. This effect may be due in part to inhibition of AMP-dependent protein kinase. This understanding of alcohol effects provides new therapeutic targets to reverse alcoholic fatty liver. Images Fig. 4 Fig. 6 PMID:17060973

  5. Direct regulation of myocardial triglyceride metabolism by the cardiomyocyte circadian clock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintenance of circadian alignment between an organism and its environment is essential to ensure metabolic homeostasis. Synchrony is achieved by cell autonomous circadian clocks. Despite a growing appreciation of the integral relation between clocks and metabolism, little is known regarding the dir...

  6. Positron emission reconstruction tomography for the assessment of regional myocardial metabolism by the administration of substrates labeled with cyclotron produced radionuclides

    NASA Technical Reports Server (NTRS)

    Ter-Pogossian, M. M.; Hoffman, E. J.; Weiss, E. S.; Coleman, R. E.; Phelps, M. E.; Welch, M. J.; Sobel, B. E.

    1975-01-01

    A positron emission transverse tomograph device was developed which provides transaxial sectional images of the distribution of positron-emitting radionuclides in the heart. The images provide a quantitative three-dimensional map of the distribution of activity unencumbered by the superimposition of activity originating from regions overlying and underlying the plane of interest. PETT is used primarily with the cyclotron-produced radionuclides oxygen-15, nitrogen-13 and carbon-11. Because of the participation of these atoms in metabolism, they can be used to label metabolic substrates and intermediary molecules incorporated in myocardial metabolism.

  7. Myocardial Po2 does not limit aerobic metabolism in the postischemic heart.

    PubMed

    Chung, Youngran

    2016-01-15

    Reperfused hypertrophic hearts are prone to develop reflow abnormalities, which are likely to impair O2 return to the myocardium. Yet, reflow deficit may not be the only factor determining postischemic oxygenation in the hypertrophic heart. Altered O2 demand may also contribute to hypoxia. In addition, the extent to which myocardial Po2 dictates energy and functional recovery in the reperfused heart remains uncertain. In the present study, moderately hypertrophied hearts from spontaneously hypertensive rats were subjected to ischemia-reperfusion, and the recovery time courses of pH and high-energy phosphates were followed by (31)P NMR. (1)H NMR measurement of intracellular myoglobin assessed tissue O2 levels. The present study found that the exacerbation of hypoxia in the postischemic spontaneously hypertensive rat heart arises mostly from impaired microvascular supply of O2. However, postischemic myocardial Po2, at least when it exceeds ∼18% of the preischemic level, does not limit mitochondrial respiration and high-energy phosphate resynthesis. It only passively reflects changes in the O2 supply-demand balance. PMID:26589325

  8. Effects of nicardipine on coronary blood flow, left ventricular inotropic state and myocardial metabolism in patients with angina pectoris

    PubMed Central

    Rousseau, M. F.; Vincent, M. F.; Cheron, P.; Van Den Berghe, G.; Charlier, A. A.; Pouleur, H.

    1985-01-01

    1 The effects of intravenous nicardipine (2.5 mg) on the left ventricular (LV) inotropic state, LV metabolism, and coronary haemodynamics were analysed in 22 patients with angina pectoris. 2 Measurements were made at fixed heart rate (atrial pacing), under basal state, and during a cold pressor test. 3 After nicardipine, coronary blood flow and oxygen content in the coronary sinus increased significantly. 4 The indices of inotropic state increased slightly, and the rate of isovolumic LV pressure fall improved. 5 Myocardial oxygen consumption was unchanged despite the significant reduction in pressure-rate product, but LV lactate uptake increased, particularly during the cold pressor test. 6 When nicardipine was administered after propranolol, the indices of inotropic state were unaffected. 7 The lack of direct effect of nicardipine on LV inotropic state was further confirmed by intracoronary injection of 0.1 and 0.2 mg in a separate group of 10 patients. 8 It is concluded that the nicardipine-induced coronary dilatation seems to improve perfusion and aerobic metabolism in areas with chronic ischaemia, resulting in reduced lactate production and augmented oxygen consumption. PMID:2862900

  9. Cardiac Per2 Functions as Novel Link between Fatty Acid Metabolism and Myocardial Inflammation during Ischemia and Reperfusion Injury of the Heart

    PubMed Central

    Bonney, Stephanie; Kominsky, Doug; Brodsky, Kelley; Eltzschig, Holger; Walker, Lori; Eckle, Tobias

    2013-01-01

    Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In contrast to Clock−/−, Per2−/− mice have larger infarct sizes with deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we measured lactate during reperfusion in Per1−/−, Per2−/− or wildtype mice. As lactate measurements in whole blood indicated an exclusive role of Per2 in controlling lactate production during myocardial ischemia, we next performed gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2−/− mice. Surprisingly, high-throughput gene array analysis revealed dominantly lipid metabolism as the differentially regulated pathway in wildtype mice when compared to Per2−/−. In all ischemia-reperfusion protocols used, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2−/− mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated ‘Per2-genes’. Subsequent studies on inflammatory markers showed increasing IL-6 or TNFα levels during reperfusion in Per2−/− mice. In summary, these studies reveal an important role of cardiac Per2 for fatty acid metabolism and inflammation during myocardial ischemia and reperfusion, respectively. PMID:23977055

  10. Total Mechanical Unloading Minimizes Metabolic Demand of Left Ventricle and Dramatically Reduces Infarct Size in Myocardial Infarction

    PubMed Central

    Kakino, Takamori; Arimura, Takahiro; Sakamoto, Takafumi; Nishikawa, Takuya; Sakamoto, Kazuo; Ikeda, Masataka; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

    2016-01-01

    Background Left ventricular assist device (LVAD) mechanically unloads the left ventricle (LV). Theoretical analysis indicates that partial LVAD support (p-LVAD), where LV remains ejecting, reduces LV preload while increases afterload resulting from the elevation of total cardiac output and mean aortic pressure, and consequently does not markedly decrease myocardial oxygen consumption (MVO2). In contrast, total LVAD support (t-LVAD), where LV no longer ejects, markedly decreases LV preload volume and afterload pressure, thereby strikingly reduces MVO2. Since an imbalance in oxygen supply and demand is the fundamental pathophysiology of myocardial infarction (MI), we hypothesized that t-LVAD minimizes MVO2 and reduces infarct size in MI. The purpose of this study was to evaluate the differential impact of the support level of LVAD on MVO2 and infarct size in a canine model of ischemia-reperfusion. Methods In 5 normal mongrel dogs, we examined the impact of LVAD on MVO2 at 3 support levels: Control (no LVAD support), p-LVAD and t-LVAD. In another 16 dogs, ischemia was induced by occluding major branches of the left anterior descending coronary artery (90 min) followed by reperfusion (300 min). We activated LVAD from the beginning of ischemia until 300 min of reperfusion, and compared the infarct size among 3 different levels of LVAD support. Results t-LVAD markedly reduced MVO2 (% reduction against Control: -56 ± 9%, p<0.01) whereas p-LVAD did less (-21 ± 14%, p<0.05). t-LVAD markedly reduced infarct size compared to p-LVAD (infarct area/area at risk: Control; 41.8 ± 6.4, p-LVAD; 29.1 ± 5.6 and t-LVAD; 5.0 ± 3.1%, p<0.01). Changes in creatine kinase-MB paralleled those in infarct size. Conclusions Total LVAD support that minimizes metabolic demand maximizes the benefit of LVAD in the treatment of acute myocardial infarction. PMID:27124411

  11. Myocardial metabolism of fluorodeoxyglucose compared to cell membrane integrity for the potassium analogue rubidium-82 for assessing infarct size in man by PET

    SciTech Connect

    Gould, K.L.; Yoshida, K.; Hess, M.J.; Haynie, M.; Mullani, N.; Smalling, R.W. )

    1991-01-01

    Potassium loss from damaged myocardial cells is linearly related to CPK enzyme loss reflecting extent of necrosis. The potassium analog, rubidium-82 (82Rb), is extracted after i.v. injection and retained in viable myocardium but is not trapped or washed out of necrotic regions. To compare myocardial cell metabolism with membrane dysfunction as indicators of necrosis/viability, 43 patients with evolving myocardial infarction and coronary arteriography had positron emission tomography using fluorodeoxyglucose (FDG) and the potassium analog 82Rb. Percent of heart showing FDG defects and 82Rb washout on sequential images indicating failure to retain the potassium analogue were visually assessed and quantified by automated software. Infarct size based on rubidium kinetics correlated closely with size and location on FDG images (visual r = 0.93, automated r = 0.82), suggesting that loss of cell membrane integrity for trapping the potassium analog 82Rb parallels loss of intracellular glucose metabolism, both comparable quantitative markers of myocardial necrosis/viability.

  12. Myocardial metabolism, perfusion, wall motion and electrical activity in Duchenne muscular dystrophy

    SciTech Connect

    Perloff, J.K.; Henze, E.; Schelbert, H.R.

    1982-01-01

    The cardiomyopathy of Duchenne's muscular dystrophy originates in the posterobasal left ventricle and extends chiefly to the contiguous lateral wall. Ultrastructural abnormalities in these regions precede connective tissue replacement. We postulated that a metabolic fault coincided with or antedated the subcellular abnormality. Accordingly, regional left ventricular metabolism, perfusion and wall motion were studied using positron computed tomography and metabolic isotopes supplemented by thallium perfusion scans, equilibrium radionuclide angiography and M-mode and two-dimensional echocardiography. To complete the assessment, electrocardiograms, vectorcardiograms, 24 hour taped electrocardiograms and chest x-rays were analyzed. Positron computed tomography utilizing F-18 2-fluoro 2-deoxyglucose (FDG) provided the first conclusive evidence supporting the hypothesis of a premorphologic regional metabolic fault. Thus, cardiac involvement in duchenne dystrophy emerges as a unique form of heart disease, genetically targeting specific regions of ventricular myocardium for initial metabolic and subcellular changes. Reported ultrastructural abnormalities of the impulse and conduction systems provide, at least in part, a basis for the clinically observed sinus node, intraatrial, internodal, AV nodal and infranodal disorders.

  13. Mapping of Regional Myocardial Strain and Work During Ventricular Pacing

    PubMed Central

    Prinzen, Frits W.; Hunter, William C.; Wyman, Bradley T.; McVeigh, Elliot R.

    2007-01-01

    OBJECTIVES The purpose of this study was to determine the spatial distribution of myocardial function (myofiber shortening and work) within the left ventricular (LV) wall during ventricular pacing. BACKGROUND Asynchronous electrical activation, as induced by ventricular pacing, causes various abnormalities in LV function, perfusion and structure. These derangements may be caused by abnormalities in regional contraction patterns. However, insight into these patterns during pacing is as yet limited. METHODS In seven anesthetized dogs, high spatial and temporal resolution magnetic resonance-tagged images were acquired in three orthogonal planes. Three-dimensional deformation data and LV cavity pressure and volume were used to determine midwall circumferential strain and external and total mechanical work at 192 sites around the left ventricle. RESULTS During ventricular pacing, systolic fiber strain and external work were approximately zero in regions near the pacing site, and gradually increased to more than twice the normal value in the most remote regions. Total mechanical work, normalized to the value during right atrial pacing, was 38 ± 13% (right ventricular apex [RVapex] pacing) and 61 ± 23% (left ventricular base [LVbase] pacing) close to the pacing site, and 125 ± 48% and 171 ± 60% in remote regions, respectively (p < 0.05 between RVapex and LVbase pacing). The number of regions with reduced work was significantly larger during RVapex than during LVbase pacing. This was associated with a reduction of global LV pump function during RVapex pacing. CONCLUSIONS Ventricular pacing causes a threefold difference in myofiber work within the LV wall. This difference appears large enough to regard local myocardial function as an important determinant for abnormalities in perfusion, metabolism, structure and pump function during asynchronous electrical activation. Pacing at sites that cause more synchronous activation may limit the occurrence of such derangements

  14. Myocardial mechanical dysfunction following endotoxemia: role of changes in energy substrate metabolism.

    PubMed

    Soraya, Hamid; Masoud, Waleed G T; Gandhi, Manoj; Garjani, Alireza; Clanachan, Alexander S

    2016-03-01

    Cardiovascular depression due to endotoxemia remains a major cause of mortality in intensive care patients. To determine whether drug-induced alterations in cardiac metabolism may be a viable strategy to reduce endotoxemia-mediated cardiac dysfunction, we assessed endotoxemia-induced changes in glucose and fatty acid metabolism under aerobic and post-ischemic conditions. Endotoxemia was induced in male Sprague-Dawley rats by lipopolysaccharide (Escherichia coli 0111:B4c, 4 mg/kg, i.p.) 6 h prior to heart removal for ex vivo assessment of left ventricular (LV) work and rates of glucose metabolism (glucose uptake, glycogen synthesis, glycolysis and glucose oxidation) and palmitate oxidation. Under aerobic conditions, endotoxemic hearts had impaired LV function as judged by echocardiography in vivo (% ejection fraction, 66.0 ± 3.2 vs 78.0 ± 2.1, p < 0.05) or by LV work ex vivo (2.14 ± 0.16 vs 3.28 ± 0.16, Joules min(-1) g dry wt(-1), p < 0.05). However, rates of glucose uptake, glycogen synthesis, glycolysis, and glucose oxidation were not altered. Palmitate oxidation was lower in endotoxemic hearts in proportion to the decreased workload, thus metabolic efficiency was unaffected. In hearts reperfused following global ischemia, untreated hearts had impaired recovery of LV work (52.3 ± 9.4 %) whereas endotoxemic hearts had significantly higher recovery (105.6 ± 11.3 %, p < 0.05). During reperfusion, fatty acid oxidation, acetyl CoA production and metabolic efficiency were similar in both groups. As impaired cardiac function appeared unrelated to depression of energy substrate oxidation, it is unlikely that drug-induced acceleration of fatty acid oxidation will improve mechanical function. The beneficial repartitioning of glucose metabolism in reperfused endotoxemic hearts may contribute to the cardioprotected phenotype. PMID:26926341

  15. Septal and Anterior Reverse Mismatch of Myocardial Perfusion and Metabolism in Patients With Coronary Artery Disease and Left Bundle Branch Block

    PubMed Central

    Wang, Jian-Guang; Fang, Wei; Yang, Min-Fu; Tian, Yue-Qin; Zhang, Xiao-Li; Shen, Rui; Sun, Xiao-Xin; Guo, Feng; Wang, Dao-Yu; He, Zuo-Xiang

    2015-01-01

    Abstract The effects of left bundle branch block (LBBB) on left ventricular myocardial metabolism have not been well investigated. This study evaluated these effects in patients with coronary artery disease (CAD). Sixty-five CAD patients with complete LBBB (mean age, 61.8 ± 9.7 years) and 65 without LBBB (mean age, 59.9 ± 8.4 years) underwent single photon emission computed tomography, positron emission tomography, and contrast coronary angiography. The relationship between myocardial perfusion and metabolism and reverse mismatch score, and that between QRS length and reverse mismatch score and wall motion score were evaluated. The incidence of left ventricular septum and anterior wall reverse mismatching between the two groups was significantly different (P < 0.001 and P = 0.002, respectively). The incidences of normal myocardial perfusion and metabolism in the left ventricular lateral and inferior walls were also significantly different between the two groups (P < 0.001 and P < 0.001, respectively). The incidence of septal reverse mismatching in patients with mild to moderate perfusion was significantly higher among those with LBBB than among those without LBBB (P < 0.001). In CAD patients with LBBB, septal reverse mismatching was significantly more common among those with mild to moderate perfusion than among those with severe perfusion defects (P = 0.002). The correlation between the septal reverse mismatch score and QRS length was significant (P = 0.026). In patients with CAD and LBBB, septal and anterior reverse mismatching of myocardial perfusion and metabolism was frequently present; the septal reverse mismatch score negatively correlated with the QRS interval. PMID:25997045

  16. Cardioselective Dominant-negative Thyroid Hormone Receptor (Δ337T) Modulates Myocardial Metabolism and Contractile Dfficiency

    SciTech Connect

    Hyyti, Outi M.; Olson, Aaron; Ge, Ming; Ning, Xue-Han; Buroker, Norman E.; Chung, Youngran; Jue, Thomas; Portman, Michael A.

    2008-06-03

    Dominant- negative thyroid hormone receptors (TRs) show elevated expression relative to ligand-binding TRs during cardiac hypertrophy. We tested the hypothesis that overexpression of a dominant-negative TR alters cardiac metabolism and contractile efficiency (CE). We used mice expressing the cardioselective dominant-negative TRβ1 mutation Δ337T. Isolated working Δ337T hearts and nontransgenic control (Con) hearts were perfused with 13C-labeled free fatty acids (FFA), acetoacetate (ACAC), lactate, and glucose at physiological concentrations for 30 min. 13C NMR spectroscopy and isotopomer analyses were used to determine substrate flux and fractional contributions (Fc) of acetyl-CoA to the citric acid cycle (CAC). Δ337T hearts exhibited rate depression but higher developed pressure and CE, defined as work per oxygen consumption (MV˙ O2). Unlabeled substrate Fc from endogenous sources was higher in Δ337T, but ACAC Fc was lower. Fluxes through CAC, lactate, ACAC, and FFA were reduced in Δ337T. CE and Fc differences were reversed by pacing Δ337T to Con rates, accompanied by an increase in FFA Fc. Δ337T hearts lacked the ability to increase MV˙ O2. Decreases in protein expression for glucose transporter-4 and hexokinase-2 and increases in pyruvate dehydrogenase kinase-2 and -4 suggest that these hearts are unable to increase carbohydrate oxidation in response to stress. These data show that Δ337T alters the metabolic phenotype in murine heart by reducing substrate flux for multiple pathways. Some of these changes are heart rate dependent, indicating that the substrate shift may represent an accommodation to altered contractile protein kinetics, which can be disrupted by pacing stress.

  17. Aging Impairs Myocardial Fatty Acid and Ketone Oxidation and Modifies Cardiac Functional and Metabolic Responses to Insulin in Mice

    SciTech Connect

    Hyyti, Outi M.; Ledee, Dolena; Ning, Xue-Han; Ge, Ming; Portman, Michael A.

    2010-07-02

    Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4–6 mo) and aged (22–24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing 13C-labeled free fatty acids (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)α and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.

  18. Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca2+ overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats

    PubMed Central

    Liu, Yue-Tao; Zhou, Chao; Jia, Hong-Mei; Chang, Xing; Zou, Zhong-Mei

    2016-01-01

    Xin-Ke-Shu (XKS) is a traditional Chinese patent medicine used for treatment of coronary heart diseases in China. However, its mechanism of action is still unclear. In this paper, the mediation of XKS on the isoproterenol (ISO)-induced myocardial infarction (MI) rat were evaluated based on a tissue-targeted metabonomics in vitro/vivo. The result indicated that twelve metabolic pathways were involved in the therapeutic effect of XKS in vivo, where seven pathways were associated with the Ca2+ overloading mechanism. In agreement with regulation on metabolic variations, XKS markedly reversed the over-expressions of three involved proteins including phospholipase A2 IIA (PLA2 IIA), calcium/calmodulin-dependent protein kinase II (CaMK II) and Pro-Caspase-3. The metabolic regulations of XKS on H9c2 cell also partially confirmed its metabolic effect. These metabolic characteristics in vitro/vivo and western blotting analysis suggested that XKS protected from MI metabolic perturbation major via inhibition of Ca2+ overloading mechanism. Furthermore, 11 active ingredients of XKS exerted steady affinity with the three proteins through the molecular docking study. Our findings indicate that the metabonomics in vitro/vivo combined with western blotting analysis offers the opportunity to gain insight into the comprehensive efficacy of TCMs on the whole metabolic network. PMID:27457884

  19. Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca(2+) overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats.

    PubMed

    Liu, Yue-Tao; Zhou, Chao; Jia, Hong-Mei; Chang, Xing; Zou, Zhong-Mei

    2016-01-01

    Xin-Ke-Shu (XKS) is a traditional Chinese patent medicine used for treatment of coronary heart diseases in China. However, its mechanism of action is still unclear. In this paper, the mediation of XKS on the isoproterenol (ISO)-induced myocardial infarction (MI) rat were evaluated based on a tissue-targeted metabonomics in vitro/vivo. The result indicated that twelve metabolic pathways were involved in the therapeutic effect of XKS in vivo, where seven pathways were associated with the Ca(2+) overloading mechanism. In agreement with regulation on metabolic variations, XKS markedly reversed the over-expressions of three involved proteins including phospholipase A2 IIA (PLA2 IIA), calcium/calmodulin-dependent protein kinase II (CaMK II) and Pro-Caspase-3. The metabolic regulations of XKS on H9c2 cell also partially confirmed its metabolic effect. These metabolic characteristics in vitro/vivo and western blotting analysis suggested that XKS protected from MI metabolic perturbation major via inhibition of Ca(2+) overloading mechanism. Furthermore, 11 active ingredients of XKS exerted steady affinity with the three proteins through the molecular docking study. Our findings indicate that the metabonomics in vitro/vivo combined with western blotting analysis offers the opportunity to gain insight into the comprehensive efficacy of TCMs on the whole metabolic network. PMID:27457884

  20. Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome.

    PubMed

    Donner, Daniel G; Elliott, Grace E; Beck, Belinda R; Bulmer, Andrew C; Lam, Alfred K; Headrick, John P; Du Toit, Eugene F

    2016-01-01

    The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS. PMID:26584015

  1. TREATMENT OF THE METABOLIC SYNDROME: THE IMPACT OF LIFESTYLE MODIFICATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Along with the increasing prevalence of obesity comes a constellation of metabolic derangements: dyslipidemias, hypertension, insulin resistance, and glucose intolerance, as well as increased prothrombotic and inflammatory markers. The association of these factors has been termed the "metabolic synd...

  2. Delayed clopidogrel transit during myocardial infarction evident on angiography.

    PubMed

    Ghobrial, Joanna; Gibson, C Michael; Pinto, Duane S

    2015-05-01

    We describe the case of a patient with non-ST segment elevation myocardial infarction (NSTEMI) where a limitation of oral clopidogrel loading prior to percutaneous coronary intervention (PCI) was directly visualized on angiography. Clopidogrel is a thienopyridine antiplatelet agent used in acute coronary syndromes. It reduces platelet aggregation via inhibition of the P2Y12 receptor. Clopidogrel is an inactive metabolite that is metabolized into the active metabolite by the cytochrome P450 isoenzymes located mostly in the liver and partly in the gastrointestinal system. As such, it requires at least 2 hours to reach maximal effect. A 63-year-old female went to an outside facility where she was diagnosed with NSTEMI and underwent angiography. She was administered 324 mg of aspirin and 600 mg of clopidogrel, and was transferred to our facility. Upon arrival, approximately 1.5 hours after the oral loading dose, the clopidogrel tablets were visualized intact in the stomach during angiography, implying a very low likelihood of adequate absorption or antiplatelet effect. This observation raises the concern that delayed gastrointestinal transit, apart from other metabolic derangements, may be a factor in achieving optimal platelet inhibition using oral agents. PMID:25929306

  3. A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism.

    PubMed

    Ko, Toshiyuki; Utanohara, Yuko; Suzuki, Yasuhiro; Kurihara, Makiko; Iguchi, Nobuo; Umemura, Jun; Sumiyoshi, Tetsuya; Tomoike, Hitonobu

    2016-01-01

    Simultaneous dual-isotope SPECT imaging with 201Tl and (123)I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion-metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, (99m)Tc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of (99m)Tc and (123)I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between (99m)Tc and (123)I. In the subsequent clinical study, (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by (99m)Tc-MIBI and (123)I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional (201)Tl

  4. Comparative analysis of changes of myocardial angiogenesis and energy metabolism in postinfarction and diabetic damage of rat heart.

    PubMed

    Afanasiev, Sergey A; Egorova, Margarita V; Kondratyeva, Dina S; Batalov, Roman E; Popov, Sergey V

    2014-01-01

    Comparative study of changes in myocardial activity of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), and capillary density distribution in the experimental models of diabetic and postinfarction damage of rat heart was performed. Data showed that decrease in LDH and SDH activities was observed in both pathologies which can suggest abnormal processes of glycolysis and oxidative phosphorylation in cardiac mitochondria. Activity of LDH and SDH in combined pathologies was comparative with the corresponding values of these parameters in control group. The authors hypothesize that these differences can be caused by specifics of myocardial vascularization. The results of the study showed that an increase in capillary density was found in all groups of rats with pathologies compared with control group. However, no significant differences in the intensity of angiogenesis processes were found between groups with pathologies. PMID:24689068

  5. /sup 13/N-labeled L-amino acids for in vivo assessment of local myocardial metabolism

    SciTech Connect

    Baumgartner, F.J.; Barrio, J.R.; Henze, E.; Schelbert, H.R.; MacDonald, N.S.; Phelps, M.E.; Kuhl, D.E.

    1981-06-01

    The hot cell synthesis of sterile, pyrogen-free /sup 13/N-labeled L-amino acids was accomplished by employing the appropriate immobilized enzymes on a CNBr-activated Sepharose support and using remote, semiautomated systems. The syntheses were completed 6-12 min after cyclotron production of (/sup 13/N)ammonia. Myocardial time-activity curves after intracoronary injection of /sup 13/N-labeled L-amino acids in dogs were triexponential in both normal and ischemic myocardium. Higher retention of /sup 13/N activity was observed in ischemic segments. Positron computed tomography imaging also showed increased uptake of /sup 13/N-labeled L-glutamate and L-alanine in ischemic segments compared with normal myocardium when blood flow corrections were made. Myocardial transaminases are primarily responsible for the observed retention fractions. It suggests the participation of the carbon skeletons of these amino acids in the Krebs cycle.

  6. Plasma Metabolic Profile Determination in Young ST-segment Elevation Myocardial Infarction Patients with Ischemia and Reperfusion: Ultra-performance Liquid Chromatography and Mass Spectrometry for Pathway Analysis

    PubMed Central

    Huang, Lei; Li, Tong; Liu, Ying-Wu; Zhang, Lei; Dong, Zhi-Huan; Liu, Shu-Ye; Gao, Ying-Tang

    2016-01-01

    Background: This study was to establish a disease differentiation model for ST-segment elevation myocardial infarction (STEMI) youth patients experiencing ischemia and reperfusion via ultra-performance liquid chromatography and mass spectrometry (UPLC/MS) platform, which searches for closely related characteristic metabolites and metabolic pathways to evaluate their predictive value in the prognosis after discharge. Methods: Forty-seven consecutive STEMI patients (23 patients under 45 years of age, referred to here as “youth,” and 24 “elderly” patients) and 48 healthy control group members (24 youth, 24 elderly) were registered prospectively. The youth patients were required to provide a second blood draw during a follow-up visit one year after morbidity (n = 22, one lost). Characteristic metabolites and relative metabolic pathways were screened via UPLC/MS platform base on the Kyoto encyclopedia of genes and genomes (KEGG) and Human Metabolome Database. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of characteristic metabolites in the prognosis after discharge. Results: We successfully established an orthogonal partial least squares discriminated analysis model (R2X = 71.2%, R2Y = 79.6%, and Q2 = 55.9%) and screened out 24 ions; the sphingolipid metabolism pathway showed the most drastic change. The ROC curve analysis showed that ceramide [Cer(d18:0/16:0), Cer(t18:0/12:0)] and sphinganine in the sphingolipid pathway have high sensitivity and specificity on the prognosis related to major adverse cardiovascular events after youth patients were discharged. The area under curve (AUC) was 0.671, 0.750, and 0.711, respectively. A follow-up validation one year after morbidity showed corresponding AUC of 0.778, 0.833, and 0.806. Conclusions: By analyzing the plasma metabolism of myocardial infarction patients, we successfully established a model that can distinguish two different factors simultaneously: pathological

  7. Energy Metabolic Re-Programming in the Hypertrophied and Early Stage Failing Heart: A Multi-systems Approach

    PubMed Central

    Lai, Ling; Leone, Teresa C.; Keller, Mark P.; Martin, Ola J.; Broman, Aimee T.; Nigro, Jessica; Kapoor, Kapil; Koves, Timothy R.; Stevens, Robert; Ilkayeva, Olga R.; Vega, Rick B.; Attie, Alan D.; Muoio, Deborah M.; Kelly, Daniel P.

    2014-01-01

    Background An unbiased systems approach was utilized to define energy metabolic events that occur during the pathologic cardiac remodeling en route to heart failure. Methods and Results Combined myocardial transcriptomic and metabolomic profiling were conducted in a well-defined mouse model of heart failure that allows comparative assessment of compensated and decompensated (heart failure) forms of cardiac hypertrophy due to pressure overload. The pressure overload datasets were also compared with the myocardial transcriptome and metabolome for an adaptive (physiological) form of cardiac hypertrophy due to endurance exercise training. Comparative analysis of the datasets led to the following conclusions: 1) expression of most genes involved in mitochondrial energy transduction were not significantly changed in the hypertrophied or failing heart, with the notable exception of a progressive downregulation of transcripts encoding proteins and enzymes involved in myocyte fatty acid transport and oxidation during the development of heart failure; 2) tissue metabolite profiles were more broadly regulated than corresponding metabolic gene regulatory changes, suggesting significant regulation at the post-transcriptional level; 3) metabolomic signatures distinguished pathologic and physiological forms of cardiac hypertrophy and served as robust markers for the onset of heart failure; and 4) the pattern of metabolite derangements in the failing heart suggests “bottlenecks” of carbon substrate flux into the Krebs cycle. Conclusions Mitochondrial energy metabolic derangements that occur during the early development of pressure overload-induced heart failure involve both transcriptional and post-transcriptional events. A subset of the myocardial metabolomic profile robustly distinguished pathologic and physiologic cardiac remodeling. PMID:25236884

  8. Alterations in myocardial metabolism and function at rest in stable angina pectoris: relations with the amount of exercise-induced thallium-201 perfusion defect

    SciTech Connect

    De Kock, M.; Melin, J.A.; Pouleur, H.; Rousseau, M.F.

    1986-01-01

    The relation between the amount of exercise-induced ischemia and alterations in left ventricular (LV) function and metabolism at rest was studied in 18 coronary patients with stable angina pectoris. An ischemic defect area score was computed from quantitative exercise thallium-201 (Tl-201) scintigraphy; this estimation of the amount of ischemic myocardium was used to classify the patients in group I (n = 8; score less than 15%, mean 6.7 +/- 2.5%) and II (n = 10; score greater than 15%; mean 27.2 +/- 8.9%). Hemodynamics and metabolism were studied in basal state. No patient had anginal pain during the study, and the extent of angiographic coronary artery disease (CAD) was comparable in the two groups. Heart rate, aortic pressure, coronary blood flow, and myocardial oxygen uptake were also similar in both groups. However, ejection fraction was reduced in group II (51 +/- 13 vs 63 +/- 5%; p less than 0.01) and LV relaxation was impaired as shown by the increase in time-constant of isovolumic pressure fall (55 +/- 16 vs 44 +/- 6 ms in group I; p less than 0.05); the LV end-diastolic pressure was also increased in group II (19 +/- 8 vs 10 +/- 4 mmHg in group l; p less than 0.05). Furthermore, in group II, myocardial lactate uptake was reduced (4 +/- 19 vs 30 +/- 29 mumole/min in group I; p less than 0.01) and the productions of alanine and glutamine were augmented (-7.5 +/- 4.4 vs -4.6 +/- 1.6 mumole/min in group I; p less than 0.05).

  9. Avoiding occlusal derangement in facial fractures: An evidence based approach.

    PubMed

    Mendonca, Derick; Kenkere, Deepika

    2013-05-01

    Facial fractures with occlusal derangement describe any fracture which directly or indirectly affects the occlusal relationship. Such fractures include dento-alveolar fractures in the maxilla and mandible, midface fractures - Le fort I, II, III and mandible fractures of the symphysis, parasymphysis, body, angle, and condyle. In some of these fractures, the fracture line runs through the dento-alveolar component whereas in others the fracture line is remote from the occlusal plane nevertheless altering the occlusion. The complications that could ensue from the management of maxillofacial fractures are predominantly iatrogenic, and therefore can be avoided if adequate care is exercised by the operating surgeon. This paper does not emphasize on complications arising from any particular technique in the management of maxillofacial fractures but rather discusses complications in general, irrespective of the technique used. PMID:24501457

  10. Body posture evaluations in subjects with internal temporomandibular joint derangement.

    PubMed

    Munhoz, Wagner Cesar; Marques, Amélia Pasqual

    2009-10-01

    The aim of this study was to verify possible relationships between global body posture and temporomandibular joint internal derangement (TMJ-id), by comparing 30 subjects presenting typical TMJ-id signs to 20 healthy subjects. Body posture was assessed using the analysis of muscle chains on several photographs. Results show a higher frequency of lifted shoulders (p=0.04) and of changes in the antero-internal hip chain (p=0.02) in the test group, but no further differences were found significant between the control and test groups. The test group was then divided into three subgroups according to the Helkimo index of temporomandibular disorder severity. Again, no significant differences were found between the subgroups. However, there was a trend noticed in the group with the most severe dysfunction, to present a forward head and shoulders posture. Results are discussed in light of previous studies using the same sample. PMID:19891257

  11. Effects of catecholamines on rat myocardial metabolism. II. Influence of catecholamines on 32p-incorporation into rat myocardial adenylic nucleotides and their turn-over.

    PubMed

    Merouze, P; Gaudemer, Y; Gautheron, D

    1975-01-01

    1. The influence of catecholamines (adrenaline and noradrenaline) on 32Pi incorporation into intracellular phosphate and adenylic nucleotides has been studied on rat myocardium slices; consequently, the turn-over of nucleotides could be determined and compared under the influence of these two hormones. 2. In order to specify the site of action of these catecholamines, several inhibitors and activators of energetic metabolism were included in the incubation medium: 3'5'-AMP, caffein, ouabain, oligomycin, rotenone + antimycin. 3. Both catecholamines favour Pi exchanges between intra and extracellular spaces; ATP turn-over is greatly increased, while ADP turn-over is slightly decreased, and 32P-incorporation into ADP is increased. 4. 3'5'-AMP and caffein are without effect on Pi penetration; however, caffein increases catecholamine effects on this penetration. ATP turn-over is slightly increased by 3'5'-AMP or caffein. 5. Ouabain decreases ATP turn-over but does not prevent the adrenaline induced acceleration. Inhibitors of oxidative phosphorylation and electron transport decrease ATP-turn-over severely; this inhibition is not released by catecholamines. 6. It is concluded that the catecholamine effects observed are dependent on the oxidative phosphorylations process. The increase of Pi exchange by catecholamines may be related to the increase of extracellular space and cation translocations we observed with the hormones. PMID:173417

  12. Assessment of the effects of dobutamine on myocardial blood flow and oxidative metabolism in normal human subjects using nitrogen-13 ammonia and carbon-11 acetate.

    PubMed

    Krivokapich, J; Huang, S C; Schelbert, H R

    1993-06-01

    The dual purposes of this study with positron emission tomography were to measure the effects of dobutamine on myocardial blood flow and oxidative metabolism, and to compare carbon-11 (C-11) acetate versus nitrogen-13 (N-13) ammonia in quantitating flow in normal subjects. Flow was quantitated with N-13 ammonia at rest and at peak dobutamine infusion (40 micrograms/kg/min) in 21 subjects. In 11 subjects, oxidative metabolism was also estimated at rest and peak dobutamine infusion using the clearance rate of C-11 acetate, k mono (min-1). A 2-compartment kinetic model was applied to the early phase of the C-11 acetate data to estimate flow. The rest and peak dobutamine rate-pressure products were 7,318 +/- 1,102 and 19,937 +/- 3,964 beats/min/mm Hg, respectively, and correlated well (r = 0.77) with rest and peak dobutamine flows of 0.77 +/- 0.14 and 2.25 ml/min/g determined using N-13 ammonia as a flow tracer. Rest and dobutamine flows estimated with C-11 acetate were highly correlated with those determined with N-13 ammonia (r = 0.92). k mono increased from 0.05 +/- 0.01 to 0.18 +/- 0.02 min-1, and correlated highly with the increase in flows (r = 0.91) and rate-pressure products (r = 0.94). Thus, the increase in cardiac demand associated with dobutamine is highly correlated with an increase in supply and oxidative metabolism. C-11 acetate is a unique tracer that can be used to image both flow and metabolism simultaneously. PMID:8498380

  13. Effects of metabolic and myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic neuropathy in type 2 diabetes mellitus: A prospective study in Japanese patients*

    PubMed Central

    Komori, Hiromi

    2005-01-01

    Background: In diabetic patients, cardiac autonomic neuropathy is an important factor affecting prognosis. Whether this condition in diabetic patients is caused directly by neurovisceral metabolic disorder and/or indirectly by micro circulation remains to be clarified. Objective: The aim of this study was to determine whether cardiac sympathetic nerve dysfunction can be detected using adenosine triphosphate (ATP) testing, while also investigating the effects of metabolic and/or myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic nerve dysfunction in patients with type 2 diabetes mellitus (DM-2) in Japan. Methods: This prospective study was performed at the Division of Diabetology Department of Internal Medicine, Toho University, Ohashi Hospital, Tokyo, Japan. Patients aged ≥ 18 years with DM-2 with no abnormalities on electrocardiography (ECG) or echocardiography were enrolled. An ATP thallium (Tl)-201 myocardial scintigraphy test (ATP test) and iodine (I)-123 metaiodobenzylguanidine (MIBG) scintigraphy were performed. ATP was administered by continuous IV infusion over 6 minutes at 0.16 mg/kg · min. Five minutes after the ATP infusion was started, T1-201 111 MBq IV was administered. Single-photon emission computed tomography (SPECT) imaging was begun immediately after the end of ATP infusion and was completed 3 hours after stress to show washout from stress to rest. I-123 MIBG 111 MBq IV was administered. A planar image from the front side and a SPECT image (early phase) was obtained 15 to 30 minutes later. After 3 hours, a planar image from the front side and a SPECT image (late phase) were obtained to show washout from stress to rest. The mean TI washout rate (ATP-WR) and heart-to-mediastinum (H/M) ratio in the late-phase scintigraphic images and the washout rate of MIBG (MIBG-WR) in the left ventricle was determined. The correlations of these measurements with the mean values of glycosylated hemoglobin (HbA1c) and fasting

  14. Clinical Disorders of Phosphorus Metabolism

    PubMed Central

    Yu, George C.; Lee, David B. N.

    1987-01-01

    Deranged phosphorus metabolism is commonly encountered in clinical medicine. Disturbances in phosphate intake, excretion and transcellular shift account for the abnormal serum levels. As a result of the essential role played by phosphate in intracellular metabolism, the clinical manifestations of hypophosphatemia and hyperphosphatemia are extensive. An understanding of the pathophysiology of various phosphate disorders is helpful in guiding therapeutic decisions. Images PMID:3321712

  15. Internal derangements of the temporomandibular joint: diagnosis by direct sagittal computed tomography

    SciTech Connect

    Manzione, J.V.; Katzberg, R.W.; Brodsky, G.L.; Seltzer, S.E.; Mellins, H.Z.

    1984-01-01

    The authors performed direct sagittal computed tomography (CT) on 4 cadaver temporomandibular joints (TMJ) and examined 51 TMJs in 47 patients clinically. The results were correlated with cadaver anatomical sections and clinical arthrographic findings. A fat plane between the bellies of the lateral pterygoid muscles, termed the ''lateral pterygoid fat pad,'' served as the anatomical basis for detection of internal derangements by CT. CT was 94% accurate in detecting meniscal derangements and 96% accurate in detecting degenerative arthritis. The authors suggest that CT rather than arthrography be employed as the primary TMJ imaging modality when internal derangement or arthritis is suspected.

  16. Inhomogeneous derangement of cardiac autonomic nerve control in diabetic rats.

    PubMed

    Sanyal, Shamarendra Nath; Arita, Makoto; Ono, Katsushige

    2002-03-01

    The present study compared autonomic nervous function in Kob [Spontaneously Diabetic, Bio-Breeding (BB)] rats with control Wistar rats to determine the development of cardiac neuropathy in diabetic rats. Telemetric ECG signals were obtained from an ECG radio-transmitter placed in a dorsal subcutaneous pouch of male Kob and Wistar rats for 30min every 6h at a sample rate of 5kHz. Heart rate (HR) and HR variability (HRV) were analyzed in each group by power spectrograms obtained by a fast Fourier transform algorithm. RR interval, total power (TP), low frequency (LF) power (0.04-0.67 Hz), high frequency (HF) power (0.79-1.48 Hz) and LF/HF ratio were also measured. The Kob rats had lower HRV than the control Wistar rats; HR, TP, and HF power, but not the LF/HF ratio, in the Kob rats were significantly lower than those of the control rats (p<0.001). However, in the Kob rats the response of these parameters to a muscarinic antagonist (atropine: 2mg/kg) was left intact, but their response to a beta-adrenergic antagonist (propranolol: 4mg/kg) was impeded. Autonomic nervous control of HR in spontaneously diabetic rats was inhomogeneously deranged in terms of the balance in sympathetic and parasympathetic tone, not only in the baseline condition, but also in the regulatory systems, including postsynaptic receptor function. PMID:11922279

  17. Maternal hypoxia decreases capillary supply and increases metabolic inefficiency leading to divergence in myocardial oxygen supply and demand.

    PubMed

    Hauton, David; Al-Shammari, Abdullah; Gaffney, Eamonn A; Egginton, Stuart

    2015-01-01

    Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14C-labelled glucose and 3H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve

  18. Maternal Hypoxia Decreases Capillary Supply and Increases Metabolic Inefficiency Leading to Divergence in Myocardial Oxygen Supply and Demand

    PubMed Central

    Hauton, David; Al-Shammari, Abdullah; Gaffney, Eamonn A.; Egginton, Stuart

    2015-01-01

    Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14C-labelled glucose and 3H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve

  19. Utility of Glycated Hemoglobin for Assessment of Glucose Metabolism in Patients With ST-Segment Elevation Myocardial Infarction.

    PubMed

    Aggarwal, Bhuvnesh; Shah, Gautam K; Randhawa, Mandeep; Ellis, Stephen G; Lincoff, Abraham Michael; Menon, Venu

    2016-03-01

    Glycated hemoglobin (HbA1c) is an approved and widely used laboratory investigation for diagnosis of diabetes that is not affected by acute changes in blood glucose. Our aim was to analyze the extent to which routine HbA1c measurements diagnose unknown diabetes mellitus (DM) in patients presenting with ST-segment elevation myocardial infarction (STEMI). We also compared outcomes in patients with newly diagnosed DM, previously established DM and those without DM. Consecutive patients undergoing PCI for STEMI from January 2005 to December 2012 were included and routinely performed admission HbA1c was used to identify patients with previously undiagnosed DM (HbA1c ≥6.5 and no history of DM or DM therapy) and pre-DM (HbA1c 5.7% to 6.4%). Overall 1,686 consecutive patients underwent primary percutaneous coronary intervention for STEMI during the study period and follow-up data were available for 1,566 patients (90%). A quarter of the patients (24%, n = 405) had history of DM, 7% (n = 118) had previously undiagnosed DM, and 38.7% (n = 652) had pre-DM. Mortality was comparable in patients with known DM and newly diagnosed DM both in-hospital (11.1% vs 11.9%, p = 0.87) and at 3-year follow-up (27.3% and 24%). Patients with DM, including those who were newly diagnosed, had higher mortality at 3 years (26.5%) compared to those with pre-DM (12.1%) or no dysglycemia (11.2%, p <0.01). In conclusion, a substantial number of patients with STEMI have previously undiagnosed DM (7%). These patients have similar in-hospital and long-term mortality as those with known DM, and outcomes are inferior to patients without dysglycemia. PMID:26768673

  20. Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice

    PubMed Central

    Qipshidze, Natia; Tyagi, Neetu; Sen, Utpal; Givvimani, Srikanth; Metreveli, Naira; Lominadze, David

    2010-01-01

    Myocardial infarction (MI) results in significant metabolic derangement, causing accumulation of metabolic by product, such as homocysteine (Hcy). Hcy is a nonprotein amino acid generated during nucleic acid methylation and demethylation of methionine. Folic acid (FA) decreases Hcy levels by remethylating the Hcy to methionine, by 5-methylene tetrahydrofolate reductase (5-MTHFR). Although clinical trials were inconclusive regarding the role of Hcy in MI, in animal models, the levels of 5-MTHFR were decreased, and FA mitigated the MI injury. We hypothesized that FA mitigated MI-induced injury, in part, by mitigating cardiac remodeling during chronic heart failure. Thus, MI was induced in 12-wk-old male C57BL/J mice by ligating the left anterior descending artery, and FA (0.03 g/l in drinking water) was administered for 4 wk after the surgery. Cardiac function was assessed by echocardiography and by a Millar pressure-volume catheter. The levels of Hcy-metabolizing enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 5-MTHFR, were estimated by Western blot analyses. The results suggest that FA administered post-MI significantly improved cardiac ejection fraction and induced tissue inhibitor of metalloproteinase, CBS, CSE, and 5-MTHFR. We showed that FA supplementation resulted in significant improvement of myocardial function after MI. The study eluted the importance of homocysteine (Hcy) metabolism and FA supplementation in cardiovascular disease. PMID:20802128

  1. Myocardial Noncompaction Presenting With Myocardial Bridge

    PubMed Central

    Shen, Yuechun; Li, Xinchun; Lu, Dongfeng; Xiao, Aiyi; Li, Jun

    2015-01-01

    Abstract Myocardial noncompaction, namly isolated noncompaction of the left ventricular myocardium (NVM), is a rare congenital disease. It can be either seen in the absence of other cardiac anomalies, or associated with other congenital cardiac defects, mostly stenotic lesions of the left ventricular outflow tract. A myocardial bridge (MB) is thought being associated with coronary heart disease, such as coronary spasm, arrhythmia, and so on. The significance of MB in association with other congenital cardiac conditions is unknown. We report a novel case who was presented NVM and MB. A 34-year-old man complained of chest prickling-like pain and dizzy for 1 year. His blood pressure was 110/70 mm Hg. Echocardiograph revealed increased trabeculations below the level of papillary muscle of left ventricle (LV); deep intertrabecular recesses in the endocardial wall of LV particularly in apex free wall; and LV ejection fraction of 57%. A coronary computerized tomography scan showed that part, 38.9 cm, of left descending artery tunnel was surrounding by cardiac muscles rather than resting on top of the myocardium. The therapeutics interventions included lifestyle cares, agents of anti-ischemia and improvement myocardial cell metabolism. The patient was followed up for 2.6 years, and his general condition was stable. This case indicates that NVM can be developed with MB, and the complete diagnosis of NVM and MB should be made by different image studies. PMID:26356695

  2. The Role of Intraarticular Platelet Rich Plasma (PRP) Injection in Patients with Internal Knee Derangements.

    PubMed

    Razaq, Sarah; Ejaz, Amer; Rao, Sajid Ejaz; Yasmeen, Rehana; Arshad, M Aleem

    2015-09-01

    Platelet Rich Plasma (PRP) is an emerging biotechnology which uses patient's own blood components to create healing effect to their own injured tissues. This study was carried out to evaluate the clinical effects, adverse reactions and patient satisfaction after intraarticular injection of platelet rich plasma in a small group of patients with internal derangements of knee at Combined Military Hospital, Panoaqil, Pakistan. In this single center, open study, 10 patients with internal derangements of knee fulfilling the inclusion criteria received two doses of 3 ml of platelet rich plasma as intraarticular knee injection at two weeks interval. All patients were evaluated at 0, 4 and 12 weeks after treatment using IKDC, TEGNER, KOOS and VAS. Adverse events and patient's satisfaction was recorded. There was significant improvement in all scores. Intraarticular PRP injection is safe and effective method in the conservative treatment of internal knee derangements. PMID:26374371

  3. Frequency of Electrolyte Derangement after Transurethral Resection of Prostate: Need for Postoperative Electrolyte Monitoring

    PubMed Central

    Aziz, Wajahat; Ather, M. Hammad

    2015-01-01

    Objective. To determine the electrolyte derangement following transurethral resection of prostate (TURP). Methods. All patients undergoing TURP from June 2012 to April 2013 were included. Preoperative electrolytes were performed within a week of procedures. Monopolar TURP using 1.5% glycine was performed. Serum Na+ and K+ were assessed within 1 hour postoperatively and subsequently if clinically indicated. Results. The study included 280 patients. Sixty-six patients (23.6%) had electrolyte derangement after TURP. Patients with deranged electrolytes were older (mean age of 73.41 ± 4.08 yrs. versus 68.93 yrs. ± 10.34) and had a longer mean resection time (42.5 ± 20.04 min versus 28.34 ± 14.64 min). Mean weight of tissue resected (41.49 ± 34.46 g versus 15.33 ± 9.74 g) and volume of irrigant used (23.55 ± 15.20 L versus 12.81 ± 7.57 L) were also significantly higher in patients with deranged electrolytes (all p = 0.00). On multivariate logistic regression analysis preoperative sodium level was found to be a significant predictor of postoperative electrolyte derangement (odds ratio 0.267, S.E. = 0.376, and p value = 0.00). Conclusion. Electrolyte derangement occurs in older patients, with larger amount of tissue and longer time of resection and higher volume of irrigant, and in those with lower serum preoperative sodium levels. PMID:26089874

  4. Myocardial Bridge

    MedlinePlus

    ... artery. See also on this site: Ask a Texas Heart Institute Doctor: Search "myocardial bridge" Updated August ... comments. Terms of Use and Privacy Policy © Copyright Texas Heart Institute All rights reserved.

  5. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

  6. Supportive Management of Mucositis and Metabolic Derangements in Head and Neck Cancer Patients.

    PubMed

    Bonomi, Marcelo; Batt, Katharine

    2015-01-01

    Oral mucositis (OM) is among the most undesirable, painful, and expensive toxicities of cytotoxic cancer therapy, and is disheartening for patients and frustrating for caregivers. Accurate assessment of the incidence of OM has been elusive, but accumulating data suggests that reported OM frequency is significantly less than its actual occurrence. It has been suggested that over 90% of head and neck cancer (HNC) patients receiving radiotherapy (RT) with concurrent cisplatin experience severe OM with symptoms of extreme pain, mucosal ulceration and consequent limitations in swallowing and achieving adequate nutritional intake. This panoply of symptoms inevitably impacts a patients' quality of life and their willingness to continue treatment. In spite of all the advances made in understanding the pathophysiology of OM, there is still no prophylactic therapy with proven efficacy. Strategies to limit the extent of OM and to manage its symptomatology include basic oral care, supportive medications, nutritional support and targeting aggressive treatments to high-risk patients. This review focuses on OM recognition, preventive measurements, and symptom-management strategies. PMID:26404378

  7. Bone mineral measurement from Apollo experiment M-078. [derangement of bone mineral metabolism in spacecrews

    NASA Technical Reports Server (NTRS)

    Vogel, J. M.; Rambaut, P. C.; Smith, M. C., Jr.

    1974-01-01

    Loss of mineral from bone during periods of immobilization, recumbency, or weightlessness is examined. This report describes the instrumentation, technique, and bone mineral changes observed preflight and postflight for the Apollo 14, 15, and 16 missions. The bone mineral changes documented during the Apollo Program are reviewed, and their relevance to future missions is discussed.

  8. Supportive Management of Mucositis and Metabolic Derangements in Head and Neck Cancer Patients

    PubMed Central

    Bonomi, Marcelo; Batt, Katharine

    2015-01-01

    Oral mucositis (OM) is among the most undesirable, painful, and expensive toxicities of cytotoxic cancer therapy, and is disheartening for patients and frustrating for caregivers. Accurate assessment of the incidence of OM has been elusive, but accumulating data suggests that reported OM frequency is significantly less than its actual occurrence. It has been suggested that over 90% of head and neck cancer (HNC) patients receiving radiotherapy (RT) with concurrent cisplatin experience severe OM with symptoms of extreme pain, mucosal ulceration and consequent limitations in swallowing and achieving adequate nutritional intake. This panoply of symptoms inevitably impacts a patients’ quality of life and their willingness to continue treatment. In spite of all the advances made in understanding the pathophysiology of OM, there is still no prophylactic therapy with proven efficacy. Strategies to limit the extent of OM and to manage its symptomatology include basic oral care, supportive medications, nutritional support and targeting aggressive treatments to high-risk patients. This review focuses on OM recognition, preventive measurements, and symptom-management strategies. PMID:26404378

  9. Mechanisms of Sudden Cardiac Death: Oxidants and Metabolism

    PubMed Central

    Yang, Kai-Chien; Kyle, John W.; Makielski, Jonathan C.; Dudley, Samuel C.

    2015-01-01

    Ventricular arrhythmia is the leading cause of sudden cardiac death (SCD). Deranged cardiac metabolism and abnormal redox state during cardiac diseases foment arrhythmogenic substrates through direct or indirect modulation of cardiac ion channel/transporter function. This review presents current evidence on the mechanisms linking metabolic derangement and excessive oxidative stress to ion channel/transporter dysfunction that predisposes to ventricular arrhythmias and SCD. As conventional anti-arrhythmic agents aiming at ion channels have proven challenging to use, targeting arrhythmogenic metabolic changes and redox imbalance may provide novel therapeutics to treat or prevent life-threatening arrhythmias and SCD. PMID:26044249

  10. Internal derangements of the temporomandibular joint: findings in the pediatric age group

    SciTech Connect

    Katzberg, R.W.; Tallents, R.H.; Hayakawa, K.; Miller, T.L.; Goske, M.J.; Wood, B.P.

    1985-01-01

    Findings in 31 pediatric patients with pain and dysfunction of the temporomandibular joint (TMJ) are reported. The average age was 14 years and the average duration of symptoms was 21.4 months. Internal derangements were found in 29 patients (94%) and degenerative arthritis in 13 (42%). In 12 patients (39%), the problem could be traced to an injury to the jaw. Secondary condylar hypoplasia was associated with the meniscal abnormality in 3 patients (10%). Further awareness of internal derangements of the TMJ in the pediatric population should permit greater recognition of their etiology. It is important that threatment be initiated as soon as possible, not only to minimize the development of osseous disease in young adults but also to prevent facial growth deformities.

  11. Derangement of the temporomandibular joint; a case study using Mechanical Diagnosis and Therapy.

    PubMed

    Krog, C; May, S

    2012-10-01

    Mechanical Diagnosis and Therapy (MDT) is widely used for spinal problems, and more recently the principles and mechanical syndromes have been applied to extremity musculoskeletal problems. One of the most common classifications is derangement syndrome, which describes a presentation in which repeated movements causes a decrease in symptoms and a restoration of restricted range of movement. The case study describes the application of repeated movements to a patient with a 7-year history of non-specific temporomandibular pain and reduced function, who had had lots of previous failed treatment. Examination using repeated movements resulted in a classification of derangement, and the patient rapidly responded in 4 treatment sessions, with an abolition of pain and full restoration of function, and remained improved after many years. The case study demonstrates the application of Mechanical Diagnosis and Therapy principles to a patient with a temporomandibular problem. PMID:22177711

  12. Evaluation of body posture in individuals with internal temporomandibular joint derangement.

    PubMed

    Munhoz, Wagner Cesar; Marques, Amélia Pasqual; de Siqueira, José Tadeu Tesseroli

    2005-10-01

    Temporomandibular dysfunctions (TMD) comprise a great number of disruptions that may affect the temporomandibular joint (TMJ), the masticatory muscles, or both. TMJ internal derangement is a specific type of TMD, of which the etiology and physiopathology are broadly unknown, but have been suggested to be linked to head, neck, and body posture factors. This study aimed at verifying possible relationships between body posture and TMJ internal derangements (TMJ-id), by comparing 30 subjects presenting typical TMJ-id signs to 20 healthy subjects. Subjects' clinical evaluations included anamnesis, stomatognatic system evaluation, and plotting analysis on body posture photographs. No statistically significant differences were found between the groups. Results do not support the assertion that body posture plays a role in causing or enhancing TMD; however, these results should be cautiously considered because of the small number of subjects evaluated and the many posture variables submitted to statistical procedures that lead to high standard deviations. PMID:16353467

  13. Suicide as a derangement of the self-sacrificial aspect of eusociality.

    PubMed

    Joiner, Thomas E; Hom, Melanie A; Hagan, Christopher R; Silva, Caroline

    2016-04-01

    Building upon the idea that humans may be a eusocial species (i.e., rely on multigenerational and cooperative care of young, utilize division of labor for successful survival), we conjecture that suicide among humans represents a derangement of the self-sacrificial aspect of eusociality. In this article, we outline the characteristics of eusociality, particularly the self-sacrificial behavior seen among other eusocial species (e.g., insects, shrimp, mole rats). We then discuss parallels between eusocial self-sacrificial behavior in nonhumans and suicide in humans, particularly with regard to overarousal states, withdrawal phenomena, and perceptions of burdensomeness. In so doing, we make the argument that death by suicide among humans is an exemplar of psychopathology and is due to a derangement of the self-sacrificial behavioral suite found among eusocial species. Implications and future directions for research are also presented. PMID:26524155

  14. Drug-Induced Metabolic Acidosis

    PubMed Central

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W.

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics. PMID:26918138

  15. Drug-Induced Metabolic Acidosis.

    PubMed

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs' characteristics. PMID:26918138

  16. [The effect of transcardiac galvanization on energy metabolism and the size of the area of the heart muscle lesion in experimental myocardial infarct].

    PubMed

    Maslov, A G; Karpov, R S; Smirnov, V P; Laptev, B I; Metelkin, A V

    1995-01-01

    A study was made of effects of transcardiac galvanization (TCG) on activities of a panel of oxidation-reduction enzymes as well as on the cardiac muscle content of high energy substrates, and size of the lesion area, in experimental myocardial infarction (EMI) in 50 albino male rats. After two TCG procedures, and at 24-h EMI, augmentation was found of activities of succinic dehydrogenase, lactate dehydrogenase, NADH-dehydrogenase, beta-hydroxybutyrate dehydrogenase, both in the area of profound ischemia and peri-infarction myocardium, this being accompanied with an increase in myocardial content of adenosine triphosphate, creatine phosphate, and glycogen, and reduction of the developing mass of necrosis. Stimulation of enzyme activity in the course on the enzyme complex and membrane-stabilizing action of this preformed physical factor. PMID:8846353

  17. [The effect of extracorporeal thermal-modified autologous plasma exchanges on dynamics of hormone-metabolic homeostasis indices in patients with acute myocardial infarction].

    PubMed

    Ust'iantseva, I M; Kreĭnes, V M; Panin, L E; Petukhova, O V; Khokhlova, O I; Agadzhanian, V V

    1998-01-01

    Changes of biochemical indexes in the blood of 56 patients with acute myocardial infarction against the background of conventional and complex treatment using plasma exchange of extracorporeal-termally modified autoplasma have been analysed. The findings show that complex treatment of patients with AMI, using plasma exchange of extracorporal-thermally modified autoplasma, leads to much earlier decrease of KPK, LDH, LDH-1 enzyme activity in blood; it indicates the reduction of the period of myocardiocyte function restoration. The usage of plasma exchange of extracorporeal-thermally modified autoplasma in patients with acute myocardial infarction is accompanied by the absence of increase of glucose concentration in blood (owing to the normalization of insulin production), favourable influence on stress-reaction of biological systems of organism decrease of atherogenity index. Optimisation and efficiency of AMI therapy during treatment in the hospital is possible, with plasma exchange of extracorporeal-thermally modified autoplasma included in complex therapy. PMID:9575618

  18. Imaging of myocardial fatty acid oxidation.

    PubMed

    Mather, Kieren J; DeGrado, Timothy R

    2016-10-01

    Myocardial fuel selection is a key feature of the health and function of the heart, with clear links between myocardial function and fuel selection and important impacts of fuel selection on ischemia tolerance. Radiopharmaceuticals provide uniquely valuable tools for in vivo, non-invasive assessment of these aspects of cardiac function and metabolism. Here we review the landscape of imaging probes developed to provide non-invasive assessment of myocardial fatty acid oxidation (MFAO). Also, we review the state of current knowledge that myocardial fatty acid imaging has helped establish of static and dynamic fuel selection that characterizes cardiac and cardiometabolic disease and the interplay between fuel selection and various aspects of cardiac function. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26923433

  19. Study Design for the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care) Trial: A Double-blind Randomized Controlled Trial of Intravenous Glucose, Insulin, and Potassium (GIK) for Acute Coronary Syndromes in Emergency Medical Services

    PubMed Central

    Selker, Harry P.; Beshansky, Joni R.; Griffith, John L.; D’Agostino, Ralph B.; Massaro, Joseph M.; Udelson, James E.; Rashba, Eric J.; Ruthazer, Robin; Sheehan, Patricia R.; Desvigne-Nickens, Patrice; Rosenberg, Yves D.; Atkins, James M.; Sayah, Assaad J.; Aufderheide, Tom P.; Rackley, Charles E.; Opie, Lionel H.; Lambrew, Costas T.; Cobb, Leonard A.; MacLeod, Bruce A.; Ingwall, Joanne S.; Zalenski, Robert J.; Apstein, Carl S.

    2014-01-01

    Background Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris (UAP) to acute myocardial infarction (AMI), and MI size. However, trials of hospital administration of IV GIK to patients with ST elevation MI (STEMI) have generally not shown favorable effects, possibly due to the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies. Objective The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK 1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and 2) administered in prehospital emergency medical service (EMS) settings, rather than later, in hospitals, following emergency department evaluation. Design IMMEDIATE was an EMS-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the US which enrolled 911 participants. Eligible were patients age 30 or older for whom a paramedic performed a 12-lead electrocardiogram (ECG)to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based ACI-TIPI (acute cardiac ischemia time-insensitive predictive instrument) indicated a > 75% probability of ACS, and/or the TPI (thrombolytic predictive instrument) indicated presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Pre-specified were the primary endpoint of progression of ACS to infarction, and as major secondary endpoints

  20. Metabolism, Metabolomics, and Nutritional Support of Patients with Sepsis.

    PubMed

    Englert, Joshua A; Rogers, Angela J

    2016-06-01

    Sepsis is characterized by profound changes in systemic and cellular metabolism that disrupt normal metabolic homeostasis. These metabolic changes can serve as biomarkers for disease severity. Lactate, a metabolite of anaerobic metabolism, is the most widely used ICU biomarker and it is incorporated into multiple management algorithms. Technological advances now make broader metabolic profiling possible, with early studies identifying metabolic changes associated with sepsis mortality. Finally, given the marked changes in metabolism in sepsis and the association of worse prognosis in patients with severe metabolic derangements, we summarize the seminal trials conducted to optimize nutrition in the ICU. PMID:27229648

  1. Metabolic endotoxemia with obesity: Is it real and is it relevant?

    PubMed

    Boutagy, Nabil E; McMillan, Ryan P; Frisard, Madlyn I; Hulver, Matthew W

    2016-05-01

    Obesity is associated with metabolic derangements in multiple tissues, which contribute to the progression of insulin resistance and the metabolic syndrome. The underlying stimulus for these metabolic derangements in obesity are not fully elucidated, however recent evidence in rodents and humans suggests that systemic, low level elevations of gut derived endotoxin (lipopolysaccharide, LPS) may play an important role in obesity related, whole-body and tissue specific metabolic perturbations. LPS initiates a well-characterized signaling cascade that elicits many pro- and anti-inflammatory pathways when bound to its receptor, Toll-Like Receptor 4 (TLR4). Low-grade elevation in plasma LPS has been termed "metabolic endotoxemia" and this state is associated with a heightened pro-inflammatory and oxidant environment often observed in obesity. Given the role of inflammatory and oxidative stress in the etiology of obesity related cardio-metabolic disease risk, it has been suggested that metabolic endotoxemia may serve a key mediator of metabolic derangements observed in obesity. This review provides supporting evidence of mechanistic associations with cell and animal models, and provides complimentary evidence of the clinical relevance of metabolic endotoxemia in obesity as it relates to inflammation and metabolic derangements in humans. Discrepancies with endotoxin detection are considered, and an alternate method of reporting metabolic endotoxemia is recommended until a standardized measurement protocol is set forth. PMID:26133659

  2. Deranged liver function tests in pregnancy: the importance of postnatal follow-up

    PubMed Central

    Stone, Sophia; Girling, Joanna C

    2009-01-01

    We report an asymptomatic 40-year-old woman with persistently deranged liver function tests found incidentally in the first trimester of her second pregnancy. No cause was apparent clinically, serologically or with imaging studies until a new finding of hepatomegaly led to a repeat ultrasound scan six weeks following delivery. A mass in the region of the common hepatic duct was confirmed to be a cholangiocarcinoma, with vascular invasion precluding curative surgical resection. This case highlights the need for close vigilance of patients with unexplained and persistently abnormal liver function tests, antenatally and postdelivery.

  3. One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial).

    PubMed

    Selker, Harry P; Udelson, James E; Massaro, Joseph M; Ruthazer, Robin; D'Agostino, Ralph B; Griffith, John L; Sheehan, Patricia R; Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin; Vickery, Ellen M; Atkins, James M; Aufderheide, Tom P; Sayah, Assaad J; Pirrallo, Ronald G; Levy, Michael K; Richards, Michael E; Braude, Darren A; Doyle, Delanor D; Frascone, Ralph J; Kosiak, Donald J; Leaming, James M; Van Gelder, Carin M; Walter, Gert-Paul; Wayne, Marvin A; Woolard, Robert H; Beshansky, Joni R

    2014-05-15

    The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (HR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced. PMID:24792735

  4. 1H-NMR-Based Metabolic Analysis of Human Serum Reveals Novel Markers of Myocardial Energy Expenditure in Heart Failure Patients

    PubMed Central

    Su, Liang; Lai, Wenyan; Wang, Peng; Xie, Zhibing; Xie, Zhiquan; Zeng, Qingchun; Ren, Hao; Xu, Dingli

    2014-01-01

    Objective Elevated myocardial energy expenditure (MEE) is related with reduced left ventricular ejection fraction, and has also been documented as an independent predictor of cardiovascular mortality. However, the serum small-molecule metabolite profiles and pathophysiological mechanisms of elevated MEE in heart failure (HF) are still lacking. Herein, we used 1H-NMR-based metabolomics analysis to screen for potential biomarkers of MEE in HF. Methods A total of 61 subjects were enrolled, including 46 patients with heart failure and 15 age-matched controls. Venous serum samples were collected from subjects after an 8-hour fast. An INOVA 600 MHz nuclear magnetic resonance spectrometer with Carr-Purcell-Melboom-Gill (CPMG) pulse sequence was employed for the metabolomics analysis and MEE was calculated using colored Doppler echocardiography. Metabolomics data were processed using orthogonal signal correction and regression analysis was performed using the partial least squares method. Results The mean MEE levels of HF patients and controls were 139.61±58.18 cal/min and 61.09±23.54 cal/min, respectively. Serum metabolomics varied with MEE changed, and 3-hydroxybutyrate, acetone and succinate were significantly elevated with the increasing MEE. Importantly, these three metabolites were independent of administration of angiotensin converting enzyme inhibitor, β-receptor blockers, diuretics and statins (P>0.05). Conclusions These results suggested that in patients with heart failure, MEE elevation was associated with significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate. These compounds could be used as potential serum biomarkers to study myocardial energy mechanism in HF patients. PMID:24505394

  5. Myocardial Ischemia: Lack of Coronary Blood Flow or Myocardial Oxygen Supply/Demand Imbalance?

    PubMed

    Heusch, Gerd

    2016-07-01

    Regional myocardial blood flow and contractile function in ischemic myocardium are well matched, and there is no evidence for an oxygen supply/demand imbalance. Thus, myocardial ischemia is lack of coronary blood flow with electric, functional, metabolic, and structural consequences for the myocardium. All therapeutic interventions must aim to improve blood flow to ischemic myocardium as much and as quickly as possible. PMID:27390331

  6. Assessment of myocardial viability.

    PubMed

    Travin, Mark I; Bergmann, Steven R

    2005-01-01

    The prevalence of left ventricular (LV) dysfunction and resultant congestive heart failure is increasing. Patients with this condition are at high risk for cardiac death and usually have significant limitations in their lifestyles. Although there have been advances in medical therapy resulting in improved survival and well being, the best and most definitive therapy, when appropriate, is revascularization. In the setting of coronary artery disease, accounting for approximately two thirds of cases of congestive heart failure, LV dysfunction often is not the result of irreversible scar but rather caused by impairment in function and energy use of still viable-myocytes, with the opportunity for improved function if coronary blood flow is restored. Patients with LV 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, whether using thallium-201, Tc-99m sestamibi, or Tc-99m 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 imaging with positron emission tomography radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularization, including some patients referred instead for cardiac transplantation. Other noninvasive modalities, such as stress echocardiography, also facilitate the assessment of myocardial viability, but there are advantages and disadvantages compared with the nuclear techniques. Nuclear imaging appears to require fewer viable cells for detection, resulting in a higher sensitivity but a lower specificity than stress

  7. [Myocardial viability, its importance for the therapeutic decision].

    PubMed

    Alexánderson, Erick; Ricalde, Alejandro; Meave, Aloha

    2005-01-01

    Myocardial viability detection is essential in patients with history of myocardial infarction whom develop ventricular dysfunction. Its detection influences the therapeutic decisions and the prognosis. Medical therapy in patients with ventricular dysfunction due to myocardial infarction and myocardial viability has been associated with higher morbidity and mortality rates than revascularization therapy, as well as improvements in the systolic function. Several imaging techniques used in the recognition of myocardial viability are available; these techniques are based on the assessment of the ventricular motion posterior to inotropic agents stimulation or on the demonstration of metabolic activity at the dysfunctional regions. In this study, some important aspects of each technique are reviewed, doing special emphasis in the utility of the Positron Emission Tomography (PET) which has been considered as the "gold standard" in the detection of myocardial viability. PMID:15909735

  8. A derangement of the brain wound healing process may cause some cases of Alzheimer's disease.

    PubMed

    Lehrer, Steven; Rheinstein, Peter H

    2016-08-01

    A derangement of brain wound healing may cause some cases of Alzheimer's disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimer's disease. Our hypothesis -- Alzheimer's disease is brain wound healing gone awry at least in some cases -- could be tested by measuring progression with biomarkers for the four stages of wound healing in humans or appropriate animal models. Autopsy studies might be done. Chronic traumatic encephalopathy might also result from the brain wound healing process. PMID:27585229

  9. Low-dose propranolol for multiple hepatic and cutaneous hemangiomas with deranged liver function.

    PubMed

    Tan, Swee Thong; Itinteang, Tinte; Leadbitter, Philip

    2011-03-01

    We report here the case of an infant with multiple hepatic and cutaneous infantile hemangiomas (IHs) associated with deranged liver function who was treated successfully with low-dose propranolol. We also discuss our recent data that show that IH is a developmental anomaly of hemogenic endothelium derived from primitive mesoderm with a neural crest-cell phenotype. We previously presented evidence that this hemogenic endothelium is governed by the renin-angiotensin system, which we propose can account for both the action of propranolol and the process of spontaneous involution of IH. We further speculate on the possibility of using inhibitors of angiotensin-converting enzyme and that of angiotensin II receptor 2 as potential alternative therapies. PMID:21357335

  10. Reactive arthritis in relation to internal derangements of the temporomandibular joint: a case control study.

    PubMed

    Lund, Bodil; Holmlund, Anders; Wretlind, Bengt; Jalal, Shah; Rosén, Annika

    2015-09-01

    The aim of this study was to find out if reactive arthritis was involved in the aetiology of chronic closed lock of the temporomandibular joint (TMJ) by looking for bacterial antigens in the synovial membrane of the TMJ, and by studying the antibody serology and carriage of human leucocyte antigen (HLA) B27 in patients with chronic closed lock. Patients with reciprocal clicking and healthy subjects acted as controls. We studied a total of 43 consecutive patients, 15 with chronic closed lock, 13 with reciprocal clicking, and 15 healthy controls with no internal derangements of the TMJ. Venous blood samples were collected from all subjects for measurement of concentrations of HLA tissue antigen and serology against Chlamydia trachomatis, Yersinia enterocolitica, Salmonella spp., Campylobacter jejuni, and Mycoplasma pneumoniae. Samples of synovial tissue from patients with closed lock and reciprocal clicking were obtained during discectomy and divided into two pieces, the first of which was tested by strand displacement amplification for the presence of C trachomatis, and the second of which was analysed for the presence of species-specific bacterial DNA using 16s rRNA pan-polymerase chain reaction (PCR). There were no significant differences between the groups in the incidence of antibodies against M pneumoniae, Salmonella spp. or Y enterocolitica. No patient had antibodies towards C trachomatis or C jejuni. We found no bacterial DNA in the synovial fluid from any patient. The HLA B27 antigen was present in 2/15 subjects in both the closed lock and control groups, and none in the reciprocal clicking group. In conclusion, reactive arthritis does not seem to be the mechanism of internal derangement of the TMJ. PMID:25957137

  11. MYC, Metabolism, and Cancer

    PubMed Central

    Stine, Zachary E.; Walton, Zandra E.; Altman, Brian J.; Hsieh, Annie L.; Dang, Chi V.

    2015-01-01

    Summary The MYC oncogene encodes a transcription factor, MYC, whose broad effects make its precise oncogenic role enigmatically elusive. The evidence to date suggests that MYC triggers selective gene expression amplification to promote cell growth and proliferation. Through its targets, MYC coordinates nutrient acquisition to produce ATP and key cellular building blocks that increase cell mass and trigger DNA replication and cell division. In cancer, genetic and epigenetic derangements silence checkpoints and unleash MYC’s cell growth- and proliferation-promoting metabolic activities. Unbridled growth in response to deregulated MYC expression creates dependence on MYC-driven metabolic pathways, such that reliance on specific metabolic enzymes provides novel targets for cancer therapy. PMID:26382145

  12. Eicosanoids in Metabolic Syndrome

    PubMed Central

    Hardwick, James P.; Eckman, Katie; Lee, Yoon Kwang; Abdelmegeed, Mohamed A.; Esterle, Andrew; Chilian, William M.; Chiang, John Y.; Song, Byoung-Joon

    2013-01-01

    Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS. PMID:23433458

  13. Myocardial imaging. Coxsackie myocarditis

    SciTech Connect

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  14. The Diagnostic Validity of Clinical Tests in Temporomandibular Internal Derangement: A Systematic Review and Meta-analysis

    PubMed Central

    Chaput, Ève; Stewart, Ryan; Nadeau, Gordon; Goldsmith, Charlie H.

    2012-01-01

    ABSTRACT Purpose: To assess the diagnostic validity of clinical tests for temporomandibular internal derangement relative to magnetic resonance imaging (MRI). Methods: MEDLINE and Embase were searched from 1994 through 2009. Independent reviewers conducted study selection; risk of bias was assessed using Quality Assessment of studies of Diagnostic Accuracy included in Systematic reviews (QUADAS); ≥9/14) and data abstraction. Overall quality of evidence was profiled using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Agreement was measured using quadratic weighted kappa (κw). Positive (+) or negative (−) likelihood ratios (LR) with 95% CIs were calculated and pooled using the DerSimonian–Laird method and a random-effects model when homogeneous (I2≥0.40, Q-test p≤0.10). Results: We selected 8 of 36 studies identified. There is very low quality evidence that deflection (+LR: 6.37 [95% CI, 2.13–19.03]) and crepitation (LR:5.88 [95% CI, 1.95–17.76]) as single tests and crepitation, deflection, pain, and limited mouth opening as a cluster of tests are the most valuable for ruling in internal derangement without reduction (+LR:6.37 [95% CI, 2.13–19.03]), (−LR:0.27 [95% CI, 0.11–0.64]) while the test cluster click, deviation, and pain rules out internal derangement with reduction (−LR: 0.09 [95% CI, 0.01–0.72]). No single test or cluster of tests was conclusive and of significant value for ruling in internal derangement with reduction. Conclusions: Findings of this review will assist clinicians in deciding which diagnostic tests to use when internal derangement is suspected. The literature search revealed a lack of high-quality studies; further research with adequate description of patient populations, blinded assessments, and both sagittal and coronal MRI planes is therefore recommended. PMID:23449757

  15. Deranged iron status in psoriasis: the impact of low body mass

    PubMed Central

    Ponikowska, Malgorzata; Tupikowska, Malgorzata; Kasztura, Monika; Jankowska, Ewa A; Szepietowski, Jacek C

    2015-01-01

    Background Iron deficiency (ID) frequently complicates inflammatory-mediated chronic disorders, irrespective of anaemia. Psoriasis is a chronic, immune-mediated skin disease with systemic pro-inflammatory activation; thus, these patients may be prone to develop ID. ID adversely affects immune cells function, which can further contribute to disease progression. This study investigates iron status in psoriasis. Methods Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), and hepcidin were assessed as the biomarkers of iron status in 39 patients with psoriasis (17 men, age: 47 ± 10 years) and 44 healthy subjects (30 men, age: 53 ± 6 years). Results Compared with healthy controls, patients with psoriasis demonstrated similar haematologic status but deranged iron status as evidenced by decreased Tsat and elevated sTfR (negative tissue iron balance) and low levels of hepcidin (depleted iron stores) (all P < 0.05 vs. controls). In patients, the levels of interleukin-6 (level of pro-inflammatory activation) significantly correlated with hepcidin (R = 0.54), but not with ferritin, Tsat, and sTfR. Biomarkers reflecting ID were not associated with the severity of the disease (assessed with the Psoriasis Area and Severity Index) but significantly correlated low body mass index (BMI). Patients with BMI < 24 kg/m2 compared with those with BMI ≥ 24 kg/m2 demonstrated lower levels of ferritin (40 ± 30 vs. 186 ± 128 ng/mL, P < 0.001) and hepcidin (4.9 ± 2.3 vs. 10.7 ± 6.7 ng/mL, P = 0.03). Conclusion Psoriasis is associated with deranged iron status characterized by depleted iron stores with concomitant unmet cellular iron requirements. The magnitude of these abnormalities is particularly strong in patients with low body mass index. Whether iron deficiency may become a therapeutic target in psoriasis needs to be investigated. PMID:26673741

  16. Perturbed Energy Metabolism and Neuronal Circuit Dysfunction in Cognitive Impairment

    PubMed Central

    Kapogiannis, Dimitrios; Mattson, Mark P.

    2010-01-01

    Summary Epidemiological, neuropathological and functional neuroimaging evidence implicates global and regional derangements in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified adaptively by excitatory and inhibitory synaptic activity and neurotrophic factors. Aging and Alzheimer’s disease (AD) cause perturbations in cellular energy metabolism, level of excitation/inhibition and neurotrophic factor release that overwhelm compensatory mechanisms and result in neuronal microcircuit and brain network dysfunction. A prolonged positive energy balance impairs the ability of neurons to respond adaptively to oxidative and metabolic stress. Experimental studies in animals demonstrate how derangements related to chronic positive energy balance, such as diabetes, set the stage for accelerated cognitive aging and AD. Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signaling) have shown efficacy in animal models and preliminary studies in humans. PMID:21147038

  17. Circadian influences on myocardial infarction.

    PubMed

    Virag, Jitka A I; Lust, Robert M

    2014-01-01

    Components of circadian rhythm maintenance, or "clock genes," are endogenous entrainable oscillations of about 24 h that regulate biological processes and are found in the suprachaismatic nucleus (SCN) and many peripheral tissues, including the heart. They are influenced by external cues, or Zeitgebers, such as light and heat, and can influence such diverse phenomena as cytokine expression immune cells, metabolic activity of cardiac myocytes, and vasodilator regulation by vascular endothelial cells. While it is known that the central master clock in the SCN synchronizes peripheral physiologic rhythms, the mechanisms by which the information is transmitted are complex and may include hormonal, metabolic, and neuronal inputs. Whether circadian patterns are causally related to the observed periodicity of events, or whether they are simply epi-phenomena is not well established, but a few studies suggest that the circadian effects likely are real in their impact on myocardial infarct incidence. Cycle disturbances may be harbingers of predisposition and subsequent response to acute and chronic cardiac injury, and identifying the complex interactions of circadian rhythms and myocardial infarction may provide insights into possible preventative and therapeutic strategies for susceptible populations. PMID:25400588

  18. Circadian influences on myocardial infarction

    PubMed Central

    Virag, Jitka A. I.; Lust, Robert M.

    2014-01-01

    Components of circadian rhythm maintenance, or “clock genes,” are endogenous entrainable oscillations of about 24 h that regulate biological processes and are found in the suprachaismatic nucleus (SCN) and many peripheral tissues, including the heart. They are influenced by external cues, or Zeitgebers, such as light and heat, and can influence such diverse phenomena as cytokine expression immune cells, metabolic activity of cardiac myocytes, and vasodilator regulation by vascular endothelial cells. While it is known that the central master clock in the SCN synchronizes peripheral physiologic rhythms, the mechanisms by which the information is transmitted are complex and may include hormonal, metabolic, and neuronal inputs. Whether circadian patterns are causally related to the observed periodicity of events, or whether they are simply epi-phenomena is not well established, but a few studies suggest that the circadian effects likely are real in their impact on myocardial infarct incidence. Cycle disturbances may be harbingers of predisposition and subsequent response to acute and chronic cardiac injury, and identifying the complex interactions of circadian rhythms and myocardial infarction may provide insights into possible preventative and therapeutic strategies for susceptible populations. PMID:25400588

  19. Idiopathic calcified myocardial mass

    PubMed Central

    Patterson, David; Gibson, Derek; Gomes, Ricardo; McDonald, Lawson; Olsen, Eckhardt; Parker, John; Ross, Donald

    1974-01-01

    Patterson, D., Gibson, D., Gomes, R., McDonald, L., Olsen, E., Parker, J., and Ross, D. (1974).Thorax,29, 589-594. Idiopathic calcified myocardial mass. Myocardial calcification can be subdivided into three groups—metastatic, dystrophic or an extension inwards from the pericardium. This case in which the calcified myocardial mass was initially delineated by radiography and by echocardiography and subsequently removed does not fit into any subdivision and has been termed idiopathic. Images PMID:4279467

  20. Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs.

    PubMed

    Mazzola, S; Forni, M; Albertini, M; Bacci, M L; Zannoni, A; Gentilini, F; Lavitrano, M; Bach, F H; Otterbein, L E; Clement, M G

    2005-12-01

    Endotoxic shock, one of the most prominent causes of mortality in intensive care units, is characterized by pulmonary hypertension, systemic hypotension, heart failure, widespread endothelial activation/injury, and clotting culminating in disseminated intravascular coagulation and multi-organ system failure. In the last few years, studies in rodents have shown that administration of low concentrations of carbon monoxide (CO) exerts potent therapeutic effects in a variety of diseases/disorders. In this study, we have administered CO (one our pretreatment at 250 ppm) in a clinically relevant, well-characterized model of LPS-induced acute lung injury in pigs. Pretreatment only with inhaled CO significantly ameliorated several of the acute pathological changes induced by endotoxic shock. In terms of lung physiology, CO pretreatment corrected the LPS-induced changes in resistance and compliance and improved the derangement in pulmonary gas exchange. In terms of coagulation and inflammation, CO reduced the development of disseminated intravascular coagulation and completely suppressed serum levels of the proinflammatory IL-1beta in response to LPS, while augmenting the anti-inflammatory cytokine IL-10. Moreover, the effects of CO blunted the deterioration of kidney and liver function, suggesting a beneficial effect in terms of end organ damage associated with endotoxic shock. Lastly, CO pretreatment prevents LPS-induced ICAM expression on lung endothelium and inhibits leukocyte marginalization on lung parenchyma. PMID:16223783

  1. Towards a metabolic therapy of cancer?

    PubMed

    Chiu, Martina; Ottaviani, Laura; Bianchi, Massimiliano G; Franchi-Gazzola, Renata; Bussolati, Ovidio

    2012-12-01

    It is increasingly appreciated that cancer cells must be endowed with specific metabolic adaptations to support enhanced growth and to ensure survival under stressful conditions. On the other hand, many oncogenic mutations of protooncogenes and tumor suppressor genes directly cause metabolic derangements and, conversely, mutations of enzymes have been found to underlie several forms of cancer. Thus, cancer-specific metabolic alterations are now considered among the hallmarks of malignant tumors. Most commonly, cancer cells exhibit enhanced glycolysis under aerobic conditions (the Warburg effect) but alterations in the metabolism of amino acids, such as glutamine, serine and proline are increasingly described as important metabolic features of selected tumor types. In theory, all these deranged cancer-specific metabolic pathways may constitute novel therapeutic targets, although the only "metabolic" drug in clinical use is still represented by the enzyme L-asparaginase. However, the increasing amount of experimental evidence, as well as the number of trials in progress, suggests that metabolic drugs will soon complement standard anti-cancer chemotherapy and modern biological drugs. PMID:23762991

  2. [Myocardial responses to ischemia].

    PubMed

    Borisenko, V G; Gubareva, E A; Kade, A Kh

    2010-01-01

    The paper details the types of a myocardial response to impaired blood flow, such as myocardial stunning, hibernation, ischemic preconditioning, warm-up phenomenon, ischemic postconditioning, remodeling, and infarction. According to the pathogenesis, the authors identify several types of myocardial dysfunction in transient ischemic attack--uptake, delivery; and a mixed one. It is concluded the myocardial response to damage depends on a combination of influencing factors, a number of pathophysiological processes starting in the acute phase of ischemia achieve its peak in the late period. PMID:20564927

  3. Peripheral disc margin shape and internal disc derangement: imaging correlation in significantly painful discs identified at provocation lumbar discography.

    PubMed

    Bartynski, W S; Rothfus, W E

    2012-06-01

    Annular margin shape is used to characterize lumbar disc abnormality on CT/MR imaging studies. Abnormal discs also have internal derangement including annular degeneration and radial defects. The purpose of this study was to evaluate potential correlation between disc-margin shape and annular internal derangement on post-discogram CT in significantly painful discs encountered at provocation lumbar discography (PLD). Significantly painful discs were encountered at 126 levels in 86 patients (47 male, 39 female) studied by PLD where no prior surgery had been performed and response to intradiscal lidocaine after provocation resulted in either substantial/total relief or no improvement after lidocaine administration. Post-discogram CT and discogram imaging was evaluated for disc-margin characteristics (bulge/protrusion), features of disc internal derangement (radial annular defect [RD: radial tear/fissure/annular gap], annular degeneration) and presence/absence of discographic contrast leakage. In discs with focal protrusion, 50 of 63 (79%) demonstrated Grade 3 RD with 13 (21%) demonstrating severe degenerative change only. In discs with generalized-bulge-only, 48 of 63 (76%) demonstrated degenerative change only (primarily Dallas Grade 3) with 15 of 63 (24%) demonstrating a RD (Dallas Grade 3). Differences were highly statistically significant (p<0.001). Pain elimination with intra-discal lidocaine correlated with discographic contrast leakage (p<0.001). Disc-margin shape correlates with features of internal derangement in significantly painful discs encountered at PLD. Discs with focal protrusion typically demonstrate RD while generalized bulging discs typically demonstrated degenerative changes only (p<0.001). Disc-margin shape may provide an important imaging clue to the cause of chronic discogenic low back pain. PMID:22681741

  4. Peripheral Disc Margin Shape and Internal Disc Derangement: Imaging Correlation in Significantly Painful Discs Identified at Provocation Lumbar Discography

    PubMed Central

    Bartynski, W.S.; Rothfus, W.E.

    2012-01-01

    Summary Annular margin shape is used to characterize lumbar disc abnormality on CT/MR imaging studies. Abnormal discs also have internal derangement including annular degeneration and radial defects. The purpose of this study was to evaluate potential correlation between disc-margin shape and annular internal derangement on post-discogram CT in significantly painful discs encountered at provocation lumbar discography (PLD). Significantly painful discs were encountered at 126 levels in 86 patients (47 male, 39 female) studied by PLD where no prior surgery had been performed and response to intradiscal lidocaine after provocation resulted in either substantial/total relief or no improvement after lidocaine administration. Post-discogram CT and discogram imaging was evaluated for disc-margin characteristics (bulge/protrusion), features of disc internal derangement (radial annular defect [RD: radial tear/fissure/annular gap], annular degeneration) and presence/absence of discographic contrast leakage. In discs with focal protrusion, 50 of 63 (79%) demonstrated Grade 3 RD with 13 (21%) demonstrating severe degenerative change only. In discs with generalized-bulge-only, 48 of 63 (76%) demonstrated degenerative change only (primarily Dallas Grade 3) with 15 of 63 (24%) demonstrating a RD (Dallas Grade 3). Differences were highly statistically significant (p<0.001). Pain elimination with intra-discal lidocaine correlated with discographic contrast leakage (p<0.001). Disc-margin shape correlates with features of internal derangement in significantly painful discs encountered at PLD. Discs with focal protrusion typically demonstrate RD while generalized bulging discs typically demonstrated degenerative changes only (p<0.001). Disc-margin shape may provide an important imaging clue to the cause of chronic discogenic low back pain. PMID:22681741

  5. Cardiac Function, Perfusion, Metabolism, and Innervation following Autologous Stem Cell Therapy for Acute ST-Elevation Myocardial Infarction. A FINCELL-INSIGHT Sub-Study with PET and MRI

    PubMed Central

    Mäki, Maija T.; Koskenvuo, Juha W.; Ukkonen, Heikki; Saraste, Antti; Tuunanen, Helena; Pietilä, Mikko; Nesterov, Sergey V.; Aalto, Ville; Airaksinen, K. E. Juhani; Pärkkä, Jussi P.; Lautamäki, Riikka; Kervinen, Kari; Miettinen, Johanna A.; Mäkikallio, Timo H.; Niemelä, Matti; Säily, Marjaana; Koistinen, Pirjo; Savolainen, Eeva-Riitta; Ylitalo, Kari; Huikuri, Heikki V.; Knuuti, Juhani

    2012-01-01

    Purpose: Beneficial mechanisms of bone marrow cell (BMC) therapy for acute ST-segment elevation myocardial infarct (STEMI) are largely unknown in humans. Therefore, we evaluated the feasibility of serial positron emission tomography (PET) and MRI studies to provide insight into the effects of BMCs on the healing process of ischemic myocardial damage. Methods: Nineteen patients with successful primary reteplase thrombolysis (mean 2.4 h after symptoms) for STEMI were randomized for BMC therapy (2.9 × 106 CD34+ cells) or placebo after bone marrow aspiration in a double-blind, multi-center study. Three days post-MI, coronary angioplasty, and paclitaxel eluting stent implantation preceded either BMC or placebo therapy. Cardiac PET and MRI studies were performed 7–12 days after therapies and repeated after 6 months, and images were analyzed at a central core laboratory. Results: In BMC-treated patients, there was a decrease in [11C]-HED defect size (−4.9 ± 4.0 vs. −1.6 ± 2.2%, p = 0.08) and an increase in [18F]-FDG uptake in the infarct area at risk (0.06 ± 0.09 vs. −0.05 ± 0.16, p = 0.07) compared to controls, as well as less left ventricular dilatation (−4.4 ± 13.3 vs. 8.0 ± 16.7 mL/m2, p = 0.12) at 6 months follow-up. However, BMC treatment was inferior to placebo in terms of changes in rest perfusion in the area at risk (−0.09 ± 0.17 vs. 0.10 ± 0.17, p = 0.03) and infarct size (0.4 ± 4.2 vs. −5.1 ± 5.9 g, p = 0.047), and no effect was observed on ejection fraction (p = 0.37). Conclusion: After the acute phase of STEMI, BMC therapy showed only minor trends of long-term benefit in patients with rapid successful thrombolysis. There was a trend of more decrease in innervation defect size and enhanced glucose metabolism in the infarct-related myocardium and also a trend of less ventricular dilatation in the BMC-treated group compared to placebo. However, no

  6. Feasibility of voxel-based statistical analysis method for myocardial PET

    NASA Astrophysics Data System (ADS)

    Ram Yu, A.; Kim, Jin Su; Paik, Chang H.; Kim, Kyeong Min; Moo Lim, Sang

    2014-09-01

    Although statistical parametric mapping (SPM) analysis is widely used in neuroimaging studies, to our best knowledge, there was no application to myocardial PET data analysis. In this study, we developed the voxel based statistical analysis method for myocardial PET which provides statistical comparison results between groups in image space. PET Emission data of normal and myocardial infarction rats were acquired For the SPM analysis, a rat heart template was created. In addition, individual PET data was spatially normalized and smoothed. Two sample t-tests were performed to identify the myocardial infarct region. This developed SPM method was compared with conventional ROI methods. Myocardial glucose metabolism was decreased in the lateral wall of the left ventricle. In the result of ROI analysis, the mean value of the lateral wall was 29% decreased. The newly developed SPM method for myocardial PET could provide quantitative information in myocardial PET study.

  7. [A case of stunned myocardium: dual SPECT findings similar to acute myocardial infarction (AMI)].

    PubMed

    Itho, K; Kohno, Y; Sudo, Y; Azuma, A; Sugihara, H; Asayama, J; Katsume, H; Nakagawa, M

    1993-02-01

    Emergent cardiac catheterization was performed on a 70-year-old female patient who was admitted for further evaluation of acute myocardial infarction. Coronary angiography didn't reveal any significant stenotic lesion, but levogram showed extensively abnormal contractility around the center of the apex region. On the second hospital day, 99mTc-PYP/201TlCl dual SPECT gave findings similar to those found in acute myocardial infarction, but myocardium--released enzyme stayed within the normal range. Two weeks after, 201TlCl myocardial scintigraphy showed disappearance of the perfusion defect, and normal contractility was observed on the levogram of the chronic phase. Since this case was clinically denied to be myocardial infarction, it was considered a typical case of stunned myocardium which showed prolonged left ventricular abnormal contractility with transient myocardial ischemia. This is a case suggestive for estimations of myocardial reversibility in patients with myocardial perfusion and metabolic disorder in dual SPECT. PMID:8434179

  8. Severe metabolic alkalosis due to baking soda ingestion: case reports of two patients with unsuspected antacid overdose.

    PubMed

    Fitzgibbons, L J; Snoey, E R

    1999-01-01

    Oral ingestion of baking soda (sodium bicarbonate) has been used for decades as a home remedy for acid indigestion. Excessive bicarbonate ingestion places patients at risk for a variety of metabolic derangements including metabolic alkalosis, hypokalemia, hypernatremia, and even hypoxia. The clinical presentation is highly variable but can include seizures, dysrhythmias, and cardiopulmonary arrest. We present two cases of severe metabolic alkalosis in patients with unsuspected antacid overdose. The presentation and pathophysiology of antacid-related metabolic alkalosis is reviewed. PMID:9950389

  9. Derangement of autonomic nerve control in rat with right ventricular failure.

    PubMed

    Sanyal, S N.; Ono, K

    2002-06-01

    The effects of right ventricular hypertrophy and eventual right ventricular failure on autonomic nerve regulation of heart rate variability were investigated using rats with monocrotaline (MCT)-induced pulmonary hypertension. ECG signals were obtained from a radio transmitter placed into the subcutaneous pouch in the back of the male MCT-treated and control rats for 30 min every 6 h at a sample rate of 5 kHz with or without injection of atropine (2 mg/kg I.P.) or propranolol (4 mg/kg I.P.), in a room equipped with a climate controller. Heart rate (HR) and HR variability (HRV) were analyzed in each group by power spectrograms obtained by the fast-Fourier transform algorithm. The RR interval, total power (TP), low-frequency (LF) power (0.04-0.73 Hz), high-frequency (HF) power (0.73-2 Hz) and LF/HF (L/H) ratio were measured. HR was significantly increased in the MCT-treated rats (P<0.001), which also presented lower HRV than that of the control Wistar rats; TP (P<0.05) and HF (P<0.05) power, but not the L/H ratio, were significantly lower than that of the control rats. Responses of these parameters to a muscarinic antagonist (atropine: 2 mg/kg) and a beta-adrenergic antagonist (propranolol: 4 mg/kg), however, remained intact in the MCT-treated rats. Only the parasympathetic component of autonomic nervous controls of HRV was deranged in rats with MCT-induced right ventricular failure. PMID:12039652

  10. Neonatal Thymulin Gene Therapy Prevents Ovarian Dysgenesis and Attenuates Reproductive Derangements in Nude Female Mice

    PubMed Central

    Reggiani, Paula C.; Barbeito, Claudio G.; Zuccolilli, Gustavo O.; Cónsole, Gloria M.; Flamini, Alicia M.; Dardenne, Mireille

    2012-01-01

    Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70–71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis. PMID:22700775

  11. Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice.

    PubMed

    Reggiani, Paula C; Barbeito, Claudio G; Zuccolilli, Gustavo O; Cónsole, Gloria M; Flamini, Alicia M; Dardenne, Mireille; Goya, Rodolfo G

    2012-08-01

    Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis. PMID:22700775

  12. The Role of Docosahexaenoic Acid (DHA) in the Control of Obesity and Metabolic Derangements in Breast Cancer

    PubMed Central

    Molfino, Alessio; Amabile, Maria Ida; Monti, Massimo; Arcieri, Stefano; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

    2016-01-01

    Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies. PMID:27058527

  13. The Role of Docosahexaenoic Acid (DHA) in the Control of Obesity and Metabolic Derangements in Breast Cancer.

    PubMed

    Molfino, Alessio; Amabile, Maria Ida; Monti, Massimo; Arcieri, Stefano; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

    2016-01-01

    Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies. PMID:27058527

  14. Myocardial protection with mild hypothermia.

    PubMed

    Tissier, Renaud; Ghaleh, Bijan; Cohen, Michael V; Downey, James M; Berdeaux, Alain

    2012-05-01

    Mild hypothermia, 32-35° C, is very potent at reducing myocardial infarct size in rabbits, dogs, sheep, pigs, and rats. The benefit is directly related to reduction in normothermic ischaemic time, supporting the relevance of early and rapid cooling. The cardioprotective effect of mild hypothermia is not limited to its recognized reduction of infarct size, but also results in conservation of post-ischaemic contractile function, prevention of no-reflow or microvascular obstruction, and ultimately attenuation of left ventricular remodelling. The mechanism of the anti-infarct effect does not appear to be related to diminished energy utilization and metabolic preservation, but rather to survival signalling that involves either the extracellular signal-regulated kinases and/or the Akt/phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Initial clinical trials of hypothermia in patients with ST-segment elevation myocardial infarction were disappointing, probably because cooling was too slow to shorten normothermic ischaemic time appreciably. New approaches to more rapid cooling have recently been described and may soon be available for clinical use. Alternatively, it may be possible to pharmacologically mimic the protection provided by cooling soon after the onset of ischaemia with an activator of mild hypothermia signalling, e.g. extracellular signal-regulated kinase activator, that could be given by emergency medical personnel. Finally, the protection afforded by cooling can be added to that of pre- and post-conditioning because their mechanisms differ. Thus, myocardial salvage might be greatly increased by rapidly cooling patients as soon as possible and then giving a pharmacological post-conditioning agent immediately prior to reperfusion. PMID:22131353

  15. Transient myocardial ischaemia after acute myocardial infarction.

    PubMed Central

    Currie, P; Saltissi, S

    1990-01-01

    The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications. PMID:2245108

  16. Factors influencing occurrence of postpartum haemorrhage in pregnant women with hepatitis E infection and deranged coagulation profile

    PubMed Central

    Puri, Manju; Patra, Sharda; Singh, Preeti; Malhotra, Nidhi; Trivedi, Shubha Sagar; Sharma, Sunita; Kumar, Ashish; Sarin, Shiv Kumar

    2011-01-01

    Coagulopathy is an important complication associated with hepatitis E virus (HEV) infection in pregnant women. Postpartum haemorrhage (PPH) remains a serious risk while managing the labour of these women. The aim of this paper is to study the factors influencing the occurrence of PPH in pregnant women with hepatitis E infection with coagulopathy. The labours of 38 pregnant women with hepatitis E and deranged coagulation profile were followed. Factors that may predict postpartum bleeding complications in women with HEV infection and deranged coagulation profile were statistically analysed. Of 38 pregnant women with acute viral hepatitis due to HEV, 13 (34%) suffered a PPH while 25 (66%) did not. On univariate analysis low alanine aminotransferase (P = 0.016), high international normalized ratio (P = 0.003), high levels of d-dimer (P = 0.008), presence of hepatic encephalopathy (P = 0.028), intrauterine fetal death (P = 0.001) and gastrointestinal bleeding (P = 0.004) were found to predict PPH. However, on multivariate analysis the only independent variable that predicted PPH was the presence gastrointestinal (GI) bleeding (odds ratio [OR] 11.363; 95% CI: 1.003, 125; P = 0.050). Women with GI bleeding have 11 times higher risk of PPH than those without a GI bleed; however, the confidence interval is very wide. Administration of fresh frozen plasma in the peripartum period reduces the risk of PPH. In conclusion, early recognition of factors which predict the risk of PPH and timely intervention with judicious use of blood and blood components in the peripartum period can improve the outcome of pregnant women with HEV infection with deranged coagulation.

  17. Eating disorders should be considered in the differential diagnosis of patients presenting with acute kidney injury and electrolyte derangement.

    PubMed

    Talbot, Ben Edward Michael; Lawman, Sarah H A

    2014-01-01

    We present a case of a 40-year-old woman with a history of ongoing anorexia nervosa and bulimia nervosa who has required multiple admissions to hospital for management of acute kidney injury (AKI) and electrolyte derangement. This case is of interest as recent studies have highlighted the significant prevalence of disordered eating and the major public health implications this may have. We discuss the unusual finding of hypercalcaemia in this case and address the investigation and management of AKI and electrolyte disturbance in a patient with anorexia and bulimia. PMID:24654247

  18. Eating disorders should be considered in the differential diagnosis of patients presenting with acute kidney injury and electrolyte derangement

    PubMed Central

    Talbot, Ben Edward Michael; Lawman, Sarah H A

    2014-01-01

    We present a case of a 40-year-old woman with a history of ongoing anorexia nervosa and bulimia nervosa who has required multiple admissions to hospital for management of acute kidney injury (AKI) and electrolyte derangement. This case is of interest as recent studies have highlighted the significant prevalence of disordered eating and the major public health implications this may have. We discuss the unusual finding of hypercalcaemia in this case and address the investigation and management of AKI and electrolyte disturbance in a patient with anorexia and bulimia. PMID:24654247

  19. Myocardial infarction and marijuana.

    PubMed

    Charles, R; Holt, S; Kirkham, N

    1979-04-01

    Myocardial infarction in the virtual absence of risk factors occurred in a 25-year old man shortly after smoking a cigarette containing marijuana. Subsequent coronary arteriography was normal. PMID:466984

  20. Cardiac MRI evaluation of myocardial disease.

    PubMed

    Captur, Gabriella; Manisty, Charlotte; Moon, James C

    2016-09-15

    Cardiovascular magnetic resonance (CMR) is a key imaging technique for cardiac phenotyping with a major clinical role. It can assess advanced aspects of cardiac structure and function, scar burden and other myocardial tissue characteristics but there is new information that can now be derived. This can fill many of the gaps in our knowledge with the potential to change thinking, disease classifications and definitions as well as patient care. Established techniques such as the late gadolinium enhancement technique are now embedded in clinical care. New techniques are coming through. Myocardial tissue characterisation techniques, particularly myocardial mapping can precisely measure tissue magnetisation-T1, T2, T2* and also the extracellular volume. These change in disease. Key biological pathways are now open for scrutiny including focal fibrosis (scar) and diffuse fibrosis, inflammation, metabolism and infiltration. Other new areas to engage in where major insights are growing include detailed assessments of myocardial mechanics and performance, spectroscopy and hyperpolarised CMR. In spite of the advances, challenges remain, particularly surrounding utilisation, technical development to improve accuracy, reproducibility and deliverability, and the role of multidisciplinary research to understand the detailed pathological basis of the MR signal changes. Collectively, these new developments are galvanising CMR uptake and having a major translational impact on healthcare globally and it is steadily becoming key imaging tool. PMID:27354273

  1. Experimental myocardial infarction

    PubMed Central

    Kumar, Raj; Joison, Julio; Gilmour, David P.; Molokhia, Farouk A.; Pegg, C. A. S.; Hood, William B.

    1971-01-01

    The hemodynamic effects of tachycardia induced by atrial pacing were investigated in left ventricular failure of acute and healing experimental myocardial infarction in 20 intact, conscious dogs. Myocardial infarction was produced by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 10-15 days prior to the study. 1 hr after acute myocardial infarction, atrial pacing at a rate of 180 beats/min decreased left ventricular end-diastolic pressure from 19 to 8 mm Hg and left atrial pressure from 17 to 12 mm Hg, without change in cardiac output. In the healing phase of myocardial infarction 1 wk later, atrial pacing decreased left ventricular end-diastolic pressure from 17 to 9 mm Hg and increased the cardiac output by 37%. This was accompanied by evidence of peripheral vasodilation. In two dogs with healing anterior wall myocardial infarction, left ventricular failure was enhanced by partial occlusion of the circumflex coronary artery. Both the dogs developed pulmonary edema. Pacing improved left ventricular performance and relieved pulmonary edema in both animals. In six animals propranolol was given after acute infarction, and left ventricular function deteriorated further. However the pacing-induced augmentation of cardiac function was unaltered and, hence, is not mediated by sympathetics. The results show that the spontaneous heart rate in left ventricular failure of experimental canine myocardial infarction may be less than optimal and that maximal cardiac function may be achieved at higher heart rates. Images PMID:4395910

  2. Increased myocardial catalase in rats fed ethanol.

    PubMed Central

    Fahimi, H. D.; Kino, M.; Hicks, L.; Thorp, K. A.; Abelman, W. H.

    1979-01-01

    The effects of chronic intake of dietary ethanol upon catalase, an enzyme capable of metabolizing ethanol, as well as upon myocardial morphology and hemodynamics, were studied in the rat. Ethanol, comprising 36% of dietary calories, administered to rats for 5 weeks, was associated with increased myocardial catalase of 45.9 +/- 3.7 IU/mg protein, compared to 21.0 +/- 1.8 IU/mg protein in pair-fed controls. The enzyme activity remained significantly elevated after 18 weeks of ethanol. Hepatic catalase did not differ in these groups. Parallel cytochemical studies confirmed the increase in myocardial catalase by demonstrating an increase in peroxisomes. Gross and light-microscopic examinations revealed no abnormalities at either 5 or 18 weeks. Remarkably few ultrastructural abnormalities were seen in this material fixed by vascular perfusion. Hemodynamic studies after 5 weeks of ethanol revealed decreased left ventricle systolic pressure and decreased mean arterial pressure but no change in ventricular filling pressure. The possibility of catalase playing a metabolic and potentially protective role in rat myocardium chronically exposed to ethanol is discussed. Images Figure 3 Figure 4-6 Figures 1 and 2 Figures 7 and 8 p[389]-a PMID:474705

  3. Amelioration of pancreatic and renal derangements in streptozotocin-induced diabetic rats by polyphenol extracts of Ginger (Zingiber officinale) rhizome.

    PubMed

    Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin

    2015-12-01

    Free and bound polyphenol extracts of Zingiber officinale rhizome were investigated for their antidiabetic potential in the pancreatic and renal tissues of diabetic rats at a dose of 500mg/kg body weight. Forty Wistar rats were completely randomized into five groups: A-E consisting of eight animals each. Group A (control) comprises normal healthy animals and were orally administered 1.0mL distilled water on a daily basis for 42 days while group B-E were made up of 50mg/kg streptozotocin (STZ)-induced diabetic rats. Group C and D received 1.0mL 500mg/kg body weight free and bound polyphenol extracts respectively while group E received 1.0mL 0.6mg/kg of glibenclamide. Administration of the extracts to the diabetic rats significantly reduced (p<0.05) serum glucose and urea concentrations, increased (p<0.05) serum insulin and Homeostatic Model Assessment for β-cell dysfunction (HOMA-β) while the level of creatinine and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were not affected. Histological examination of the pancreas and kidney revealed restoration of the structural derangements caused by streptozotocin in the polyphenol extracts treated diabetic rats compared to the control groups. Therefore, polyphenols from Zingiber officinale could ameliorate diabetes-induced pancreatic and renal derangements in rats. PMID:26349770

  4. Donizetti and the music of mental derangement: Anna Bolena, Lucia di Lammermoor, and the composer's neurobiological illness.

    PubMed Central

    Peschel, E.; Peschel, R.

    1992-01-01

    The composer Gaetano Donizetti, who died in a state of mental derangement due to neurosyphilis, created some of opera's greatest scenes of psychosis. His letters reveal the clinical progression of his neurobiological illness, which was confirmed by autopsy. One can hypothesize that the composer's brain disease, which led to his psychosis and death, may have had an influence on his ability to create the powerful and unforgettable scenes of psychosis in his operas. In Anna Bolena, he captured in musical and dramatic terms Anne Boleyn's historically corroborated mental disorder during her imprisonment in the Tower of London. Sixteen years after having composed Anna Bolena, Donizetti himself would be locked up, against his will, in a mental institution. In Lucia di Lammermoor, Donizetti portrayed a girl given to hallucinations who, in her unforgettable "mad" scene, comes on stage, a pathetic embodiment of a human being in the throes of psychosis. Thirteen years after Lucia's première, Donizetti would die, psychotic and paralyzed, of untreated neurosyphilis. Studying Donizetti's neurosyphilis and the portrayals of psychosis in his operas can help one to appreciate the pain of human beings trapped in the prison of a brain subjected to the devastation of mental derangement. PMID:1285447

  5. [EEG manifestations in metabolic encephalopathy].

    PubMed

    Lin, Chou-Ching K

    2005-09-01

    Normal brain function depends on normal neuronal metabolism, which is closely related to systemic homeostasis of metabolites, such as glucose, electrolytes, amino acids and ammonia. "Metabolic encephalopathy" indicates diffuse brain dysfunction caused by various systemic derangements. Electroencephalogram (EEG) is widely used to evaluate metabolic encephalopathy since 1937, when Berger first observed slow brain activity induced by hypoglycemia. EEG is most useful in differentiating organic from psychiatric conditions, identifying epileptogenicity, and providing information about the degree of cortical or subcortical dysfunction. In metabolic encephalopathy, EEG evolution generally correlates well with the severity of encephalopathy. However, EEG has little specificity in differentiating etiologies in metabolic encephalopathy. For example, though triphasic waves are most frequently mentioned in hepatic encephalopathy, they can also be seen in uremic encephalopathy, or even in aged psychiatric patients treated with lithium. Spike-and-waves may appear in hyper- or hypo-glycemia, uremic encephalopathy, or vitamin deficiencies, etc. Common principles of EEG changes in metabolic encephalopathy are (1) varied degrees of slowing, (2) assorted mixtures of epileptic discharge, (3) high incidence of triphasic waves, and (4), as a rule, reversibility after treatment of underlying causes. There are some exceptions to the above descriptions in specific metabolic disorders and EEG manifestations are highly individualized. PMID:16252619

  6. The metabolic syndrome: definition, global impact, and pathophysiology.

    PubMed

    Potenza, Matthew V; Mechanick, Jeffrey I

    2009-01-01

    The metabolic syndrome (MS) is a cluster of metabolic derangements that are associated with primary disturbances in adipose tissue. Abnormal visceral fat accumulates from physical inactivity and excess calories in genetically susceptible individuals. This increased adipocyte mass acts as an endocrine organ and communicates with other organ systems via increases in inflammatory cytokines. The resulting disorders define MS as increased waist circumference, decreased serum high-density lipoprotein, and increased serum triglyceride levels, hypertension, and insulin resistance. MS accounts for the majority of cardiovascular disease risk in the U.S. population. Dietary interventions, such as the Mediterranean diet, have been shown to improve these metabolic derangements. Many substances found in these diets are being investigated as specific therapies for MS, and when scientific substantiation is lacking, they may be considered as part of complementary and alternative medicine (CAM). However, as scientific evidence accumulates, these CAM treatments may become part of conventional medicine. This review will scrutinize the emerging evidence behind many, though not all, CAM treatments currently thought to target the various derangements found in MS. PMID:19841245

  7. Recognition of Fibrotic Infarct Density by the Pattern of Local Systolic-Diastolic Myocardial Electrical Impedance

    PubMed Central

    Amorós-Figueras, Gerard; Jorge, Esther; García-Sánchez, Tomás; Bragós, Ramón; Rosell-Ferrer, Javier; Cinca, Juan

    2016-01-01

    Myocardial electrical impedance is a biophysical property of the heart that is influenced by the intrinsic structural characteristics of the tissue. Therefore, the structural derangements elicited in a chronic myocardial infarction should cause specific changes in the local systolic-diastolic myocardial impedance, but this is not known. This study aimed to characterize the local changes of systolic-diastolic myocardial impedance in a healed myocardial infarction model. Six pigs were successfully submitted to 150 min of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 4 weeks later, myocardial impedance spectroscopy (1–1000 kHz) was measured at different infarction sites. The electrocardiogram, left ventricular (LV) pressure, LV dP/dt, and aortic blood flow (ABF) were also recorded. A total of 59 LV tissue samples were obtained and histopathological studies were performed to quantify the percentage of fibrosis. Samples were categorized as normal myocardium (<10% fibrosis), heterogeneous scar (10–50%) and dense scar (>50%). Resistivity of normal myocardium depicted phasic changes during the cardiac cycle and its amplitude markedly decreased in dense scar (18 ± 2 Ω·cm vs. 10 ± 1 Ω·cm, at 41 kHz; P < 0.001, respectively). The mean phasic resistivity decreased progressively from normal to heterogeneous and dense scar regions (285 ± 10 Ω·cm, 225 ± 25 Ω·cm, and 162 ± 6 Ω·cm, at 41 kHz; P < 0.001 respectively). Moreover, myocardial resistivity and phase angle correlated significantly with the degree of local fibrosis (resistivity: r = 0.86 at 1 kHz, P < 0.001; phase angle: r = 0.84 at 41 kHz, P < 0.001). Myocardial infarcted regions with greater fibrotic content show lower mean impedance values and more depressed systolic-diastolic dynamic impedance changes. In conclusion, this study reveals that differences in the degree of myocardial fibrosis can be detected in vivo by local measurement of phasic systolic

  8. Myocardial diseases of animals.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1986-01-01

    In this review we have attempted a comprehensive compilation of the cardiac morphologic changes that occur in spontaneous and experimental myocardial diseases of animals. Our coverage addresses diseases of mammals and birds and includes these diseases found in both domesticated and wild animals. A similar review of the myocardial diseases in this broad range of animal species has not been attempted previously. We have summarized and illustrated the gross, microscopic, and ultrastructural alterations for these myocardial diseases; and, whenever possible, we have reviewed their biochemical pathogenesis. We have arranged the myocardial diseases for presentation and discussion according to an etiologic classification with seven categories. These include a group of idiopathic or primary cardiomyopathies recognized in man (hypertrophic, dilated, and restrictive types) and a large group of secondary cardiomyopathies with known causes, such as inherited tendency; nutritional deficiency; toxicity; physical injury and shock; endocrine disorders, and myocarditides of viral, bacterial, and protozoal causation. Considerable overlap exists between each of the etiologic groups in the spectrum of pathologic alterations seen in the myocardium. These include various degenerative changes, myocyte necrosis, and inflammatory lesions. However, some diseases show rather characteristic myocardial alterations such as vacuolar degeneration in anthracycline cardiotoxicity, myofibrillar lysis in furazolidone cardiotoxicity, calcification in calcinosis of mice, glycogen accumulation in the glycogenoses, lipofuscinosis in cattle, fatty degeneration in erucic acid cardiotoxicity, myofiber disarray in hypertrophic cardiomyopathy, and lymphocytic inflammation with inclusion bodies in canine parvoviral myocarditis. The myocardial diseases represent the largest group in the spectrum of spontaneous cardiac diseases of animals. Pericardial and endocardial diseases and congential cardiac diseases are

  9. Immune Derangements in Patients with Myelofibrosis: The Role of Treg, Th17, and sIL2Rα

    PubMed Central

    Wang, Jen C.; Sindhu, Hemant; Chen, Chi; Kundra, Ajay; Kafeel, Muhammad I.; Wong, Ching; Lichter, Stephen

    2015-01-01

    Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis. PMID:25793623

  10. Bovine myocardial epithelial inclusions.

    PubMed

    Baker, D C; Schmidt, S P; Langheinrich, K A; Cannon, L; Smart, R A

    1993-01-01

    Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis. PMID:7680178

  11. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

    PubMed

    van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state. PMID:26824042

  12. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats

    PubMed Central

    van den Brom, Charissa E.; Boly, Chantal A.; Bulte, Carolien S. E.; van den Akker, Rob F. P.; Kwekkeboom, Rick F. J.; Loer, Stephan A.; Boer, Christa; Bouwman, R. Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state. PMID:26824042

  13. Perioperative Assessment of Myocardial Deformation

    PubMed Central

    Duncan, Andra E.; Alfirevic, Andrej; Sessler, Daniel I.; Popovic, Zoran B.; Thomas, James D.

    2014-01-01

    Evaluation of left ventricular performance improves risk assessment and guides anesthetic decisions. However, the most common echocardiographic measure of myocardial function, the left ventricular ejection fraction (LVEF), has important limitations. LVEF is limited by subjective interpretation which reduces accuracy and reproducibility, and LVEF assesses global function without characterizing regional myocardial abnormalities. An alternative objective echocardiographic measure of myocardial function is thus needed. Myocardial deformation analysis, which performs quantitative assessment of global and regional myocardial function, may be useful for perioperative care of surgical patients. Myocardial deformation analysis evaluates left ventricular mechanics by quantifying strain and strain rate. Strain describes percent change in myocardial length in the longitudinal (from base to apex) and circumferential (encircling the short-axis of the ventricle) direction and change in thickness in the radial direction. Segmental strain describes regional myocardial function. Strain is a negative number when the ventricle shortens longitudinally or circumferentially and is positive with radial thickening. Reference values for normal longitudinal strain from a recent meta-analysis using transthoracic echocardiography are (mean ± SD) −19.7 ± 0.4%, while radial and circumferential strain are 47.3 ± 1.9 and −23.3 ± 0.7%, respectively. The speed of myocardial deformation is also important and is characterized by strain rate. Longitudinal systolic strain rate in healthy subjects averages −1.10 ± 0.16 sec−1. Assessment of myocardial deformation requires consideration of both strain (change in deformation), which correlates with LVEF, and strain rate (speed of deformation), which correlates with rate of rise of left ventricular pressure (dP/dt). Myocardial deformation analysis also evaluates ventricular relaxation, twist, and untwist, providing new and noninvasive methods to

  14. PET/CT Imaging in Mouse Models of Myocardial Ischemia

    PubMed Central

    Gargiulo, Sara; Greco, Adelaide; Gramanzini, Matteo; Petretta, Maria Piera; Ferro, Adele; Larobina, Michele; Panico, Mariarosaria; Brunetti, Arturo; Cuocolo, Alberto

    2012-01-01

    Different species have been used to reproduce myocardial infarction models but in the last years mice became the animals of choice for the analysis of several diseases, due to their short life cycle and the possibility of genetic manipulation. Many techniques are currently used for cardiovascular imaging in mice, including X-ray computed tomography (CT), high-resolution ultrasound, magnetic resonance imaging, and nuclear medicine procedures. Cardiac positron emission tomography (PET) allows to examine noninvasively, on a molecular level and with high sensitivity, regional changes in myocardial perfusion, metabolism, apoptosis, inflammation, and gene expression or to measure changes in anatomical and functional parameters in heart diseases. Currently hybrid PET/CT scanners for small laboratory animals are available, where CT adds high-resolution anatomical information. This paper reviews mouse models of myocardial infarction and discusses the applications of dedicated PET/CT systems technology, including animal preparation, anesthesia, radiotracers, and images postprocessing. PMID:22505813

  15. PET/CT imaging in mouse models of myocardial ischemia.

    PubMed

    Gargiulo, Sara; Greco, Adelaide; Gramanzini, Matteo; Petretta, Maria Piera; Ferro, Adele; Larobina, Michele; Panico, Mariarosaria; Brunetti, Arturo; Cuocolo, Alberto

    2012-01-01

    Different species have been used to reproduce myocardial infarction models but in the last years mice became the animals of choice for the analysis of several diseases, due to their short life cycle and the possibility of genetic manipulation. Many techniques are currently used for cardiovascular imaging in mice, including X-ray computed tomography (CT), high-resolution ultrasound, magnetic resonance imaging, and nuclear medicine procedures. Cardiac positron emission tomography (PET) allows to examine noninvasively, on a molecular level and with high sensitivity, regional changes in myocardial perfusion, metabolism, apoptosis, inflammation, and gene expression or to measure changes in anatomical and functional parameters in heart diseases. Currently hybrid PET/CT scanners for small laboratory animals are available, where CT adds high-resolution anatomical information. This paper reviews mouse models of myocardial infarction and discusses the applications of dedicated PET/CT systems technology, including animal preparation, anesthesia, radiotracers, and images postprocessing. PMID:22505813

  16. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction.

    PubMed

    Perez-Downes, Julio; Hritani, Abdulwahab; Baldeo, Candice; Antoun, Patrick

    2016-01-01

    Weight loss is one of the most researched and marketed topics in American society. Dietary regimens, medications that claim to boost the metabolism, and the constant pressure to fit into society all play a role in our patient's choices regarding new dietary products. One of the products that are well known to suppress appetite and cause weight loss is amphetamines. While these medications suppress appetite, most people are not aware of the detrimental side effects of amphetamines, including hypertension, tachycardia, arrhythmias, and in certain instances acute myocardial infarction. Here we present the uncommon entity of an acute myocardial infarction due to chronic use of an amphetamine containing dietary supplement in conjunction with an exercise regimen. Our case brings to light further awareness regarding use of amphetamines. Clinicians should have a high index of suspicion of use of these substances when young patients with no risk factors for coronary artery disease present with acute arrhythmias, heart failure, and myocardial infarctions. PMID:27516911

  17. Protective Effect of Tetramethylpyrazine on Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Qian, Weidong; Xiong, Xingjiang; Fang, Zhuyuan; Lu, Haiting; Wang, Zhensheng

    2014-01-01

    Myocardial ischemia-reperfusion injury (MIRI) is a common pathological and physiological phenomenon. Tetramethylpyrazine is the extract of the traditional Chinese medicine Chuanxiong, which can exert protective effects on MIRI in multiple ways. This paper reviewed the current research progress and evidence about the cardiovascular effects of tetramethylpyrazine, which included protecting mitochondria and improving energy metabolism, scavenging oxygen free radicals (OFRs) to inhibit lipid peroxidation, attenuating calcium (Ca2+) overload and maintaining Ca2+ homeostasis in cells, inhibiting apoptosis and protecting myocardial cells, interfering with the inflammatory reaction and mitigating cell injury, interfering with cell signaling pathways, and improving function of endothelial cells and protecting myocardial cells. However, further rigorously designed randomized controlled trials are warranted. PMID:25152756

  18. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction

    PubMed Central

    Hritani, Abdulwahab; Antoun, Patrick

    2016-01-01

    Weight loss is one of the most researched and marketed topics in American society. Dietary regimens, medications that claim to boost the metabolism, and the constant pressure to fit into society all play a role in our patient's choices regarding new dietary products. One of the products that are well known to suppress appetite and cause weight loss is amphetamines. While these medications suppress appetite, most people are not aware of the detrimental side effects of amphetamines, including hypertension, tachycardia, arrhythmias, and in certain instances acute myocardial infarction. Here we present the uncommon entity of an acute myocardial infarction due to chronic use of an amphetamine containing dietary supplement in conjunction with an exercise regimen. Our case brings to light further awareness regarding use of amphetamines. Clinicians should have a high index of suspicion of use of these substances when young patients with no risk factors for coronary artery disease present with acute arrhythmias, heart failure, and myocardial infarctions. PMID:27516911

  19. Morphogenesis of myocardial trabeculae in the mouse embryo.

    PubMed

    Captur, Gabriella; Wilson, Robert; Bennett, Michael F; Luxán, Guillermo; Nasis, Arthur; de la Pompa, José Luis; Moon, James C; Mohun, Timothy J

    2016-08-01

    Formation of trabeculae in the embryonic heart and the remodelling that occurs prior to birth is a conspicuous, but poorly understood, feature of vertebrate cardiogenesis. Mutations disrupting trabecular development in the mouse are frequently embryonic lethal, testifying to the importance of the trabeculae, and aberrant trabecular structure is associated with several human cardiac pathologies. Here, trabecular architecture in the developing mouse embryo has been analysed using high-resolution episcopic microscopy (HREM) and three-dimensional (3D) modelling. This study shows that at all stages from mid-gestation to birth, the ventricular trabeculae comprise a complex meshwork of myocardial strands. Such an arrangement defies conventional methods of measurement, and an approach based upon fractal algorithms has been used to provide an objective measure of trabecular complexity. The extent of trabeculation as it changes along the length of left and right ventricles has been quantified, and the changes that occur from formation of the four-chambered heart until shortly before birth have been mapped. This approach not only measures qualitative features evident from visual inspection of 3D models, but also detects subtle, consistent and regionally localised differences that distinguish each ventricle and its developmental stage. Finally, the combination of HREM imaging and fractal analysis has been applied to analyse changes in embryonic heart structure in a genetic mouse model in which trabeculation is deranged. It is shown that myocardial deletion of the Notch pathway component Mib1 (Mib1(flox/flox) ; cTnT-cre) results in a complex array of abnormalities affecting trabeculae and other parts of the heart. PMID:27020702

  20. Acute myocardial infarction.

    PubMed

    Rischpler, Christoph

    2016-09-01

    Inflammatory processes after myocardial infarction have gained major interest in recent cardiovascular research. It is believed that not only the degree of cell recruitment to the heart plays a pivotal role in the quality of wound healing after myocardial infarction, but also the balance between different types or even subtypes of cells. It is also this balance which is thought to control key processes in tissue repair, such as apoptosis and neoangiogenesis. In this paper, we aim to review imaging strategies (with a special focus on nuclear molecular imaging strategies) that target cells and processes involved in postischemic inflammation and that have a high potential to be translated into clinic or that are already being used and evaluated in humans. PMID:27225319

  1. Detection and Assessment Using Positron Emission Tomography of Genetically Determined Defects in Myocardial Fatty Acid Utilization. Final report, 8/1/93-6/30/97

    SciTech Connect

    Bergmann, Steven R.

    2000-04-09

    An approach using positron emission tomography (PET) was developed, validated and used to measure myocardial fatty acid metabolism in patients with inherited forms of heart failure. Abnormalities were correlated with the severity of the clinical illness. The approach developed was also shown to identify abnormalities in myocardial fatty acid metabolism in some patients with acquired forms of heart failure. The PET technique thus permits identification of abnormal fatty acid metabolism and provides an approach to evaluate the efficacy of interventional strategies.

  2. Leucine metabolism in patients with Hepatic Encephalopathy

    SciTech Connect

    McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.

    1986-03-01

    A primed continuous infusion of (/sup 15/N, 1-/sup 13/C)leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet (0.6 g protein per kg ideal body weight (IBW)). An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO/sub 2/ enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy.

  3. [Coenzyme metabolic therapy in infectious allergic myocarditis].

    PubMed

    Mazurets, A F; Gurevich, M A; Kubyshkin, V F; Dziuba, M V; Vikharev, N P

    1995-01-01

    A trial was performed of clinical efficacy of the coenzyme complex incorporating piridoxalphosphate, cobamamide and phosphaden in patients with infectious allergic myocarditis. Myo- cardial dystrophy and correlations of the myocardial enzymatic status with blood lymphocytes in the above patients were taken in consideration. Corrective action of metabolic therapy on myocardial bioenergy was coupled with positive antiarrhythmic and cardiotonic effects. Cytochemical follow-up investigations enabled long-term monitoring over the patients' condition and further catamnesis. PMID:8815275

  4. Nitroglycerin Use in Myocardial Infarction Patients: Risks and Benefits

    PubMed Central

    Ferreira, Julio C.B.; Mochly-Rosen, Daria

    2012-01-01

    Acute myocardial infarction and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin remains a first-line treatment for angina pectoris and acute myocardial infarction. Nitroglycerin achieves its benefit by giving rise to nitric oxide, which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of nitroglycerin results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is due, at least in part, to inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts nitroglycerin to the vasodilator, nitric oxide. We have recently found that, in addition to nitroglycerin’s effect on the vasculature, sustained treatment with nitroglycerin negatively affects cardiomyocyte viability following ischemia, thus resulting in increased infarct size in a myocardial infarction model in animals. Co-administration of Alda-1, an activator of ALDH2, with nitroglycerin improves metabolism of reactive aldehyde adducts and prevents the nitroglycerin-induced increase in cardiac dysfunction following myocardial infarction. In this review, we describe the molecular mechanisms associated with the benefits and risks of nitroglycerin administration in myocardial infarction. (167 of 200). PMID:22040938

  5. Nuclear cardiac imaging for the assessment of myocardial viability

    PubMed Central

    Slart, R.H.J.A.; Bax, J.J.; van der Wall, E.E.; van Veldhuisen, D.J.; Jager, P.L.; Dierckx, R.A.

    2005-01-01

    An important aspect of the diagnostic and prognostic work-up of patients with ischaemic cardiomyopathy is the assessment of myocardial viability. Patients with left ventricular dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischaemia but at the same time benefit most from revascularisation. 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 201thallium, 99mTc-sestamibi, or 99mTc- 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 radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularisation. New techniques in the nuclear cardiology field, such as 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 noninvasive coronary angiography to myocardial perfusion imaging and quantification. ImagesFigure 1Figure 2Figure 3 PMID:25696432

  6. Regional myocardial shape and dimensions of the working isolated canine left ventricle

    NASA Technical Reports Server (NTRS)

    Ritman, E. L.; Tsuiki, K.; Donald, D.; Wood, E. H.

    1975-01-01

    The extent to which the dynamic shape and dimensions of the isolated left ventricular myocardial wall differ throughout the myocardium and how these differences are characteristic of the anatomic location was demonstrated. The use of a biplane X-ray technique and a metabolically-supported isolated canine left ventricle preparation provided an angiographically ideal means of measuring mechanical dynamics of the myocardium while the intact left ventricular myocardial structure and electrical activation pattern retains most of the in situ ventricular characteristics.

  7. [Mortality of myocardial infarction].

    PubMed

    Bonnefoy, E; Kirkorian, G

    2011-12-01

    Coronary disease is a major cause of death and disability. From 1975 to 2000, coronary mortality was reduced by half. Better treatments and reduction of risk factors are the main causes. This phenomenon is observed in most developed countries, but mortality from coronary heart disease continues to increase in developing countries. In-hospital mortality of ST elevation myocardial infarction (STEMI) is in the range of 7 to 10% in registries. In infarction without ST segment elevation (NSTEMI), in-hospital mortality is around 5%. More recent studies found a similar in-hospital mortality for STEMI and NSTEMI. Because of patient selection and monitoring, mortality in clinical trials is much lower. After adjustment for the extent of coronary disease, age, risk factors, history of myocardial infarction, the excess mortality observed in women is fading. Many clinical, biological and laboratory parameters are associated with mortality in myocardial infarction. They refer to the immediate risk of death (ventricular rhythm disturbances, shock…), the extent of infarction (number of leads with ST elevation on the ECG, release of biomarkers, ejection fraction…), the presence of heart failure, the failure of reperfusion and the patient's baseline risk (age, renal function…). Risk scores, and more specifically the GRACE risk score, synthesize these different markers to predict the risk of death in a given patient. However, their use for the treatment of myocardial only concerns NSTEMI. Only a limited number of mechanical or pharmacological interventions reduces mortality of heart attack. The main benefits are observed with reperfusion by thrombolysis or primary angioplasty in STEMI, aspirin, heparin, beta-blockers, angiotensin converting enzyme inhibitors. Some medications such as bivalirudin and fondaparinux reduce mortality by decreasing the incidence of hemorrhagic complications. The guidelines classify interventions according to their benefit and especially their ability

  8. PGC-1α Regulates Expression of Myocardial Mitochondrial Antioxidants and Myocardial Oxidative Stress After Chronic Systolic Overload

    PubMed Central

    Lu, Zhongbing; Xu, Xin; Hu, Xinli; Fassett, John; Zhu, Guangshuo; Tao, Yi; Li, Jingxin; Huang, Yimin; Zhang, Ping; Zhao, Baolu

    2010-01-01

    Abstract Mitochondria are a principal site for generation of reactive oxygen species (ROS) in the heart. Peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) plays an important role in regulating mitochondrial biogenesis and myocardial metabolism, but whether PGC-1α can simultaneously upregulate myocardial mitochondrial antioxidants has not been studied. In the present study, we examined the effect of PGC-1α deficiency (PGC-1α−/−) on oxidative stress and expression of a group of mitochondrial antioxidants in normal hearts and in hearts exposed to chronic systolic pressure overload produced by transverse aortic constriction (TAC). We found that PGC-1α−/− caused moderate but significant decreases of myocardial mitochondrial antioxidant enzymes such as SOD2, and thioredoxin (Trx2), but had no effect on expression of myocardial oxidative stress markers and left ventricular (LV) function under basal conditions. However, in response to TAC for 6 weeks, PGC-1α−/− mice showed greater increases of myocardial oxidative stress markers 3’-nitrotyrosine and 4-hydroxynonenal, more severe LV hypertrophy and dilatation, pulmonary congestion, and a greater reduction of LV fractional shortening and dP/dtmax than did wild-type hearts. SOD mimetic MnTMPyP treatment (6 mg/kg/day) significantly attenuated TAC-induced LV hypertrophy and dysfunction in PGC-1α−/− mice. These data indicate that PGC-1α plays an important role in regulating expression of myocardial mitochondrial antioxidants SOD2 and Trx2 and in protecting hearts against TAC-induced myocardial oxidative stress, hypertrophy, and dysfunction. Antioxid. Redox Signal. 13, 1011–1022. PMID:20406135

  9. Noninvasive estimation of regional myocardial oxygen consumption by positron emission tomography with carbon-11 acetate in patients with myocardial infarction

    SciTech Connect

    Walsh, M.N.; Geltman, E.M.; Brown, M.A.; Henes, C.G.; Weinheimer, C.J.; Sobel, B.E.; Bergmann, S.R. )

    1989-11-01

    We previously demonstrated in experimental studies that myocardial oxygen consumption (MVO2) can be estimated noninvasively with positron emission tomography (PET) from analysis of the myocardial turnover rate constant (k) after administration of carbon-11 (11C) acetate. To determine regional k in healthy human subjects and to estimate alterations in MVO2 accompanying myocardial ischemia, we administered (11C)acetate to five healthy human volunteers and to six patients with myocardial infarction. Extraction of (11C)acetate by the myocardium was avid and clearance from the blood-pool rapid yielding myocardial images of excellent quality. Regional k was homogeneous in myocardium of healthy volunteers (coefficient variation = 11%). In patients, k in regions remote from the area of infarction was not different from values in myocardium of healthy human volunteers (0.061 +/- 0.025 compared with 0.057 +/- 0.008 min-1). In contrast, MVO2 in the center of the infarct region was only 6% of that in remote regions (p less than 0.01). In four patients studied within 48 hr of infarction and again more than seven days after the acute event, regional k and MVO2 did not change. The approach developed should facilitate evaluation of the efficacy of interventions designed to enhance recovery of jeopardized myocardium and permit estimation of regional MVO2 and metabolic reserve underlying cardiac disease of diverse etiologies.

  10. Rapamycin Treatment of Healthy Pigs Subjected to Acute Myocardial Ischemia-Reperfusion Injury Attenuates Cardiac Functions and Increases Myocardial Necrosis

    PubMed Central

    Lassaletta, Antonio D; Elmadhun, Nassrene Y; Zanetti, Arthus V D; Feng, Jun; Anduaga, Javier; Gohh, Reginald Y.; Sellke, Frank W; Bianchi, Cesario

    2013-01-01

    Background The Mechanistic Target of Rapamycin (mTOR) pathway is a major regulator of cell immunity and metabolism. mTOR is a well-known suppressor of tissue rejection in organ transplants, however, it has other non-immune functions including in the cardiovascular system, where it is a regulator of heart hypertrophy and locally, in coated vascular stents, inhibits vascular wall cell growth and hence neointimal formation/restenosis. Because the mTOR pathway plays major roles in normal cell growth, metabolism and survival, we hypothesized that inhibiting it with rapamycin, prior to an acute myocardial ischemia-reperfusion injury (IRI), would confer cardioprotection by virtue of slowing down cardiac function and metabolism. Methods Yorkshire pigs received orally either placebo or 4 mg/day rapamycin for 7 days before the IRI. All animals underwent median sternotomy and the mid-left anterior descending coronary artery was occluded for 60 min followed by 120 min of reperfusion. Left ventricular pressure-volume data was collected throughout the operation. The ischemic and infarcted areas were determined by monastral blue and triphenyltetrazolium chloride staining, respectively and plasma cardiac troponin I concentration. mTOR kinase activities were monitored in remote cardiac tissue by western blotting with specific antibodies against specific substrates phosphorylating sites. Results Rapamycin pre-treatement impaired endothelial-dependent vasorelaxation, attenuated cardiac function during IRI, and increased myocardial necrosis. Western blotting confirmed effective inhibition of myocardial mTOR kinase activities. Conclusions Pre-treatment of healthy pigs with rapamycin prior to acute myocardial IRI is associated with decreased cardiac function and higher myocardial necrosis. PMID:24266948

  11. Mortality and testicular derangements in red flour beetles, Tribolium castaneum (Herbst) exposed to hen's egg white proteins.

    PubMed

    Parshad, Ranjit K; Kansal, Megha

    2012-03-01

    Red flour beetle (T. castaneum) is a major pest of stored grains and is known for its adaptability to all classes of insecticides. The present study was carried out to determine the insecticidal potential of egg white proteins to manage beetle population. Protein samples obtained through salt fractionation were lyophilized and were used separately and simultaneously in different concentrations by adding them to wheat flour and milk powder. The results indicated that the mortality rate of the adult beetles was dependent on the type of treatment, concentration of protein samples and duration of feeding. In multiple-choice feeding trials beetles showed their movement towards the control section as the concentration of treatment increases. Marked abnormalities were observed in appearance and dimensions of the testes which indicated that the egg white proteins caused considerable effect on the process of spermatogenesis and sperm functions. SEM study revealed the formation of deep wrinkles and folds on the testicular surface of the testes of beetles fed on treated diets, points towards the depletion of internal cellular material. The results suggest that egg white protein affects the survival and cause subsequent derangements in the testis of red flour beetle. PMID:22439439

  12. Management of open bite that developed during treatment for internal derangement and osteoarthritis of the temporomandibular joint

    PubMed Central

    Choi, Jae Won; Nakaoka, Kazutoshi; Hamada, Yoshiki; Nakamura, Yoshiki

    2015-01-01

    This case report describes the orthodontic treatment performed for open bite caused by internal derangement (ID) and osteoarthritis (OA) of the temporomandibular joint (TMJ). A Japanese woman, aged 31 years and 11 months, referred to our department by an oral surgeon had an open bite with clockwise rotation of the mandible and degeneration of the condyle. The overbite was corrected through intrusion of the maxillary and mandibular molars using mini-screw implants to induce counterclockwise rotation of the mandible. Then, the mandibular second premolars were extracted and comprehensive orthodontic treatment was performed to establish a Class I molar relationship with distalization of the maxillary arch and to eliminate anterior crowding. Following treatment, her facial profile improved and a functional and stable occlusion was achieved without recurrence of the TMJ symptoms. These results suggest that orthodontic intrusion of the molars is one of the safer and less stressful alternatives for the management of open bite due to degeneration of the condyles caused by ID and OA of TMJ. PMID:26023542

  13. Derangement of body representation in complex regional pain syndrome: report of a case treated with mirror and prisms

    PubMed Central

    Rafal, Robert D.

    2009-01-01

    Perhaps the most intriguing disorders of body representation are those that are not due to primary disease of brain tissue. Strange and sometimes painful phantom limb sensations can result from loss of afference to the brain; and Complex Regional Pain Syndrome (CRPS)—the subject of the current report—can follow limb trauma without pathology of either the central or peripheral nervous system. This enigmatic and vexing condition follows relatively minor trauma, and can result in enduring misery and a useless limb. It manifests as severe pain, autonomic dysfunction, motor disability and ‘neglect-like’ symptoms with distorted body representation. For this special issue on body representation we describe the case of a patient suffering from CRPS, including symptoms suggesting a distorted representation of the affected limb. We report contrasting effects of mirror box therapy, as well as a new treatment—prism adaptation therapy—that provided sustained pain relief and reduced disability. The benefits were contingent upon adapting with the affected limb. Other novel observations suggest that: (1) pain may be a consequence, not the cause, of a disturbance of body representation that gives rise to the syndrome; (2) immobilisation, not pain, may precipitate this reorganisation of somatomotor circuits in susceptible individuals; and (3) limitation of voluntary movement is neither due to pain nor to weakness but, rather, to derangement of body representation which renders certain postures from the repertoire of hand movements inaccessible. PMID:19967390

  14. Management of open bite that developed during treatment for internal derangement and osteoarthritis of the temporomandibular joint.

    PubMed

    Arai, Chihiro; Choi, Jae Won; Nakaoka, Kazutoshi; Hamada, Yoshiki; Nakamura, Yoshiki

    2015-05-01

    This case report describes the orthodontic treatment performed for open bite caused by internal derangement (ID) and osteoarthritis (OA) of the temporomandibular joint (TMJ). A Japanese woman, aged 31 years and 11 months, referred to our department by an oral surgeon had an open bite with clockwise rotation of the mandible and degeneration of the condyle. The overbite was corrected through intrusion of the maxillary and mandibular molars using mini-screw implants to induce counterclockwise rotation of the mandible. Then, the mandibular second premolars were extracted and comprehensive orthodontic treatment was performed to establish a Class I molar relationship with distalization of the maxillary arch and to eliminate anterior crowding. Following treatment, her facial profile improved and a functional and stable occlusion was achieved without recurrence of the TMJ symptoms. These results suggest that orthodontic intrusion of the molars is one of the safer and less stressful alternatives for the management of open bite due to degeneration of the condyles caused by ID and OA of TMJ. PMID:26023542

  15. Derangement of body representation in complex regional pain syndrome: report of a case treated with mirror and prisms.

    PubMed

    Bultitude, Janet H; Rafal, Robert D

    2010-07-01

    Perhaps the most intriguing disorders of body representation are those that are not due to primary disease of brain tissue. Strange and sometimes painful phantom limb sensations can result from loss of afference to the brain; and Complex Regional Pain Syndrome (CRPS)-the subject of the current report-can follow limb trauma without pathology of either the central or peripheral nervous system. This enigmatic and vexing condition follows relatively minor trauma, and can result in enduring misery and a useless limb. It manifests as severe pain, autonomic dysfunction, motor disability and 'neglect-like' symptoms with distorted body representation. For this special issue on body representation we describe the case of a patient suffering from CRPS, including symptoms suggesting a distorted representation of the affected limb. We report contrasting effects of mirror box therapy, as well as a new treatment-prism adaptation therapy-that provided sustained pain relief and reduced disability. The benefits were contingent upon adapting with the affected limb. Other novel observations suggest that: (1) pain may be a consequence, not the cause, of a disturbance of body representation that gives rise to the syndrome; (2) immobilisation, not pain, may precipitate this reorganisation of somatomotor circuits in susceptible individuals; and (3) limitation of voluntary movement is neither due to pain nor to weakness but, rather, to derangement of body representation which renders certain postures from the repertoire of hand movements inaccessible. PMID:19967390

  16. Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome

    PubMed Central

    Mahmood, Feroze; Owais, Khurram; Bardia, Amit; Khabbaz, Kamal R.; Liu, David; Senthilnathan, Venkatachalam; Lassaletta, Antonio D.; Sellke, Frank; Matyal, Robina

    2016-01-01

    Background Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome. Methods Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD). Results There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and–dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group. Conclusion Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification. PMID:26766185

  17. Dipyridamole thallium-201 myocardial scintigraphy

    SciTech Connect

    Not Available

    1988-09-01

    Thallium-201 (/sup 201/Tl) myocardial scintigraphy is a sensitive technique for detecting coronary artery disease. Standardized exercise testing is the most common method for inducing myocardial stress for /sup 201/Tl imaging. Unfortunately, a significant number of patients are unable to undergo adequate treadmill or bicycle exercise. In these patients, pharmacologic stress with dipyridamole provides a safe, efficacious, and reliable alternative.

  18. Optimization of Cardiac Metabolism in Heart Failure

    PubMed Central

    Nagoshi, Tomohisa; Yoshimura, Michihiro; Rosano, Giuseppe M. C; Lopaschuk, Gary D; Mochizuki, Seibu

    2011-01-01

    The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metabolized. In contrast, glucose becomes an important preferential substrate for metabolism and ATP generation under specific pathological conditions, because it can provide greater efficiency in producing high energy products per oxygen consumed compared to fatty acids. Manipulations that shift energy substrate utilization away from fatty acids toward glucose can improve the cardiac function and slow the progression of heart failure. However, insulin resistance, which is highly prevalent in the heart failure population, impedes this adaptive metabolic shift. Therefore, the acceleration of the glucose metabolism, along with the restoration of insulin sensitivity, would be the ideal metabolic therapy for heart failure. This review discusses the therapeutic potential of modifying substrate utilization to optimize cardiac metabolism in heart failure. PMID:21933140

  19. Optimization of cardiac metabolism in heart failure.

    PubMed

    Nagoshi, Tomohisa; Yoshimura, Michihiro; Rosano, Giuseppe M C; Lopaschuk, Gary D; Mochizuki, Seibu

    2011-12-01

    The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metabolized. In contrast, glucose becomes an important preferential substrate for metabolism and ATP generation under specific pathological conditions, because it can provide greater efficiency in producing high energy products per oxygen consumed compared to fatty acids. Manipulations that shift energy substrate utilization away from fatty acids toward glucose can improve the cardiac function and slow the progression of heart failure. However, insulin resistance, which is highly prevalent in the heart failure population, impedes this adaptive metabolic shift. Therefore, the acceleration of the glucose metabolism, along with the restoration of insulin sensitivity, would be the ideal metabolic therapy for heart failure. This review discusses the therapeutic potential of modifying substrate utilization to optimize cardiac metabolism in heart failure. PMID:21933140

  20. Spiral MR myocardial tagging.

    PubMed

    Ryf, Salome; Kissinger, Kraig V; Spiegel, Marcus A; Börnert, Peter; Manning, Warren J; Boesiger, Peter; Stuber, Matthias

    2004-02-01

    In the present study, complementary spatial modulation of magnetization (CSPAMM) myocardial tagging was extended with an interleaved spiral imaging sequence. The use of a spiral sequence enables the acquisition of grid-tagged images with a tagline distance as low as 4 mm in a single breath-hold. Alternatively, a high temporal resolution of 77 frames per second was obtained with 8-mm grid spacing. Ten healthy adult subjects were studied. With this new approach, high-quality images can be obtained and the tags persist throughout the entire cardiac cycle. PMID:14755646

  1. Valsartan after myocardial infarction.

    PubMed

    Güleç, Sadi

    2014-12-01

    One of the important problems of the patients undergoing acute myocardial infarction (MI) is early development of heart failure. It has been revealed in various studies that renin-angiotensin-aldosterone system (RAAS) has a significant role in this process. The studies conducted with angiotensin converting enzyme (ACE) inhibitors have resulted in decreased mortality rate. Another RAAS blocker which was discovered about ten years later than other ACE inhibitors in historical process is angiotensin receptor blockers (ARB) inhibiting the efficiency of angiotensin 2 by binding to angiotensin 1 receptor. Valsartan is one of the molecules of this group, which has higher number of large-scale randomized clinical studies. In this review, following presentation of a general overview on heart failure after acute MI, the efficiency of ARBs in this patient group will be discussed. This discussion will mostly emphasize the construction, outcomes and clinical importance of VALIANT (VALsartan In Acute myocardial iNfarcTion), which is the study on valsartan after acute MI heart failure. PMID:25604205

  2. Trauma Induced Myocardial Infarction

    PubMed Central

    Lolay, Georges A.; Abdel-Latef, Ahmed K.

    2016-01-01

    Chest Trauma in athletes is a common health problem. However, myocardial infarction secondary to coronary dissection in the setting of blunt chest trauma is extremely rare. We report a case of acute inferior wall myocardial infarction following blunt chest trauma. A 32-year-old male with no relevant medical problems was transferred to our medical center for retrosternal chest pain after being elbowed in the chest during a soccer game. Few seconds later, he started experiencing sharp retrosternal chest pain that was severe to that point where he called the emergency medical service. Upon arrival to the Trauma department patient was still complaining of chest pain. ECG demonstrated ST segment elevation in the inferior leads with reciprocal changes in the lateral leads all consistent with active ischemia. After rolling out Aortic dissection, patient was loaded with ASA, ticagerlor, heparin and was emergently taken to the cardiac catheterization lab. Coronary angiography demonstrated 100% thrombotic occlusion in the distal right coronary artery with TIMI 0 flow distally. After thrombus aspiration, a focal dissection was noted on the angiogram that was successfully stented. Two days after admission patient was discharged home. Echocardiography prior to discharge showed inferior wall akinesis, normal right ventricular systolic function and normal overall ejection fraction. PMID:26490501

  3. Effect of biomechanical disturbance of the temporomandibular joint on the prevalence of internal derangement in mandibular asymmetry.

    PubMed

    Buranastidporn, B; Hisano, M; Soma, K

    2006-06-01

    The aim of the present study was to elucidate the relationship between biomechanical changes of the temporomandibular joint (TMJ) and internal derangement (ID) symptoms in mandibular asymmetry. Posteroanterior cephalograms (PA) of 140 patients with TMJ ID associated with mandibular asymmetry were used to investigate the inclination of the frontal occlusal plane (FOP), and were analysed in conjunction with the results of a report providing information on ID symptoms. A three-dimensional (3D) finite element model (FEM) of the entire mandible was created to investigate the distribution of TMJ forces during clenching. The inclination of the FOP was modified to simulate various degrees of vertical asymmetry. The stresses on the TMJ on the ipsilateral and contralateral sides were analysed and their values were compared with those of the standard model. The results showed that the symptomatic sides were significantly related to the degree of inclination of the FOP. Increasing its angulation resulted in a decrease of the symptoms on the ipsilateral side and an increase of those on the contralateral side. The analysis showed that stress-distribution patterns and overall stresses of the articular disc were influenced by the angulation of inclination of the FOP. These mechanical changes exhibited a distinct relationship with the prevalence of ID in the patients. These results suggest that disturbances in the stresses either in amount or direction due to occlusal inclination can be responsible for ID. Therefore, an attempt to establish a flat occlusal plane is an important orthodontic treatment objective in maintaining the normal health and structure of the TMJ. PMID:16230327

  4. Blood protein concentrations in the first two postnatal weeks associated with early postnatal blood gas derangements among infants born before the 28th week of gestation. The ELGAN Study

    PubMed Central

    Leviton, Alan; Allred, Elizabeth N.; Kuban, Karl C. K.; Dammann, Olaf; Fichorova, Raina N; O’Shea, T. Michael; Paneth, Nigel

    2016-01-01

    Aim To explore the relationships between blood gas derangements and blood concentrations of inflammation-related proteins shortly after preterm birth. Design Observational cohort Setting 14 neonatal intensive care units Subjects 734 infants born before the 28th week of gestation who were classified by their blood gas derangements during the first three postnatal days and by the concentrations of 25 proteins in their blood on days 1, 7, and 14. We classified these newborns by whether or not they had a highest or lowest PaO2, PCO2, and lowest pH in the most extreme quartile, and by whether or not they had a protein concentration in the highest quartile. Results Blood gas derangements on two days were much more likely to be accompanied or followed by sustained or recurrent systemic inflammation than a derangement on only one day. This was most evident for acidemia, and slightly less so for hypercapnia. Conclusions Our finding that protein concentration patterns indicative of systemic inflammation are associated with several blood gas derangements raises the possibility that organ damage attributed to these derangements might be accompanied by or involve an inflammatory response. PMID:21821429

  5. +Ophitoxaemia and myocardial infarction--the issues during primary angioplasty: a review.

    PubMed

    Gupta, Prabha Nini; Thomas, Jinesh; Francis, Preetham Kumar; Shylaja, Sajith Vamadevan

    2014-01-01

    'The Big four' are the most poisonous snakes in India, and especially in Kerala. These include the cobra, the viper, the krait and the sea snake. Most of the poisonous snakebites in India occur in Kerala. We believe there are only a few reports of myocardial infarction after snakebites and most of these are viper bites. We believe this is the second case of primary angioplasty for a snakebite. There are at least a few potential issues in performing a primary angioplasty in a snakebite case, namely (1) Is it a thrombus or a spasm? (2) Are the bleeding parameters deranged? Will the patient tolerate tirofiban and other glycoprotein (GB) 2b3a inhibitors? Will he develop dangerous bleeding due to the high dose of heparin needed? Further, would we save the patient from myocardial infarction only to lose him to renal failure, both due to the nephrotoxicity of the venom, the kidney being further damaged by the contrast media used for the angioplasty? We discuss all these issues as they crossed our mind, and hope it will help further treatment in others. We would like to review the available literature on these points and describe a recent case of ours. PMID:25342187

  6. Renalase deficiency aggravates ischemic myocardial damage.

    PubMed

    Wu, Yanling; Xu, Jianchao; Velazquez, Heino; Wang, Peili; Li, Guoyong; Liu, Dinggang; Sampaio-Maia, Benedita; Quelhas-Santos, Janete; Russell, Kerry; Russell, Raymond; Flavell, Richard A; Pestana, Manuel; Giordano, Frank; Desir, Gary V

    2011-04-01

    Chronic kidney disease (CKD) leads to an 18-fold increase in cardiovascular complications not fully explained by traditional risk factors. Levels of renalase, a recently discovered oxidase that metabolizes catecholamines, are decreased in CKD. Here we show that renalase deficiency in a mouse knockout model causes increased plasma catecholamine levels and hypertension. Plasma blood urea nitrogen, creatinine, and aldosterone were unaffected. However, knockout mice had normal systolic function and mild ventricular hypertrophy but tolerated cardiac ischemia poorly and developed myocardial necrosis threefold more severe than that found in wild-type mice. Treatment with recombinant renalase completely rescued the cardiac phenotype. To gain insight into the mechanisms mediating this cardioprotective effect, we tested if gene deletion affected nitrate and glutathione metabolism, but found no differences between hearts of knockout and wild-type mice. The ratio of oxidized (NAD) to reduced (NADH) nicotinamide adenine dinucleotide in cardiac tissue, however, was significantly decreased in the hearts of renalase knockout mice, as was plasma NADH oxidase activity. In vitro studies confirmed that renalase metabolizes NADH and catecholamines. Thus, renalase plays an important role in cardiovascular pathology and its replacement may reduce cardiac complications in renalase-deficient states such as CKD. PMID:21178975

  7. PPARs: Protectors or Opponents of Myocardial Function?

    PubMed Central

    Pol, Christine J.; Lieu, Melissa; Drosatos, Konstantinos

    2015-01-01

    Over 5 million people in the United States suffer from the complications of heart failure (HF), which is a rapidly expanding health complication. Disorders that contribute to HF include ischemic cardiac disease, cardiomyopathies, and hypertension. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family. There are three PPAR isoforms: PPARα, PPARγ, and PPARδ. They can be activated by endogenous ligands, such as fatty acids, as well as by pharmacologic agents. Activators of PPARs are used for treating several metabolic complications, such as diabetes and hyperlipidemia that are directly or indirectly associated with HF. However, some of these drugs have adverse effects that compromise cardiac function. This review article aims to summarize the current basic and clinical research findings of the beneficial or detrimental effects of PPAR biology on myocardial function. PMID:26713088

  8. An unusual myocardial infarction

    PubMed Central

    Di Michele, Sara; Mirabelli, Francesca; Mankad, Sunil

    2014-01-01

    Summary We present a 74-year-old male with a chondrosarcoma, who presented with chest pain. The history, electrocardiogram (ECG), and biomarkers established the diagnosis of myocardial infarction (MI); angiography did not show coronary atherosclerosis and, both initial transthoracic echocardiogram and chest computed tomography (CT), did not demonstrate any cardiac abnormalities. A second echocardiogram following a routine ECG showed presence of a mass involving the right ventricle and the cardiac apex that was confirmed by chest CT scan. We underline the importance of considering cardiac tumors in the clinical arena of MI management. Learning points Cardiac tumors cause ECG changes similar to ischemic heart diseases.Keep in mind cardiac tumors when performing transthoracic echocardiogram (TTE) in the setting of suspected MI.TTE is the technique of choice in detecting cardiac tumors. PMID:26693309

  9. Masquerades of myocardial infarction.

    PubMed Central

    Bean, W. B.

    1976-01-01

    I summarize these observations in Figure 1. It represents every person in a hypothetical population who has myocardial infarction. A large but unknown number, some believe almost half, never get help. Mobile coronary care units are reducing this group, but so far only a little. When the diagnosis is not understood the disease is not recognized. Then come discovery and popularization. Hereafter masquerades hide some cases and the diagnosis is missed. Somewhere fairly early the diagnostic fad leads to false positive diagnosis. As new techniques are discovered, perfected and mastered, false positive errors and masquerades leading to oversights diminish but still exist. All the skill and technical virtuosity in the world will not be applied if we do not think of the disease. When we think of it, even obscure cases may be resolved easily. PMID:960416

  10. Respiratory muscle endurance is limited by lower ventilatory efficiency in post-myocardial infarction patients

    PubMed Central

    Neves, Laura M. T.; Karsten, Marlus; Neves, Victor R.; Beltrame, Thomas; Borghi-Silva, Audrey; Catai, Aparecida M.

    2014-01-01

    Background Reduced respiratory muscle endurance (RME) contributes to increased dyspnea upon exertion in patients with cardiovascular disease. Objective The objective was to characterize ventilatory and metabolic responses during RME tests in post-myocardial infarction patients without respiratory muscle weakness. Method Twenty-nine subjects were allocated into three groups: recent myocardial infarction group (RG, n=9), less-recent myocardial infarction group (LRG, n=10), and control group (CG, n=10). They underwent two RME tests (incremental and constant pressure) with ventilatory and metabolic analyses. One-way ANOVA and repeated measures one-way ANOVA, both with Tukey post-hoc, were used between groups and within subjects, respectively. Results Patients from the RG and LRG presented lower metabolic equivalent and ventilatory efficiency than the CG on the second (50± 06, 50± 5 vs. 42± 4) and third part (50± 11, 51± 10 vs. 43± 3) of the constant pressure RME test and lower metabolic equivalent during the incremental pressure RME test. Additionally, at the peak of the incremental RME test, RG patients had lower oxygen uptake than the CG. Conclusions Post-myocardial infarction patients present lower ventilatory efficiency during respiratory muscle endurance tests, which appears to explain their inferior performance in these tests even in the presence of lower pressure overload and lower metabolic equivalent. PMID:24675907

  11. Non-ischemic diabetic cardiomyopathy may initially exhibit a transient subclinical phase of hyperdynamic myocardial performance.

    PubMed

    Hensel, Kai O

    2016-09-01

    Cardiovascular complications are the key cause for mortality in diabetes mellitus. Besides ischemia-related cardiac malfunction there is growing evidence for non-ischemic diabetes-associated heart failure in both type 1 and type 2 diabetes mellitus. The underlying pathophysiology of non-ischemic diabetic cardiomyopathy (NIDC) is poorly understood and data on myocardial mechanics in early stages of the disease are rare. However, several studies in both human and experimental animal settings have reported prima facie unexplained features indicating myocardial hyperdynamics early in the course of the disease. The new hypothesis is that - other than previously thought - NIDC may be non-linear and initially feature an asymptomatic subclinical phase of myocardial hypercontractility that precedes the long-term development of diabetes-associated cardiac dysfunction and ultimately heart failure. Diabetes-induced metabolic imbalances may lead to a paradoxic inotropic increase and inefficient myocardial mechanics that finally result in a gradual deterioration of myocardial performance. In conclusion, diabetic patients should be screened regularly and early in the course of the disease utilizing ultra-sensitive myocardial deformation imaging in order to identify patients at risk for diabetes-associated heart failure. Moreover, hyperdynamic myocardial deformation might help distinguish non-ischemic from ischemic diabetic cardiomyopathy. Further studies are needed to illuminate the underlying pathophysiological mechanisms, the exact spatiotemporal evolvement of diabetic cardiomyopathy and its long-term relation to clinical outcome parameters. PMID:27515189

  12. Myocardial steatosis as a possible mechanistic link between diastolic dysfunction and coronary microvascular dysfunction in women.

    PubMed

    Wei, Janet; Nelson, Michael D; Szczepaniak, Edward W; Smith, Laura; Mehta, Puja K; Thomson, Louise E J; Berman, Daniel S; Li, Debiao; Bairey Merz, C Noel; Szczepaniak, Lidia S

    2016-01-01

    Women with coronary microvascular dysfunction (CMD) and no obstructive coronary artery disease (CAD) have increased rates of heart failure with preserved ejection fraction (HFpEF). The mechanisms of HFpEF are not well understood. Ectopic fat deposition in the myocardium, termed myocardial steatosis, is frequently associated with diastolic dysfunction in other metabolic diseases. We investigated the prevalence of myocardial steatosis and diastolic dysfunction in women with CMD and subclinical HFpEF. In 13 women, including eight reference controls and five women with CMD and evidence of subclinical HFpEF (left ventricular end-diastolic pressure >12 mmHg), we measured myocardial triglyceride content (TG) and diastolic function, by proton magnetic resonance spectroscopy and magnetic resonance tissue tagging, respectively. When compared with reference controls, women with CMD had higher myocardial TG content (0.83 ± 0.12% vs. 0.43 ± 0.06%; P = 0.025) and lower diastolic circumferential strain rate (168 ± 12 vs. 217 ± 15%/s; P = 0.012), with myocardial TG content correlating inversely with diastolic circumferential strain rate (r = -0.779; P = 0.002). This study provides proof-of-concept that myocardial steatosis may play an important mechanistic role in the development of diastolic dysfunction in women with CMD and no obstructive CAD. Detailed longitudinal studies are warranted to explore specific treatment strategies targeting myocardial steatosis and its effect on diastolic function. PMID:26519031

  13. Characterization of nontransmural myocardial infarction by positron-emission tomography

    SciTech Connect

    Geltman, E.M.; Biello, D.; Welch, M.J.; Ter-Pogossian, M.M.; Roberts, R.; Sobel, B.E.

    1982-04-01

    The present study was performed to determine whether positron emission tomography (PET) performed after i.v. 11C-palmitate permits detection and characterization of nontransmural myocardial infarction. PET was performed after the i.v. injection of 11C-palmitate in 10 normal subjects, 24 patients with initial nontransmural myocardial infarction (defined electrocardiographically), and 22 patients with transmural infarction. Depressed accumulation of 11C-palmitate was detected with sagittal, coronal and transverse reconstructions, and quantified based on 14 contiguous transaxial reconstructions. Defects with homogeneously intense depression of accumulation of tracer were detected in all 22 patients with transmural infarction (100%). Abnormalities of the distribution of 11C-palmitate in the myocardium were detected in 23 patients with nontransmural infarction (96%). Thallium scintigrams were abnormal in only 11 of 18 patients with nontransmural infarction (61%). Tomographically estimated infarct size was greater among patients with transmural infarction (50.4 +/- 7.8 PET-g-Eq/m2 (+/- SEM SEM)) compared with those with nontransmural infarction (19 +/- 4 PET-g-Eq, p less than 0.01). Residual accumulation of 11C-palmitate within regions of infarction was more intensely depressed among patients with transmural compared to nontransmural infarction (33 +/- 1 vs 39 +/- 1% maximal myocardial radioactivity, p less than 0.01). Thus, PET and metabolic imaging with 11C-palmitate is a sensitive means of detecting, quantifying and characterizing nontransmural and transmural myocardial infarction.

  14. Myocardial performance and perfusion during exercise in patients with coronary artery disease caused by Kawasaki disease

    SciTech Connect

    Paridon, S.M.; Ross, R.D.; Kuhns, L.R.; Pinsky, W.W. )

    1990-01-01

    For a study of the natural history of coronary artery lesions after Kawasaki disease and their effect on myocardial blood flow reserve with exercise, five such patients underwent exercise testing on a bicycle. Oxygen consumption, carbon dioxide production, minute ventilation, and electrocardiograms were monitored continuously. Thallium-201 scintigraphy was performed for all patients. One patient stopped exercise before exhaustion of cardiovascular reserve but had no evidence of myocardial perfusion abnormalities. Four patients terminated exercise because of exhaustion of cardiovascular reserve; one had normal cardiovascular reserve and thallium scintiscans, but the remaining patients had diminished cardiovascular reserve. Thallium scintigrams showed myocardial ischemia in two and infarction in one. No patient had exercise-induced electrocardiographic changes. These results indicate that patients with residual coronary artery lesions after Kawasaki disease frequently have reduced cardiovascular reserve during exercise. The addition of thallium scintigraphy and metabolic measurements to exercise testing improved the detection of exercise-induced abnormalities of myocardial perfusion.

  15. One-Year Outcomes of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients with Suspected Acute Coronary Syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care] Trial)

    PubMed Central

    Selker, Harry P.; Udelson, James E.; Massaro, Joseph M.; Ruthazer, Robin; D’Agostino, Ralph B.; Griffith, John L.; Sheehan, Patricia R.; Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin; Vickery, Ellen M.; Atkins, James M.; Aufderheide, Tom P.; Sayah, Assaad J.; Pirrallo, Ronald G.; Levy, Michael K.; Richards, Michael E.; Braude, Darren A.; Doyle, Delanor D.; Frascone, Ralph J.; Kosiak, Donald J.; Leaming, James M.; Van Gelder, Carin M.; Walter, Gert-Paul; Wayne, Marvin A.; Woolard, Robert H.; Beshansky, Joni R.

    2014-01-01

    The IMMEDIATE Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefit. Here we report 1-year outcomes. Pre-specified 1-year endpoints of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality, and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Among 871 participants randomized to GIK vs. placebo, respectively, death occurred within 1 year in 11.6% vs. 13.5% (unadjusted hazard ratio [HR] 0.83; 95% CI 0.57, 1.23, P=0.36). The composite of cardiac arrest or 1-year mortality was 12.8% vs. 17.0% (HR 0.71; 95% CI 0.50, 1.02, P=0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% vs. 17.2% (HR 0.98; 95% CI 0.70, 1.37, P=0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% vs. 20.4% (HR 0.85; 95% CI 0.62, 1.16, P=0.30). Among patients presenting with suspected ST elevation myocardial infarction (STEMI), hazard ratios for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33, 1.27, P=0.21); 0.52 (95% CI 0.30, 0.92, P=0.03); 0.63 (95% CI 0.35, 1.16, P=0.14); and 0.51 (95% CI 0.30, 0.87, P=0.01). Among patients with suspected ACS, serious endpoints generally were lower with GIK than placebo, but the differences were not statistically significant. However, among those with STEMI, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced. PMID:24792735

  16. Myocardial protection after whole body heat stress in the rabbit is dependent on metabolic substrate and is related to the amount of the inducible 70-kD heat stress protein.

    PubMed Central

    Marber, M S; Walker, J M; Latchman, D S; Yellon, D M

    1994-01-01

    The aims of this study were to examine the effects of whole body heat stress and subsequent stress protein induction on glycolytic metabolism, mitochondrial metabolism, and calcium handling within the heart. The effect of heat stress on glycolytic and mitochondrial pathways was examined by measuring contractile performance in the presence of glucose and pyruvate, respectively. Calcium handling was assessed using force-interval relationships. Right ventricular papillary muscles taken from heat-stressed and control rabbit hearts were superfused with Kreb's solution containing either glucose or pyruvate and rendered hypoxic for 30 min. After reoxygenation, the greatest recovery of contractile function occurred in the heat-stressed muscles with pyruvate as substrate; there was, however, no difference in the force-interval relationship between the groups. The degree of contractile recovery was related to the content of the inducible 70-kD but not the 65-kD, heat stress protein. This study suggests that heat stress enhances the ability of rabbit papillary muscle to use pyruvate, but not glucose, after reoxygenation, and that the differences seen in contractility may be secondary to induction of the 72-kD stress protein. Images PMID:8132747

  17. Improvement of myocardial ischemic dysfunction with dichloroacetic acid: experimental study by repeated ischemia in dogs.

    PubMed

    Okuda, K; Nohara, R; Fujita, M; Tamaki, N; Konishi, J; Sasayama, S

    1995-12-01

    We investigated metabolic factors related to the recovery of myocardial function during ischemia and after reperfusion using dichloroacetic acid (DCA) in canine models with repeated 10-min regional ischemia and reperfusion. Administration of 100 mg/kg DCA, which activates pyruvate dehydrogenase, improved regional wall motion significantly as compared with the nontreated controls (p < 0.05). The mechanism was studied by determining changes in myocardial levels of pH, glucose, lactate, and nonesterified fatty acids (NEFA). Glucose extraction was increased significantly during ischemia and reperfusion by the pretreatment of DCA (p < 0.01). the calculated contribution of glucose to myocardial oxidative metabolism during ischemia and reperfusion was greater than that of NEFA and lactate in case of DCA treatment. The uptake of [99mTc]pyrophosphate (PYP), which reflects myocardial injury, was also significantly suppressed by DCA (p < 0.01). pH was not affected by an infusion of DCA. These findings suggest that the activation of glucose metabolism by DCA, which is impaired and reduced during ischemia and reperfusion, may be responsible for the improved myocardial function after reperfusion. PMID:8606539

  18. Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

    SciTech Connect

    Som, P.; Wang, G.J.; Oster, Z.H.; Knapp, F.F. Jr.; Yonekura, Y.; Fujibayashi, Y.; Yamamoto, K.; Kubota, K.

    1992-12-31

    Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

  19. Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

    SciTech Connect

    Som, P.; Wang, G.J. ); Oster, Z.H. ); Knapp, F.F. Jr. ); Yonekura, Y. . Faculty of Medicine); Fujibayashi, Y. . Hospital); Yamamoto, K. . Medical School); Kubota, K. (Tohoku Univ., Sendai

    1992-01-01

    Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

  20. Myocardial Salvaging Effects of Berberine in Experimental Diabetes Co-Existing with Myocardial Infarction

    PubMed Central

    Borde, Manjusha K.; Mohanty, Ipseeta Ray; Maheshwari, Ujwala; Deshmukh, Y.A.

    2016-01-01

    Introduction Berberine, an isoquinoline alkaloid isolated from the Berberis aristata, has been shown to display a wide array of pharmacological activities (hypoglycaemic and hypolipidemic). Aim The present study was designed to investigate whether these pharmacological properties translate into the cardioprotective effects of Berberine in the setting of diabetes mellitus. Materials and Methods Necessary approval from the Institutional Animal Ethics Committee was taken for the study. Experimental diabetes was produced with single dose of Streptozotocin (STZ): 45mg/kg ip and myocardial infarction was induced by administering Isoproterenol (ISP): 85mg/kg, sc to rats on 35th & 36th day. After the confirmation of diabetes on 7th day (>200mg/dl), Berberine (100 mg/kg) was administered orally to experimental rats from day 8 and continued for 30 days thereafter. Various anti-diabetic (Glucose, HbA1c), cardioprotective (CPK-MB), metabolic (lipid profile), safety {liver function (SGPT, kidney function (Creatinine)} and histopathological indices of injury were evaluated in Healthy Control, Diabetic Control and Berberine treated groups. Results Administration of STZ-ISP resulted in a significant decrease in body weight (p<0.001), diabetic changes (increase in blood glucose, HbA1c), cardiac injury (leakage of myocardial CPK-MB), altered lipid profile, SGPT, creatinine levels (p<0.001) in the diabetic control group rats as compared to healthy control. Berberine treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB levels (p<0.001) compared to diabetic control group. In addition, Berberine favourably modulated the lipid parameters (total cholesterol, triglycerides, HDL, LDL). Subsequent to ISP challenge, histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Berberine in setting of diabetes. In addition, Berberine

  1. N-13 ammonia as an indicator of myocardial blood flow. [Dogs

    SciTech Connect

    Schelbert, H.R.; Phelps, M.E.; Huang, S.C.; MacDonald, N.S.; Hansen, H.; Selin, C.; Kuhl, D.E.

    1981-06-01

    We have characterized N-13 ammonia as a myocardial blood flow imaging agent suitable for positron-emission computed tomography. However, the mechanisms of uptake and retention of this agent in myocardium are not known, and effects of altered metabolism were not considered. Therefore, we studied the uptake and retention of N-13 ammonia in myocardium under various hemodynamic and metabolic conditions in open-chest dogs. N-13 ammonia was extracted nearly 100% during its initial capillary transit, followed by metabolic trapping that competed with flow-dependent back diffusion. At control flows, the first capillary transit extraction fraction (E) of N-13 ammonia averaged 0.82 +- 0.06. Inhibition of glutamine synthetase with L-methionine sulfoximine impaired metabolic trapping of N-13 ammonia and implicates te glutamic acid-glutamine reaction as the primary mechanism for ammonia fixation. Blood flow and metabolic trapping are the primary determinants of myocardial uptake and retention of N-13 ammonia. The relative constancy of metabolic trapping over a wide range of hemodynamic and metabolic conditions demonstrates the value of N-13 ammonia as a myocardial blood flow imaging agent.

  2. Ketone body metabolism and cardiovascular disease

    PubMed Central

    Cotter, David G.; Schugar, Rebecca C.

    2013-01-01

    Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states. PMID:23396451

  3. Wave Propagation of Myocardial Stretch: Correlation with Myocardial Stiffness

    PubMed Central

    Pislaru, Cristina; Pellikka, Patricia A.; Pislaru, Sorin V.

    2015-01-01

    The mechanism of flow propagation during diastole in the left ventricle (LV) has been well described. Little is known about the associated waves propagating along the heart wall s. These waves may have a mechanism similar to pulse wave propagation in arteries. The major goal of the study was to evaluate the effect of myocardial stiffness and preload on this wave transmission. Methods Longitudinal late diastolic deformation and wave speed (Vp) of myocardial stretch in the anterior LV wall were measured using sonomicrometry in sixteen pigs. Animals with normal and altered myocardial stiffness (acute myocardial infarction) were studied with and without preload alterations. Elastic modulus estimated from Vp (EVP; Moens-Korteweg equation) was compared to incremental elastic modulus obtained from exponential end -diastolic stress-strain relation (ESS). Myocardial distensibility and α-and β-coefficients of stress-strain relations were calculated. Results Vp was higher at reperfusion compared to baseline (2.6±1.3 m/s vs. 1.3±0.4 m/s; p=0.005) and best correlated with ESS (r 2=0.80, p<0.0001), β-coefficient (r2=0.78, p<0.0001), distensibility (r2=0.47, p=0.005), and wall thickness/diameter ratio (r2=0.42, p=0.009). Elastic moduli (EVP and ESS) were strongly correlated (r2=0.83, p<0.0001). Increasing preload increased Vp and EVP and decreased distensibility. At multivariate analysis, ESS, wall thickness, and end-diastolic and systolic LV pressures were independent predictors of Vp (r2model=0.83, p<0.0001). Conclusions The main determinants of wave propagation of longitudinal myocardial stretch were myocardial stiffness and LV geometry and pressure. This local wave speed could potentially be measured noninvasively by echocardiography. PMID:25193091

  4. Overnutrition, ectopic lipid and the metabolic syndrome.

    PubMed

    Grundy, Scott M

    2016-08-01

    The metabolic syndrome is a constellation of metabolic risk factors including atherogenic dyslipidemia (elevated serum triglycerides, reduced high-density lipoprotein (HDL) cholesterol), elevated blood pressure, dysglycemia (insulin resistance and elevated serum glucose), a pro-inflammatory state, and a prothrombotic state. Most persons with metabolic syndrome are obese, and usually have abdominal obesity. Generally, obesity is a reflection of overnutrition. A current view is that when adipose tissue fails to store all excess nutrients as triglyceride, lipid begins to accumulate in various tissues (eg, muscle, liver, pancreas, and heart). This accumulation is called ectopic lipid. Various mechanisms have been proposed whereby ectopic lipid is detrimental in different tissues; these derangements induce metabolic risk factors. The foundation of the metabolic syndrome thus appears to be overnutrition, that is, more nutrient intake than can be safely disposed by lipid oxidation. Excess dietary carbohydrate also induces ectopic lipid. Of interest, less than half of obese individuals develop metabolic syndrome. Through various mechanisms they adapt to overnutrition so as to minimize lipid overload in tissues, and consequently, prevent the syndrome. PMID:27194746

  5. ‘Progressive-Onset' versus Injury-Associated Discogenic Low Back Pain: Features of Disc Internal Derangement in Patients Studied with Provocation Lumbar Discography

    PubMed Central

    Bartynski, W.S.; Dejohn, L.M.; Rothfus, W.E.; Gerszten, P.C.

    2013-01-01

    Summary Chronic low back pain (LBP) can be ‘progressive onset' or injury-related. This study compares the patient-reported cause of chronic LBP to features of disc internal derangement at painful concordant discs evaluated by provocation lumbar discography. Concordant LBP was identified in 114 patients with chronic LBP studied by provocation discography. LBP cause, discogram pain response and discogram/post-discogram CT features of internal derangement were retrospectively reviewed. ‘Progressive-onset' LBP was reported in 32 (28%) patients, injury-related LBP in 75 (66%) with LBP equated to non-specific causes in seven. Injury-related LBP was more commonly identified in men (52 of 63 [83%]) with women reporting near-equal frequency of ‘progressive-onset' (23 of 44 [52%]) and injury-related (21 of 44 [48%]) LBP (p=0.002). In 172 concordant painful discs, near-equal frequency of severely degenerative (Dallas grade-3: 82 of 172 [47.3%]) and full-thickness radial fissure discs (Dallas grade-3: 90 of 172 [52.7%]) were identified. Women with ‘progressive-onset' LBP demonstrated more frequent severely degenerative discs (24 of 37 [65%]); women with injury-related LBP demonstrated more frequent radial-defect discs (21 of 31 [68%]; p=0.01). In men with injury-related LBP, severe degeneration-only (44 of 89 [49%]) and radial defect discs (45 of 89 [51%] were seen with equal frequency. In men with ‘progressive-onset' LBP, radial defects are more common (11 of 15 [73%]). ‘Progressive-onset' and injury-related chronic LBP subgroups are definable. Gender-related differences in incidence and internal derangement features at concordant discs are identified at discogram/post-discogram CT. These differences may have implications related to LBP origin/treatment-response. PMID:23472733

  6. The PPAR-α activator fenofibrate fails to provide myocardial protection in ischemia and reperfusion in pigs

    PubMed Central

    Xu, Ya; Lu, Li; Greyson, Clifford; Rizeq, Mona; Nunley, Karin; Wyatt, Beata; Bristow, Michael R.; Long, Carlin S.; Schwartz, Gregory G.

    2010-01-01

    Rodent studies suggest that peroxisome proliferator-activated receptor-α (PPAR-α) activation reduces myocardial ischemia-reperfusion (I/R) injury and infarct size; however, effects of PPAR-α activation in large animal models of myocardial I/R are unknown. We determined whether chronic treatment with the PPAR-α activator fenofibrate affects myocardial I/R injury in pigs. Domestic farm pigs were assigned to treatment with fenofibrate 50 mg·kg−1 ·day−1 orally or no drug treatment, and either a low-fat (4% by weight) or a high-fat (20% by weight) diet. After 4 wk, 66 pigs underwent 90 min low-flow regional myocardial ischemia and 120 min reperfusion under anesthetized open-chest conditions, resulting in myocardial stunning. The high-fat group received an infusion of triglyceride emulsion and heparin during this terminal experiment to maintain elevated arterial free fatty acid (FFA) levels. An additional 21 pigs underwent 60 min no-flow ischemia and 180 min reperfusion, resulting in myocardial infarction. Plasma concentration of fenofibric acid was similar to the EC50 for activation of PPAR-α in vitro and to maximal concentrations achieved in clinical use. Myocardial expression of PPAR-α mRNA was prominent but unaffected by fenofibrate treatment. Fenofibrate increased expression of carnitine palmitoyltransferase (CPT)-I mRNA in liver and decreased arterial FFA and lactate concentrations (each P < 0.01). However, fenofibrate did not affect myocardial CPT-I expression, substrate uptake, lipid accumulation, or contractile function during low-flow I/R in either the low- or high-fat group, nor did it affect myocardial infarct size. Despite expression of PPAR-α in porcine myocardium and effects of fenofibrate on systemic metabolism, treatment with this PPAR-α activator does not alter myocardial metabolic or contractile responses to I/R in pigs. PMID:16339839

  7. Quantitative genetic analysis of the metabolic syndrome in Hispanic children.

    PubMed

    Butte, Nancy F; Comuzzie, Anthony G; Cole, Shelley A; Mehta, Nitesh R; Cai, Guowen; Tejero, Maria; Bastarrachea, Raul; Smith, E O'Brian

    2005-12-01

    Childhood obesity is associated with a constellation of metabolic derangements including glucose intolerance, hypertension, and dyslipidemia, referred to as metabolic syndrome. The purpose of this study was to investigate genetic and environmental factors contributing to the metabolic syndrome in Hispanic children. Metabolic syndrome, defined as having three or more metabolic risk components, was determined in 1030 Hispanic children, ages 4-19 y, from 319 families enrolled in the VIVA LA FAMILIA study. Anthropometry, body composition by dual energy x-ray absorptiometry, clinical signs, and serum biochemistries were measured using standard techniques. Risk factor analysis and quantitative genetic analysis were performed. Of the overweight children, 20%, or 28% if abnormal liver function is included in the definition, presented with the metabolic syndrome. Odds ratios for the metabolic syndrome were significantly increased by body mass index z-score and fasting serum insulin; independent effects of sex, age, puberty, and body composition were not seen. Heritabilities +/- SE for waist circumference, triglycerides (TG), HDL, systolic blood pressure (SBP), glucose, and alanine aminotransferase (ALT) were highly significant. Pleiotropy (a common set of genes affecting two traits) detected between SBP and waist circumference, SBP and glucose, HDL and waist circumference, ALT and waist circumference, and TG and ALT may underlie the clustering of the components of the metabolic syndrome. Significant heritabilities and pleiotropy seen for the components of the metabolic syndrome indicate a strong genetic contribution to the metabolic syndrome in overweight Hispanic children. PMID:16306201

  8. [Metabolic therapy of postperitoneal intoxication].

    PubMed

    Vlasov, A P; Anaskin, S G; Vlasova, T I; Chivisov, S M; Shibitov, V A; Potyanova, I V; Selentsov, P V

    2012-01-01

    This clinico-laboratory study showed that antihypoxant remaxol promoted normalization of lipid metabolism in acute peritonitis and significantly reduced membrane-destabilizing events. This resulted in rapid elimination of the inflammatory process in the abdominal cavity and lowering of the intensity of endogenous intoxication. This beneficial effect decreased the severity of myocardial lesions and resulted in the normalization of erythrocyte function. It is concluded that the regulatory action of remaxol on lipid metabolism is due to its ability to control free radicals in lipid peroxidation and reduce phospholipase A2 activity. PMID:23285765

  9. CAD of myocardial perfusion

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2007-03-01

    Our purpose is in the automated evaluation of the physiological relevance of lesions in coronary angiograms. We aim to extract as much as possible quantitative information about the physiological condition of the heart from standard angiographic image sequences. Coronary angiography is still the gold standard for evaluating and diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. The dimensions of the stenosis can be assessed nowadays successfully with image processing based Quantitative Coronary Angiography (QCA) techniques. Our purpose is to assess the clinical relevance of the pertinent stenosis. We therefore analyze the myocardial perfusion as revealed in standard angiographic image sequences. In a Region-of-Interest (ROI) on the angiogram (without an overlaying major blood vessel) the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In order to minimize motion artifacts we select based on the recorded ECG signal end-diastolic images in both a basal and a hyperemic run in the same projection to position the ROI. We present the development of the algorithms together with results of a small study of 20 patients which have been catheterized following the standard protocol.

  10. Experimental myocardial infarction

    PubMed Central

    Hood, William B.; Bianco, Jesus A.; Kumar, Raj; Whiting, Richard B.

    1970-01-01

    Compliance of the infarcted left ventricle was studied in dogs 3-5 days after occlusion of the left anterior descending coronary artery. Compliance was assessed from postmortem pressure-volume curves and from pressure-length measurements (mercury-in-silastic segment length gauges) made both in vivo and postmortem. Postmortem pressure-volume curves showed reduced compliance compared to sham-operated animals. Postmortem pressure-length curves of infarcted and adjacent normal myocardium indicated that the diminished total compliance could be attributed to an increase in stiffness of the infarcted area. This was confirmed by in vivo end-diastolic pressure-length changes produced by transient aortic occlusion. The infarcted area was akinetic, showing neither contraction nor aneurysmal bulging. In addition, anesthetized dogs with infarcts, when compared with sham-operated animals, had similar left ventricular end-diastolic volumes (indicator dilution method), but higher left ventricular end-diastolic pressures. Taken with previous observations, which show that systolic aneurysmal bulging is uniformly present at the onset of ischemia, these results indicate that stiffening of the ischemic myocardium occurs during the first 5 days after infarction, and show that elevation of left ventricular filling pressure does not necessarily signify ventricular dilatation. The results also suggest a mechanism whereby ventricular performance may improve during recovery from acute myocardial infarction. Images PMID:4914678

  11. Role of cytokines in myocardial ischemia and reperfusion.

    PubMed

    Sharma, H S; Das, D K

    1997-01-01

    Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia-reperfusion injury. Furthermore, ischemia-reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-alpha) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart. PMID:18472818

  12. Myocardial perfusion imaging for detection of silent myocardial ischemia

    SciTech Connect

    Beller, G.A.

    1988-04-21

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references.

  13. MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

    PubMed Central

    Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

    2013-01-01

    One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

  14. How reliable is myocardial imaging in the diagnosis of acute myocardial infarction

    SciTech Connect

    Willerson, J.T.

    1983-01-01

    Myocardial scintigraphic techniques available presently allow a sensitive and relatively specific diagnosis of acute myocardial infarction when they are used correctly, although every technique has definite limitations. Small myocardial infarcts (less than 3 gm.) may be missed, and there are temporal limitations in the usefulness of the scintigraphic techniques. The development of tomographic methodology that may be used with single-photon radionuclide emitters (including technetium and /sup 201/Tl will allow the detection of relatively small abnormalities in myocardial perfusion and regions of myocardial infarction and will help to provide a more objective interpretation of the myocardial scintigrams. The use of overlay techniques allowing simultaneous assessment of myocardial perfusion, infarct-avid imaging, and radionuclide ventriculograms will provide insight into the relevant aspects of the extent of myocardial damage, the relationship of damage to myocardial perfusion, and the functional impact of myocardial infarction on ventricular performance.

  15. Mitochondria, myocardial remodeling, and cardiovascular disease.

    PubMed

    Verdejo, Hugo E; del Campo, Andrea; Troncoso, Rodrigo; Gutierrez, Tomás; Toro, Barbra; Quiroga, Clara; Pedrozo, Zully; Munoz, Juan Pablo; Garcia, Lorena; Castro, Pablo F; Lavandero, Sergio

    2012-12-01

    The process of muscle remodeling lies at the core of most cardiovascular diseases. Cardiac adaptation to pressure or volume overload is associated with a complex molecular change in cardiomyocytes which leads to anatomic remodeling of the heart muscle. Although adaptive at its beginnings, the sustained cardiac hypertrophic remodeling almost unavoidably ends in progressive muscle dysfunction, heart failure and ultimately death. One of the features of cardiac remodeling is a progressive impairment in mitochondrial function. The heart has the highest oxygen uptake in the human body and accordingly it has a large number of mitochondria, which form a complex network under constant remodeling in order to sustain the high metabolic rate of cardiac cells and serve as Ca(2+) buffers acting together with the endoplasmic reticulum (ER). However, this high dependence on mitochondrial metabolism has its costs: when oxygen supply is threatened, high leak of electrons from the electron transport chain leads to oxidative stress and mitochondrial failure. These three aspects of mitochondrial function (Reactive oxygen species signaling, Ca(2+) handling and mitochondrial dynamics) are critical for normal muscle homeostasis. In this article, we will review the latest evidence linking mitochondrial morphology and function with the process of myocardial remodeling and cardiovascular disease. PMID:22972531

  16. Metabolic Adaptation to Muscle Ischemia

    NASA Technical Reports Server (NTRS)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  17. Effect of bariatric surgery on humoral control of metabolic derangements in obese patients with type 2 diabetes mellitus: How it works

    PubMed Central

    Cetinkunar, Suleyman; Erdem, Hasan; Aktimur, Recep; Sozen, Selim

    2015-01-01

    Obesity and diabetes is a co-pandemic and a major health concern that is expanding. It has many psychosocial and economic consequences due to morbidity and mortality of this disease combination. The pathophysiology of obesity and related diabetes is complex and multifactorial. One arm of this disease process is the genetic susceptibility. Other arm is dependent on the intricate neuro-humoral factors that converge in the central nerve system. Gut hormones and the adipose tissue derived factors plays an important role in this delicate network. Bariatric surgery provides the only durable option for treatment of obesity and furthermore it provides a remission in the concomitant diseases that accompany obesity. This review provides a brief insight to all these mechanisms and tries to deduce the possible reasons of remission of type 2 diabetes after bariatric surgery. PMID:26090370

  18. End-stage anorexia nervosa in a young man: multifaceted metabolic, endocrine and infectious derangements managed in an internal medicine setting.

    PubMed

    Foppiani, Luca; Cascio, Christian; Pinto, Valeria; Lo Pinto, Giuliano

    2014-12-01

    Anorexia nervosa (AN) in males is an overlooked disease which requires early diagnosis and proper treatment. Clinical presentation is often severe and the risk of death is not negligible. We report the case of a young man with a 1-year history of AN who was admitted to our internal medicine department for a dramatic malnutrition (BMI: 10.5 kg/m(2)). Several biochemical and hormonal alterations were ascertained. Partial parenteral nutrition and a balanced diet were started. Asymptomatic refeeding syndrome occurred and was managed by enhanced electrolyte parenteral supplementation. Many hematologic abnormalities (anaemia, leukopenia and thrombocytopenia) were present and worsened during the occurrence of sepsis which required hemotransfusions and targeted parenteral antibiotics with improvement of both clinical condition and hematologic parameters. Bone marrow aspiration and cytofluorimetric evaluation showed hyperplasia and dysplasia of erythroid lineage and reduction of myeloid lineage. Significant body weight gain (+17 % vs. admission) was obtained and the patient was discharged with stable cardiovascular parameters and referred to an eating disorders centre where is currently followed. PMID:24821487

  19. Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats

    PubMed Central

    Wilson, Christopher R.; Tran, Mai K.; Salazar, Katrina L.; Young, Martin E.; Taegtmeyer, Heinrich

    2007-01-01

    Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal-muscle insulin resistance. We tested the hypothesis that ‘Western’ and high fat diets differentially cause maladaptation of cardiac- and skeletal-muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar rats were fed on low fat, ‘Western’ or high fat (10, 45 or 60% calories from fat respectively) diet for acute (1 day to 1 week), short (4–8 weeks), intermediate (16–24 weeks) or long (32–48 weeks) term. Oleate oxidation in heart muscle ex vivo increased with high fat diet at all time points investigated. In contrast, cardiac oleate oxidation increased with Western diet in the acute, short and intermediate term, but not in the long term. Consistent with fatty acid oxidation maladaptation, cardiac power decreased with long-term Western diet only. In contrast, soleus muscle oleate oxidation (ex vivo) increased only in the acute and short term with either Western or high fat feeding. Fatty acid-responsive genes, including PDHK4 (pyruvate dehydrogenase kinase 4) and CTE1 (cytosolic thioesterase 1), increased in heart and soleus muscle to a greater extent with feeding a high fat diet compared with a Western diet. In conclusion, we implicate inadequate induction of a cassette of fatty acid-responsive genes, and impaired activation of fatty acid oxidation, in the development of cardiac dysfunction with Western diet. PMID:17550347

  20. Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal muscle insulin resistance. We tested the hypothesis...

  1. Deranged bioenergetics and defective redox capacity in T lymphocytes and neutrophils are related to cellular dysfunction and increased oxidative stress in patients with active systemic lupus erythematosus.

    PubMed

    Li, Ko-Jen; Wu, Cheng-Han; Hsieh, Song-Chou; Lu, Ming-Chi; Tsai, Chang-Youh; Yu, Chia-Li

    2012-01-01

    Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyl)lysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE) than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox) capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T) and polymorphonuclear neutrophils (PMN) of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px) and γ-glutamyl-transpeptidase (GGT), was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients. PMID:22007252

  2. Circadian Disruption and Metabolic Disease: Findings from Animal Models

    PubMed Central

    Arble, Deanna Marie; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-01-01

    Social opportunities and work demands have caused humans to become increasingly active during the late evening hours, leading to a shift from the predominantly diurnal lifestyle of our ancestors to a more nocturnal one. This voluntarily decision to stay awake long into the evening hours leads to circadian disruption at the system, tissue, and cellular levels. These derangements are in turn associated with clinical impairments in metabolic processes and physiology. The use of animal models for circadian disruption provides an important opportunity to determine mechanisms by which disorganization in the circadian system can lead to metabolic dysfunction in response to genetic, environmental, and behavioral perturbations. Here we review recent key animal studies involving circadian disruption and discuss the possible translational implications of these studies for human health and particularly for the development of metabolic disease. PMID:21112026

  3. Clinical nuclear imaging techniques for the diagnosis and evaluation of acute myocardial infarction.

    PubMed

    Williams, K A; Garvin, A A; Taillon, L A

    1992-02-01

    The use of nuclear imaging techniques allows the accurate detection of myocardial infarction, determination of the impact of infarction on ventricular performance, assessment of the myocardial salvage with thrombolysis, identification of preserved regional metabolism in jeopardized myocardial segments, and the elucidation of inducible reversible ischemia requiring aggressive therapeutic intervention. Assessment of myocardial salvage after thrombolysis or revascularization can be accomplished with serial perfusion imaging. Infarct-avid imaging with Tc-99m-PYP can be used to rapidly determine the size and location of the acute transmural myocardial infarction. In the future, however, the improved image quality and diagnostic accuracy of immunoscintigraphy with antimyosin antibodies may supplant PYP imaging. Studies of global ventricular function can be performed at rest, or with multiple interventions using portable scintigraphic devices. The measurement of the dynamic response of left ventricular ejection fraction over time shows promise for risk stratification. As yet, there has been no comprehensive comparison of the relative predictive value of metabolic imaging parameters, perfusion/antibody uptake mismatch, Tl-201 redistribution, or ejection fraction response data. Such a comparison could optimize the diagnostic algorithm for post-infarction damage assessment and risk stratification. PMID:1532141

  4. Myocardial infarction following bee sting.

    PubMed

    Puvanalingam, A; Karpagam, P; Sundar, C; Venkatesan, S; Ragunanthanan

    2014-08-01

    Bee stings are commonly encountered worldwide. Various manifestations after bee sting have been described. Local reactions are common. Unusually, manifestations like vomiting, diarrhoea, dyspnoea, generalised oedema, acute renal failure, hypotension and collapse may occur. Rarely vasculitis, serum sickness, neuritis and encephalitis have been described which generally develop days to weeks after a sting. Acute coronary syndromes after hymenoptera stings and other environmental exposures are referred to as the Kounis syndrome or allergic myocardial ischaemia and infarction. We report a 60 year old male who developed myocardial infarction after multiple bee stings over his body. PMID:25856951

  5. Thallium-201 myocardial scintigraphy in acute myocardial infarction and ischemia

    SciTech Connect

    Wackers, F.J.

    1982-04-01

    Thallium-201 scintigraphy provides a sensitive and reliable method of detecting acute myocardial infarction and ischemia when imaging is performed with understanding of the temporal characteristics and accuracy of the technique. The results of scintigraphy are related to the time interval between onset of symptoms and time of imaging. During the first 6 hr after chest pain almost all patients with acute myocardial infarction and approximately 50% of the patients with unstable angina will demonstrate /sup 201/TI pefusion defects. Delayed imaging at 2-4 hr will permit distinction between ischemia and infarction. In patients with acute myocardial infarction, the size of the perfusion defect accurately reflects the extent of the infarcted and/or jeopardized myocardium, which may be used for prognostic stratification. In view of the characteristics of /sup 201/TI scintigraphy, the most practical application of this technique is in patients in whom myocardial infarction has to be ruled out, and for early recognition of patients at high risk for complications.

  6. Acute myocardial infarction

    PubMed Central

    Domes, Trustin; Szafran, Olga; Bilous, Cheryl; Olson, Odell; Spooner, G. Richard

    2006-01-01

    OBJECTIVE To assess the quality of care of acute myocardial infarction (AMI) in a rural health region. DESIGN Clinical audit employing multiple explicit criteria of care elements for emergency department and in-hospital AMI management. The audit was conducted using retrospective chart review. SETTING Twelve acute care health centres and hospitals in the East Central Health Region, a rural health region in Alberta, where medical and surgical services are provided almost entirely by family physicians. PARTICIPANTS Hospital inpatients with a confirmed discharge diagnosis of AMI (ICD-9-CM codes 410.xx) during the period April 1, 2001, to March 31, 2002, were included (177 confirmed cases). MAIN OUTCOME MEASURES Quality of AMI care was assessed using guidelines from the American College of Cardiology and the American Heart Association and the Canadian Cardiovascular Outcomes Research Team and Canadian Cardiovascular Society. Quality of care indicators at three stages of patient care were assessed: at initial recognition and AMI management in the emergency department, during in-hospital AMI management, and at preparation for discharge from hospital. RESULTS In the emergency department, the quality of care was high for most procedural and therapeutic audit elements, with the exception of rapid electrocardiography, urinalysis, and provision of nitroglycerin and morphine. Average door-to-needle time for thrombolysis was 102.5 minutes. The quality of in-hospital care was high for most elements, but low for nitroglycerin and angiotensin-converting enzyme (ACE) inhibitors, daily electrocardiography, and counseling regarding smoking cessation and diet. Few patients received counseling for lifestyle changes at hospital discharge. Male and younger patients were treated more aggressively than female and older patients. Sites that used care protocols achieved better results in initial AMI management than sites that did not. Stress testing was not readily available in the rural

  7. Myocardial contusion following nonfatal blunt chest trauma

    SciTech Connect

    Kumar, S.A.; Puri, V.K.; Mittal, V.K.; Cortez, J.

    1983-04-01

    Currently available diagnostic techniques for myocardial contusion following blunt chest trauma were evaluated. We investigated 30 patients prospectively over a period of 1 year for the presence of myocardial contusion. Among the 30 patients, eight were found to have myocardial contusion on the basis of abnormal electrocardiograms, elevated creatine phosphokinase MB fraction (CPK-MB), and positive myocardial scan. Myocardial scan was positive in seven of eight patients (87.5%). CPK-MB fraction was elevated in four of eight patients (50%). Definitive electrocardiographic changes were seen in only two of eight patients (25%). It appears that myocardial scan using technetium pyrophosphate and CPK-MB fraction determinations are the most reliable aids in diagnosis of myocardial contusion following blunt chest trauma.

  8. Spousal Adjustment to Myocardial Infarction.

    ERIC Educational Resources Information Center

    Ziglar, Elisa J.

    This paper reviews the literature on the stresses and coping strategies of spouses of patients with myocardial infarction (MI). It attempts to identify specific problem areas of adjustment for the spouse and to explore the effects of spousal adjustment on patient recovery. Chapter one provides an overview of the importance in examining the…

  9. [Sewer gas induced myocardial toxicity].

    PubMed

    Antonelli, Dante; Sabanchiev, Avi; Rosner, Ehud; Turgeman, Yoav

    2014-07-01

    We report the case of a 19 year-old worker who collapsed after acute exposure to sewer gas. He rapidly developed cardiorespiratory failure with electrocardiographic, echocardiographic and laboratory findings of myocardial involvement. The mainstay of the therapy was mainly supportive treatment with a successful outcome. PMID:25189024

  10. Thrombolysis for Acute Myocardial Infarction

    PubMed Central

    Webb, John; Thompson, Christopher

    1992-01-01

    Thrombolysis has an important role in the management of acute myocardial infarction. Early treatment can markedly reduce mortality and morbidity. This new standard of care requires knowledge of accepted indications and contraindications for thrombolysis as well as familiarity with available agents and regimens. ImagesFigure 3 PMID:21221398

  11. Effects of glucosamine-chondroitin combination on synovial fluid IL-1β, IL-6, TNF-α and PGE2 levels in internal derangements of temporomandibular joint

    PubMed Central

    Esen, Emin; Tatli, Ufuk

    2015-01-01

    Background The aim of the present study was to evaluate the effects of glucosamine-chondroitin sulphate combination on internal derangements of temporomandibular joint in clinical and biochemical manners. Material and Methods This randomized clinical study included 31 cases reporting joint tenderness, in which disc displacement was detected on MR imaging. In all patients, synovial fluid sampling was performed under local anesthesia. In the study group, the patients were prescribed a combination of 1500 mg glucosamine and 1200 mg chondroitin sulphate, while patients in the control group were only prescribed 50 mg tramadol HCl (twice daily) for pain control. After 8 weeks, synovial fluid sampling was repeated in the same manner. The levels of pain, maximum mouth opening (MMO), synovial fluid IL-1ß, IL-6, TNF-α and PGE2 measured before and after pharmacological intervention were compared. Results The reduction in pain levels was significant in both groups. There was no significant difference between two groups in terms of pain reduction. The improvement in MMO was significant in the study group but it was not in the control group. The MMO improvement was significantly higher in the study group compared to the control group. In the study group, significant decrease was observed in PGE2 level, while the decreases in IL-1β, IL-6 and TNF-α levels were not significant. In the control group, no significant decrease was observed in any of the inflammatory cytokines after 8 weeks, moreover IL-1ß and IL-6 levels were increased. Alterations of IL-1ß and IL-6 levels were significant in study group while TNF-α and PGE2 levels were not, compared to control group. Conclusions In conclusion, these results might suggest that glucosamine-chondroitin combination significantly increases the MMO and decreases the synovial fluid IL1β and IL6 levels in internal derangements of TMJ compared to tramadol. The modifications of synovial fluid TNF-α and PGE2 levels do not reach

  12. Influence of myocardial substrate utilization on the oxygen consumption of the heart.

    PubMed

    Kahles, H; Hellige, G; Hunneman, D H; Mezger, V A; Bretschneider, H J

    1982-04-01

    The effect of changing myocardial metabolism from predominantly lipid to predominantly carbohydrate utilization on myocardial oxygen consumption (MVO2) was studied in 10 closed-chest dogs. Oxygen saving potency of different metabolic interventions was quantified over a wide hemodynamic range by comparing the directly determined MVO2 with the hemodynamic parameter total left ventricular energy demand (Et), which correlates closely under control conditions with MVO2 (r = 0.98). Stimulation of carbohydrate metabolism by addition of glucose and beta-pyridyl carbinol or by activation of pyruvate dehydrogenase with dichloroacetate (DCA) shifted the cardiac respiratory quotient during beta-stimulation from 0.73 to 1.00 and 0.89, respectively, the nonesterified fatty acid/albumin ratio decreased from 4.0 to 0.5, or remained unchanged with DCA, and MVO2 was reduced by 25 and 16%, respectively. Therapeutic approaches aimed at decreasing MVO2 by changing substrate utilization are discussed. PMID:7083652

  13. Mapping of cerebral oxidative metabolism with MRI

    PubMed Central

    Mellon, Eric A.; Beesam, R. Shashank; Elliott, Mark A.; Reddy, Ravinder

    2010-01-01

    Using a T1ρ MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of gas. The study was performed by inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9%+/-2.5% per mg/kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T1ρ MRI following administration of gas. Metabolism was calculated from the change in the T1ρ weighted MRI signal due to H217O generated from inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H217O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive gas. Given the demonstrated high efficiency in use of and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements. PMID:20547874

  14. To Assess the Association between Glucose Metabolism and Ectopic Lipid Content in Different Clinical Classifications of PCOS

    PubMed Central

    Göbl, Christian S.; Ott, Johannes; Bozkurt, Latife; Feichtinger, Michael; Rehmann, Victoria; Cserjan, Anna; Heinisch, Maike; Steinbrecher, Helmut; JustKukurova, Ivica; Tuskova, Radka; Leutner, Michael; Vytiska-Binstorfer, Elisabeth; Kurz, Christine; Weghofer, Andrea; Tura, Andrea; Egarter, Christian; Kautzky-Willer, Alexandra

    2016-01-01

    Aims There are emerging data indicating an association between PCOS (polycystic ovary syndrome) and metabolic derangements with potential impact on its clinical presentation. This study aims to evaluate the pathophysiological processes beyond PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their possible interaction. Differences between the two established classifications of the disease should be additionally evaluated. Methods A metabolic characterization was performed in 53 untreated PCOS patients as well as 20 controls including an extended oral glucose tolerance test (OGTT, to assess insulin sensitivity, secretion and ß-cell function) in addition to a detailed examination of ectopic lipid content in muscle and liver by nuclear magnetic resonance spectroscopy. Results Women with PCOS classified by the original NIH 1990 definition showed a more adverse metabolic risk profile compared to women characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic derangements were observed in both subgroups, including altered shapes of OGTT curves, impaired insulin action and hyperinsulinemia due to increased secretion and attenuated hepatic extraction. No differences were observed for ectopic lipids between the groups. However, particularly hepatocellular lipid content was significantly related to clinical parameters of PCOS like whole body insulin sensitivity, dyslipidemia and free androgen index. Conclusions Subtle alterations in carbohydrate metabolism are present in both PCOS classifications, but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS and controls did not differ in ectopic lipids, however, liver fat was tightly related to hyperandrogenism and an adverse metabolic risk profile. PMID:27505055

  15. [Discordant pattern, visual identification of myocardial viability with PET].

    PubMed

    Alexánderson, E; Ricalde, A; Zerón, J; Talayero, J A; Cruz, P; Adame, G; Mendoza, G; Meave, A

    2006-01-01

    PET (positron emission tomography) as a non-invasive imaging method for studying cardiac perfusion and metabolism has turned into the gold standard for detecting myocardial viability. The utilization of 18 FDG as a tracer for its identification permits to spot the use of exogenous glucose by the myocardium segments. By studying and comparing viability and perfusion results, for which the latter uses tracers such as 13N-ammonia, three different patterns for myocardial viability evaluation arise:. transmural concordant pattern, non-transmural concordant pattern, and the discordant pattern; the last one exemplifies the hibernating myocardium and proves the presence of myocardial viability. The importance of its detection is fundamental for the study of an ischemic patient, since it permits the establishment of and exact diagnosis, prognosis, and the best treatment option. It also allows foreseeing functional recovery of the affected region as well as the ejection fraction rate after revascularization treatment if this is determined as necessary. All these elements regarding viability are determinant in order to reduce adverse events and help improving patients' prognosis. PMID:17315610

  16. No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure

    PubMed Central

    Dass, Sairia; Holloway, Cameron J.; Cochlin, Lowri E.; Rider, Oliver J.; Mahmod, Masliza; Robson, Matthew; Sever, Emily; Clarke, Kieran; Watkins, Hugh; Ashrafian, Houman; Karamitsos, Theodoros D.

    2015-01-01

    Background— Whether the myocardium in nonischemic heart failure experiences oxygen limitation remains a long-standing controversy. We addressed this question in patients with dilated cardiomyopathy (DCM) using a dual approach. First, we tested the changes in myocardial oxygenation between rest and stress states, using oxygenation-sensitive cardiovascular magnetic resonance. Second, we sought to assess the functional consequences of oxygen limitation at rest by measuring myocardial energetics before and after short-term oxygen supplementation. Methods and Results— Twenty-six subjects (14 DCM and 12 normal) underwent cardiac magnetic resonance imaging at 3 Tesla to assess cardiac volumes, function, oxygenation, and first-pass perfusion (0.03 mmol/kg Gd-DTPA bolus) at stress and rest (4–6 minutes IV adenosine, 140 μg/kg per minute). Signal intensity change (SIΔ) and myocardial perfusion reserve index (MPRI) were measured from oxygenation and perfusion images, respectively. Furthermore, the effect of oxygen supplementation on resting myocardial energy metabolism was tested using 31P MR spectroscopy, measuring PCr/ATP ratios in both groups at baseline and after 4 hours of oxygen via facemask in the DCM group. During stress, there were equivalent rises in rate pressure product in both groups (DCM, 76±15% and normal, 79±9%; P=0.84). MPRI was significantly reduced in DCM (1.51±0.11 versus normal 1.86±0.10; P=0.03). However, there was no difference in oxygenation between groups: SIΔ in DCM 17±3% versus normal 20±2% (P=0.38). Furthermore, at a left ventricular segmental level, there was no correlation between oxygenation-sensitive SIΔ and MPRI (R=0.06; P=0.43). Resting PCr/ATP was reduced in DCM (1.66±0.07 versus normal 2.12±0.06; P=0.002). With oxygen supplementation, there was no change in PCr/ATP (1.61±0.08; P=0.58; Δ=0.04±0.05). There was also no effect of oxygen on systolic function (ejection fraction pre oxygen, 34±1%; post oxygen, 36±2%; P=0

  17. Metabolic neuropathies

    MedlinePlus

    Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk for ...

  18. Black Cohosh Ameliorates Metabolic Disorders in Female Ovariectomized Rats.

    PubMed

    Sun, Yu; Yu, Qiuxiao; Shen, Qiyang; Bai, Wenpei; Kang, Jihong

    2016-06-01

    Estrogen deficiency is associated with metabolic derangements in menopausal women. Black cohosh has been widely used as an alternative therapy in the treatment of menopausal syndrome. However, its role in metabolism needs to be defined. The aim of the present study was to investigate the long-term effect of black cohosh on glucose and lipid metabolism in a rat model of post-menopause. Adult female Sprague-Dawley rats were sham operated (SHAM), ovariectomized (OVX), OVX with the treatment of estradiol valerate (OVX + E), or OVX with the treatment of isopropanolic black cohosh extract (OVX + iCR). Body weight, body composition, and blood glucose levels of the animals were monitored. The rats were then sacrificed after 3 months of the treatments. At the end of the experiment, OVX + iCR and OVX + E rats exhibited a significant decrease in body weight gain, body and abdominal fat mass, serum triglycerides levels, hepatic fat accumulation, and adipocyte hypertrophy compared with OVX rats. In addition, insulin resistance and glucose intolerance were improved in OVX + iCR but not in OVX + E rats. No hepatotoxicity was detected in OVX + iCR animals. Furthermore, western blot analysis suggested the increased lipolysis in adipose tissue of OVX + iCR and OVX + E rats. Data from in vitro experiments using cultured primary rat adipocytes also showed that black cohosh could affect lipolysis of adipocytes. In conclusion, the long-term treatment of black cohosh at a proper dosage ameliorated metabolic derangements in OVX rats. Thus, this drug is promising for the treatment of metabolic disorders in menopausal and post-menopausal women. PMID:26414761

  19. Calpain inhibition preserves myocardial structure and function following myocardial infarction.

    PubMed

    Mani, Santhosh K; Balasubramanian, Sundaravadivel; Zavadzkas, Juozas A; Jeffords, Laura B; Rivers, William T; Zile, Michael R; Mukherjee, Rupak; Spinale, Francis G; Kuppuswamy, Dhandapani

    2009-11-01

    Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca(2+)-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated (n = 6) and untreated (n = 6) MI mice were used to study changes in myocardial structure and function after 4 days of MI, where end-diastolic volume (EDV) and left ventricular ejection fraction (EF) were measured by echocardiography. Calpain activation and programmed cell death were measured by immunohistochemistry, Western blotting, and TdT-mediated dUTP nick-end labeling (TUNEL). In MI mice, calpeptin treatment resulted in a significant improvement in EF [EF decreased from 67 + or - 2% pre-MI to 30 + or - 4% with MI only vs. 41 + or - 2% with MI + calpeptin] and attenuated the increase in EDV [EDV increased from 42 + or - 2 microl pre-MI to 73 + or - 4 microl with MI only vs. 55 + or - 4 microl with MI + calpeptin]. Furthermore, calpeptin treatment resulted in marked reduction in calpain- and caspase-3-associated changes and TUNEL staining. These studies indicate that calpain contributes to MI-induced alterations in myocardial structure and function and that it could be a potential therapeutic target in treating MI patients. PMID:19734364

  20. Glucose metabolism and cardiac hypertrophy

    PubMed Central

    Kolwicz, Stephen C.; Tian, Rong

    2011-01-01

    The most notable change in the metabolic profile of hypertrophied hearts is an increased reliance on glucose with an overall reduced oxidative metabolism, i.e. a reappearance of the foetal metabolic pattern. In animal models, this change is attributed to the down-regulation of the transcriptional cascades promoting gene expression for fatty acid oxidation and mitochondrial oxidative phosphorylation in adult hearts. Impaired myocardial energetics in cardiac hypertrophy also triggers AMP-activated protein kinase (AMPK), leading to increased glucose uptake and glycolysis. Aside from increased reliance on glucose as an energy source, changes in other glucose metabolism pathways, e.g. the pentose phosphate pathway, the glucosamine biosynthesis pathway, and anaplerosis, are also noted in the hypertrophied hearts. Studies using transgenic mouse models and pharmacological compounds to mimic or counter the switch of substrate preference in cardiac hypertrophy have demonstrated that increased glucose metabolism in adult heart is not harmful and can be beneficial when it provides sufficient fuel for oxidative metabolism. However, improvement in the oxidative capacity and efficiency rather than the selection of the substrate is likely the ultimate goal for metabolic therapies. PMID:21502371

  1. Allometry of left ventricular myocardial innervation.

    PubMed

    Schipke, Julia; Mayhew, Terry M; Mühlfeld, Christian

    2014-04-01

    Body mass (BM) of terrestrial mammalian species ranges from a few grams in the case of the Etruscan shrew to a few tonnes for an elephant. The mass-specific metabolic rate, as well as heart rate, decrease with increasing BM, whereas heart mass is proportional to BM. In the present study, we investigated the scaling behaviour of several compartments of the left ventricular myocardium, notably its innervation, capillaries and cardiomyocytes. Myocardial samples were taken from 10 mammalian species with BM between approximately 2 g and 900 kg. Samples were analysed by design-based stereology and electron microscopy and the resulting data were subjected to linear regression and correlation analyses. The total length of nerve fibres (axons) in the left ventricle increased from 0.017 km (0.020 km) in the shrew to 7237 km (13,938 km) in the horse. The innervation density was similar among species but the mean number of axons per nerve fibre profile increased with rising BM. The total length of capillaries increased from 0.119 km (shrew) to 10,897 km (horse). The volume of cardiomyocytes was 0.017 cm(3) in the shrew and 1818 cm(3) in the horse. Scaling of the data against BM indicated a higher degree of complexity of the axon tree in larger animals and an allometric relationship between total length of nerve fibres/axons and BM. In contrast, the density of nerve fibres is independent of BM. It seems that the structural components of the autonomic nervous system in the heart are related to BM and heart mass rather than to functional parameters such as metabolic rate. PMID:24325466

  2. Perioperative myocardial ischemia reperfusion injury.

    PubMed

    Shernan, Stanton K

    2003-09-01

    Myocardial I-R injury contributes to adverse cardiovascular outcomes after cardiac surgery. The pathogenesis of I-R injury is complex and involves the activation, coordination, and amplification of several systemic and local proinflammatory pathways (Fig. 4). Treatment and prevention of perioperative morbidity associated with myocardial I-R will ultimately require a multifocal approach. Combining preoperative risk stratification (co-morbidity and surgical complexity), minimizing initiating factors predisposing to SIRS, limiting ischemia duration, and administering appropriate immunotherapy directed toward systemic and local proinflammatory mediators of I-R injury, should all be considered. In addition, the role of the genetic-environmental interactions in the pathogenesis of cardiovascular disease is also being examined. Thus, in the near future, preoperative screening for polymorphisms of certain inflammatory and coagulation genes should inevitably help reduce morbidity by permitting the identification of high-risk cardiac surgical patients and introducing the opportunity for gene therapy or pharmacogenetic intervention [42,64]. PMID:14562561

  3. Myocardialization of the cardiac outflow tract

    NASA Technical Reports Server (NTRS)

    van den Hoff, M. J.; Moorman, A. F.; Ruijter, J. M.; Lamers, W. H.; Bennington, R. W.; Markwald, R. R.; Wessels, A.

    1999-01-01

    During development, the single-circuited cardiac tube transforms into a double-circuited four-chambered heart by a complex process of remodeling, differential growth, and septation. In this process the endocardial cushion tissues of the atrioventricular junction and outflow tract (OFT) play a crucial role as they contribute to the mesenchymal components of the developing septa and valves in the developing heart. After fusion, the endocardial ridges in the proximal portion of the OFT initially form a mesenchymal outlet septum. In the adult heart, however, this outlet septum is basically a muscular structure. Hence, the mesenchyme of the proximal outlet septum has to be replaced by cardiomyocytes. We have dubbed this process "myocardialization." Our immunohistochemical analysis of staged chicken hearts demonstrates that myocardialization takes place by ingrowth of existing myocardium into the mesenchymal outlet septum. Compared to other events in cardiac septation, it is a relatively late process, being initialized around stage H/H28 and being basically completed around stage H/H38. To unravel the molecular mechanisms that are responsible for the induction and regulation of myocardialization, an in vitro culture system in which myocardialization could be mimicked and manipulated was developed. Using this in vitro myocardialization assay it was observed that under the standard culture conditions (i) whole OFT explants from stage H/H20 and younger did not spontaneously myocardialize the collagen matrix, (ii) explants from stage H/H21 and older spontaneously formed extensive myocardial networks, (iii) the myocardium of the OFT could be induced to myocardialize and was therefore "myocardialization-competent" at all stages tested (H/H16-30), (iv) myocardialization was induced by factors produced by, most likely, the nonmyocardial component of the outflow tract, (v) at none of the embryonic stages analyzed was ventricular myocardium myocardialization-competent, and finally

  4. Acute care of myocardial infarction.

    PubMed Central

    Gutman, M. B.; Lee, T. F.; Gin, K.; Ho, K.

    1996-01-01

    Patients with acute myocardial infarct (AMI) need rapid diagnosis and prompt initiation of thrombolytic therapy. Patients with suspected cardiac ischemia must receive a coordinated team response by the emergency room staff including rapid electrocardiographic analysis and a quick but thorough history and physical examination to diagnose AMI. Thrombolysis and adjunct therapies should be administered promptly when indicated. The choice of thrombolytics is predicated by the location of the infarct. PMID:8754702

  5. Myocardial Infarction in the Elderly

    PubMed Central

    Carro, Amelia; Kaski, Juan Carlos

    2011-01-01

    Advances in pharmacological treatment and effective early myocardial revascularization have –in recent years- led to improved clinical outcomes in patients with acute myocardial infarction (AMI). However, it has been suggested that compared to younger subjects, elderly AMI patients are less likely to receive evidence-based treatment, including myocardial revascularization therapy. Several reasons have been postulated to explain this trend, including uncertainty regarding the true benefits of the interventions commonly used in this setting as well as increased risk mainly associated with comorbidities. The diagnosis, management, and post-hospitalization care of elderly patients presenting with an acute coronary syndrome pose many difficulties at present. A complex interplay of variables such as comorbidities, functional and socioeconomic status, side effects associated with multiple drug administration, and individual biologic variability, all contribute to creating a complex clinical scenario. In this complex setting, clinicians are often required to extrapolate evidence-based results obtained in cardiovascular trials from which older patients are often, implicitly or explicitly, excluded. This article reviews current recommendations regarding management of AMI in the elderly. PMID:22396870

  6. 31-Phosphorus nuclear magnetic resonance study of neonatal myocardial metabolism

    SciTech Connect

    Kost, G.J.; Anderson, S.E.

    1986-03-05

    A modified Langendorff heart preparation was designed for use with a 4.7 Tesla Nicolet NMR spectrometer operated at 80.98 MHz in the pulsed Fourier transform mode. The perfusion system delivered constant temperature (37/sup 0/C) modified Krebs-Henseleit solution containing glucose as the exogenous substrate. Experiments were performed with constant perfusion pressure, which was adjusted according to the age of the rabbit. Neonatal hearts weighted about 0.5 g. A special 16mm Dadok-type NMR probe was designed to accommodate these small hearts in a vertical bore spectrometer configuration. Spectral standardization was accomplished with a capillary tube placed in the B1 window of the probe. The principal theme of the experiments was to determine the effects of ischemic stress on the neonatal heart by measuring changes in intracellular pH, inorganic phosphate (Pi), phosphocreatine (PCr) and ATP from 31-phosphorus spectra gathered over five minute intervals by signal averaging 148 FIDs using 4K data files and 5000 Hz spectral width. Hearts were subjected to different durations of ischemic stress. The responses of neonatal hearts were compared with those of more mature hearts.

  7. Linking the cardiomyocyte circadian clock to myocardial metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The energetic demands imposed upon the heart vary dramatically over the course of the day. In the face of equally commanding oscillations in the neurohumoral mileu, the heart must respond both rapidly and appropriately to its diurnal environment, for the survival of the organism. A major response of...

  8. [Vectorcardiographic diagnosis of the myocardial inactivatable zone].

    PubMed

    de Micheli, A; Medrano, G A

    1989-01-01

    Clinical importance of the vectorcardiographic exploration (distant and spatial) of the myocardial electrical phenomenon is emphasized. This technique constitutes a useful integration of electrocardiographic exploration (near and analytical). The more characteristic morphological and chronological changes due to an inactivatable area are discussed in the light of ventricular myocardial depolarization. Some typical vectorcardiographic features corresponding to the presence of a myocardial inactivatable zone are presented. The utility of the complementary elements which vectorcardiography can bring to electrocardiography is emphasized. Both of these procedures integrate a rational exploration of electrical activity of the myocardium, the solid base of prognostic and therapeutic decisions in cases of myocardial infarction. PMID:2669657

  9. Myocardial perfusion imaging using contrast echocardiography.

    PubMed

    Pathan, Faraz; Marwick, Thomas H

    2015-01-01

    Microbubbles are an excellent intravascular tracer, and both the rate of myocardial opacification (analogous to coronary microvascular perfusion) and contrast intensity (analogous to myocardial blood volume) provide unique insights into myocardial perfusion. A strong evidence base has been accumulated to show comparability with nuclear perfusion imaging and incremental diagnostic and prognostic value relative to wall motion analysis. This technique also provides the possibility to measure myocardial perfusion at the bedside. Despite all of these advantages, the technique is complicated, technically challenging, and has failed to scale legislative and financial hurdles. The development of targeted imaging and therapeutic interventions will hopefully rekindle interest in this interesting modality. PMID:25817740

  10. Myocardial ischaemia during tracheal intubation and extubation.

    PubMed

    Edwards, N D; Alford, A M; Dobson, P M; Peacock, J E; Reilly, C S

    1994-10-01

    The incidence of myocardial ischaemia during tracheal intubation and extubation was compared using ambulatory ECG monitoring in 60 patients undergoing a variety of different surgical operations. Seven patients had myocardial ischaemia after tracheal intubation and seven patients during tracheal extubation. The patients who developed myocardial ischaemia during tracheal extubation had significantly greater rate-pressure products immediately before tracheal extubation (P < 0.05) and 1 min after tracheal extubation (P < 0.01) compared with those patients who did not develop myocardial ischaemia during extubation. PMID:7999498

  11. Altered Gene Expression Pattern in Peripheral Blood Mononuclear Cells in Patients with Acute Myocardial Infarction

    PubMed Central

    Kiliszek, Marek; Burzynska, Beata; Michalak, Marcin; Gora, Monika; Winkler, Aleksandra; Maciejak, Agata; Leszczynska, Agata; Gajda, Ewa; Kochanowski, Janusz; Opolski, Grzegorz

    2012-01-01

    Background Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients. Methods and Results Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI) were included. The blood was collected on the 1st day of myocardial infarction, after 4–6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease, without history of myocardial infarction. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST microarrays and GCS3000 TG system. Lists of genes showing altered expression levels (fold change >1.5, p<0.05) were submitted to Ingenuity Pathway Analysis. Gene lists from each group were examined for canonical pathways and molecular and cellular functions. Comparing acute phase of MI with the same patients after 6 months (stable phase) and with control group we found 24 genes with changed expression. In canonical analysis three pathways were highlighted: signaling of PPAR (peroxisome proliferator-activated receptor), IL-10 and IL-6 (interleukin 10 and 6). Conclusions In the acute phase of STEMI, dozens of genes from several pathways linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability show altered expression. Up-regulation of SOCS3 and FAM20 genes in the first days of myocardial infarction is observed in the vast majority of patients. PMID:23185530

  12. Effects of glutamine treatment on myocardial damage and cardiac function in rats after severe burn injury

    PubMed Central

    Yan, Hong; Zhang, Yong; Lv, Shang-jun; Wang, Lin; Liang, Guang-ping; Wan, Qian-xue; Peng, Xi

    2012-01-01

    Treatment with glutamine has been shown to reduce myocardial damage associated with ischemia/reperfusion injury. However, the cardioprotective effect of glutamine specifically after burn injury remains unclear. The present study explores the ability of glutamine to protect against myocardial damage in rats that have been severely burned. Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B) and a glutamine-treated group (G). Groups B and G were subjected to full thickness burns comprising 30% of total body surface area. Group G was administered 1.5 g/ (kg•d) glutamine and group B was given the same dose of alanine via intragastric administration for 3 days. Levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and blood lactic acid were measured, as well as myocardial ATP and glutathione (GSH) contents. Cardiac function indices and histopathological changes were analyzed at 12, 24, 48 and 72 post-burn hours. In both burned groups, levels of serum CK, LDH, AST and blood lactic acid increased significantly, while myocardial ATP and GSH contents decreased. Compared with group B, CK, LDH, and AST levels were lower and blood lactic acid, myocardial ATP and GSH levels were higher in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage were significantly reduced in group G compared to B. Taken together, these results show that glutamine supplementation protects myocardial structure and function after burn injury by improving energy metabolism and by promotedthe synthesis of ATP and GSH in cardiac myocytes. PMID:22977661

  13. PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs.

    PubMed

    Xu, Ya; Gen, Michael; Lu, Li; Fox, Jennifer; Weiss, Sara O; Brown, R Dale; Perlov, Daniel; Ahmad, Hasan; Zhu, Peili; Greyson, Clifford; Long, Carlin S; Schwartz, Gregory G

    2005-03-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-gamma activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-gamma activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both alpha-tocopherol and thiazolidinedione moieties, whether PPAR-gamma activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone (75 mg x kg(-1) x day(-1)), rosiglitazone (3 mg x kg(-1) x day(-1)), or alpha-tocopherol (73 mg x kg(-1) x day(-1), equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-gamma, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or alpha-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an alpha-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-gamma activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its alpha-tocopherol moiety. These findings, in

  14. [Advances in metabolic and nutritional management of patients in critical care].

    PubMed

    Hasebe, M; Suzuki, H; Nakatani, T; Kobayashi, K

    1999-07-01

    Nutritional management often fails in critically ill patients such as trauma and sepsis because of their acutely progressive malnutrition and metabolic derangement being characteristic of such clinical settings. Nutritional strategies for these patients have been almost established by the methods of clinical epidemiology. A considerable amount of clinical evidences suggests that the following should be of benefit for the patients, enteral delivery of nutrition, a nutrition assessment including metabolic evaluation such as liver function or energy requirements, and supplementation of specialty nutrients. Our current data suggest that the metabolic evaluation should include measurement of energy expenditure, assessment of hepatic mitochondrial function, and measurement of the magnitude of body water deviations. Energy expenditure and hepatic mitochondrial function can be observed by the methods of indirect calorimetry and arterial ketone body measurement, respectively. These parameters are helpful to prevent overfeeding from the patients. We emphasize that application of a new method, body impedance spectrum analysis, is important and useful to evaluate the change of body water distributions resulting from metabolic derangement. PMID:10481846

  15. A neurologist's approach to delirium: diagnosis and management of toxic metabolic encephalopathies.

    PubMed

    Krishnan, Vaishnav; Leung, Lester Y; Caplan, Louis R

    2014-02-01

    Toxic metabolic encephalopathies (TMEs) present as an acute derangement in consciousness, cognition and behavior, and can be brought about by various triggers, including endocrine and metabolic disturbances, exogenous toxins, pain and infection. Also referred to as "delirium" or "acute confusional states," TMEs are characterized by (1) an altered level of consciousness and activity, (2) global changes in cognition with inattention, (3) a fluctuating course with disturbances in the sleep-wake cycle, and (4) asterixis and myoclonus. The pathophysiology of this syndrome is poorly understood. Imbalanced neurotransmitter signaling and pathologically heightened brain inflammatory cytokine signaling have been proposed as candidate mechanisms. Focal brain lesions can also occasionally mimic TMEs. A neurological examination is required to identify the presence of focal findings, which when present, identify a new focal lesion or the recrudescence of prior ischemic, inflammatory or neoplastic insults. Diagnostic testing must include a search for metabolic and infectious derangements. Offending medications should be withdrawn. Magnetic resonance imaging, cerebrospinal fluid analysis and electroencephalography should be considered in select clinical situations. In addition to being an unpleasant experience for the patient and family, this condition is associated with extended hospital stays, increased mortality and high costs. In individuals with diminished cognitive reserve, episodes of TME lead to an accelerated decline in cognitive functioning. Starting with an illustrative case, this paper provides a neurologist's approach to the diagnosis, differential diagnosis and management of toxic metabolic encephalopathies. PMID:24332366

  16. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-01-01

    Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice. PMID:26950150

  17. Myocardial perfusion scintigraphy: the evidence.

    PubMed

    Underwood, S R; Anagnostopoulos, C; Cerqueira, M; Ell, P J; Flint, E J; Harbinson, M; Kelion, A D; Al-Mohammad, A; Prvulovich, E M; Shaw, L J; Tweddel, A C

    2004-02-01

    This review summarises the evidence for the role of myocardial perfusion scintigraphy (MPS) in patients with known or suspected coronary artery disease. It is the product of a consensus conference organised by the British Cardiac Society, the British Nuclear Cardiology Society and the British Nuclear Medicine Society and is endorsed by the Royal College of Physicians of London and the Royal College of Radiologists. It was used to inform the UK National Institute of Clinical Excellence in their appraisal of MPS in patients with chest pain and myocardial infarction. MPS is a well-established, non-invasive imaging technique with a large body of evidence to support its effectiveness in the diagnosis and management of angina and myocardial infarction. It is more accurate than the exercise ECG in detecting myocardial ischaemia and it is the single most powerful technique for predicting future coronary events. The high diagnostic accuracy of MPS allows reliable risk stratification and guides the selection of patients for further interventions, such as revascularisation. This in turn allows more appropriate utilisation of resources, with the potential for both improved clinical outcomes and greater cost-effectiveness. Evidence from modelling and observational studies supports the enhanced cost-effectiveness associated with MPS use. In patients presenting with stable or acute chest pain, strategies of investigation involving MPS are more cost-effective than those not using the technique. MPS also has particular advantages over alternative techniques in the management of a number of patient subgroups, including women, the elderly and those with diabetes, and its use will have a favourable impact on cost-effectiveness in these groups. MPS is already an integral part of many clinical guidelines for the investigation and management of angina and myocardial infarction. However, the technique is underutilised in the UK, as judged by the inappropriately long waiting times and by

  18. Direct imaging of myocardial ischemia: a potential new paradigm in nuclear cardiovascular imaging.

    PubMed

    Jain, Diwakar; He, Zuo-Xiang

    2008-01-01

    Myocardial perfusion imaging has been in clinical use for over 30 years, serving as an effective, reliable, and relatively simple tool for diagnosis, risk stratification, and long-term follow-up of patients with suspected or known coronary artery disease. However, a unique strength of nuclear imaging is its ability to provide tools for imaging biochemical and metabolic processes and receptor and transporter functions at molecular and cellular levels in intact organisms under a wide variety of physiologic conditions. Despite their high resolution and technical sophistication, other imaging modalities currently do not have this capability. Metabolic imaging techniques using radiolabeled free fatty acid and glucose analogs provide a unique ability to image myocardial ischemia directly in patients with known or suspected coronary artery disease. These techniques can potentially overcome some of the limitations of currently used stress-rest perfusion imaging and also provide a unique opportunity to detect and image an episode of ischemia in the preceding hours even in the absence of other markers of ongoing myocardial ischemia. We describe recent studies using fluorine 18-labeled deoxyglucose and iodine 123 beta-methyl-p-iodophenyl-pentadecanoic acid for imaging myocardial ischemia. PMID:18761264

  19. Diosmin exhibits anti-hyperlipidemic effects in isoproterenol induced myocardial infarcted rats.

    PubMed

    Queenthy, S Sharmila; John, Babu

    2013-10-15

    The aim of the present study was to evaluate the protective effects of diosmin on experimentally induced myocardial infarcted rats. Diosmin (5 and 10mg/kg body weight) was administered orally as pretreatment daily for a period of 10 days. Then isoproterenol (100mg/kg) was injected subcutaneously into rats at an interval of 24h for 2 days (on 11th and 12th day). Isoproterenol-induced myocardial infarcted rats showed significant changes in electrocardiogram and an increase in the levels of cardiac markers, compared with normal rats. Additionally, increased plasma lipid peroxidation products and altered lipid metabolism in the plasma were observed in the isoproterenol-induced myocardial infarcted rats. Pretreatment with diosmin (5 and 10mg/kg body weight) minimized the electrocardiographic changes, decreased the levels of serum cardiac marker enzymes reduced plasma lipid peroxidation and minimized the alterations in the lipid metabolism of isoproterenol-induced myocardial infarcted rats. Also, diosmin inhibited the enhanced activity of liver HMG CoA reductase. The in vitro study revealed the free radical scavenging activity of diosmin. The free radical scavenging and anti-hyperlipidaemic effects are the reasons for the cardioprotective effects of diosmin. PMID:24036254

  20. Obstructive sleep apnea and metabolic bone disease: Insights in to the relationship between bone and sleep

    PubMed Central

    Swanson, Christine M.; Shea, Steven A.; Stone, Katie L.; Cauley, Jane A.; Rosen, Clifford J.; Redline, Susan; Karsenty, Gerard; Orwoll, Eric S.

    2015-01-01

    Obstructive sleep apnea (OSA) and low bone mass are two prevalent conditions, particularly among older adults, a section of the U.S. population that is expected to grow dramatically over the coming years. OSA, the most common form of sleep disordered breathing, has been linked to multiple cardiovascular, metabolic, hormonal and inflammatory derangements and may have adverse effects on bone. However, little is known about how OSA (including the associated hypoxia and sleep loss) affects bone metabolism. In order to gain insight into the relationship between sleep and bone, we review the growing information on OSA and metabolic bone disease and discuss the pathophysiological mechanisms by which OSA may affect bone metabolism/architecture. PMID:25639209

  1. Exotic Fruits as Therapeutic Complements for Diabetes, Obesity and Metabolic Syndrome

    PubMed Central

    Devalaraja, Samir; Jain, Shalini; Yadav, Hariom

    2011-01-01

    The prevalence and severity of obesity, type 2-diabetes, and the resultant metabolic syndrome are rapidly increasing. As successful preventive and therapeutic strategies for these life-threatening health ailments often come with adverse side effects, nutritional elements are widely used in many countries as preventive therapies to prevent or manage metabolic syndrome. Fruits are important dietary components, and contain various bioactive constituents. Many of these constituents have been proven to be useful to manage and treat various chronic diseases such as diabetes, obesity, cancer and cardiovascular diseases. Although exotic fruits are understudied throughout the world due to their limited regional presence, many studies reveal their potent ability to ameliorate metabolic derangements and the resultant conditions i.e. diabetes and obesity. The aim of this article is to review the role of exotic fruits and their constituents in the regulation of metabolic functions, which can beneficially alter diabetes and obesity pathophysiology. PMID:21857774

  2. Disorders of Carbohydrate Metabolism

    MedlinePlus

    ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Carbohydrates are sugars. ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism NOTE: This is ...

  3. [Metabolic therapy for heart failure].

    PubMed

    Loiacono, Ferdinando; Alberti, Luca; Lauretta, Ludovica; Puccetti, Patrizia; Silipigni, Carmen; Margonato, Alberto; Fragasso, Gabriele

    2014-01-01

    Heart failure may promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. The results of current research are supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure. Trimetazidine is the most studied drug in this context. Several small studies have evidenced the usefulness of such additional therapeutic tools for heart failure. More specifically, recent meta-analyses and a multicenter retrospective study have shown that additional use of trimetazidine in patients with heart failure, along with symptoms and cardiac function improvement, also provides a significant protective effect on all-cause mortality, cardiovascular events and hospitalization due to cardiac causes. Nevertheless, the exact role of metabolic therapy in heart failure is yet to be established, and a large multicenter randomized trial is necessary. PMID:25072544

  4. Myocardial contusion in patients with blunt chest trauma as evaluated by thallium 201 myocardial scintigraphy

    SciTech Connect

    Bodin, L.; Rouby, J.J.; Viars, P.

    1988-07-01

    Fifty five patients suffering from blunt chest trauma were studied to assess the diagnosis of myocardial contusion using thallium 201 myocardial scintigraphy. Thirty-eight patients had consistent scintigraphic defects and were considered to have a myocardial contusion. All patients with scintigraphic defects had paroxysmal arrhythmias and/or ECG abnormalities. Of 38 patients, 32 had localized ST-T segment abnormalities; 29, ST-T segment abnormalities suggesting involvement of the same cardiac area as scintigraphic defects; 21, echocardiographic abnormalities. Sixteen patients had segmental hypokinesia involving the same cardiac area as the scintigraphic defects. Fifteen patients had clinical signs suggestive of myocardial contusion and scintigraphic defects. Almost 70 percent of patients with blunt chest trauma had scintigraphic defects related to areas of myocardial contusion. When thallium 201 myocardial scintigraphy directly showed myocardial lesion, two-dimensional echocardiography and standard ECG detected related functional consequences of cardiac trauma.

  5. EVALUATION AND TREATMENT OF A PATIENT DIAGNOSED WITH ADHESIVE CAPSULITIS CLASSIFIED AS A DERANGEMENT USING THE MCKENZIE METHOD: A CASE REPORT

    PubMed Central

    Swanson, Brian T.

    2016-01-01

    ABSTRACT Background/Purpose The McKenzie Method of mechanical diagnosis and therapy (MDT) is supported in the literature as a valid and reliable approach to the management of spine injuries. It can also be applied to the peripheral joints, but has not been explored through research to the same extent. This method sub-classifies an injury based on tissue response to mechanical loading and repeated motion testing, with directional preferences identified in the exam used to guide treatment. The purpose of this case report is to demonstrate the assessment, intervention, and clinical outcomes of a subject classified as having a shoulder derangement syndrome using MDT methodology. Case Description The subject was a 52-year-old female with a four-week history of insidious onset left shoulder pain, referred to physical therapy with a medical diagnosis of adhesive capsulitis. She presented with pain (4-7/10 on the visual analog scale [VAS]) and decreased shoulder range of motion that limited her activities of daily living and work capabilities (Upper Extremity Functional Index (UEFI) score: 55/80). Active and passive ranges of motion (A/PROM) were limited in all planes. Repeated motion testing was performed, with an immediate reduction in pain and increased shoulder motion in all planes following repeated shoulder extension. As a result, her MDT classification was determined to be derangement syndrome. Treatment involved specific exercises, primarily repeated motions, identified as symptom alleviating during the evaluation process. Outcomes The subject demonstrated significant improvements in the UEFI (66/80), VAS (0-2/10), and ROM within six visits over eight weeks. At the conclusion of treatment, A/PROM was observed to be equal to the R shoulder without pain. Discussion This subject demonstrated improved symptoms and functional abilities following evaluation and treatment using MDT methodology. While a cause-effect relationship cannot be determined with a single case, MDT

  6. Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia

    PubMed Central

    JianXin, Chen; Xue, Xu; ZhongFeng, Li; Kuo, Gao; FeiLong, Zhang; ZhiHong, Li; Xian, Wang; HongCai, Shang

    2016-01-01

    Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. 1H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine. PMID:27075394

  7. Myocardial ischaemia in infancy and childhood

    PubMed Central

    Berry, C. L.

    1967-01-01

    Examination of 135 consecutive necropsy specimens has shown that ischaemic myocardial injury is not uncommon in infancy and childhood. The extent of the myocardial change has been assessed by a technique of staining with acid fuchsin, first described by Selye (1958). The significance of the findings is discussed. Images PMID:4163355

  8. Hepatic Steatosis as a Marker of Metabolic Dysfunction

    PubMed Central

    Fabbrini, Elisa; Magkos, Faidon

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the complex metabolic derangements associated with obesity. NAFLD is characterized by excessive deposition of fat in the liver (steatosis) and develops when hepatic fatty acid availability from plasma and de novo synthesis exceeds hepatic fatty acid disposal by oxidation and triglyceride export. Hepatic steatosis is therefore the biochemical result of an imbalance between complex pathways of lipid metabolism, and is associated with an array of adverse changes in glucose, fatty acid, and lipoprotein metabolism across all tissues of the body. Intrahepatic triglyceride (IHTG) content is therefore a very good marker (and in some cases may be the cause) of the presence and the degree of multiple-organ metabolic dysfunction. These metabolic abnormalities are likely responsible for many cardiometabolic risk factors associated with NAFLD, such as insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Understanding the factors involved in the pathogenesis and pathophysiology of NAFLD will lead to a better understanding of the mechanisms responsible for the metabolic complications of obesity, and hopefully to the discovery of novel effective treatments for their reversal. PMID:26102213

  9. Mitigating efficacy of piperine in the physiological derangements of high fat diet induced obesity in Sprague Dawley rats.

    PubMed

    BrahmaNaidu, Parim; Nemani, Harishankar; Meriga, Balaji; Mehar, Santosh Kumar; Potana, Sailaja; Ramgopalrao, Sajjalaguddam

    2014-09-25

    An increased risk of obesity has become a common public health concern as it is associated with hypertension, diabetes, osteoarthritis, heart diseases, liver steatosis etc. Pharmacological intervention with natural product-based drugs is considered a healthier alternative to treat obesity. This study was aimed to evaluate anti-obesity effects of piperine on high fat diet (HFD) induced obesity in rats. Piperine was isolated from methanolic extract of Piper nigrum by using column chromatography and confirmed by LC-MS analysis. Male SD rats were fed HFD initially for 15weeks to induce obesity. After induction of obesity, piperine was supplemented in different doses (20, 30 and 40mg/kgb.wt) through HFD for 42days to experimental rats. HFD induced changes in body weight, body composition, fat percentage, adiposity index, blood pressure, plasma levels of glucose, insulin resistance, leptin, adiponectin, plasma and tissue lipid profiles, liver antioxidants were explained. The activities of lipase, amylase and lipid metabolic marker enzymes such as HMG-CoA reductase, carnitine palmitoyl transferase (CPT), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lecithin-cholesterol acyl transferase (LCAT) and lipoprotein lipase (LPL) were assessed in experimental rats. Supplementation of piperine at a dose of 40mg/kgb.wt has significantly (p<0.05) reversed the HFD-induced alterations in experimental rats in a dose dependant manner, the maximum therapeutic effect being noted at a dose of 40mg/kgb.wt. Our study concludes that piperine can be well considered as an effective bioactive molecule to suppress of body weight, improve insulin and leptin sensitivity, ultimately leading to regulate obesity. PMID:25087745

  10. Risk stratification after myocardial infarction. Clinical overview

    SciTech Connect

    O'Rourke, R.A. )

    1991-09-01

    Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification.

  11. [Fibrinolysis in acute myocardial infarct].

    PubMed

    Bleifeld, W

    1987-10-24

    Fibrinolysis has opened up a new avenue in the treatment of acute myocardial infarction (AMI). In principle, the rate of reperfusion depends on the type of compound used, the mode of administration and the time between onset of symptoms and the beginning of treatment. With intracoronary streptokinase the reperfusion rate is of the order of 85%. Intravenous urokinase administered as a bolus results in a reopening rate of 50-60%; a similar rate of reperfusion is achieved with rt-PA as infusion, while i.v. streptokinase produces about 50% reopened coronary vessels. The final infarct size is decreased in 70% of patients if fibrinolysis is initiated within 2.5 hours after the onset of symptoms and followed by reopening of the occluded vessel. This results in a lowering of in-hospital mortality, which in various studies is of the order of 45-60%.- Bearing in mind the contraindications, fibrinolysis should be initiated within 3 hours. Hemodynamic improvement by a decrease of infarct size may also be achieved beyond 3 hours in large anterior myocardial infarctions and in posterior infarctions with cardiogenic shock. Early initiation of thrombolysis is of major importance in improving left ventricular function and lowering mortality following acute myocardial infarction. Therefore, prehospital thrombolytic therapy should be considered. - In the postinfarction phase coronary angiography is indicated in patients with angina at rest, stable angina of ECG signs of ischemia. In this situation transfer to a specialized cardiology division for possible percutaneous transluminal angioplasty is indicated. - Reocclusion after successful thrombolysis occurs in 20-30%, and it is therefore important to avoid reinfarction to improve the long term prognosis after AMI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3321420

  12. Metabolic Management during Critical Illness: Glycemic Control in the ICU.

    PubMed

    Honiden, Shyoko; Inzucchi, Silvio E

    2015-12-01

    Hyperglycemia is a commonly encountered metabolic derangement in the ICU. Important cellular pathways, such as those related to oxidant stress, immunity, and cellular homeostasis, can become deranged with prolonged and uncontrolled hyperglycemia. There is additionally a complex interplay between nutritional status, ambient glucose concentrations, and protein catabolism. While the nuances of glucose management in the ICU have been debated, results from landmark studies support the notion that for most critically ill patients moderate glycemic control is appropriate, as reflected by recent guidelines. Beyond the target population and optimal glucose range, additional factors such as hypoglycemia and glucose variability are important metrics to follow. In this regard, new technologies such as continuous glucose sensors may help alleviate the risks associated with such glucose fluctuations in the ICU. In this review, we will explore the impact of hyperglycemia upon critical cellular pathways and how nutrition provided in the ICU affects blood glucose. Additionally, important clinical trials to date will be summarized. A practical and comprehensive approach to glucose management in the ICU will be outlined, touching upon important issues such as glucose variability, target population, and hypoglycemia. PMID:26595046

  13. Effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury: an overview.

    PubMed

    Zughaib, M E; Sun, J Z; Bolli, R

    1993-01-01

    There are multiple mechanisms whereby ACE inhibitors could be beneficial during myocardial ischemia and reperfusion, including: i) reduced formation of angiotensin II, ii) decreased metabolism of bradykinin, iii) antioxidant activity, and iv) possibly other unknown mechanisms. Reduced formation of angiotensin II should be beneficial because this peptide exerts several actions that are potentially detrimental to the ischemic/reperfused myocardium, including vasoconstriction, increased release of norepinephrine, stimulation of phospholipase C and/or A2, and increased afterload with an attendant increase in oxygen demands. Reduced metabolism of bradykinin could be beneficial by increasing myocardial glucose uptake, by causing vasodilation, and by stimulating production of endothelium-derived relaxing factor and prostacyclin. Although earlier studies suggested that sulfhydryl-containing ACE inhibitors scavenge superoxide anions, recent data have shown that these drugs scavenge hydroxyl radical and hypochlorous acid with no effect on superoxide anion. Studies in isolated hearts have demonstrated that ACE inhibitors attenuate the metabolic, arrhythmic, and contractile dearrangements associated with ischemia and reperfusion, and have suggested that such beneficial effects are mediated by potentiation of bradykinin and/or increased synthesis of prostacyclin. Studies in models of myocardial stunning after brief (15-min) ischemia in vivo (anesthetized dogs) suggest that ACE inhibitors enhance the recovery of contractile function after a single brief ischemic episode. No data are available regarding the effect of these drugs on myocardial stunning after a prolonged, partly reversible episode, after multiple consecutive brief ischemic episodes, and after global ischemia. The mechanism for the salutary effects of ACE inhibitors on stunning remains a mystery. It may involve an antioxidant action (in the case of thiol-containing molecules) or potentiation of prostaglandins (in

  14. Solar activity and myocardial infarction.

    PubMed

    Szczeklik, E; Mergentaler, J; Kotlarek-Haus, S; Kuliszkiewicz-Janus, M; Kucharczyk, J; Janus, W

    1983-01-01

    The correlation between the incidence of myocardial infarction, sudden cardiac death, the solar activity and geomagnetism in the period 1969-1976 was studied, basing on Wrocław hospitals material registered according to WHO standards; sudden death was assumed when a person died within 24 hours after the onset of the disease. The highest number of infarctions and sudden deaths was detected for 1975, which coincided with the lowest solar activity, and the lowest one for the years 1969-1970 coinciding with the highest solar activity. Such an inverse, statistically significant correlation was not found to exist between the studied biological phenomena and geomagnetism. PMID:6851574

  15. [Cardiac rehabilitation after myocardial infarction].

    PubMed

    Ghannem, M; Ghannem, L; Ghannem, L

    2015-12-01

    Although the proofs of the benefits of cardiac rehabilitation accumulate, many patients are not sent to rehabilitation units, especially younger and very elderly patients. As the length of stay in acute care units decreases, rehabilitation offers more time to fully assess the patients' conditions and needs. Meta-analyses of randomised trials suggest that mortality can be improved by as much as 20-30%. In addition, rehabilitation helps managing risk factors, including hyperlipidemia, diabetes, smoking and sedentary behaviours. Physical training also helps improving exercise capacity. Because of all of these effects, cardiac rehabilitation for post-myocardial infarction patients has been given a class IA recommendation in current guidelines. PMID:26548984

  16. Experimental Cardiac Necrosis and Potassium

    PubMed Central

    Prioreschi, P.

    1967-01-01

    In recent years evidence has been brought forward supporting the hypothesis that myocardial infarction is not due to thrombotic occlusion of a coronary artery but to a metabolic derangement in a myocardium “conditioned” by coronary atherosclerosis. The author briefly reviews metabolic necroses experimentally induced in the animal and discusses the action of potassium in preventing their development. The basis for the clinical use of potassium and magnesium salts for the prevention of myocardial infarction is also discussed. PMID:5336956

  17. Metabolic Disorders

    MedlinePlus

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  18. Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema.

    PubMed

    Desai, Ketaki V; Laine, Glen A; Stewart, Randolph H; Cox, Charles S; Quick, Christopher M; Allen, Steven J; Fischer, Uwe M

    2008-06-01

    Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures. PMID:18375722

  19. Cell therapy for myocardial infarction.

    PubMed

    Kwon, Yoo-Wook; Yang, Han-Mo; Cho, Hyun-Jai

    2010-05-01

    Ischemic heart disease, particularly acute myocardial infarction (MI), is the worldwide health care problem and the leading cause of morbidity and mortality. The fundamental treatment of MI remains a major unmet medical need. Although recent tremendous advances have been made in the treatment for acute MI such as percutaneous coronary intervention (PCI) and medical and surgical therapies, myocardial cell loss after ischemia and subsequent, adverse cardiac remodeling and heart failure are demanding for new therapeutic strategy. Since the first experimental studies of adult stem cell therapy into the ischemic heart were performed in the early 1990s, the identification and potential application of stem and/or progenitor cells has triggered attempts to regenerate damaged heart tissue and cell-based therapy is a promising option for treatment of MI. In this review, we would like to discuss the pathogenesis of acute MI, current standard treatments and their limitation, clinical results of recent stem or progenitor cell therapy which have shown a favorable safety profile with modest improvement in cardiac function, and putative mechanisms of benefits. PMID:24855535

  20. [Acute myocardial infarction during sport].

    PubMed

    Fujiwara, M; Asakuma, S; Nakamura, K; Nakamura, T; Yasutomi, N; Iwasaki, T

    1995-10-01

    Thirty patients with acute myocardial infarction which occurred during sport were investigated to identify the type of sport, prodromata, situations at the onset of disease, habit of exercise, preceding medical evaluation, coronary risk factors, and coronary angiographic findings. Infarction occurred during golf in 12 patients, bowling in 4, gateball in 4, jogging or running in 5, baseball in 2, and tennis or table tennis in 3. The majority of the patients were playing ball games. Twenty-seven patients were men (90%) and 3 were women (10%). All patients had played the same kind of sport for several years. Twenty-four patients had one or more coronary risk factors, and especially 18 patients smoked cigarettes. Nine patients had experienced anterior chest pain but only two patients had received medical evaluation. Coronary angiography was performed in 25 patients (83.3%), revealing single-vessel disease in 14, two-vessel disease in 6, three-vessel disease in 4, and disease of all left main coronary trunks in 1. The acute episode of infarction occurred mainly in spring or fall. Many patients with acute myocardial infarction occurring during sport participate in sports of low or moderate dynamic and low static exercises which are generally regarded safe. Many patients had enjoyed their sports regularly for a long time. Though many patients had coronary risk factors, only a few had received a medical check before their heart attack. PMID:7500263

  1. Myocardial Fat Accumulation Is Independent of Measures of Insulin Sensitivity

    PubMed Central

    Noureldin, Radwa; Ouwerkerk, Ronald; Liu, Elizabeth Y.; Madan, Ritu; Abel, Brent S.; Mullins, Katherine; Walter, Mary F.; Skarulis, Monica C.; Gharib, Ahmed M.

    2015-01-01

    Background: Myocardial steatosis, an independent predictor of diastolic dysfunction, is frequently present in type 2 diabetes mellitus. High free fatty acid flux, hyperglycemia, and hyperinsulinemia may play a role in myocardial steatosis. There are no prior studies examining the relationship between insulin sensitivity (antilipolytic and glucose disposal actions of insulin) and cardiac steatosis. Objective: Using a cross-sectional study design of individuals with and without metabolic syndrome (MetSyn), we examined the relationships between cardiac steatosis and the sensitivity of the antilipolytic and glucose disposal actions of insulin. Methods: Pericardial fat (PF) volume, intramyocardial and hepatic fat (MF and HF) content, visceral fat (VF) and sc fat content were assessed by magnetic resonance imaging in 77 subjects (49 without MetSyn and 28 with MetSyn). In a subset of the larger cohort (n = 52), peripheral insulin sensitivity index (SI) and adipocyte insulin sensitivity (Adipo-SI) were determined from an insulin-modified frequently sampled iv glucose tolerance test. The Quantitative Insulin Sensitivity Check Index was used as a surrogate for hepatic insulin sensitivity. Results: Individuals with the MetSyn had significantly higher body mass index, total body fat, and MF, PF, HF, and VF content. HF and VF, but not MF, were negatively correlated with the Quantitative Insulin Sensitivity Check Index, Adipo-SI, and SI. Stepwise regression revealed that waist circumference and serum triglyceride levels independently predicted MF and PF, respectively. Adipo-SI and serum triglyceride levels independently predict HF. Conclusion: Myocardial steatosis is unrelated to hepatic, adipocyte, or peripheral insulin sensitivity. Although it is frequently observed in insulin-resistant subjects, further studies are necessary to identify and delineate pathogenic mechanisms that differentially affect cardiac and hepatic steatosis. PMID:26020762

  2. Assessment of myocardial perfusion and viability by positron emission tomography.

    PubMed

    Anagnostopoulos, Constantinos; Georgakopoulos, Alexandros; Pianou, Nikoletta; Nekolla, Stephan G

    2013-09-01

    An important evolution has taken place recently in the field of cardiovascular Positron Emission Tomography (PET) imaging. Being originally a highly versatile research tool that has contributed significantly to advance our understanding of cardiovascular physiology and pathophysiology, PET has gradually been incorporated into the clinical cardiac imaging portfolio contributing to diagnosis and management of patients investigated for coronary artery disease (CAD). PET myocardial perfusion imaging (MPI) has an average sensitivity and specificity around 90% for the detection of angiographically significant CAD and it is also a very accurate technique for prognostication of patients with suspected or known CAD. In clinical practice, Rubidium-82 ((82)Rb) is the most widely used radiopharmaceutical for MPI that affords also accurate and reproducible quantification in absolute terms (ml/min/g) comparable to that obtained by cyclotron produced tracers such as Nitrogen-13 ammonia ((13)N-ammonia) and Oxygen-15 labeled water ((15)O-water). Quantification increases sensitivity for detection of multivessel CAD and it may also be helpful for detection of early stages of atherosclerosis or microvascular dysfunction. PET imaging combining perfusion with myocardial metabolism using (18)F-Fluorodeoxyglucose ((18)F FDG), a glucose analog, is an accurate standard for assessment of myocardial hibernation and risk stratification of patients with left ventricular dysfunction of ischemic etiology. It is helpful for guiding management decisions regarding revascularization or medical treatment and predicting improvement of symptoms, exercise capacity and quality of life post-revascularization. The strengths of PET can be increased further with the introduction of hybrid scanners, which combine PET with computed tomography (PET/CT) or with magnetic resonance imaging (PET/MRI) offering integrated morphological, biological and physiological information and hence, comprehensive evaluation of

  3. Use of thallium 201 myocardial imaging to exclude myocardial infarction after dissection in congenital coarctation of the aorta

    SciTech Connect

    Halon, D.A.; Weiss, A.T.; Tzivoni, D.; Atlan, H.; Gotsman, M.S.

    1981-10-01

    The use of a mobile gamma camera with thallium 201 myocardial imaging is described to exclude myocardial infarction in a patient admitted to the coronary care unit in shock and with clinical, enzyme, and ECG changes consistent with infarction. The patient suffered from acute aortic dissection associated with congenital coarctation of the aorta. The myocardial scan excluded transmural myocardial injury.

  4. Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats.

    PubMed

    Lam, Vy; Su, Jidong; Hsu, Anna; Gross, Garrett J; Salzman, Nita H; Baker, John E

    2016-01-01

    Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host's metabolism. Hierarchical clustering of dissimilarities separated the levels of 284 identified metabolites from treated vs. untreated rats; 193 were altered by the antibiotic treatments with a tendency towards decreased metabolite levels. Catabolism of the aromatic amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway comprising 33 affected metabolites. Both antibiotic treatments decreased the severity of an induced myocardial infarction in vivo by 27% and 29%, respectively. We then determined whether microbial metabolites of the amino acids phenylalanine, tryptophan and tyrosine were linked to decreased severity of myocardial infarction. Vancomycin-treated rats were administered amino acid metabolites prior to ischemia/reperfusion studies. Oral or intravenous pretreatment of rats with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 μM), Src kinase (PP1, 20 μM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059, 10 μM), p38 MAPK (SB203580, 10 μM), or KATP channels (glibenclamide, 3 μM) abolished cardioprotection by vancomycin, indicating microbial metabolites are interacting with cell surface receptors to transduce their signals through Src kinase, cell survival pathways and KATP channels. These inhibitors have no effect on myocardial infarct size in

  5. Cardioplegia and myocardial preservation during cardiopulmonary bypass.

    PubMed

    Engelman, R M; Levitsky, S; O'Donoghue, M J; Auvil, J

    1978-09-01

    A standard experimental protocol was developed to explore the role of hypothermia and potassium cardioplegia in myocardial preservation during 120 minutes of ischemic arrest followed by 30 minutes of reperfusion. Seven different experimental groups of six animals each were evaluated using an in-vivo pig heart preparation. Hypothermic arrest without cardioplegia and cardioplegic arrest at normothermia were each compared to hypothermic cardioplegia. In addition, the use of an asanguineous hypothermic coronary perfusate without cardioplegia was compared to both multidose cardioplegia and single-dose cardioplegia followed by the same asanguineous perfusate. The parameters measured included: myocardial contractility and compliance, myocardial blood flow, endocardial/epicardial blood flow ratio, and electron microscopic studies. Myocardial preservation was inadequate with hypothermic arrest alone (without cardioplegia; and with cardioplegia at normothermia. In both experimental groups, myocardial contractility and compliance were so depressed that the) could not be accurately measured following ischemia and reperfusion while coronary blood flow remained significantly elevated. Preservation was improved but still inadequate following myocardial washout with a normokalemic or hypokalemic perfusate and following single dose cardioplegia plus myocardial washout. In the latter four groups, contractility ranged from 42 to 78% of control, and there was a decrease in compliance of 16 to 78%. Adequate preservation was found only after hypothermia and multidose potassium (35 mEq/L) cardioplegia. In this group, contractility was 129 +/- 13% of control and compliance increased by 21 +/- 24% compared to that of the control. PMID:14740689

  6. Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers

    ClinicalTrials.gov

    2016-01-25

    Acute Myocardial Infarction (AMI); Acute Coronary Syndrome (ACS); ST Elevation (STEMI) Myocardial Infarction; Ischemic Reperfusion Injury; Non-ST Elevation (NSTEMI) Myocardial Infarction; Angina, Unstable

  7. Cardiac Overexpression of Metallothionein Rescues Cold Exposure-Induced Myocardial Contractile Dysfunction through Attenuation of Cardiac Fibrosis Despite Cardiomyocyte Mechanical Anomalies

    PubMed Central

    Zhang, Yingmei; Hu, Nan; Hua, Yinan; Richmond, Kacy L.; Dong, Feng; Ren, Jun

    2012-01-01

    Cold exposure is associated with an increased prevalence for cardiovascular disease although the mechanism is unknown. Metallothionein, a heavy metal scavenging antioxidant, protects against cardiac anomalies. This study was designed to examine the impact of metallothionein on cold exposure-induced myocardial dysfunction, intracellular Ca2+ derangement, fibrosis, ER stress and apoptosis. Echocardiographic, cardiomyocyte function and Masson trichrome staining were evaluated in friendly virus B (FVB) and cardiac-specific metallothionein transgenic mice following cold exposure (3 mo, 4°C). Cold exposure increased plasma levels of norepinephrine, endothelin-1 and TGF-β, reduced plasma NO levels and cardiac antioxidant capacity, enlarged ventricular end systolic diameter, compromised fractional shortening, promoted ROS production and apoptosis, and suppressed ER stress marker Bip, calregulin and phospho-eIF2α accompanied with cardiac fibrosis and elevated levels of matrix metalloproteinases and Smad-2/3 in FVB mice. Cold exposure-induced echocardiographic, histological, ER stress, ROS, apoptotic and fibrotic signaling changes (but not plasma markers) were greatly improved by metallothionein. In vitro metallothionein induction by zinc chloride ablated H2O2- but not TGF-β-induced cell proliferation in fibroblasts. In summary, our data suggested that metallothionein protects against cold exposure-induced cardiac anomalies possibly through attenuation of myocardial fibrosis. PMID:22565031

  8. Lipid metabolism and signaling in cardiac lipotoxicity.

    PubMed

    D'Souza, Kenneth; Nzirorera, Carine; Kienesberger, Petra C

    2016-10-01

    The heart balances uptake, metabolism and oxidation of fatty acids (FAs) to maintain ATP production, membrane biosynthesis and lipid signaling. Under conditions where FA uptake outpaces FA oxidation and FA sequestration as triacylglycerols in lipid droplets, toxic FA metabolites such as ceramides, diacylglycerols, long-chain acyl-CoAs, and acylcarnitines can accumulate in cardiomyocytes and cause cardiomyopathy. Moreover, studies using mutant mice have shown that dysregulation of enzymes involved in triacylglycerol, phospholipid, and sphingolipid metabolism in the heart can lead to the excess deposition of toxic lipid species that adversely affect cardiomyocyte function. This review summarizes our current understanding of lipid uptake, metabolism and signaling pathways that have been implicated in the development of lipotoxic cardiomyopathy under conditions including obesity, diabetes, aging, and myocardial ischemia-reperfusion. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26924249

  9. Congenital generalized lipodystrophies--new insights into metabolic dysfunction.

    PubMed

    Patni, Nivedita; Garg, Abhimanyu

    2015-09-01

    Congenital generalized lipodystrophy (CGL) is a heterogeneous autosomal recessive disorder characterized by a near complete lack of adipose tissue from birth and, later in life, the development of metabolic complications, such as diabetes mellitus, hypertriglyceridaemia and hepatic steatosis. Four distinct subtypes of CGL exist: type 1 is associated with AGPAT2 mutations; type 2 is associated with BSCL2 mutations; type 3 is associated with CAV1 mutations; and type 4 is associated with PTRF mutations. The products of these genes have crucial roles in phospholipid and triglyceride synthesis, as well as in the formation of lipid droplets and caveolae within adipocytes. The predominant cause of metabolic complications in CGL is excess triglyceride accumulation in the liver and skeletal muscle owing to the inability to store triglycerides in adipose tissue. Profound hypoleptinaemia further exacerbates metabolic derangements by inducing a voracious appetite. Patients require psychological support, a low-fat diet, increased physical activity and cosmetic surgery. Aside from conventional therapy for hyperlipidaemia and diabetes mellitus, metreleptin replacement therapy can dramatically improve metabolic complications in patients with CGL. In this Review, we discuss the molecular genetic basis of CGL, the pathogenesis of the disease's metabolic complications and therapeutic options for patients with CGL. PMID:26239609

  10. Kinetic analysis of complex metabolic networks

    SciTech Connect

    Stephanopoulos, G.

    1996-12-31

    A new methodology is presented for the analysis of complex metabolic networks with the goal of metabolite overproduction. The objective is to locate a small number of reaction steps in a network that have maximum impact on network flux amplification and whose rate can also be increased without functional network derangement. This method extends the concepts of Metabolic Control Analysis to groups of reactions and offers the means for calculating group control coefficients as measures of the control exercised by groups of reactions on the overall network fluxes and intracellular metabolite pools. It is further demonstrated that the optimal strategy for the effective increase of network fluxes, while maintaining an uninterrupted supply of intermediate metabolites, is through the coordinated amplification of multiple (as opposed to a single) reaction steps. Satisfying this requirement invokes the concept of the concentration control to coefficient, which emerges as a critical parameter in the identification of feasible enzymatic modifications with maximal impact on the network flux. A case study of aromatic aminoacid production is provided to illustrate these concepts.

  11. Rethinking cardiac metabolism: metabolic cycles to refuel and rebuild the failing heart

    PubMed Central

    Lubrano, Genna

    2014-01-01

    The heart is a self-renewing biological pump that converts chemical energy into mechanical energy. The entire process of energy conversion is subject to complex regulation at the transcriptional, translational and post-translational levels. Within this system, energy transfer occurs with high efficiency, facilitated by a series of compound-conserved cycles. At the same time, the constituent myocardial proteins themselves are continuously made and degraded in order to adjust to changes in energy demand and changes in the extracellular environment. We recently have identified signals arising from intermediary metabolism that regulate the cycle of myocardial protein turnover. Using a new conceptual framework, we discuss the principle of metabolic cycles and their importance for refueling and for rebuilding the failing heart. PMID:25374668

  12. The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis

    PubMed Central

    Saponaro, Chiara; Gaggini, Melania; Carli, Fabrizia; Gastaldelli, Amalia

    2015-01-01

    Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD), cardiovascular diseases (CVD) and hepatocellular carcinoma (HCC). The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance. The aims of this review are to investigate the subtle balances that underlie lipolytic, lipogenic and oxidative pathways, to evaluate critical points and the complexities of these processes and to better understand which are the metabolic derangements resulting from their imbalance, such as type 2 diabetes and non alcoholic fatty liver disease. PMID:26580649

  13. SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

    PubMed

    Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

    2016-01-01

    Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions. PMID:26053731

  14. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome

    PubMed Central

    Thorp, Alicia A.; Schlaich, Markus P.

    2015-01-01

    Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS). Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts. PMID:26064978

  15. Ventricular Aneurysm Following Myocardial Infarction

    PubMed Central

    Walters, M. B.

    1966-01-01

    Cineradiographic examination appears to be the best method for the study of cardiac pulsations. Fifty consecutive patients, who had sustained transmural myocardial infarction at least six months previously, were studied by this technique. Thirty-six had some abnormality of pulsation and eight had dynamic ventricular aneurysm. Six of the eight had suffered severe infarct. Functional recovery in those with aneurysm was not as complete as in the rest of the group. Two made a poor functional recovery, two a fair recovery, and four a moderately good recovery. Clinically, there were no systemic emboli in the patients with dynamic aneurysms. Five of the 50 had persistent ST-segment elevation and “coving” of the T waves; three of these patients had aneurysms. There was no good correlation between the electrocardiographic site of the infarct and the site of the abnormal pulsation. ImagesFig. 1 PMID:5928534

  16. Myocardial infarction in young adults

    PubMed Central

    Egred, M; Viswanathan, G; Davis, G

    2005-01-01

    Although myocardial infarction (MI) mainly occurs in patients older than 45, young men or women can suffer MI. Fortunately, its incidence is not common in patients younger than 45 years. However, the disease carries a significant morbidity, psychological effects, and financial constraints for the person and the family when it occurs at a young age. The causes of MI among patients aged less than 45 can be divided into four groups: (1) atheromatous coronary artery disease; (2) non-atheromatous coronary artery disease; (2) hyper-coagulable states; (4) MI related to substance misuse. There is a considerable overlap between all the groups. This article reviews the literature and highlights the practical issues involved in the management of young adults with MI. PMID:16344295

  17. [Thrombolytic treatment of acute myocardial infarct. 1].

    PubMed

    Soares-Costa, J T; Soares-Costa, T J; Gabriel, H M

    1998-05-01

    I-Rationale of thrombolytic therapy in acute myocardial infarction (AMI). II-Thrombolytic drugs. III-Effects of thrombolytic therapy on mortality. IV-Studies comparing the effects of various thrombolytic agents on mortality. PMID:9951051

  18. Repetitive Myocardial Infarctions Secondary to Delirium Tremens

    PubMed Central

    Schwartzberg, David; Shiroff, Adam

    2014-01-01

    Delirium tremens develops in a minority of patients undergoing acute alcohol withdrawal; however, that minority is vulnerable to significant morbidity and mortality. Historically, benzodiazepines are given intravenously to control withdrawal symptoms, although occasionally a more substantial medication is needed to prevent the devastating effects of delirium tremens, that is, propofol. We report a trauma patient who required propofol sedation for delirium tremens that was refractory to benzodiazepine treatment. Extubed prematurely, he suffered a non-ST segment myocardial infarction followed by an ST segment myocardial infarction requiring multiple interventions by cardiology. We hypothesize that his myocardial ischemia was secondary to an increased myocardial oxygen demand that occurred during his stress-induced catecholamine surge during the time he was undertreated for delirium tremens. This advocates for the use of propofol for refractory benzodiazepine treatment of delirium tremens and adds to the literature on the instability patients experience during withdrawal. PMID:25197580

  19. Repetitive myocardial infarctions secondary to delirium tremens.

    PubMed

    Schwartzberg, David; Shiroff, Adam

    2014-01-01

    Delirium tremens develops in a minority of patients undergoing acute alcohol withdrawal; however, that minority is vulnerable to significant morbidity and mortality. Historically, benzodiazepines are given intravenously to control withdrawal symptoms, although occasionally a more substantial medication is needed to prevent the devastating effects of delirium tremens, that is, propofol. We report a trauma patient who required propofol sedation for delirium tremens that was refractory to benzodiazepine treatment. Extubed prematurely, he suffered a non-ST segment myocardial infarction followed by an ST segment myocardial infarction requiring multiple interventions by cardiology. We hypothesize that his myocardial ischemia was secondary to an increased myocardial oxygen demand that occurred during his stress-induced catecholamine surge during the time he was undertreated for delirium tremens. This advocates for the use of propofol for refractory benzodiazepine treatment of delirium tremens and adds to the literature on the instability patients experience during withdrawal. PMID:25197580

  20. Myocardial hypoperfusion on conventional contrast computed tomography.

    PubMed

    Ching, Shing; Chung, Tak Shun

    2015-10-01

    Non–electrocardiogram (ECG)–gated contrast computed tomography (CT) is commonly performed to exclude aortic dissection in chest pain patients. Besides evaluating the aorta for dissection flap, attention should be paid to the myocardium for areas of hypoenhancement that may suggest ischemia. Current models of multidetector CT enable assessment of myocardial perfusion with minimal motion artifact even without ECG gating. Transmural hypoenhancement with preserved wall thickness in a coronary distribution is highly specific for acute myocardial infarction. We report 2 cases of acute chest pain with initial nondiagnostic studies that underwent CT aortogram to exclude dissection. Instead, the CT showed myocardial hypoenhancement in left anterior descending artery territory. Myocardial hypoenhancement occurred before ST-segment elevation on ECG, suggesting that recognition of this important finding may lead to earlier revascularization decisions. PMID:26321167

  1. Prognostic Significance of Imaging Myocardial Sympathetic Innervation.

    PubMed

    Malhotra, Saurabh; Fernandez, Stanley F; Fallavollita, James A; Canty, John M

    2015-08-01

    There has been a longstanding interest in understanding whether the presence of inhomogeneity in myocardial sympathetic innervation can predict patients at risk of sudden cardiac arrest from lethal ventricular arrhythmias. The advent of radiolabeled norepinephrine analogs has allowed this to be imaged in patients with ischemic and non-ischemic cardiomyopathy using single, photon emission computed tomography (SPECT) and positron emission tomography (PET). Several observational studies have demonstrated that globally elevated myocardial sympathetic tone (as reflected by reduced myocardial norepinephrine analog uptake) can predict composite cardiac end-points including total cardiovascular mortality. More recent studies have indicated that quantifying the extent of regional denervation can predict the risk of lethal ventricular arrhythmias and sudden cardiac death. This review will summarize our current understanding of the prognostic significance of altered myocardial sympathetic innervation. PMID:26087899

  2. Cardiovascular risk evaluation and prevalence of silent myocardial ischemia in subjects with asymptomatic carotid artery disease

    PubMed Central

    Ciccone, Marco Matteo; Niccoli-Asabella, Artor; Scicchitano, Pietro; Gesualdo, Michele; Notaristefano, Antonio; Chieppa, Domenico; Carbonara, Santa; Ricci, Gabriella; Sassara, Marco; Altini, Corinna; Quistelli, Giovanni; Lepera, Mario Erminio; Favale, Stefano; Rubini, Giuseppe

    2011-01-01

    Introduction: Silent ischemia is an asymptomatic form of myocardial ischemia, not associated with angina or anginal equivalent symptoms, which can be demonstrated by changes in ECG, left ventricular function, myocardial perfusion, and metabolism. The aim of this study was to evaluate the prevalence of silent myocardial ischemia in a group of patients with asymptomatic carotid stenosis. Methods: A total of 37 patients with asymptomatic carotid plaques, without chest pain or dyspnea, was investigated. These patients were studied for age, sex, hypertension, diabetes, dyslipidemia, smoking, and family history of cardiac disease, and underwent technetium-99 m sestamibi myocardial stress-rest scintigraphy and echo-color Doppler examination of carotid arteries. Results: A statistically significant relationship (P = 0.023) was shown between positive responders and negative responders to scintigraphy test when both were tested for degree of stenosis. This relationship is surprising in view of the small number of patients in our sample. Individuals who had a positive scintigraphy test had a mean stenosis degree of 35% ± 7% compared with a mean of 44% ± 13% for those with a negative test. Specificity of our detection was 81%, with positive and negative predictive values of 60% and 63%, respectively. Conclusion: The present study confirms that carotid atherosclerosis is associated with coronary atherosclerosis and highlights the importance of screening for ischemic heart disease in patients with asymptomatic carotid plaques, considering eventually plaque morphology (symmetry, composition, eccentricity or concentricity of the plaque, etc) for patient stratification. PMID:21468172

  3. Perichondrium phenotype and border function are regulated by Ext1 and heparan sulfate in developing long bones: a mechanism likely deranged in Hereditary Multiple Exostoses.

    PubMed

    Huegel, Julianne; Mundy, Christina; Sgariglia, Federica; Nygren, Patrik; Billings, Paul C; Yamaguchi, Yu; Koyama, Eiki; Pacifici, Maurizio

    2013-05-01

    During limb skeletogenesis the cartilaginous long bone anlagen and their growth plates become delimited by perichondrium with which they interact functionally. Yet, little is known about how, despite being so intimately associated with cartilage, perichondrium acquires and maintains its distinct phenotype and exerts its border function. Because perichondrium becomes deranged and interrupted by cartilaginous outgrowths in Hereditary Multiple Exostoses (HME), a pediatric disorder caused by EXT mutations and consequent heparan sulfate (HS) deficiency, we asked whether EXT genes and HS normally have roles in establishing its phenotype and function. Indeed, conditional Ext1 ablation in perichondrium and lateral chondrocytes flanking the epiphyseal region of mouse embryo long bone anlagen - a region encompassing the groove of Ranvier - caused ectopic cartilage formation. A similar response was observed when HS function was disrupted in long bone anlagen explants by genetic, pharmacological or enzymatic means, a response preceded by ectopic BMP signaling within perichondrium. These treatments also triggered excess chondrogenesis and cartilage nodule formation and overexpression of chondrogenic and matrix genes in limb bud mesenchymal cells in micromass culture. Interestingly, the treatments disrupted the peripheral definition and border of the cartilage nodules in such a way that many nodules overgrew and fused with each other into large amorphous cartilaginous masses. Interference with HS function reduced the physical association and interactions of BMP2 with HS and increased the cell responsiveness to endogenous and exogenous BMP proteins. In sum, Ext genes and HS are needed to establish and maintain perichondrium's phenotype and border function, restrain pro-chondrogenic signaling proteins including BMPs, and restrict chondrogenesis. Alterations in these mechanisms may contribute to exostosis formation in HME, particularly at the expense of regions rich in progenitor

  4. Metabolic myopathies

    NASA Technical Reports Server (NTRS)

    Martin, A.; Haller, R. G.; Barohn, R.; Blomqvist, C. G. (Principal Investigator)

    1994-01-01

    Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

  5. [The latest treatments for myocardial infarction].

    PubMed

    Leclercq, Florence

    2015-03-01

    Ischemic heart disease and its main complication, myocardial infarction, remain the leading cause of death after the age of forty in developed countries. Myocardial infarction is the consequence of a sudden obstruction of a coronary artery by a thrombus. Thrombolysis and coronary angioplasty are the two emergency coronary artery revascularisation techniques. A medication-based treatment and adapted lifestyle aim to prevent repeat infarction. PMID:26040139

  6. Myocardial perfusion imaging with 201Tl.

    PubMed

    Pagnanelli, Robert A; Basso, Danny A

    2010-03-01

    The object of this review is to provide information about (201)Tl-thallous chloride in radionuclide myocardial perfusion imaging. This technique has experienced a recent resurgence because of the shortage of (99m)Tc. After reading this article, the technologist will be able to describe the properties and uptake mechanism of (201)Tl, the procedure for myocardial perfusion imaging with this agent, and the advantages and disadvantages of thallium, compared with the technetium agents. PMID:20159930

  7. Improved exercise myocardial perfusion during lidoflazine therapy

    SciTech Connect

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-11-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise.

  8. Metabolic ecology.

    PubMed

    Humphries, Murray M; McCann, Kevin S

    2014-01-01

    Ecological theory that is grounded in metabolic currencies and constraints offers the potential to link ecological outcomes to biophysical processes across multiple scales of organization. The metabolic theory of ecology (MTE) has emphasized the potential for metabolism to serve as a unified theory of ecology, while focusing primarily on the size and temperature dependence of whole-organism metabolic rates. Generalizing metabolic ecology requires extending beyond prediction and application of standardized metabolic rates to theory focused on how energy moves through ecological systems. A bibliometric and network analysis of recent metabolic ecology literature reveals a research network characterized by major clusters focused on MTE, foraging theory, bioenergetics, trophic status, and generalized patterns and predictions. This generalized research network, which we refer to as metabolic ecology, can be considered to include the scaling, temperature and stoichiometric models forming the core of MTE, as well as bioenergetic equations, foraging theory, life-history allocation models, consumer-resource equations, food web theory and energy-based macroecology models that are frequently employed in ecological literature. We conclude with six points we believe to be important to the advancement and integration of metabolic ecology, including nomination of a second fundamental equation, complementary to the first fundamental equation offered by the MTE. PMID:24028511

  9. Relationship between myocardial bridging and coronary arteriosclerosis.

    PubMed

    Sun, Jian Ling; Huang, Wei Min; Guo, Ji Hong; Li, Xiao Ying; Ma, Xian Lin; Wang, Chong Yu

    2013-04-01

    The objective of the study was to explore the prevalence and characteristics of myocardial bridging in patients who underwent coronary angiography and to also evaluate the correlation between bridged coronary segments and atherosclerosis. For this purpose, clinical materials of 1,500 patients who had received coronary angiography were retrospectively analyzed. The location and length of the myocardial bridge were recorded as well as the extent and location of coronary artery stenosis was described. Segments proximal and distal to the bridging were evaluated for coronary arteriosclerosis as were the remaining coronary segments. We found that myocardial bridging was present in 179 (11.9 %) patients. Bridges were frequently (84.9 %) localized in the mid-distal segment of the left anterior descending (LAD) artery. Myocardial bridging was not considered a significant risk factor for coronary atherosclerosis (odds ratio 0.58) compared with traditional cardiovascular risk factors. The incidence of coronary arteriosclerosis in the distal segments was significantly less affected than the proximal segments (P < 0.01). It was, therefore, concluded that myocardial bridging frequently localized in the mid-distal segment of the LAD artery. The presence of myocardial bridging promotes proximal atherosclerosis but it is not an additional risk factor for coronary atherosclerosis. PMID:23076634

  10. Computational modeling of acute myocardial infarction.

    PubMed

    Sáez, P; Kuhl, E

    2016-01-01

    Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size. PMID:26583449

  11. Myocardial Sleeve Tissues in Surgical Lung Specimens.

    PubMed

    Yoshida, Akihiko; Kamata, Tsugumasa; Iwasa, Takeshi; Watanabe, Shun-ichi; Tsuta, Koji

    2015-10-01

    Left atrial myocardial extensions over the pulmonary veins (PVs), known as myocardial sleeves, are present in the physiological anatomy of most individuals. Although this structure has recently received clinical attention as a major origin of paroxysmal atrial fibrillation (AF), it has not been documented in surgical specimens. Here, we examine incidentally identified myocardial sleeve tissue in routinely processed lung resection specimens to determine its incidence and diagnostic implications. Among 694 lung resection specimens with evaluable PV margins, myocardial sleeve tissue was identified in 26 cases (3.7%). The tissue was located within the adventitia of the PVs, mostly in margin preparations, and existed outside the pericardium in the majority of cases. Carcinoma infiltration of the sleeves was evident in 6 cases. No heart injuries were observed, and no tumors invaded the heart. Preoperative electrocardiography showed sinus rhythm in all cases, whereas postoperative monitoring revealed sinus rhythm in all patients except one who showed AF and flutter. Myocardial sleeve tissue is an underrecognized incidental finding in lung resection specimens, and it is not indicative of heart injury. Cancer infiltration into this tissue indicates neither heart invasion nor, by itself, invasion into the pericardium. Although surgical transection of the myocardial sleeve did not evoke immediate arrhythmia in most cases, the overall influence of this procedure on the postsurgical risk of AF remains to be determined in further studies involving extensive rhythm assessment. PMID:26099012

  12. Myocardial Dysfunction and Shock after Cardiac Arrest

    PubMed Central

    Jentzer, Jacob C.; Chonde, Meshe D.; Dezfulian, Cameron

    2015-01-01

    Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies. PMID:26421284

  13. Respiratory chain defect of myocardial mitochondria in idiopathic dilated cardiomyopathy of Doberman pinscher dogs.

    PubMed

    McCutcheon, L J; Cory, C R; Nowack, L; Shen, H; Mirsalami, M; Lahucky, R; Kovac, L; O'Grady, M; Horne, R; O'Brien, P J

    1992-11-01

    Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause. We tested the hypothesis that IDCM was associated with a myocardial metabolic defect by determining a comprehensive biochemical profile of metabolite concentrations and enzyme activities for the major metabolic pathways of the myocardium. We used the Doberman pinscher breed as a naturally occurring canine model of IDCM and compared its myocardial profile with that of healthy adult mongrels. Compared with controls, myocardium in IDCM had markedly reduced mitochondrial electron transport activity and myoglobin concentration, in association with acidosis and energy depletion following anoxic challenge: 60% decreased NADH dehydrogenase and 50% decreased ATP synthetase activities; 90% decreased myoglobin concentration; and 30% reduced ATP and 50% increased lactate and proton concentrations. Sarcoplasmic reticulum Ca(2+)-transport ATPase was decreased by 42%. There was a 15% compensatory increase in fatty acid oxidation and Krebs cycle activity. Other biochemical changes were mild by comparison with the mitochondrial defects. We conclude that IDCM is associated with a marked impairment of mitochondrial production of ATP, arising from decreased activity of the mitochondrial electron transport system, including myoglobin. These changes may be secondary to an underlying genetic defect or may indicate a deficiency of the mitochondrial respiratory chain that predisposes this breed to heart failure. PMID:1338376

  14. The molecular and metabolic influence of long term agmatine consumption.

    PubMed

    Nissim, Itzhak; Horyn, Oksana; Daikhin, Yevgeny; Chen, Pan; Li, Changhong; Wehrli, Suzanne L; Nissim, Ilana; Yudkoff, Marc

    2014-04-01

    Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used (13)C or (15)N tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor-α and its coactivator, PGC1α, and (b) increased expression of peroxisomal proliferator-activated receptor-γ and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased β-oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming. PMID:24523404

  15. Apelin-13 protects against myocardial infarction-induced myocardial fibrosis.

    PubMed

    Zhang, Xuemin; Hu, Wenyu; Feng, Feng; Xu, Jian; Wu, Fang

    2016-06-01

    Myocardial infarction is a serious health threat. Apelin is an endogenous ligand of angiotensin II receptor-like 1 (APJ) and the apelin/APJ system is associated with various types of heart disease. However, whether apelin protects against myocardial infarction‑induced myocardial fibrosis remains unclear. The present study aimed to investigate the function of apelin‑13 during myocardial infarction‑induced myocardial fibrosis, and to determine the mechanism underlying the effects of apelin‑13. Apelin‑13 was demonstrated to improve left ventricular function and results of hematoxylin and eosin staining, Masson's trichrome staining and western blotting showed that apelin‑13 attenuated myocardial fibrosis. Further mechanistic investigation was performed by enzyme‑linked immunosorbent assay, western blotting and electrophoretic mobility shift assay. The results demonstrated that apelin‑13 inhibited the activation of nuclear factor (NF)‑κB signaling in vitro and in vivo. To the best of our knowledge, the present study was the first to demonstrate that apelin‑13 may attenuate myocardial infarction‑induced myocardial fibrosis, and that this protective function may be mediated by inhibition of NF‑κB signaling. The present study suggests a theoretical basis for the effects of apelin‑13 and provides insight into the potential clinical application of apelin-13. PMID:27109054

  16. Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder.

    PubMed

    Frye, Richard E

    2015-06-01

    Autism spectrum disorder (ASD) affects a significant number of individuals in the United States, with the prevalence continuing to grow. A significant proportion of individuals with ASD have comorbid medical conditions such as epilepsy. In fact, treatment-resistant epilepsy appears to have a higher prevalence in children with ASD than in children without ASD, suggesting that current antiepileptic treatments may be suboptimal in controlling seizures in many individuals with ASD. Many individuals with ASD also appear to have underlying metabolic conditions. Metabolic conditions such as mitochondrial disease and dysfunction and abnormalities in cerebral folate metabolism may affect a substantial number of children with ASD, while other metabolic conditions that have been associated with ASD such as disorders of creatine, cholesterol, pyridoxine, biotin, carnitine, γ-aminobutyric acid, purine, pyrimidine, and amino acid metabolism and urea cycle disorders have also been associated with ASD without the prevalence clearly known. Interestingly, all of these metabolic conditions have been associated with epilepsy in children with ASD. The identification and treatment of these disorders could improve the underlying metabolic derangements and potentially improve behavior and seizure frequency and/or severity in these individuals. This paper provides an overview of these metabolic disorders in the context of ASD and discusses their characteristics, diagnostic testing, and treatment with concentration on mitochondrial disorders. To this end, this paper aims to help optimize the diagnosis and treatment of children with ASD and epilepsy. This article is part of a Special Issue entitled "Autism and Epilepsy". PMID:25440829

  17. Radionuclide imaging of myocardial perfusion and viability in assessment of acute myocardial infarction

    SciTech Connect

    Berman, D.S.; Kiat, H.; Maddahi, J.; Shah, P.K.

    1989-07-18

    Technical advances in radionuclide imaging have important implications for the management of patients with acute myocardial infarction. Single-photon emission computerized tomography with thallium 201 (TI-201) offers greater accuracy than planar imaging in detecting, localizing and sizing myocardial perfusion defects. Use of single-photon emission computerized tomography with TI-201 should allow for a more accurate assessment of prognosis after myocardial infarction. A new radiopharmaceutical, technetium 99-m methoxyisobutyl isonitrile, provides a number of advantages over TI-201, including higher quality images, lack of redistribution, and the ability to assess first-pass ventricular function. Applications of TI-201 and technetium 99-m methoxyisobutyl isonitrile include assessment of arterial patency and myocardial salvage immediately after thrombolytic therapy, detection of resting ischemia after thrombolytic therapy, targeting of subsets of patients for further intervention, and predischarge assessment to predict the future course of patients after an acute myocardial infarction.

  18. Incidence of acute myocardial infarction in patients with exercise-induced silent myocardial ischemia

    SciTech Connect

    Assey, M.E.; Walters, G.L.; Hendrix, G.H.; Carabello, B.A.; Usher, B.W.; Spann, J.F. Jr.

    1987-03-01

    Fifty-five patients with angiographically proved coronary artery disease (CAD) underwent Bruce protocol exercise stress testing with thallium-201 imaging. Twenty-seven patients (group I) showed myocardial hypoperfusion without angina pectoris during stress, which normalized at rest, and 28 patients (group II) had a similar pattern of reversible myocardial hypoperfusion but also had angina during stress. Patients were followed for at least 30 months. Six patients in group I had an acute myocardial infarction (AMI), 3 of whom died, and only 1 patient in group II had an AMI (p = 0.05), and did not die. Silent myocardial ischemia uncovered during exercise stress thallium testing may predispose to subsequent AMI. The presence of silent myocardial ischemia identified in this manner is of prognostic value, independent of angiographic variables such as extent of CAD and left ventricular ejection fraction.

  19. Regional myocardial shape and dimensions of the working isolated canine left ventricle

    NASA Technical Reports Server (NTRS)

    Ritman, E.; Tsuiki, K.; Donald, D.; Wood, E. H.

    1975-01-01

    Angiographic experiments were performed on isolated canine left ventricle preparations using donor dog to supply blood to the coronary circulation via a rotary pump to control coronary flow. The angiographic record was transferred from video tape to video disk for detailed uninterrupted sequential analysis at a frequency of 60 fields/sec. It is shown that the use of a biplane X-ray technique and a metabolically supported isolated canine left ventricle preparation provides an angiographically ideal means of measuring the mechanical dynamics of the myocardium while the intact left ventricular myocardial structure and electrical activation pattern retain most of the in situ ventricular characteristics. In particular, biplane X-ray angiography of the left ventricle can provide estimates of total ventricular function such as ejection fraction, stroke volume, and myocardial mass correct to within 15% under the angiographically ideal conditions of the preparation.

  20. Immunological results in myocardial diseases.

    PubMed Central

    Bolte, H. D.; Schultheiss, P.

    1978-01-01

    Immunological studies have shown new diagnostically important changes in alcoholic and viral myocarditis, as well as in congestive cardiomyopathy. Increased heart size correlated with the degree of congestive heart failure, as well as with negative immunofluorescence and an increased IgA concentration in the serum. These findings may serve as a diagnostic aid in patients with myocardial disease due to alcohol abuse. Viral heart disease is characterized by a variety of symptoms and nuclear antibodies (IgM) can be of help in the differential diagnosis. Heart muscle tissue of patients with congestive cardiomyopathy preferentially binds IgG and IgA. In addition to the other changes these findings are of diagnostic importance. It seems likely that results similar to those obtained for humoral antibodies in congestive cardiomyopathy will apply in the correlation of the haemodynamic status of the patients. The pathophysiological implication of these findings is not clear at present, but the evolution of congestive cardiomyopathy appears to be associated with binding of immunoglobulin to the myocardium, as well as with humoral antiheart antibodies. PMID:704517

  1. [Occupational stress and myocardial infarction].

    PubMed

    Consoli, Silla M

    2015-01-01

    Besides the best-known role of depressed mood, occupational stress deserves to be taken as a coronary risk factor. There are two basic models to define occupational stress: Karasek's model (high job psychological demands associated with low decision latitude, or even low social support at work) and Siegrist's model (imbalance between efforts and rewards received). The combination of the two models better reflects the coronary risk than each model alone. Occupational stress appears both as a risk factor and a prognostic factor after the occurrence of myocardial infarction. The relevance of the models is best in men or in younger age subjects. In women, role conflicts (occupational/domestic), the existence of excessive "intrinsic" efforts (job over investment) and association with marital stress provide more specific information. Burnout, particularly among health professionals, and bullying at work are also linked to cardiovascular risk. Occupational stress is a collective indicator of health at work, valuable to the employer. At an individual level, it can lead to therapeutic preventive approaches. PMID:26150284

  2. Molecular genetics of myocardial infarction

    PubMed Central

    Ichihara, Sahoko; Nishida, Tamotsu

    2008-01-01

    Abstract Myocardial infarction (MI) is an important clinical problem because of its large contribution to mortality. The main causal and treatable risk factors for MI include hypertension, hypercholesterolemia or dyslipidemia, diabetes mellitus, and smoking. In addition to these risk factors, recent studies have shown the importance of genetic factors and interactions between multiple genes and environmental factors. Disease prevention is an important strategy for reducing the overall burden of MI, with the identification of markers for disease risk being key both for risk prediction and for potential intervention to lower the chance of future events. Although genetic linkage analyses of families and sib-pairs as well as candidate gene and genome-wide association studies have implicated several loci and candidate genes in predisposition to coronary heart disease (CHD) or MI, the genes that contribute to genetic susceptibility to these conditions remain to be identified definitively. In this review, we summarize both candidate loci for CHD or MI identified by linkage analyses and candidate genes examined by association studies. We also review in more detail studies that have revealed the association with MI or CHD of polymorphisms in MTHFR, LPL, and APOE by the candidate gene approach and those in LTA and at chromosomal region 9p21.3 by genome-wide scans. Such studies may provide insight into the function of implicated genes as well as into the role of genetic factors in the development of CHD and MI. PMID:18704761

  3. Echocardiographic assessment of myocardial ischemia

    PubMed Central

    Dworrak, Birgit; Sanchis-Gomar, Fabian; Lucia, Alejandro; Buck, Thomas; Erbel, Raimund

    2016-01-01

    Over the last 60 years, echocardiography has emerged as a dominant and indispensable technique for the detection and assessment of coronary heart disease (CHD). In this review, we will describe and discuss this powerful tool of cardiology, especially in the hands of an experienced user, with a focus on myocardial ischemia. Technical development is still on-going, and various new ultrasound techniques have been established in the field of echocardiography in the last several years, including tissue Doppler imaging (TDI), contrast echocardiography, three-dimensional echocardiography (3DE), and speckle tracking echocardiography (i.e., strain/strain rate-echocardiography). High-end equipment with harmonic imaging, high frame rates and the opportunity to adjust mechanical indices has improved imaging quality. Like all new techniques, these techniques must first be subjected to comprehensive scientific assessment, and appropriate training that accounts for physical and physiological limits should be provided. These limits will constantly be redefined as echocardiographic techniques continue to change, which will present new challenges for the further development of ultrasound technology. PMID:27500160

  4. Echocardiographic assessment of myocardial ischemia.

    PubMed

    Leischik, Roman; Dworrak, Birgit; Sanchis-Gomar, Fabian; Lucia, Alejandro; Buck, Thomas; Erbel, Raimund

    2016-07-01

    Over the last 60 years, echocardiography has emerged as a dominant and indispensable technique for the detection and assessment of coronary heart disease (CHD). In this review, we will describe and discuss this powerful tool of cardiology, especially in the hands of an experienced user, with a focus on myocardial ischemia. Technical development is still on-going, and various new ultrasound techniques have been established in the field of echocardiography in the last several years, including tissue Doppler imaging (TDI), contrast echocardiography, three-dimensional echocardiography (3DE), and speckle tracking echocardiography (i.e., strain/strain rate-echocardiography). High-end equipment with harmonic imaging, high frame rates and the opportunity to adjust mechanical indices has improved imaging quality. Like all new techniques, these techniques must first be subjected to comprehensive scientific assessment, and appropriate training that accounts for physical and physiological limits should be provided. These limits will constantly be redefined as echocardiographic techniques continue to change, which will present new challenges for the further development of ultrasound technology. PMID:27500160

  5. Adenosine enhances myocardial glucose uptake only in the presence of insulin.

    PubMed

    Law, W R; McLane, M P

    1991-09-01

    Better understood in other tissues, the effects of adenosine on insulin-stimulated glucose uptake in the heart are poorly understood. Under pentobarbital anesthesia, we instrumented mongrel dogs to obtain general hemodynamics (blood pressure and heart rate), and arterial and coronary sinus blood samples for measuring oxygen and glucose concentrations. An electromagnetic blood flow probe around the circumflex coronary artery allowed determinations of blood flow, and calculation of substrate uptake by the heart (Fick principle). Somatostatin (SRIF) was infused intravenously (0.8 micrograms/kg/min) along with 0, 0.5, 1.0, 5.0, or 10 mU/kg/min regular insulin, and variable quantities of glucose to maintain euglycemia. Concomitant with the SRIF, insulin, and glucose infusions, adenosine was infused in logarithmically increasing rates (0, 0.01, 0.1, 1.0, 10 or 100 mumol/min) for 30 minutes each into the main left coronary arteries. Insulin infusions increased myocardial glucose uptake in a dose-dependent manner. The heart displayed exquisite sensitivity to insulin, with an ED50 of approximately 14 microU/mL (serum insulin). Adenosine infusions in the absence of insulin (SRIF infusion) increased coronary blood flow, but did not alter myocardial glucose uptake. In the presence of insulin, adenosine increased the maximal value for glucose uptake without changing sensitivity to insulin. These results indicate that adenosine enhances myocardial responsiveness to insulin, with respect to glucose uptake, independent of changes in blood flow. Since glucose can be used for anaerobic metabolism, and adenosine levels are known to increase under situations in which myocardial oxygenation is inadequate, these data have serious implications for conditions such as myocardial ischemia or hypoxia, when glycolytic substrate availability is vital. PMID:1680214

  6. Kinetics of /sup 13/N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow

    SciTech Connect

    Rauch, B.; Helus, F.; Grunze, M.; Braunwell, E.; Mall, G.; Hasselbach, W.; Kuebler, W.

    1985-02-01

    To study kinetics and principles of cellular uptake of /sup 13/N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of /sup 13/N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 37 degrees C). Total extraction, 80 sec after the reaction start, was 786 +/- 159 mumol/ml cell volume. Cells destroyed by calcium overload were unable to extract /sup 13/N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. /sup 13/N-Ammonia uptake could also be reduced by 50 muM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 micrograms/ml 1-methionine sulfoximine, and by preincubation with 5 muM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of /sup 13/N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of /sup 13/N-ammonia may not always provide a valid measurement of myocardial perfusion.

  7. Metabolic Shifts during Aging and Pathology

    PubMed Central

    Ma, Yina; Li, Ji

    2016-01-01

    The heart is a very special organ in the body and has a high requirement for metabolism due to its constant workload. As a consequence, to provide a consistent and sufficient energy a high steady-state demand of metabolism is required by the heart. When delicately balanced mechanisms are changed by physiological or pathophysiological conditions, the whole system’s homeostasis will be altered to a new balance, which contributes to the pathologic process. So it is no wonder that almost every heart disease is related to metabolic shift. Furthermore, aging is also found to be related to the reduction in mitochondrial function, insulin resistance, and dysregulated intracellular lipid metabolism. Adenosine monophosphate-activated protein kinase (AMPK) functions as an energy sensor to detect intracellular ATP/AMP ratio and plays a pivotal role in intracellular adaptation to energy stress. During different pathology (like myocardial ischemia and hypertension), the activation of cardiac AMPK appears to be essential for repairing cardiomyocyte’s function by accelerating ATP generation, attenuating ATP depletion, and protecting the myocardium against cardiac dysfunction and apoptosis. In this overview, we will talk about the normal heart’s metabolism, how metabolic shifts during aging and different pathologies, and how AMPK regulates metabolic changes during these conditions. PMID:25880509

  8. Myocardial perfusion and oxygenation are impaired during stress in severe aortic stenosis and correlate with impaired energetics and subclinical left ventricular dysfunction

    PubMed Central

    2014-01-01

    Background Left ventricular (LV) hypertrophy in aortic stenosis (AS) is characterized by reduced myocardial perfusion reserve due to coronary microvascular dysfunction. However, whether this hypoperfusion leads to tissue deoxygenation is unknown. We aimed to assess myocardial oxygenation in severe AS without obstructive coronary artery disease, and to investigate its association with myocardial energetics and function. Methods Twenty-eight patients with isolated severe AS and 15 controls underwent cardiovascular magnetic resonance (CMR) for assessment of perfusion (myocardial perfusion reserve index-MPRI) and oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change) during adenosine stress. LV circumferential strain and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were assessed using tagging CMR and 31P MR spectroscopy, respectively. Results AS patients had reduced MPRI (1.1 ± 0.3 vs. controls 1.7 ± 0.3, p < 0.001) and BOLD SI change during stress (5.1 ± 8.9% vs. controls 18.2 ± 10.1%, p = 0.001), as well as reduced PCr/ATP (1.45 ± 0.21 vs. 2.00 ± 0.25, p < 0.001) and LV strain (−16.4 ± 2.7% vs. controls −21.3 ± 1.9%, p < 0.001). Both perfusion reserve and oxygenation showed positive correlations with energetics and LV strain. Furthermore, impaired energetics correlated with reduced strain. Eight months post aortic valve replacement (AVR) (n = 14), perfusion (MPRI 1.6 ± 0.5), oxygenation (BOLD SI change 15.6 ± 7.0%), energetics (PCr/ATP 1.86 ± 0.48) and circumferential strain (−19.4 ± 2.5%) improved significantly. Conclusions Severe AS is characterized by impaired perfusion reserve and oxygenation which are related to the degree of derangement in energetics and associated LV dysfunction. These changes are reversible on relief of pressure overload and hypertrophy regression. Strategies aimed at improving oxygen demand–supply balance to preserve myocardial

  9. Myocardial infarction size: measurement and modification

    PubMed Central

    Cairns, John A.

    1977-01-01

    The majority of in-hospital deaths from acute myocardial infarction occur as a result of the “power failure” syndrome (severe congestive heart failure and cardiogenic shock), which results from extensive loss of myocardium. The death of myocardial cells is sequential over many hours. Surrounding the central zone of necrosis in an acute myocardial infarction is a zone of ischemic myocardium whose fate might be altered by interventions during the early phase of the infarction. ST-segment mapping, serial measurement of the serum concentration of creatine phosphokinase and myocardial imaging by means of radionuclides are being developed for the noninvasive assessment of infarct size in animals and humans. A number of interventions appear to limit infarct size in animals. There have been relatively few studies in humans to date, but preliminary results suggest that infarct size might be limited by certain interventions. The research has provided important practical benefits in terms of understanding the course of acute myocardial infarction and the potential effects of conventional therapies. For the present, interventions designed to limit infarct size remain in the realm of clinical research; routine clinical use would be inappropriate. PMID:69481

  10. Contemporary perspective on endogenous myocardial regeneration

    PubMed Central

    Milasinovic, Dejan; Mohl, Werner

    2015-01-01

    Considering the complex nature of the adult heart, it is no wonder that innate regenerative processes, while maintaining adequate cardiac function, fall short in myocardial jeopardy. In spite of these enchaining limitations, cardiac rejuvenation occurs as well as restricted regeneration. In this review, the background as well as potential mechanisms of endogenous myocardial regeneration are summarized. We present and analyze the available evidence in three subsequent steps. First, we examine the experimental research data that provide insights into the mechanisms and origins of the replicating cardiac myocytes, including cell populations referred to as cardiac progenitor cells (i.e., c-kit+ cells). Second, we describe the role of clinical settings such as acute or chronic myocardial ischemia, as initiators of pathways of endogenous myocardial regeneration. Third, the hitherto conducted clinical studies that examined different approaches of initiating endogenous myocardial regeneration in failing human hearts are analyzed. In conclusion, we present the evidence in support of the notion that regaining cardiac function beyond cellular replacement of dysfunctional myocardium via initiation of innate regenerative pathways could create a new perspective and a paradigm change in heart failure therapeutics. Reinitiating cardiac morphogenesis by reintroducing developmental pathways in the adult failing heart might provide a feasible way of tissue regeneration. Based on our hypothesis “embryonic recall”, we present first supporting evidence on regenerative impulses in the myocardium, as induced by developmental processes. PMID:26131310

  11. Metabolic Syndrome

    MedlinePlus

    ... cause of metabolic syndrome. The cause might be insulin resistance. Insulin is a hormone your body produces to help ... into energy for your body. If you are insulin resistant, too much sugar builds up in your ...

  12. Metabolic Myopathies

    MedlinePlus

    ... muscles. Metabolic refers to chemical reactions that provide energy, nutrients and substances necessary for health and growth. ... occur when muscle cells don’t get enough energy. Without enough energy, the muscle lacks enough fuel ...

  13. Metabolic Syndrome

    MedlinePlus

    ... is not known but genetic factors, too much body fat (especially in the waist area, the most dangerous ... Metabolic Risk Factors Measurement Large amount of abdominal body fat Waist measurement of more than 40 inches (101 ...

  14. Depression Increases Sympathetic Activity and Exacerbates Myocardial Remodeling after Myocardial Infarction: Evidence from an Animal Experiment

    PubMed Central

    Liu, Tao; Yuan, Xiaoran; Ruan, Bing; Sun, Lifang; Tang, Yanhong; Yang, Bo; Hu, Dan; Huang, Congxin

    2014-01-01

    Depression is an independent risk factor for cardiovascular events and mortality in patients with myocardial infarction (MI). Excessive sympathetic activation and serious myocardial remodeling may contribute to this association. The aim of this study was to discuss the effect of depression on sympathetic activity and myocardial remodeling after MI. Wild-type (WT) rats were divided into a sham group (Sham), a myocardial infarction group (MI), a depression group (D), and a myocardial infarction plus depression group (MI+D). Compared with controls, the MI+D animals displayed depression-like behaviors and attenuated body weight gain. The evaluation of sympathetic activity showed an increased level in plasma concentrations of epinephrine and norepinephrine and higher expression of myocardial tyrosine hydroxylase in the MI+D group than the control groups (p<0.05 for all). Cardiac function and morphologic analyses revealed a decreased fractional shortening accompanied by increased left ventricular dimensions, thinning myocardium wall, and reduced collagen repair in the MI+D group compared with the MI group (p<0.05 for all). Frequent premature ventricular contractions, prolonged QT duration and ventricular repolarization duration, shorted effective refractory period, and increased susceptibility to ventricular arrhythmia were displayed in MI+D rats. These results indicate that sympathetic hyperactivation and exacerbated myocardial remodeling may be a plausible mechanism linking depression to an adverse prognosis after MI. PMID:25036781

  15. Spontaneous changes in /sup 201/Tl myocardial perfusion imaging after myocardial infarction

    SciTech Connect

    Buda, A.J.; Dubbin, J.D.; MacDonald, I.L.; Strauss, H.D.; Orr, S.A.; Meindok, H.

    1982-12-01

    To examine regional myocardial perfusion after myocardial infarction, 26 patients underwent exercise electrocardiographic testing with /sup 201/Tl myocardial perfusion imaging 3 weeks and 3 months after infarction. At 3 weeks, 9 of 26 patients (35%) had myocardial ischemia by exercise electrocardiographic testing, whereas 18 of 26 (69%) had ischemia by /sup 201/Tl imaging. The /sup 201/Tl scintigrams were scored by dividing each image, in 3 views, into 5 segments, using a 5-point scoring scheme. The exercise /sup 201/Tl score was 44.3 +/- 1.2 and increased to 47.3 +/- 1.2 in the redistribution study (p less than 0.001). Three months after infarction, although there was a significantly greater rate-pressure product which would predict a larger ischemic defect and a decrease in the stress /sup 201/Tl score, the stress score was improved (48.3 +/- 1.1, p less than 0.001). The redistribution score was similar, that is, 48.9 +/- 1.0. The improvement in /sup 201/Tl myocardial perfusion was associated with a loss of stress-induced ischemia in 8 patients (30%). These results indicate that spontaneous improvements in /sup 201/Tl myocardial perfusion imaging may occur after myocardial infarction.

  16. Role of myocardial perfusion imaging in evaluating thrombolytic therapy for acute myocardial infarction

    SciTech Connect

    Beller, G.A.

    1987-03-01

    Myocardial thallium-201 scintigraphy is being increasingly employed as a method for assessing the efficacy of coronary reperfusion in acute myocardial infarction. New thallium uptake after intracoronary tracer administration after successful recanalization indicates that nutrient blood flow has been successfully restored. One may also presume that some myocardial salvage occurred if thallium administered in this manner is transported intracellularly by myocytes with intact sarcolemmal membranes. However, if one injects thallium by way of the intracoronary route immediately after reperfusion, the initial uptake of thallium in reperfused myocardium may predominantly represent hyperemic flow and regional thallium counts measured may not be proportional to the mass of viable myocytes. When thallium is injected intravenously during the occlusion phase the degree of redistribution after thrombolysis is proportional to the degree of flow restoration and myocardial viability. When thallium is injected for the first time intravenously immediately after reperfusion, an overestimation of myocardial salvage may occur because of excess thallium uptake in the infarct zone consequent to significant hyperemia. Another approach to myocardial thallium scintigraphy in patients undergoing thrombolytic therapy is to administer two separate intravenous injections before and 24 hours or later after treatment. Finally, patients with acute myocardial infarction who receive intravenous thrombolytic therapy are candidates for predischarge exercise thallium-201 scintigraphy for risk stratification and detection of residual ischemia.

  17. Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report

    PubMed Central

    2012-01-01

    Background Chest pain, a key element in the investigation of coronary artery disease is often regarded as a benign prognosis when present in panic attacks. However, panic disorder has been suggested as an independent risk factor for long-term prognosis of cardiovascular diseases and a trigger of acute myocardial infarction. Objective Faced with the extreme importance in differentiate from ischemic to non-ischemic chest pain, we report a case of panic attack induced by inhalation of 35% carbon dioxide triggering myocardial ischemia, documented by myocardial perfusion imaging study. Discussion Panic attack is undoubtedly a strong component of mental stress. Patients with coronary artery disease may present myocardial ischemia in mental stress response by two ways: an increase in coronary vasomotor tone or a sympathetic hyperactivity leading to a rise in myocardial oxygen consumption. Coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. Possibly the carbon dioxide challenge test could trigger myocardial ischemia by the same mechanisms. Conclusion The use of mental stress has been suggested as an alternative method for myocardial ischemia investigation. Based on translational medicine objectives the use of CO2 challenge followed by Sestamibi SPECT could be a useful method to allow improved application of research-based knowledge to the medical field, specifically at the interface of PD and cardiovascular disease. PMID:22999016

  18. PPAR-γ activation fails to provide myocardial protection in ischemia and reperfusion in pigs

    PubMed Central

    Xu, Ya; Gen, Michael; Lu, Li; Fox, Jennifer; Weiss, Sara O.; Brown, R. Dale; Perlov, Daniel; Ahmad, Hasan; Zhu, Peili; Greyson, Clifford; Long, Carlin S.; Schwartz, Gregory G.

    2010-01-01

    Peroxisome proliferator-activated receptor (PPAR)-γ modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-γ activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-γ activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both α-tocopherol and thiazolidinedione moieties, whether PPAR-γ activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone (75 mg·kg−1 ·day−1), rosiglitazone (3 mg·kg−1 ·day−1), or α-tocopherol (73 mg·kg−1 ·day−1, equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-γ, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or α-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an α-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-γ activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its α-tocopherol moiety. These findings, in conjunction with prior rat studies, suggest

  19. Energetics and Metabolism in the Failing Heart: Important But Poorly Understood

    PubMed Central

    Turer, Aslan T.; Malloy, Craig R.; Newgard, Christopher B.; Podgoreanu, Mihai V.

    2010-01-01

    Purpose of review Profound abnormalities in myocardial energy metabolism occur in heart failure and correlate with clinical symptoms and survival. Available comprehensive human metabolic data comes from small studies, enrolling patients across heart failure etiologies, at different disease stages, and using different methodologies, and is often contradictory. Remaining fundamental gaps in knowledge include whether observed shifts in cardiac substrate utilization are adaptive or maladaptive, causal or an epiphenomenon of heart failure. Recent findings Recent studies have characterized the temporal changes in myocardial substrate metabolism involved in progression of heart failure, the role of insulin resistance, and the mechanisms of mitochondrial dysfunction in heart failure. The concept of metabolic inflexibility has been proposed to explain the lack of energetic and mechanical reserve in the failing heart. Summary Despite current therapies, which provide substantial benefits to patients, heart failure remains a progressive disease, and new approaches to treatment are necessary. Developing metabolic interventions would be facilitated by systems-level integration of current knowledge on myocardial metabolic control. Although preliminary evidence suggests that metabolic modulators inducing a shift towards carbohydrate utilization seem generally beneficial in the failing heart, such interventions should be matched to the stage of metabolic deregulation in the progression of heart failure. PMID:20453645

  20. [Ventricular Septal Perforation after Inferior Myocardial Infarction].

    PubMed

    Sato, Hisashi; Nakayama, Yoshihiro; Tanaka, Hideya; Takahashi, Baku

    2016-07-01

    We report a rare case of ventricular septal perforation (VSP) after inferior myocardial infarction. Surgical repair of VSP after inferior infarction is technically difficult because of its anatomical location. An 81-year-old female presented with dyspnea on the 8th day after percutaneous coronary intervention for acute inferior myocardial infarction. Echocardiography revealed a ventricular septal perforation. Urgent operation was performed. There was a VSP around the base of the ventricular septum. The myocardial infarction extended to the adjacent muscle of the mitral valve annulus. Two bovine pericardial patches were used in the left ventricular cavity. The patches were sewn on the mitral valve annulus which was the only normal tissue in the region. The 1st patch was used to close the VSP directly, and the 2nd patch was sutured to the normal myocardium to exclude the infracted area. No residual shunt flow was observed. The postoperative course was uneventful. PMID:27365060

  1. Myocardial infarction--fusion or confusion?

    PubMed

    Ardhanari, Sivakumar; Shah, Ashok J; Thakur, Ranjan K

    2009-09-01

    A patient with a dualchamber pacemaker with dynamic atrioventricular delay (AVD) experienced acute substernal chest pain. The rhythm strip in the ambulance showed intermittent ST elevation in the inferior leads. An emergent cardiac catheterization revealed nonobstructive coronary artery disease. Rate-responsive dual-chamber pacing with dynamic AVD was responsible for varying devvgrees of ventricular fusion due to competition with the patient's normal conduction. Intermittent ST elevation, evident only during ventricular fusion should have suggested secondary ventricular repolarization and not myocardial injury, but concomitant chest pain and inconspicuous bipolar pacing artifacts added to the confusion. Ventricular pacing may not only mask acute ST-T changes due to myocardial injury, but can also mimic acute myocardial infarction. PMID:19726827

  2. Action of acetylstrophanthidin on experimental myocardial infarction.

    NASA Technical Reports Server (NTRS)

    Nola, G. T.; Pope, S. E.; Harrison, D. C.

    1972-01-01

    An experimental animal model with acute myocardial infarction of a size insufficient to produce profound heart failure or shock was used to study the effects of acute infarction on digitalis tolerance and the hemodynamic changes produced by moderate and large doses of acetylstrophanthidin. With acute myocardial infarction, digitalis toxic arrhythmias could be precipitated with significantly lower doses of digitalis than in animals without myocardial infarction. There was no precise correlation between the size of infarction and the toxic dose of glycoside. Coronary artery ligation produced a stable but relatively depressed circulatory state, as evidenced by lowered cardiac output and stroke volume and elevated systemic vascular resistance and left atrial mean pressure. When digitalis was infused, the following significant changes were observed at nontoxic doses: (1) elevation of aortic and left ventricular pressures; (2) further decline in cardiac output; and (3) decreased left atrial mean pressure.

  3. [Recurrent myocardial infarctions: specific changes in biomarkers and in myocardial remodeling (case-control study)].

    PubMed

    Volkova, E G; Malykhina, O P; Levashov, S Iu

    2007-01-01

    Basing on a case-control study (n=81) with the use of standard methods of myocardial infarction verification, examination of hemogram, troponin T, C-reactive protein, echocardiography data it was established that markers of myocardial infarction (troponin T level) and inflammation (C reactive protein level, lymphopenia) during recurrent infarctions are less pronounced than during first infarctions. Remodeling in recurrent infarctions had the following specific characteristics: increase of left ventricular end diastolic dimension, myocardial mass index, diastolic dysfunction and stroke volume with unchanged ejection fraction. PMID:18260891

  4. Myocardial disarray in Noonan syndrome

    PubMed Central

    Burch, Michael; Mann, Jessica M; Sharland, Michael; Shinebourne, Elliot A; Patton, Michael A; McKenna, William J

    1992-01-01

    Objective—To characterise the histopathology of the left ventricular hypertrophy commonly associated with Noonan syndrome by assessing the extent of myocyte disarray and therefore to define one aspect of the relation between this disease and idiopathic hypertrophic cardiomyopathy. Design—Blinded histological analysis. Setting—Hospital medical school. Patients—Six hearts of children with the Noonan phenotype and isolated ventricular hypertrophy were compared with age and sex matched controls. Methods—Histological analysis was performed with an image analyser under light microscopy. Representative sections from the entire left ventricular free wall were examined. Results were expressed as the percentage of fields showing disarray related to the number of fields evaluated: 100 fields were examined for each patient. Results—In the patients with Noonan syndrome myocardial disarray was present in the ventricular septum in 24 (5·7)% (mean (SD)) of fields and in the free wall in 22·2 (6·8)%. In the controls disarray was present in the septum in 3·8 (2·3)% of fields and in the free wall in 2·4 (2·8)%. In both regions the extent of disarray was significantly greater in patients with Noonan syndrome (p < 0·0005; 95% confidence interval 14 to 26·3 for the septum: p < 0·005, 95% confidence interval 11·4 to 28·2 for the free wall). Conclusions—The ventricular hypertrophy associated with Noonan syndrome is histologically similar to hypertrophic cardiomyopathy but whether the two diseases are the expression of the same genetic defect remains to be determined. PMID:1467053

  5. Myocardial Infarction: Symptoms and Treatments.

    PubMed

    Lu, Lei; Liu, Min; Sun, RongRong; Zheng, Yi; Zhang, Peiying

    2015-07-01

    Myocardial infarction (MI) is a term used for an event of heart attack which is due to formation of plaques in the interior walls of the arteries resulting in reduced blood flow to the heart and injuring heart muscles because of lack of oxygen supply. The symptoms of MI include chest pain, which travels from left arm to neck, shortness of breath, sweating, nausea, vomiting, abnormal heart beating, anxiety, fatigue, weakness, stress, depression, and other factors. The immediate treatment of MI include, taking aspirin, which prevents blood from clotting, and nitro-glycerin to treat chest pain and oxygen. The heart attack can be prevented by taking an earlier action to lower those risks by controlling diet, fat, cholesterol, salt, smoking, nicotine, alcohol, drugs, monitoring of blood pressure every week, doing exercise every day, and loosing body weight. The treatment of MI includes, aspirin tablets, and to dissolve arterial blockage injection of thrombolytic or clot dissolving drugs such as tissue plasminogen activator, streptokinase or urokinase in blood within 3 h of the onset of a heart attack. The painkillers such as morphine or meperidine can be administered to relieve pain. Nitroglycerin and antihypertensive drugs such as beta-blockers, ACE inhibitors or calcium channel blockers may also be used to lower blood pressure and to improve the oxygen demand of heart. The ECG, coronary angiography and X-ray of heart and blood vessels can be performed to observe the narrowing of coronary arteries. In this article the causes, symptoms and treatments of MI are described. PMID:25638347

  6. Microparticles as biomarkers of vascular dysfunction in metabolic syndrome and its individual components.

    PubMed

    Agouni, Abdelali; Andriantsitohaina, Ramaroson; Martinez, Maria C

    2014-05-01

    Heterogeneous in size (0.1-1 µm), microparticles are small membrane vesicles released from activated and/or apoptotic cells. Although described since 1967 by Wolf, it is only since the 1990's that microparticles have been considered as biomarkers as well as potential mediators of biological messages between cells by acting as paracrine and endocrine vectors. Detection of microparticles has been performed in biological fluids (blood, synovial fluid, saliva for instance) and some solid tissues but also from the culture medium. Levels of circulating microparticles are enhanced in a large number of pathological states including cardiovascular and metabolic disorders associated with insulin resistance and this has been linked to deleterious effects on cells from the vascular wall, mainly, endothelial cells. This review highlights the increasing impact of microparticles in major cardiovascular pathological situations associated with metabolic derangements. PMID:24846237

  7. Asymptomatic myocardial ischemia following cold provocation

    SciTech Connect

    Shea, M.J.; Deanfield, J.E.; deLandsheere, C.M.; Wilson, R.A.; Kensett, M.; Selwyn, A.P.

    1987-09-01

    Cold is thought to provoke angina in patients with coronary disease either by an increase in myocardial demand or an increase in coronary vascular resistance. We investigated and compared the effects of cold pressor stimulation and symptom-limited supine bicycle exercise on regional myocardial perfusion in 35 patients with stable angina and coronary disease and in 10 normal subjects. Regional myocardial perfusion was assessed with positron emission tomography and rubidium-82. Following cold pressor stimulation 24 of 35 patients demonstrated significant abnormalities of regional myocardial perfusion with reduced cation uptake in affected regions of myocardium: 52 +/- 9 to 43 +/- 9 (p less than 0.001 vs normal subjects). Among these 24 patients only nine developed ST depression and only seven had angina. In contrast, 29 of 35 patients underwent supine exercise, and abnormal regional myocardial perfusion occurred in all 29, with a reduction in cation intake from 48 +/- 10 to 43 +/- 14 (p less than 0.001 vs normal subjects). Angina was present in 27 of 29 and ST depression in 25 of 29. Although the absolute decrease in cation uptake was somewhat greater following cold as opposed to exercise, the peak heart rate after cold was significantly lower than that after exercise (82 +/- 12 vs 108 +/- 16 bpm, p less than 0.05). Peak systolic blood pressures after cold and exercise were similar (159 +/- 24 vs 158 +/- 28). Thus, cold produces much more frequent asymptomatic disturbances of regional myocardial perfusion in patients with stable angina and coronary disease than is suggested by pain or ECG changes.

  8. Recurrent myocardial infarction with patent coronary arteries.

    PubMed Central

    Haywood, L. J.; Khan, A. H.; Bornheimer, J.; Finck, E.; Tatter, D.

    1997-01-01

    Two separate episodes of severe chest pain occurred several years apart in a 25-year-old male patient with typical clinical findings of acute myocardial infarction with each episode. Cardiac catheterization following the second infarction confirmed the presence of myocardial dysfunction with apical akinesis and dyskinesis. Both coronary arteries were radiologically patent; however, there was evidence of probable recanalization of the right coronary artery. Several months later, the patient developed flank pain, hematuria, progressive renal failure, and cardiac decompensation, and died with intractable arrhythmias. At autopsy, a large apical mitral thrombosis was found and was the presumptive source of multiple systemic emboli. Images Figure 3 Figure 4 PMID:9195802

  9. Molecular and cellular mechanisms of myocardial stunning.

    PubMed

    Bolli, R; Marbán, E

    1999-04-01

    The past two decades have witnessed an explosive growth of knowledge regarding postischemic myocardial dysfunction or myocardial "stunning." The purpose of this review is to summarize current information regarding the pathophysiology and pathogenesis of this phenomenon. Myocardial stunning should not be regarded as a single entity but rather as a "syndrome" that has been observed in a wide variety of experimental settings, which include the following: 1) stunning after a single, completely reversible episode of regional ischemia in vivo; 2) stunning after multiple, completely reversible episodes of regional ischemia in vivo; 3) stunning after a partly reversible episode of regional ischemia in vivo (subendocardial infarction); 4) stunning after global ischemia in vitro; 5) stunning after global ischemia in vivo; and 6) stunning after exercise-induced ischemia (high-flow ischemia). Whether these settings share a common mechanism is unknown. Although the pathogenesis of myocardial stunning has not been definitively established, the two major hypotheses are that it is caused by the generation of oxygen-derived free radicals (oxyradical hypothesis) and by a transient calcium overload (calcium hypothesis) on reperfusion. The final lesion responsible for the contractile depression appears to be a decreased responsiveness of contractile filaments to calcium. Recent evidence suggests that calcium overload may activate calpains, resulting in selective proteolysis of myofibrils; the time required for resynthesis of damaged proteins would explain in part the delayed recovery of function in stunned myocardium. The oxyradical and calcium hypotheses are not mutually exclusive and are likely to represent different facets of the same pathophysiological cascade. For example, increased free radical formation could cause cellular calcium overload, which would damage the contractile apparatus of the myocytes. Free radical generation could also directly alter contractile filaments in a

  10. Hemodialysis-Induced Myocardial Stunning: A Review.

    PubMed

    Brown, Maxine; Burrows, LaVonne; Pruett, Timothy; Burrows, Thaddeus

    2015-01-01

    Patients on hemodialysis have a high incidence of cardiac morbidity and mortality, and echocardiographic evidence of hemodialysis-related myocardial stunning supports a potential link between the hemodialysis treatment itself and cardiac sequelae. Fluid removal rates exceeding 13 mL/kg/hour during hemodialysis have been implicated in the development of myocardial stunning. Providers caring for patients on chronic hemodialysis might improve patient outcomes by the use of modified treatment monitoring methods, alternative dialysis delivery methods, and enhanced patient education regarding risks of excessive interdialytic weight gains. PMID:26290919

  11. Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis

    PubMed Central

    Maya, Lisandro; Villarreal, Francisco J.

    2009-01-01

    In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies is termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, it is imperative the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stands as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications. PMID:19595694

  12. Acute Myocardial Histopathology in Normal and Arteriosclerotic Rats During Isoproterenol-induced Infarction

    PubMed Central

    Wexler, B. C.; Judd, J. T.

    1970-01-01

    Arteriosclerotic and non-arteriosclerotic, male Sprague-Dawley rats were given 2 s.c. injections of isoproterenol known to produce extensive myocardial infarction. The appearance of positive fuchsinophilia was used as an index of focal myocardial acidosis and of anaerobic metabolism. After one injection of isoproterenol, positive fuchsinophilia appeared within 30 min., reached a zenith at 4 hr and then promptly disappeared. Following the second injection of isoproterenol, fuchsinophilia reappeared briefly but was not as intense. The arteriosclerotic animals showed markedly less evidence of heart failure outwardly and less evidence of fuchsinophilia, histopathologically. Apparently, the first episode of cardiac stimulation caused only temporary cardiac ischaemia, positive fuchsinophilia and anaerobic cardiac metabolism. After the second injection, however, irreversible cardiac damage occurred and despite an abortive attempt towards anaerobic metabolic readjustment overt cardiac necrosis became dominant. ImagesFigs. 9-10Figs. 11-12Figs. 1-2Figs. 13-14Figs. 7-8Figs. 5-6Figs. 3-4 PMID:4099593

  13. Abnormal Myocardial Blood Flow Reserve Observed in Cardiac Amyloidosis

    PubMed Central

    Nel, Karen; Senior, Roxy; Greaves, Kim

    2016-01-01

    We performed real-time myocardial contrast echocardiography on a patient with cardiac amyloidosis and previous normal coronary angiography presenting with atypical chest pain to assess myocardial blood flow reserve (MBFR). Myocardial contrast echocardiography was performed and flash microbubble destruction and replenishment analysis was used to calculate myocardial blood flow. Dipyridamole was used to achieve hyperemia. MBFR was derived from the ratio of peak myocardial blood flow at hyperemia and rest. The results show a marked reduction in MBFR in our patient. Previous reports of luminal obstruction of intramyocardial rather than epicardial vessels by amyloid deposition may be causing microvascular dysfunction. PMID:27081447

  14. Relationship between pancreatic hormones and glucose metabolism: A cross-sectional study in patients after acute pancreatitis.

    PubMed

    Pendharkar, Sayali A; Asrani, Varsha M; Xiao, Amy Y; Yoon, Harry D; Murphy, Rinki; Windsor, John A; Petrov, Maxim S

    2016-07-01

    Abnormal glucose metabolism is present in almost 40% of patients after acute pancreatitis, but its pathophysiology has been poorly investigated. Pancreatic hormone derangements have been sparingly studied to date, and their relationship with abnormal glucose metabolism is largely unknown. The aim was to investigate the associations between pancreatic hormones and glucose metabolism after acute pancreatitis, including the effect of potential confounders. This was a cross-sectional study of 83 adult patients after acute pancreatitis. Fasting venous blood was collected from all patients and used for analysis of insulin, glucagon, pancreatic polypeptide, amylin, somatostatin, C-peptide, glucose, and hemoglobin A1c. Statistical analyses were conducted using the modified Poisson regression, multivariable linear regression, and Spearman's correlation. Age, sex, body mass index, recurrence of acute pancreatitis, duration from first attack, severity, and etiology were adjusted for. Increased insulin was significantly associated with abnormal glucose metabolism after acute pancreatitis, in both unadjusted (P = 0.038) and adjusted (P = 0.001) analyses. Patients with abnormal glucose metabolism also had significantly decreased pancreatic polypeptide (P = 0.001) and increased amylin (P = 0.047) in adjusted analyses. Somatostatin, C-peptide, and glucagon were not changed significantly in both unadjusted and adjusted analyses. Increased insulin resistance and reduced insulin clearance may be important components of hyperinsulinemic compensation in patients after acute pancreatitis. Increased amylin and reduced pancreatic polypeptide fasting levels characterize impaired glucose homeostasis. Clinical studies investigating islet-cell hormonal responses to mixed-nutrient meal testing and euglycemic-hyperinsulinemic clamps are now warranted for further insights into the role of pancreatic hormones in glucose metabolism derangements secondary to pancreatic diseases. PMID:27173509

  15. Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia

    SciTech Connect

    Zimmermann, R.; Tillmanns, H.; Knapp, W.H.; Helus, F.; Georgi, P.; Rauch, B.; Neumann, F.J.; Girgensohn, S.; Maier-Borst, W.; Kuebler, W.

    1988-03-01

    The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium.

  16. Relationship between post-cardiac arrest myocardial oxidative stress and myocardial dysfunction in the rat

    PubMed Central

    2014-01-01

    Background Reperfusion after resuscitation from cardiac arrest (CA) is an event that increases reactive oxygen species production leading to oxidative stress. More specifically, myocardial oxidative stress may play a role in the severity of post-CA myocardial dysfunction. This study investigated the relationship between myocardial oxidative stress and post-CA myocardial injury and dysfunction in a rat model of CA and cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced in 26 rats and was untreated for 6 min. CPR, including mechanical chest compression, ventilation, and epinephrine, was then initiated and continued for additional 6 min prior to defibrillations. Resuscitated animals were sacrificed at two h (n = 9), 4 h (n = 6) and 72 h (n = 8) following resuscitation, and plasma collected for assessment of: high sensitivity cardiac troponin T (hs-cTnT), as marker of myocardial injury; isoprostanes (IsoP), as marker of lipid peroxidation; and 8-hydroxyguanosine (8-OHG), as marker of DNA oxidative damage. Hearts were also harvested for measurement of tissue IsoP and 8-OHG. Myocardial function was assessed by echocardiography at the corresponding time points. Additional 8 rats were not subjected to CA and served as baseline controls. Results Compared to baseline, left ventricular ejection fraction (LVEF) was reduced at 2 and 4 h following resuscitation (p < 0.01), while it was similar at 72 h. Inversely, plasma hs-cTnT increased, compared to baseline, at 2 and 4 h post-CA (p < 0.01), and then recovered at 72 h. Similarly, plasma and myocardial tissue IsoP and 8-OHG levels increased at 2 and 4 h post-resuscitation (p < 0.01 vs. baseline), while returned to baseline 72 h later. Myocardial IsoP were directly related to hs-cTnT levels (r = 0.760, p < 0.01) and inversely related to LVEF (r = -0.770, p < 0.01). Myocardial 8-OHG were also directly related to hs-cTnT levels (r = 0.409, p < 0.05) and

  17. Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin–oxygen affinity

    PubMed Central

    Weiss, Robert G.; Mejia, Marco A.; Kass, David A.; DiPaula, Anthony F.; Becker, Lewis C.; Gerstenblith, Gary; Chacko, V.P.

    1999-01-01

    Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin–oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin–oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment–length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin–oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia. J. Clin. Invest. 103:739–746 (1999) PMID:10074492

  18. Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin-oxygen affinity.

    PubMed

    Weiss, R G; Mejia, M A; Kass, D A; DiPaula, A F; Becker, L C; Gerstenblith, G; Chacko, V P

    1999-03-01

    Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment-length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin-oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia. PMID:10074492

  19. 131Cs myocardial scintigraphy. Application to assessment of anterior myocardial infarction.

    PubMed Central

    Burguet, W; Merchie, G; Kulbertus, H

    1975-01-01

    Earlier studies have indicated that caesium-131 is a good myocardial scanning agent for the demonstration of anterior infarcts. One hundred and ten patients with documented anterior myocardial infarction were studied by 131Cs myocardial scintigraphy. An anterior area of decreased uptake of caesium was noted in all but 3 subjects whose necrotic zone was likely to be of small dimensions. In 20 cases, the scintigram showed a definite, sometimes very large, cold area whereas the electrocardiogram failed to display any diagnostic feature of myocardial necrosis. In most of the latter instances, the electrocardiographic diagnosis was obscured by the presence of intraventricular conduction disturbances. In order to visualize the intracardiac cavities, the 131Cs investigation was usually completed by a 113mIn scintigram, which allowed recognition of a parietal aneurysm in 12 of the 18 patients with extensive anterior lesions. In each case, an index of necrosis was computed from planimetric measurements of the infarcted area as compared to the total left ventricular surfact in both the anteroposterior and left anterior oblique projections. This index was shown to correlate with the incidence of major complications developing after the acute episode of coronary occlusion. The sensitivity, specificity, and accuracy of the method are briefly discussed. It is felt that myocardial scintigraphy represents a sound approach to the semiquantitative assessment of anterior myocardial infarction; the clinical usefulness of the technique seems sufficiently demonstrated to prompt further research in this field. Images PMID:1191417

  20. Metabolic microspheres

    NASA Astrophysics Data System (ADS)

    Fox, Sidney W.

    1980-08-01

    A systematic review of catalytic activities in thermal proteinoids and microspheres aggregated therefrom yields some new inferences on the origins and evolution of metabolism. Experiments suggest that, instead of being inert, protocells were already biochemically and cytophysically competent. The emergence and refinement of metabolism ab initio is thus partly traced conceptually. When the principle of molecular self-instruction, as of amino acids in peptide synthesis, is taken into account as a concomitant of natural selection, an expanded theory of organismic evolution, including saltations, emerges.

  1. Metabolic analyzer

    NASA Technical Reports Server (NTRS)

    Lem, J. D.

    1977-01-01

    The metabolic analyzer was designed to support experiment M171. It operates on the so-called open circuit method to measure a subject's metabolic activity in terms of oxygen consumed, carbon dioxide produced, minute volume, respiratory exchange ratio, and tidal volume or vital capacity. The system operates in either of two modes. (1) In Mode I, inhaled respiratory volumes are actually measured by a piston spirometer. (2) In Mode II, inhaled volumes are calculated from the exhaled volume and the measured inhaled and exhaled nitrogen concentrations. This second mode was the prime mode for Skylab. Following is a brief description of the various subsystems and their operation.

  2. Myocardial ischemic protection in natural mammalian hibernation

    PubMed Central

    Yan, Lin; Kudej, Raymond K.; Vatner, Dorothy E.

    2015-01-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  3. Thrombolytic therapy in acute myocardial infarction.

    PubMed

    Woo, K S; White, H D

    1994-07-01

    Thrombolytic therapy has revolutionized the treatment of acute myocardial infarction by reducing mortality and preserving left ventricular function. It is relatively safe and cost-effective. However, it is currently underused in most countries. Patients in whom thrombolysis is indicated include those with ST elevation on the electrocardiogram or bundle branch block pattern who present within 12 hours of myocardial infarction; the indications should be widened to include the elderly, patients who have undergone nontraumatic cardiopulmonary resuscitation, and women during menstruation. The risk-benefit ratio should be assessed for the individual patient. Prehospital thrombolytic treatment has been shown to be feasible with the support of well-trained staff and resuscitation equipment, and may be cost-effective in communities with time delays before hospitalization greater than 1 hour. The most important strategy is to shorten the "door to needle" time in hospital. The importance of full infarct-related artery flow (Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow) for preservation of ventricular function and survival has been documented in the second Thrombolysis Trial of Eminase in Acute Myocardial Infarction (TEAM 2) and the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) studies. Aspirin and heparin are beneficial adjunctive regimens to thrombolytic therapy but optimal epicardial reperfusion is achieved in only about half of patients. Improved thrombolytic, adjunctive antiplatelet, and antithrombotic regimens are required to achieve early full reperfusion, which is crucial to improve survival and quality of life. PMID:7919592

  4. Myocardial protection: what the anesthesiologist does.

    PubMed

    Merin, R G

    1990-09-01

    The role of the anesthesiologist in myocardial protection is to optimize myocardial oxygen balance during the perioperative period. Nonpharmacological steps that can be taken to achieve this revolve around maintaining a satisfactory hemoglobin concentration and oxyhemoglobin saturation through maximizing ventilation. In addition, alkalosis and hypothermia should be prevented since they cause a left shift of the oxyhemoglobin dissociation curve, thus interfering with tissue oxygen delivery. Hypocarbia increases coronary vascular resistance. Blood volume must be adequate with an optimal hemoglobin concentration. Pharmacological measures should also be used, and it is important to continue through the perioperative period any previously administered cardioactive drugs. Furthermore, in the prebypass period, tachycardia may not be controlled by anesthetics; unless the tachycardia is paroxysmal, beta blockers are the drugs of choice. Depending on the cause, diastolic hypotension also needs to be treated either with volume, vasoconstrictors, or inotropes. Likewise, major hypertension can produce increased demand and, again depending on the cause, either anesthetics, vasodilators, beta blockers, or calcium blockers may be useful. Finally, myocardial ischemia without obvious cause probably should be treated with nitroglycerin or calcium blockers. During surgery, the effect of the anesthetic drugs on myocardial oxygen balance is important. PMID:2133851

  5. Myocardial infarction complicated by ventricular septal rupture.

    PubMed

    Sahjian, Michael; Ventriglia, Rich; Bolton, Lauri

    2012-01-01

    Transporting patients with an ST segment elevation myocardial infarction (STEMI) is a fairly common practice for most critical care transport teams. When a STEMI is complicated by ventricular septal rupture, the care can become more challenging, especially if the rupture is not yet diagnosed. This article describes such a transport and reviews the pathophysiology of the process along with treatment options. PMID:22225564

  6. Decreased selenium levels in acute myocardial infarction

    SciTech Connect

    Kok, F.J.; Hofman, A.; Witteman, J.C.M.; de Bruijn, A.M.; Kruyssen, D.H.C.M.; de Bruin, M.; Valkenburg, H.A. )

    1989-02-24

    To study the association between selenium status and the risk of myocardial infarction, the authors compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls. Because toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.

  7. Rehabilitation of Patients Following Myocardial Infarction.

    ERIC Educational Resources Information Center

    Blumenthal, James A.; Emery, Charles F.

    1988-01-01

    Examines three behavioral strategies in cardiac rehabilitation (CR) for formal treatment for physical and psychosocial sequelae of myocardial infarction (MI): exercise therapy, Type A modification, and nonspecific psychological therapies. Concludes CR improves the quality of life among post-MI patients, but does not prolong life or significantly…

  8. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  9. Thrombus aspiration in acute myocardial infarction.

    PubMed

    Mahmoud, Karim D; Zijlstra, Felix

    2016-07-01

    The success of primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is often hampered by incomplete microvascular myocardial reperfusion owing to distal embolization of thrombus resulting in microvascular obstruction. To address this problem, thrombus aspiration devices have been developed that can be used to evacuate coronary thrombus either manually or mechanically. Thrombus aspiration has the potential to reduce the local thrombus load, minimize the need for balloon predilatation, facilitate direct stenting, prevent distal embolization, and ultimately improve myocardial reperfusion. Furthermore, thrombus aspiration has enabled us to study coronary thrombus in vivo, and has facilitated recognition of distinct mechanisms of coronary thrombosis. Clinical trials focusing on manual thrombus aspiration in primary PCI have generally shown improved myocardial reperfusion. However, in two large trials powered for clinical end points, no reduction in 1-year mortality or other adverse clinical events was observed with the use of this strategy. Moreover, one of these trials showed a marginally increased risk of stroke. Consequently, current guidelines do not recommend routine use of thrombus aspiration. Future studies should focus on the identification of subgroups of patients with STEMI who might derive benefit from manual thrombus aspiration, and establish the effect of operator performance on the efficacy and safety of the procedure. PMID:26961064

  10. Perceived Neighborhood Social Cohesion and Myocardial Infarction

    PubMed Central

    Kim, Eric S.; Hawes, Armani M.; Smith, Jacqui

    2015-01-01

    Background The main strategy for alleviating heart disease has been to target individuals and encourage them to change their health behaviors. Though important, emphasis on individuals has diverted focus and responsibility away from neighborhood characteristics, which also strongly influence people’s behaviors. Although a growing body of research has repeatedly demonstrated strong associations between neighborhood characteristics and cardiovascular health, it has typically focused on negative neighborhood characteristics. Only a few studies have examined the potential health enhancing effects of positive neighborhood characteristics, such as perceived neighborhood social cohesion. Methods Using multiple logistic regression models, we tested whether higher perceived neighborhood social cohesion was associated with lower incidence of myocardial infarction. Prospective data from the Health and Retirement Study—a nationally representative panel study of American adults over the age of 50—were used to analyze 5,276 participants with no history of heart disease. Respondents were tracked for four years and analyses adjusted for relevant sociodemographic, behavioral, biological, and psychosocial factors. Results In a model that adjusted for age, gender, race, marital status, education, and total wealth, each standard deviation increase in perceived neighborhood social cohesion was associated with a 22% reduced odds of myocardial infarction (OR = 0.78, 95% CI, 0.63–0.94. The association between perceived neighborhood social cohesion and myocardial infarction remained even after adjusting for behavioral, biological, and psychosocial covariates. Conclusions Higher perceived neighborhood social cohesion may have a protective effect against myocardial infarction. PMID:25135074

  11. Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development.

    PubMed

    Moraes-Silva, Ivana Cinthya; Mostarda, Cristiano; Moreira, Edson Dias; Silva, Kleiton Augusto Santos; dos Santos, Fernando; de Angelis, Kátia; Farah, Vera de Moura Azevedo; Irigoyen, Maria Claudia

    2013-03-15

    High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg · dl(-1) · min(-1): F: 3.4 ± 0.2; C: 4.7 ± 0.2; CT: 5.0 ± 0.5 FT: 4.6 ± 0.4), mean BP (in mmHG: F: 117 ± 2; C: 100 ± 2; CT: 98 ± 2; FT: 105 ± 2), and Lee index (in g/mm: F = 0.31 ± 0.001; C = 0.29 ± 0.001; CT = 0.27 ± 0.002; FT = 0.28 ± 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an ≈ 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption. PMID:23329818

  12. [Prehospital thrombolytic therapy in acute myocardial infarction].

    PubMed

    Carlsson, J; Schuster, H P; Tebbe, U

    1997-10-01

    The extent of myocardial damage occurring during acute myocardial infarction is time dependent, and there is abundant evidence from most clinical trials that mortality reduction is greatest in patients treated early with thrombolytic agents, although beneficial effects have been shown with treatment initiated up to 12 h after onset of symptoms. All studies on prehospital thrombolysis have conclusively shown the practicability and safety of patient selection and administration of the thrombolytic agent. The accuracy of diagnosis in the prehospital setting was comparable to trials of in-hospital thrombolysis, e.g., in the Myocardial Infarction Triage and Intervention Project (MITI) 98% of the patients enrolled had subsequent evidence of acute myocardial infarction. With regard to time savings, all randomized studies showed positive results. The smallest time gain was observed in the MITI trial: prehospital-treated patients received thrombolytic therapy an average of 33 min earlier than those treated in hospital. In the European Myocardial Infarction Project (EMIP) the difference in time between prehospital and hospital treatment was a median of 55 min. However, none of these trials was able to show a significant short-term mortality difference between the two groups. Only a meta analysis of five randomized studies with a combined median time gain of about 60 min showed a significant 17% reduction in short-term mortality for patients who received thrombolytic therapy in the prehospital phase. In the Grampian Region Early Anistreplase Trial (GREAT), a study performed in a more rural area than other studies, the time gain by prehospital initiation of thrombolysis was a median of 130 min. GREAT was the only study to date reporting a significant mortality benefit for prehospital-treated patients after 3 months and 1 year. In conclusion, prehospital thrombolysis is feasible and safe. Patients with acute myocardial infarction can be correctly identified and treated with

  13. Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma.

    PubMed

    Steiner, Johann; Bernstein, Hans-Gert; Schiltz, Kolja; Müller, Ulf J; Westphal, Sabine; Drexhage, Hemmo A; Bogerts, Bernhard

    2014-01-01

    Impaired glucose metabolism and the development of metabolic syndrome contribute to a reduction in the average life expectancy of individuals with schizophrenia. It is unclear whether this association simply reflects an unhealthy lifestyle or whether weight gain and impaired glucose tolerance in patients with schizophrenia are directly attributable to the side effects of atypical antipsychotic medications or disease-inherent derangements. In addition, numerous previous studies have highlighted alterations in the immune system of patients with schizophrenia. Increased concentrations of interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-β) appear to be state markers, whereas IL-12, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and soluble IL-2 receptor (sIL-2R) appear to be trait markers of schizophrenia. Moreover, the mononuclear phagocyte system (MPS) and microglial activation are involved in the early course of the disease. This review illustrates a "chicken-egg dilemma", as it is currently unclear whether impaired cerebral glucose utilization leads to secondary disturbances in peripheral glucose metabolism, an increased risk of cardiovascular complications, and accompanying pro-inflammatory changes in patients with schizophrenia or whether immune mechanisms may be involved in the initial pathogenesis of schizophrenia, which leads to disturbances in glucose metabolism such as metabolic syndrome. Alternatively, shared underlying factors may be responsible for the co-occurrence of immune system and glucose metabolism disturbances in schizophrenia. PMID:23085507

  14. 1-alkenyl-2-acyl glycerol is an intermediate in myocardial plasmenylcholine biosynthesis

    SciTech Connect

    Ford, D.; Gross, R.

    1987-05-01

    The present study was undertaken to identify the metabolic pathway(s) responsible for myocardial plasmenylcholine biosynthesis. Rabbit myocardium contained .46 +/- .09 nmol/g wet wight of 1-alkenyl-2-acyl glycerol (AAG) which predominantly consisted of 16:0 molecular species at the sn-1 position. Incubation of rabbit myocardial microsomes (RMM) with (/sup 14/C)CDP-choline (/sup 14/C-CDPC) resulted in the rapid incorporation of radiolabeled choline into the choline glycerophospholipid pool. RP-HPLC separation of molecular species demonstrated that nearly equal amounts of radiolabel were incorporated into plasmenylcholine and phosphatidylcholine subclasses despite the fact that RMM contained 21 times the mass of diacyl glycerol as compared to AAG. RMM incorporation of /sup 14/C-CDPC into choline glycerophospholipids was substantially greater than incorporation of (/sup 14/C) phosphorylcholine or (/sup 14/C) choline. RMM incorporation of /sup 14/C-CDPC into plasmalogen molecular species was stimulated two fold by 500 ..mu..M CMP. Taken together, these results demonstrate that rabbit myocardium contains substantial quantities of AAG and that endogenous AAG is an efficient precursor of myocardial plasmenylcholine.

  15. Effect of drugs used in different type of myocardial infarction (STEMI or (NTEMI) on mortality.

    PubMed

    Vincze, Z; Brugos, B; Lorincz, I; Paragh, G

    2014-06-01

    We examined 416 patients with acute myocardial infarction. 249 patients had STEMI and 167 NSTEMI. 227 were men and 189 women. 142 men had STEMI and 85 men had NSTEMI. 107 women were diagnosed with STEMI and 82 with NSTEMI. 22.5% of patient with STEMI and 20.2% of patients with NSTEMI died (p = 0.58). We compared the effect of anticoagulant treatment, clopidogrel, salicylate, nitrate, beta-blocker, angiotensin-converting enzyme inhibitor, statin and trimetazidine therapy on mortality in function of the type of myocardial infarction. There were no differences between mortality of patients with STEMI and NSTEMI with respect of use of heparine, salicylate, nitrate, beta-blocker, ACE inhibitor, statin and trimetazidine. While examining the effect of clopidogrel, we observed a significantly lower mortality rate in patients with NSTEMI compared to the STEMI group (p = 0.005). These differences are due to the known variability in clopidogrel absorption and metabolism, which could be influenced by the type of myocardial infarction. PMID:24974579

  16. Myocardial Tissue Doppler Velocity in Child Growth

    PubMed Central

    Choi, Sun-Ha; Kim, Nam Kyun; Jung, Jo Won; Choi, Jae Young

    2016-01-01

    Background In adults, tissue Doppler imaging (TDI) is a recommended component of routine echocardiography. However, TDI velocities are less accepted in pediatrics, due to their strong variability and age dependence in children. This study examines the distribution of myocardial tissue Doppler velocities in healthy children to assess the effect of age with cardiac growth on the various echocardiographic measurements. Methods Total 144 healthy children were enrolled in this study. They were recruited from the pediatric outpatient clinic for routine well-child visits. The statistical relationships between age and TDI values were analyzed. Also, the statistical relationships between body surface area (BSA) and TDI values, left ventricle end-diastolic dimension (LVEDD) and TDI values were analyzed. Also, we conducted multivariate analysis of cardiac growth parameters such as, age, BSA, LVEDD and TDI velocity data. Results All of the age, BSA, and LVEDD had positive correlations with deceleration time (DT), pressure half-time (PHT), peak early diastolic myocardial velocity, peak systolic myocardial velocity, and had negative correlations with peak late diastolic velocity (A) and the ratio of trans-mitral inflow velocity to early diastolic velocity of mitral annulus (E/E'). In the multivariate analysis, all of the age, BSA, and LVEDD had positive correlations with DT, PHT, and negative correlations with A and E/E'. Conclusion The cardiac growth parameters related alterations of E/E' may suggest that diastolic myocardial velocities are cardiac growth dependent, and diastolic function has positive correlation with cardiac growth in pediatric group. This cardiac growth related myocardial functional variation would be important for assessment of cardiac involvement either in healthy and sick child. PMID:27081443

  17. Metabolic Syndrome

    MedlinePlus

    ... If you already have metabolic syndrome, making these healthy lifestyle choices can help reduce your risk of heart disease and other health problems. If lifestyle changes alone can’t control your ... to help. Maintain a healthy weight Your doctor can measure your body mass ...

  18. Metabolic Syndrome

    MedlinePlus

    ... from Nemours for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot ... > Metabolic Syndrome Print A A A Text Size ...

  19. Metabolic Analysis

    NASA Astrophysics Data System (ADS)

    Tolstikov, Vladimir V.

    Analysis of the metabolome with coverage of all of the possibly detectable components in the sample, rather than analysis of each individual metabolite at a given time, can be accomplished by metabolic analysis. Targeted and/or nontargeted approaches are applied as needed for particular experiments. Monitoring hundreds or more metabolites at a given time requires high-throughput and high-end techniques that enable screening for relative changes in, rather than absolute concentrations of, compounds within a wide dynamic range. Most of the analytical techniques useful for these purposes use GC or HPLC/UPLC separation modules coupled to a fast and accurate mass spectrometer. GC separations require chemical modification (derivatization) before analysis, and work efficiently for the small molecules. HPLC separations are better suited for the analysis of labile and nonvolatile polar and nonpolar compounds in their native form. Direct infusion and NMR-based techniques are mostly used for fingerprinting and snap phenotyping, where applicable. Discovery and validation of metabolic biomarkers are exciting and promising opportunities offered by metabolic analysis applied to biological and biomedical experiments. We have demonstrated that GC-TOF-MS, HPLC/UPLC-RP-MS and HILIC-LC-MS techniques used for metabolic analysis offer sufficient metabolome mapping providing researchers with confident data for subsequent multivariate analysis and data mining.

  20. Assessment of Myocardial Triglyceride Oxidation with PET and 11C-Palmitate

    PubMed Central

    Kisrieva-Ware, Zulfia; Coggan, Andrew R.; Sharp, Terry L.; Dence, Carmen S.; Gropler, Robert J.; Herrero, Pilar

    2010-01-01

    Background The goal of this study was to test whether myocardial triglyceride (TG) turnover including oxidation of TG-derived fatty acids could be assessed with PET and 11C-palmitate. Methods and Results 26 dogs were studied fasted (FAST), during Intralipid infusion (IL), during a hyperinsulinemic-euglycemic clamp without (HIEG) or with Intralipid infusion (HIEG+IL). 11C-palmitate was injected, and 45 min were allowed for labeling of myocardial TG pool. 3-D PET data were then acquired for 60 min, with first 15 min at baseline followed by 45 min during cardiac work stimulated with constant infusion of either phenylephrine (FAST, n=6; IL, n=6; HIEG+IL, n=6) or dobutamine (FAST, n=4; HIEG, n=4). Myocardial 11C washout during adrenergic stimulation (AS) was fitted to a mono-exponential function (Km(PET)). To determine the source of this 11C clearance, Km(PET) was compared to direct coronary sinus-arterial measurements of total 11C activity, 11C-palmitate, and 11CO2. Before AS, PET curves in all groups were flat indicating absence of net clearance of 11C activity from heart. In both FAST groups, AS resulted in negligible net 11C activity and 11CO2 production higher than net 11C-palmitate uptake. AS with phenylephrine resulted in net myocardial uptake of total 11C activity and 11C-palmitate in IL and HIEG+IL, and 11CO2 production lower than 11C-palmitate uptake. In contrast, AS with dobutamine in HIEG resulted in net clearance of all 11C metabolites (total 11C activity, 11C-palmitate and 11CO2) with 11CO2 contributing 66% to endogenous FA oxidation. AS resulted in significant Km(PET) in all groups, except HIEG+IL. However, positive correlation between Km(PET) and 11CO2 was observed only in HIEG (R2=0.83, P=0.09). Conclusions This is the first study to demonstrate that using PET and pre-labeling of intracardiac TG pool with 11C-palmitate, noninvasive assessment of myocardial TG use is feasible under metabolic conditions that favor endogenous TG use such as increased

  1. Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats

    PubMed Central

    Lam, Vy; Su, Jidong; Hsu, Anna; Gross, Garrett J.; Salzman, Nita H.

    2016-01-01

    Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host’s metabolism. Hierarchical clustering of dissimilarities separated the levels of 284 identified metabolites from treated vs. untreated rats; 193 were altered by the antibiotic treatments with a tendency towards decreased metabolite levels. Catabolism of the aromatic amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway comprising 33 affected metabolites. Both antibiotic treatments decreased the severity of an induced myocardial infarction in vivo by 27% and 29%, respectively. We then determined whether microbial metabolites of the amino acids phenylalanine, tryptophan and tyrosine were linked to decreased severity of myocardial infarction. Vancomycin-treated rats were administered amino acid metabolites prior to ischemia/reperfusion studies. Oral or intravenous pretreatment of rats with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 μM), Src kinase (PP1, 20 μM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059, 10 μM), p38 MAPK (SB203580, 10 μM), or KATP channels (glibenclamide, 3 μM) abolished cardioprotection by vancomycin, indicating microbial metabolites are interacting with cell surface receptors to transduce their signals through Src kinase, cell survival pathways and KATP channels. These inhibitors have no effect on myocardial infarct size in

  2. Type 2 myocardial infarction: the chimaera of cardiology?

    PubMed

    Collinson, Paul; Lindahl, Bertil

    2015-11-01

    The term type 2 myocardial infarction first appeared as part of the universal definition of myocardial infarction. It was introduced to cover a group of patients who had elevation of cardiac troponin but did not meet the traditional criteria for acute myocardial infarction although they were considered to have an underlying ischaemic aetiology for the myocardial damage observed. Since first inception, the term type 2 myocardial infarction has always been vague. Although attempts have been made to produce a systematic definition of what constitutes a type 2 myocardial infarction, it has been more often characterised by what it is not rather than what it is. Clinical studies that have used type 2 myocardial infarction as a diagnostic criterion have produced disparate incidence figures. The range of associated clinical conditions differs from study to study. Additionally, there are no agreed or evidence-based treatment strategies for type 2 myocardial infarction. The authors believe that the term type 2 myocardial infarction is confusing and not evidence-based. They consider that there is good reason to stop using this term and consider instead the concept of secondary myocardial injury that relates to the underlying pathophysiology of the primary clinical condition. PMID:26220812

  3. Oligophrenin1 protects mice against myocardial ischemia and reperfusion injury by modulating inflammation and myocardial apoptosis.

    PubMed

    Niermann, Christina; Gorressen, Simone; Klier, Meike; Gowert, Nina S; Billuart, Pierre; Kelm, Malte; Merx, Marc W; Elvers, Margitta

    2016-08-01

    The Rho family of small GTPases has been analyzed in cardiac physiology and pathophysiology including myocardial infarction (MI) in the last years. Contradictory results show either a protective or a declined effect of RhoA and the RhoA effector Rho-associated protein kinase (ROCK) in myocardial ischemia and reperfusion injury that is associated with cardiomyocyte survival and caspase-3 activation. Cardiac-specific deletion of Rac1 reduced ischemia reperfusion injury in diabetic hearts, whereas cardiomyocyte specific overexpression of active Rac1 predisposes the heart to increased myocardial injury with enhanced contractile dysfunction. GTPase-activating proteins (GAPs) control the activation of Rho proteins through stimulation of GTP hydrolysis. However, the impact of GAPs in myocardial ischemia and reperfusion injury remains elusive. Here we analyzed the role of oligophrenin1 (OPHN1), a RhoGAP with Bin/Amphiphysin/Rvs (BAR) domain known to regulate the activity of RhoA, Rac1 and Cdc42 in MI. The expression of Ophn1, RhoA and Rac1 is strongly upregulated 24h after myocardial ischemia. Loss of OPHN1 induced enhanced activity of Rho effector molecules leading to elevated cardiomyocyte apoptosis and increased migration of inflammatory cells into the infarct border zone of OPHN1 deficient mice. Consequently, echocardiography 24h after myocardial ischemia revealed declined left ventricle function in OPHN1 deficient mice. Our results indicate that OPHN1 mediated regulation of RhoA, Rac1 and Cdc42 is crucial for the preservation of cardiac function after myocardial injury. PMID:27117132

  4. Transient myocardial ischaemia after acute myocardial infarction does not induce ventricular arrhythmias.

    PubMed Central

    Currie, P; Saltissi, S

    1993-01-01

    OBJECTIVE--To see whether transient myocardial ischaemia on ambulatory monitoring after myocardial infarction is associated with ventricular arrhythmias. DESIGN--A prospective study. SETTING--The coronary care unit, general medical wards, and cardiorespiratory department of a major teaching hospital. PATIENTS--203 consecutive patients without specific exclusion criteria admitted with acute myocardial infarction. INTERVENTIONS--24 hour ambulatory electrocardiographic monitoring for ventricular arrhythmias and ST depression both early (mean 6.3 days after infarction, n = 201) and late (mean 38 days, n = 177). MAIN OUTCOME MEASURES--Episodes of myocardial ischaemia were identified during ambulatory monitoring by transient ST depression of > or = 1.0 mm lasting for > or = 30 s. Ventricular arrhythmias were single extrasystoles, couplets, or ventricular tachycardia. RESULTS--All ventricular arrhythmias were significantly more frequent in late than early monitoring. The arrhythmias included couplets (in 83/174 (48%) v 49/200 (25%) of patients, p = 0.0000028) and ventricular tachycardia (29/174 (17%) v 15/199 (8%), p = 0.0064). Patients with ST depression (29 early; 56 late), compared with those without ischaemia, did not experience a significant increase in single extrasystoles, couplets (31% v 23% early; 47% v 48% late), or ventricular tachycardia (3% v 8% early; 18% v 16% late). Even patients with frequent (> or = 3 episodes), and deep (> or = 1.5 mm) or prolonged (> or = 20 min) ST depression had no increase in arrhythmias. CONCLUSIONS--Ventricular arrhythmias after myocardial infarction are not associated with transient myocardial ischaemia during daily activities. This study does not support the belief that to abolish silent ischaemia would reduce the incidence of sudden death due to uncontrollable ventricular arrhythmias after myocardial infarction. PMID:8489860

  5. Myocardial ATP hydrolysis rates in vivo: a porcine model of pressure overload-induced hypertrophy

    PubMed Central

    Xiong, Qiang; Zhang, Pengyuan; Guo, Jing; Swingen, Cory; Jang, Albert

    2015-01-01

    Left ventricular (LV) hypertrophy (LVH) and congestive heart failure are accompanied by changes in myocardial ATP metabolism. However, the rate of ATP hydrolysis cannot be measured in the in vivo heart with the conventional techniques. Here, we used a double-saturation phosphorous-31 magnetic resonance spectroscopy-magnetization saturation transfer protocol to monitor ATP hydrolysis rate in swine hearts as the hearts became hypertrophic in response to aortic banding (AOB). Animals that underwent AOB (n = 22) were compared with animals that underwent sham surgery (n = 8). AOB induced severe LVH (cardiac MRI). LV function (ejection fraction and systolic thickening fraction) declined significantly, accompanied by deferent levels of pericardial effusion, and wall stress increased in aorta banded animals at week 1 after AOB, suggesting acute heart failure, which recovered by week 8 when concentric LVH restored LV wall stresses. Severe LV dysfunction was accompanied by corresponding declines in myocardial bioenergetics (phosphocreatine-to-ATP ratio) and in the rate of ATP production via creatine kinase at week 1. For the first time, the same linear relationships of the rate increase of the constants of the ATP hydrolysis rate (kATP→Pi) vs. the LV rate-pressure product increase during catecholamine stimulation were observed in vivo in both normal and LVH hearts. Collectively, these observations demonstrate that the double-saturation, phosphorous-31 magnetic resonance spectroscopy-magnetization saturation transfer protocol can accurately monitor myocardial ATP hydrolysis rate in the hearts of living animals. The severe reduction of LV chamber function during the acute phase of AOB is accompanied by the decrease of myocardial bioenergetic efficiency, which recovers as the compensated LVH restores the LV wall stresses. PMID:26024682

  6. DNA Content in Extracellular Vesicles Isolated from Porcine Coronary Venous Blood Directly after Myocardial Ischemic Preconditioning

    PubMed Central

    Rodsand, Pouria; Hellman, Urban; Waldenström, Anders; Lundholm, Marie; Ahrén, Dag; Biber, Björn; Ronquist, Gunnar; Haney, Michael

    2016-01-01

    Background Extracellular vesicles (EV) are nano-sized membranous structures released from most cells. They have the capacity to carry bioactive molecules and gene expression signals between cells, thus mediating intercellular communication. It is believed that EV confer protection after ischemic preconditioning (IPC). We hypothesize that myocardial ischemic preconditioning will lead to rapid alteration of EV DNA content in EV collected from coronary venous effluent. Materials and Methods In a porcine myocardial ischemic preconditioning model, EV were isolated from coronary venous blood before and after IPC by differential centrifugation steps culminating in preparative ultracentrifugation combined with density gradient ultracentrifugation. The EV preparation was validated, the DNA was extracted and further characterized by DNA sequencing followed by bioinformatics analysis. Results Porcine genomic DNA fragments representing each chromosome, including mitochondrial DNA sequences, were detected in EV isolated before and after IPC. There was no difference detected in the number of sequenced gene fragments (reads) or in the genomic coverage of the sequenced DNA fragments in EV isolated before and after IPC. Gene ontology analysis showed an enrichment of genes coding for ion channels, enzymes and proteins for basal metabolism and vesicle biogenesis and specific cardiac proteins. Conclusions This study demonstrates that porcine EV isolated from coronary venous blood plasma contain fragments of DNA from the entire genome, including the mitochondria. In this model we did not find specific qualitative or quantitative changes of the DNA content in EV collected immediately after an in vivo myocardial IPC provocation. This does not rule out the possibility that EV DNA content changes in response to myocardial IPC which could occur in a later time frame. PMID:27434143

  7. Can you boost your metabolism?

    MedlinePlus

    Resting metabolism rate (RMR); Total daily energy expenditure (TDEE); Non-exercise activity thermogenesis (NEAT); Weight loss - metabolism; Overweight - metabolism; Obesity - metabolism; Diet - metabolism

  8. [Interesting PYP, 201Tl, MIBG, AM and BMIPP myocardial SPECT images in a patient under successful reperfusion therapy].

    PubMed

    Tanaka, T; Aizawa, T; Katou, K; Ogasawara, K; Kirigaya, H; Okamoto, K; Hosoi, H; Oota, A

    1992-06-01

    Various types of radiopharmacons such as 201Tl, 99mTc-pyrophosphate(PYP), 123I-metaiodobenzyl-guanidine(MIBG), 111In-antimyosin Fab (AM) and 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) were applied to a patient under successful reperfusion therapy. In the patient, elevated serum enzyme activity region in the subacute phase. Ten months after the ischemic event, AM uptake was noted at the region which maintained contractility. Two years after the ischemic event, depressed BMIPP uptake and delayed washout were noted at the apical region and the basal anteroseptal region. From these findings, the following conclusions were reached. Depressed 201Tl uptake was noted in the salvaged jeopardized myocardium. The lesions noted in the MIBG images showed depressed myocardial norepenephrine activity. This suggested that depressed sympathetic nervous function caused by severe ischemia persisted long after both myocardial perfusion and myocardial contractility had been restored. From abnormal AM uptake in the contractile myocardium myocardial cell damage, which permitted AM uptake, was persistent ten months after the ischemic event. Depressed BMIPP uptake and delayed washout suggested that abnormal fatty acid metabolism caused by severe ischemia was persistent. Severe ischemia caused various types of pathological states in the myocardium and radioisotope image was useful for studying these states. PMID:1535723

  9. Hepatic Atypical Protein Kinase C: An Inherited Survival-Longevity Gene that Now Fuels Insulin-Resistant Syndromes of Obesity, the Metabolic Syndrome and Type 2 Diabetes Mellitus

    PubMed Central

    Farese, Robert V.; Lee, Mackenzie C.; Sajan, Mini P.

    2014-01-01

    This review focuses on how insulin signals to metabolic processes in health, why this signaling is frequently deranged in Western/Westernized societies, how these derangements lead to, or abet development of, insulin-resistant states of obesity, the metabolic syndrome and type 2 diabetes mellitus, and what our options are for restoring insulin signaling, and glucose/lipid homeostasis. A central theme in this review is that excessive hepatic activity of an archetypal protein kinase enzyme, “atypical” protein kinase C (aPKC), plays a critically important role in the development of impaired glucose metabolism, systemic insulin resistance, and excessive hepatic production of glucose, lipids and proinflammatory factors that underlie clinical problems of glucose intolerance, obesity, hepatosteatosis, hyperlipidemia, and, ultimately, type 2 diabetes. The review suggests that normally inherited genes, in particular, the aPKC isoforms, that were important for survival and longevity in times of food scarcity are now liabilities in times of over-nutrition. Fortunately, new knowledge of insulin signaling mechanisms and how an aberration of excessive hepatic aPKC activation is induced by over-nutrition puts us in a position to target this aberration by diet and/or by specific inhibitors of hepatic aPKC. PMID:26237474

  10. Childhood cancer and later development of the metabolic syndrome.

    PubMed

    Talvensaari, K; Knip, M

    1997-10-01

    The improving survival rate of patients with childhood cancer has led to a growing awareness of the long-term effects of malignant disease and its treatment. Various endocrine abnormalities have been reported as frequent long-term adverse effects of cancer treatment in childhood, and among these growth hormone (GH) deficiency is the most common one, especially after cranial irradiation. Besides promoting growth, GH has well-established metabolic effects. Patients with GH deficiency tend to be obese, and obesity per se is also associated with insulin resistance which plays a key role in a cluster of metabolic derangements including glucose intolerance, hypertension, lipid abnormalities and atherosclerotic cardiovascular disease. This condition is known as the metabolic syndrome. Our recent observations indicate that a combination of obesity, glucose intolerance, hyperinsulinaemia and an abnormal lipid profile can be observed in long-term survivors of childhood cancer. Every sixth patient had the triad of obesity, hyperinsulinaemia and low HDL cholesterol, whereas this combination was not seen in any of the controls. The survivors with such a high-risk profile for cardiovascular disease had markedly reduced spontaneous GH secretion, and also additional features of the metabolic syndrome, such as higher systolic blood pressure and higher plasma glucose and serum triglyceride levels. Accordingly, decreased GH secretion, or alternatively some other disturbance in the hypothalamic-pituitary axis, emerging as a consequence of cranial radiation, may expose long-term survivors of childhood cancer to premature evolution of the metabolic syndrome. This can have an important impact on the long-term prognosis in these patients, because the syndrome as such results in an increased risk of cardiovascular morbidity and mortality. PMID:9453278

  11. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*

    PubMed Central

    Carrer, Michele; Liu, Ning; Grueter, Chad E.; Williams, Andrew H.; Frisard, Madlyn I.; Hulver, Matthew W.; Bassel-Duby, Rhonda; Olson, Eric N.

    2012-01-01

    Obesity and metabolic syndrome are associated with mitochondrial dysfunction and deranged regulation of metabolic genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional coactivator that regulates metabolism and mitochondrial biogenesis through stimulation of nuclear hormone receptors and other transcription factors. We report that the PGC-1β gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which counterbalance the metabolic actions of PGC-1β. Mice genetically lacking miR-378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Among the many targets of these miRNAs, carnitine O-acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and MED13, a component of the Mediator complex that controls nuclear hormone receptor activity, are repressed by miR-378 and miR-378*, respectively, and are elevated in the livers of miR-378/378* KO mice. Consistent with these targets as contributors to the metabolic actions of miR-378 and miR-378*, previous studies have implicated carnitine O-acetyltransferase and MED13 in metabolic syndrome and obesity. Our findings identify miR-378 and miR-378* as integral components of a regulatory circuit that functions under conditions of metabolic stress to control systemic energy homeostasis and the overall oxidative capacity of insulin target tissues. Thus, these miRNAs provide potential targets for pharmacologic intervention in obesity and metabolic syndrome. PMID:22949648

  12. MRS: a noninvasive window into cardiac metabolism.

    PubMed

    van Ewijk, Petronella A; Schrauwen-Hinderling, Vera B; Bekkers, Sebastiaan C A M; Glatz, Jan F C; Wildberger, Joachim E; Kooi, M Eline

    2015-07-01

    A well-functioning heart requires a constant supply of a balanced mixture of nutrients to be used for the production of adequate amounts of adenosine triphosphate, which is the main energy source for most cellular functions. Defects in cardiac energy metabolism are linked to several myocardial disorders. MRS can be used to study in vivo changes in cardiac metabolism noninvasively. MR techniques allow repeated measurements, so that disease progression and the response to treatment or to a lifestyle intervention can be monitored. It has also been shown that MRS can predict clinical heart failure and death. This article focuses on in vivo MRS to assess cardiac metabolism in humans and experimental animals, as experimental animals are often used to investigate the mechanisms underlying the development of metabolic diseases. Various MR techniques, such as cardiac (31) P-MRS, (1) H-MRS, hyperpolarized (13) C-MRS and Dixon MRI, are described. A short overview of current and emerging applications is given. Cardiac MRS is a promising technique for the investigation of the relationship between cardiac metabolism and cardiac disease. However, further optimization of scan time and signal-to-noise ratio is required before broad clinical application. In this respect, the ongoing development of advanced shimming algorithms, radiofrequency pulses, pulse sequences, (multichannel) detection coils, the use of hyperpolarized nuclei and scanning at higher magnetic field strengths offer future perspective for clinical applications of MRS. PMID:26010681

  13. Disorders of Lipid Metabolism

    MedlinePlus

    ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Fats (lipids) are ... carbohydrates and low in fats. Supplements of the amino acid carnitine may be helpful. The long-term outcome ...

  14. Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage.

    PubMed

    Guarini, Giacinta; Kiyooka, Takahiko; Ohanyan, Vahagn; Pung, Yuh Fen; Marzilli, Mario; Chen, Yeong Renn; Chen, Chwen Lih; Kang, Patrick T; Hardwick, James P; Kolz, Christopher L; Yin, Liya; Wilson, Glenn L; Shokolenko, Inna; Dobson, James G; Fenton, Richard; Chilian, William M

    2016-05-01

    Mitochondrial dysfunction in obesity and diabetes can be caused by excessive production of free radicals, which can damage mitochondrial DNA. Because mitochondrial DNA plays a key role in the production of ATP necessary for cardiac work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and arterial pressure, i.v. norepinephrine). In ZLN increased metabolism augmented coronary blood flow, but in ZOF metabolic hyperemia was attenuated. Mitochondrial respiration was impaired and ROS production was greater in ZOF than ZLN. These were associated with mitochondrial DNA (mtDNA) damage in ZOF. To determine if coronary metabolic dilation, the hyperemic response induced by heightened cardiac metabolism, is linked to mitochondrial function we introduced recombinant proteins (intravenously or intraperitoneally) in ZLN and ZOF to fragment or repair mtDNA, respectively. Repair of mtDNA damage restored mitochondrial function and metabolic dilation, and reduced ROS production in ZOF; whereas induction of mtDNA damage in ZLN reduced mitochondrial function, increased ROS production, and attenuated metabolic dilation. Adequate metabolic dilation was also associated with the extracellular release of ADP, ATP, and H2O2 by cardiac myocytes; whereas myocytes from rats with impaired dilation released only H2O2. In conclusion, our results suggest that mitochondrial function plays a seminal role in connecting myocardial blood flow to metabolism, and integrity of mtDNA is central to this process. PMID:27040114

  15. Regional left ventricular myocardial contractility and stress in a finite element model of posterobasal myocardial infarction.

    PubMed

    Wenk, Jonathan F; Sun, Kay; Zhang, Zhihong; Soleimani, Mehrdad; Ge, Liang; Saloner, David; Wallace, Arthur W; Ratcliffe, Mark B; Guccione, Julius M

    2011-04-01

    Recently, a noninvasive method for determining regional myocardial contractility, using an animal-specific finite element (FE) model-based optimization, was developed to study a sheep with anteroapical infarction (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001). Using the methodology developed in the previous study (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001), which incorporates tagged magnetic resonance images, three-dimensional myocardial strains, left ventricular (LV) volumes, and LV cardiac catheterization pressures, the regional myocardial contractility and stress distribution of a sheep with posterobasal infarction were investigated. Active material parameters in the noninfarcted border zone (BZ) myocardium adjacent to the infarct (T(max_B)), in the myocardium remote from the infarct (T(max_R)), and in the infarct (T(max_I)) were estimated by minimizing the errors between FE model-predicted and experimentally measured systolic strains and LV volumes using the previously developed optimization scheme. The optimized T(max_B) was found to be significantly depressed relative to T(max_R), while T(max_I) was found to be zero. The myofiber stress in the BZ was found to be elevated, relative to the remote region. This could cause further damage to the contracting myocytes, leading to heart failure. PMID:21428685

  16. Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

    PubMed Central

    Wu, Aiming; Zhai, Jianying; Zhang, Dongmei; Lou, Lixia; Zhu, Haiyan; Gao, Yonghong; Chai, Limin; Xing, Yanwei; Lv, Xiying; Zhu, Lingqun; Zhao, Mingjing; Wang, Shuoren

    2013-01-01

    Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI). Methods. Male Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group) with sample size (n) of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion). Wenxin Granule (1.35 g/kg/day), metoprolol (12 mg/kg/day), and distilled water (5 mL/kg/day for the control and model groups) were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E) dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Serum angiotensin II (Ang II) concentration was measured using the enzyme-linked immunosorbent assay (ELISA). Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI. Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI. PMID:23997803

  17. [Quantitative evaluation of acute myocardial infarction by In-111 antimyosin Fab myocardial imaging].

    PubMed

    Naruse, H; Morita, M; Itano, M; Yamamoto, J; Kawamoto, H; Fukutake, N; Ohyanagi, M; Iwasaki, T; Fukuchi, M

    1991-11-01

    For quantitative evaluation of acute myocardial infarction, In-111 antimyosin Fab myocardial imaging (InAM) was performed in 17 patients with myocardial infarction who underwent Tl-201 (TL) and Tc-99m pyrophosphate (PYP) myocardial imaging in acute phase. For calculating the infarct size, voxel counter method was used for analysis in PYP and InAM, and extent and severity score were used on bull's-eye polar map in TL. The most appropriate cut-off level ranged from 65 to 80% by the fundamental experiment using cardiac phantom. The cut-off level of 0.70 (InAM) and 0.65 (PYP) were used for clinical application of voxel counter analysis. The infarct size calculated by InAM and PYP was compared with wall motion abnormality index by echocardiography (WMAI), TL extent score, TL severity score, peak CK and sigma CK. Infarct size by InAM showed the following correlations with other indices. PYP: r = 0.26 (ns), TL extent score: r = 0.72 (p less than 0.01), TL severity score: r = 0.65 (p less than 0.05), WMAI: r = 0.69 (p less than 0.05). The infarct size by PYP did not show any correlations with these indices. Therefore, the infarct size by InAM showed better correlations with TL and WMAI than that of PYP. So InAM was considered superior to PYP for quantitative evaluation of acute myocardial infarction. PMID:1770642

  18. Cardiac NO signalling in the metabolic syndrome

    PubMed Central

    Pechánová, O; Varga, Z V; Cebová, M; Giricz, Z; Pacher, P; Ferdinandy, P

    2015-01-01

    It is well documented that metabolic syndrome (i.e. a group of risk factors, such as abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides and low cholesterol level in high-density lipoprotein), which raises the risk for heart disease and diabetes, is associated with increased reactive oxygen and nitrogen species (ROS/RNS) generation. ROS/RNS can modulate cardiac NO signalling and trigger various adaptive changes in NOS and antioxidant enzyme expressions/activities. While initially these changes may represent protective mechanisms in metabolic syndrome, later with more prolonged oxidative, nitrosative and nitrative stress, these are often exhausted, eventually favouring myocardial RNS generation and decreased NO bioavailability. The increased oxidative and nitrative stress also impairs the NO-soluble guanylate cyclase (sGC) signalling pathway, limiting the ability of NO to exert its fundamental signalling roles in the heart. Enhanced ROS/RNS generation in the presence of risk factors also facilitates activation of redox-dependent transcriptional factors such as NF-κB, promoting myocardial expression of various pro-inflammatory mediators, and eventually the development of cardiac dysfunction and remodelling. While the dysregulation of NO signalling may interfere with the therapeutic efficacy of conventional drugs used in the management of metabolic syndrome, the modulation of NO signalling may also be responsible for the therapeutic benefits of already proven or recently developed treatment approaches, such as ACE inhibitors, certain β-blockers, and sGC activators. Better understanding of the above-mentioned pathological processes may ultimately lead to more successful therapeutic approaches to overcome metabolic syndrome and its pathological consequences in cardiac NO signalling. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this

  19. Early Myocardial Repolarization Heterogeneity Is Detected by Magnetocardiography in Diabetic Patients with Cardiovascular Risk Factors

    PubMed Central

    Lin, Chih-Hung; Wu, Yen-Wen; Yang, Ying-Chieh; Chang, Tien-Jyun; Jiang, Yi-Der; Chuang, Lee-Ming

    2015-01-01

    Multi-channel magnetocardiography (MCG) is a sensitive technique to map spatial ventricular repolarization with high resolution and reproducibility. Spatial ventricular repolarization heterogeneity measured by MCG has been shown to accurately detect and localize myocardial ischemia. Here, we explored whether these measurements correlated with cardiovascular risk factors in patients with type 2 diabetes. Two hundreds and seventy-seven type 2 diabetic patients without known coronary artery disease (CAD) and arrhythmia were recruited consecutively from the outpatient clinic of National Taiwan University Hospital. The spatially distributed QTc contour maps were constructed with 64-channel MCG using the superconducting quantum interference device (SQUID) system. Indices of myocardial repolarization heterogeneity including the smoothness index of QTc (SI-QTc) and QTc dispersion were derived and analyzed for association with conventional cardiovascular risk factors. SI-QTc correlated strongly with the QTc dispersion (r = 0.70, p <0.0001). SI-QTc was significantly higher in patients with presence of metabolic syndrome in comparison to those without metabolic syndrome (8.56 vs. 7.96 ms, p = 0.02). In univariate correlation analyses, QTc dispersion was associated with smoking status (average 79.90, 83.83, 86.51, and 86.00 ms for never smokers, ex-smokers, current smokers reporting less than 10 cigarettes daily, and current smoker reporting more than 10 cigarettes daily, respectively, p = 0.03), body weight (r = 0.15, p = 0.01), and hemoglobin A1c (r = 0.12, p = 0.04). In stepwise multivariate regression analyses, QTc dispersion was associated with smoking (p = 0.02), body weight (p = 0.04), total cholesterol levels (p = 0.05), and possibly estimated glomerular filtration rate (p = 0.07). In summary, spatial heterogeneity of myocardial repolarization measured by MCG is positively associated cardiovascular risk factors including adiposity, smoking, and total cholesterol levels

  20. Recent developments and future prospects of SPECT myocardial perfusion imaging.

    PubMed

    Zaman, Maseeh Uz; Hashmi, Ibrahim; Fatima, Nosheen

    2010-10-01

    Myocardial perfusion SPECT imaging is the most commonly performed functional imaging for assessment of coronary artery disease. High diagnostic accuracy and incremental prognostic value are the major benefits while suboptimal spatial resolution and significant radiation exposure are the main limitations. Its ability to detect hemodynamic significance of lesions seen on multidetector CT angiogram (MDCTA) has paved the path for a successful marriage between anatomical and functional imaging modalities in the form of hybrid SPECT/MDCTA system. In recent years, there have been enormous efforts by industry and academia to develop new SPECT imaging systems with better sensitivity, resolution, compact design and new reconstruction algorithms with ability to improve image quality and resolution. Furthermore, expected arrival of Tc-99m-labeled deoxyglucose in next few years would further strengthen the role of SPECT in imaging hibernating myocardium. In view of these developments, it seems that SPECT would enjoy its pivotal role in spite of major threat to be replaced by fluorine-18-labeled positron emission tomography perfusion and glucose metabolism imaging agents. PMID:20652774

  1. Prophylactic lidocaine in suspected acute myocardial infarction.

    PubMed

    Goodman, S L; Geiderman, J M; Bernstein, I J

    1979-06-01

    The incidence of serious ventricular arrhythmias following acute myocardial infarction is highest during the first few hours after injury, and thereafter declines. Several investigations into the prophylactic use of lidocaine to prevent the development of arrhythmias have shown that lidocaine, given in therapeutic doses, is effective in preventing ventricular fibrillation and in reducing early mortality. Lidocaine was found to be effective when given either by the intravenous or by the intramuscular routes. The recommended dosage is 100 mg given as an intravenous bolus followed by 2 to 4 mg/min as an infusion, which should be given by infusion pump. Another recommendation is to use two 100 mg boluses 20 minutes apart, along with the same infusion. We recommend that lidocaine be started as soon as possible in all patients suspected of having suffered acute myocardial infarction. PMID:449144

  2. Amphetamine Abuse Related Acute Myocardial Infarction

    PubMed Central

    Lewis, O'Dene; Kumar, Rajan; Yeruva, Sri Lakshmi Hyndavi; Curry, Bryan H.

    2016-01-01

    Amphetamine abuse is a global problem. The cardiotoxic manifestations like acute myocardial infarction (AMI), heart failure, or arrhythmia related to misuse of amphetamine and its synthetic derivatives have been documented but are rather rare. Amphetamine-related AMI is even rarer. We report two cases of men who came to emergency department (ED) with chest pain, palpitation, or seizure and were subsequently found to have myocardial infarction associated with the use of amphetamines. It is crucial that, with increase in amphetamine abuse, clinicians are aware of this potentially dire complication. Patients with low to intermediate risk for coronary artery disease with atypical presentation may benefit from obtaining detailed substance abuse history and urine drug screen if deemed necessary. PMID:26998366

  3. Painless acute myocardial infarction on Mount Kilimanjaro.

    PubMed

    Jamal, Nasiruddin; Rajhy, Mubina; Bapumia, Mustaafa

    2016-01-01

    An individual experiencing dyspnoea or syncope at high altitude is commonly diagnosed to have high-altitude pulmonary edema or cerebral edema. Acute myocardial infarction (AMI) is generally not considered in the differential diagnosis. There have been very rare cases of AMI reported only from Mount Everest. We report a case of painless ST segment elevation myocardial infarction (STEMI) that occurred while climbing Mount Kilimanjaro. A 51-year-old man suffered dyspnoea and loss of consciousness near the mountain peak, at about 5600 m. At a nearby hospital, he was treated as a case of high-altitude pulmonary edema. ECG was not obtained. Two days after the incident, he presented to our institution with continued symptoms of dyspnoea, light-headedness and weakness, but no pain. He was found to have inferior wall and right ventricular STEMI complicated by complete heart block. He was successfully managed with coronary angioplasty, with good recovery. PMID:26989121

  4. Admission glucose and left ventricular systolic function in non-diabetic patients with acute myocardial infarction.

    PubMed

    Gierach, Joanna; Gierach, Marcin; Świątkiewicz, Iwona; Woźnicki, Marek; Grześk, Grzegorz; Sukiennik, Adam; Koziñski, Marek; Kubica, Jacek

    2016-03-01

    Carbohydrate metabolism disorder in patients hospitalized due to acute ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. The association is even stronger in non-diabetic patients compared to the diabetics. Poor outcome of patients with elevated parameters of carbohydrate metabolism may be associated with negative impact of these disorders on left ventricular (LV) function. The aim of the study was to determine the impact of admission glycemia on LV systolic function in acute phase and 6 months after myocardial infarction in STEMI patients treated with primary angioplasty, without carbohydrate disorders. The study group consisted of 52 patients (9 female, 43 male) aged 35-74 years, admitted to the Department of Cardiology and Internal Medicine, Collegium Medicum in Bydgoszcz, due to the first STEMI treated with primary coronary angioplasty with stent implantation, without diabetes in anamnesis and carbohydrate metabolism disorders diagnosed during hospitalization. Echocardiography was performed in all patients in acute phase and 6 months after MI. Plasma glucose were measured at hospital admission. In the subgroup with glycemia ≥7.1 mmol/l, in comparison to patients with glycemia <7.1 mmol/l, significantly lower ejection fraction (EF) was observed in acute phase of MI (44.4 ± 5.4 vs. 47.8 ± 6.3 %, p = 0.04) and trend to lower EF 6 months after MI [47.2 ± 6.5 vs. 50.3 ± 6.3 %, p = 0.08 (ns)]. Higher admission glycemia in patients with STEMI and without carbohydrate metabolism disturbances, may be a marker of poorer prognosis resulting from lower LV ejection fraction in the acute phase and in the long-term follow-up. PMID:25539622

  5. Metabolic markers in sports medicine.

    PubMed

    Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

    2012-01-01

    Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should

  6. Delayed Myocardial Enhancement in Cardiac Magnetic Resonance Imaging

    PubMed Central

    Franco, Arie; Javidi, Saeed; Ruehm, Stefan G

    2015-01-01

    Delayed myocardial enhancement MRI is a highly valuable but non-specific imaging technique that is ancillary in the diagnosis of a variety of diseases including myocardial viability, cardiomyopathy, myocarditis and other infiltrative myocardial processes. The lack of specificity stems from the wide variety of differential diagnoses that may present with overlapping patterns of delayed enhancement. Many of these differential diagnoses have been presented and discussed in this article. PMID:26622933

  7. Radioiodine therapy of hyperthyroidism precludes thallium-201 myocardial scintigraphy

    SciTech Connect

    Orzel, J.A.; Kruyer, W.B.; Borchert, R.D.

    1987-02-01

    The authors attempted to perform Tl-201 myocardial perfusion scintigraphy in a 42-year-old man 23 and 35 days after he received 9.8 mCi of oral I-131 for documented Graves' disease. Interference from primary and scattered photons from residual thyroid I-131 made Tl-201 myocardial scintigraphy technically impossible. A series of phantom and patient studies using I-131 and Tl-201 were performed, yielding guidelines for planning Tl-201 myocardial scintigraphy following radioiodine therapy.

  8. [Mosaic portrait method in the prognosis of myocardial infarct complications].

    PubMed

    Iakovlev, G M; Ardashev, V N; Kats, M D; Galkina, T A

    1981-06-01

    A mosaic portrait of variants of the course of myocardial infarction differing in the clinical picture of the first days of the disease was created by means of methods of Boolean algebra and electronic computers. A total of 354 patients with transmural myocardial infarction were examined., The created models allow the development of some complications of myocardial infarction to be prognosticated exact within 90%. PMID:7021950

  9. Acute Myocardial Infarction in Nephrotic Syndrome.

    PubMed

    Krishna, Kavita; Hiremath, Shirish; Lakade, Sachin; Davakhar, Sudarshan

    2015-11-01

    A 28 year old male, known case of nephrotic syndrome since 12 years, hypertensive presented with acute myocardial infarction (AMI) and accelerated hypertension. Coronary angiography revealed 100% thrombotic occlusion of mid left anterior descending artery, treated with thrombus aspiration and intracoronary tirofiban and nitroglycerine. He was stabilized within 24 hours. The pathogenesis of AMI in nephrotic syndrome has been discussed with this case report. PMID:27608787

  10. PICSO: from myocardial salvage to tissue regeneration.

    PubMed

    Mohl, Werner; Gangl, Clemens; Jusić, Alem; Aschacher, Thomas; De Jonge, Martin; Rattay, Frank

    2015-01-01

    Despite advances in primary percutaneous interventions (PPCI), management of microvascular obstructions in reperfused myocardial tissue remains challenging and is a high-risk procedure. This has led to renewed interest in the coronary venous system as an alternative route of access to the myocardium. This article reviews historical data describing therapeutic options via cardiac veins as well as discussing the clinical potential and limitations of a catheter intervention: pressure controlled intermittent coronary sinus occlusion (PICSO). Collected experimental and clinical information suggest that PICSO also offers the potential for tissue regeneration beyond myocardial salvage. A meta-analysis of observer controlled pICSO application in animal studies showed a dose dependent reduction in infarct size of 29.3% (p < 0.001). Additionally, a 4-fold increase of hemeoxygenase-1 gene expression (p < 0.001) in the center of infarction and a 2.5 fold increase of vascular endothelial growth factor (VEGF) (p < 0.002) in border zones suggest that molecular pathways are initiating structural maintenance. Early clinical evidence confirmed significant salvage and event free survival in patients with acute myocardial infarction and risk reduction for event free survival 5 years after the acute event (p < 0.0001). This experimental and clinical evidence was recently corroborated using modern PICSO technology in PPCI showing a significant reduction of infarct size, when compared to matched controls (p < 0.04). PICSO enhances redistribution of flow towards deprived zones, clearing microvascular obstruction and leading to myocardial protection. Beyond salvage, augmentation of molecular regenerative networks suggests a second mechanism of PICSO involving the activation of vascular cells in cardiac veins, thus enhancing structural integrity and recovery. PMID:25616738

  11. Myocardial Calcinosis in Chronic Renal Failure

    PubMed Central

    Kempf, Ashley E.; Momeni, Maryam Golshan; Saremi, Farhood

    2009-01-01

    The authors are presenting an 18 year old male with history of end stage renal disease and rejected renal transplant. In his workup echocardiogram and non contract CT of chest revealed diffuse endocardial and myocardial calcifications. Extensive cardiac calcification is a rare but important entity in relation to end stage renal disease as it may cause complications such as valvular dysfunction and fatal arrhythmia. PMID:22470643

  12. Thallium-201 myocardial imaging in children

    SciTech Connect

    Sty, J.R.; Starshak, R.J.

    1985-01-01

    The clinical applications of thallium-201 scintigraphy are less well defined in children than in adults. However, the published data indicate several potential applications including assessment of: 1) deficit in left ventricular myocardial perfusion, 2) early right ventricular volume or pressure overload, or both, and 3) the right ventricle in both cyanotic and acyanotic congenital heart disease. In this report, the applications of thallium imaging to pediatric diseases are described and the advantages and disadvantages of the procedure are enumerated.

  13. [Myocardial depression in the burn patient].

    PubMed

    Carrillo-Esper, Raúl; Sánchez-Zúñiga, Martín de Jesús

    2006-01-01

    Myocardial depression and heart failure are frequent complications in critically ill burn patients. The physiopathology is complex and involves the activation of inflammatory pathways, ischemia-reperfusion, oxidative stress and endothelial lesion. Diagnosis should be made early by means of hemodynamic monitoring. Treatment is accomplished by inotropics that act on different pathways of the contractile function and immune response associated with antioxidants and allopurinol. PMID:16887086

  14. Sirt1 protects against high-fat diet-induced metabolic damage

    PubMed Central

    Pfluger, Paul T.; Herranz, Daniel; Velasco-Miguel, Susana; Serrano, Manuel; Tschöp, Matthias H.

    2008-01-01

    The identification of new pharmacological approaches to effectively prevent, treat, and cure the metabolic syndrome is of crucial importance. Excessive exposure to dietary lipids causes inflammatory responses, deranges the homeostasis of cellular metabolism, and is believed to constitute a key initiator of the metabolic syndrome. Mammalian Sirt1 is a protein deacetylase that has been involved in resveratrol-mediated protection from high-fat diet-induced metabolic damage, but direct proof for the implication of Sirt1 has remained elusive. Here, we report that mice with moderate overexpression of Sirt1 under the control of its natural promoter exhibit fat mass gain similar to wild-type controls when exposed to a high-fat diet. Higher energy expenditure appears to be compensated by a parallel increase in food intake. Interestingly, transgenic Sirt1 mice under a high-fat diet show lower lipid-induced inflammation along with better glucose tolerance, and are almost entirely protected from hepatic steatosis. We present data indicating that such beneficial effects of Sirt1 are due to at least two mechanisms: induction of antioxidant proteins MnSOD and Nrf1, possibly via stimulation of PGC1α, and lower activation of proinflammatory cytokines, such as TNFα and IL-6, via down-modulation of NFκB activity. Together, these results provide direct proof of the protective potential of Sirt1 against the metabolic consequences of chronic exposure to a high-fat diet. PMID:18599449

  15. Adenylate Kinase and AMP Signaling Networks: Metabolic Monitoring, Signal Communication and Body Energy Sensing

    PubMed Central

    Dzeja, Petras; Terzic, Andre

    2009-01-01

    Adenylate kinase and downstream AMP signaling is an integrated metabolic monitoring system which reads the cellular energy state in order to tune and report signals to metabolic sensors. A network of adenylate kinase isoforms (AK1-AK7) are distributed throughout intracellular compartments, interstitial space and body fluids to regulate energetic and metabolic signaling circuits, securing efficient cell energy economy, signal communication and stress response. The dynamics of adenylate kinase-catalyzed phosphotransfer regulates multiple intracellular and extracellular energy-dependent and nucleotide signaling processes, including excitation-contraction coupling, hormone secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and repair, and developmental programming. Metabolomic analyses indicate that cellular, interstitial and blood AMP levels are potential metabolic signals associated with vital functions including body energy sensing, sleep, hibernation and food intake. Either low or excess AMP signaling has been linked to human disease such as diabetes, obesity and hypertrophic cardiomyopathy. Recent studies indicate that derangements in adenylate kinase-mediated energetic signaling due to mutations in AK1, AK2 or AK7 isoforms are associated with hemolytic anemia, reticular dysgenesis and ciliary dyskinesia. Moreover, hormonal, food and antidiabetic drug actions are frequently coupled to alterations of cellular AMP levels and associated signaling. Thus, by monitoring energy state and generating and distributing AMP metabolic signals adenylate kinase represents a unique hub within the cellular homeostatic network. PMID:19468337

  16. [Transition of myocardial ischemia to heart failure].

    PubMed

    Ertl, G; Fraccarollo, D; Gaudron, P; Hu, K; Laser, A; Neubauer, S; Schorb, W

    1998-09-01

    Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance. PMID:9816648

  17. Multispectral optoacoustic tomography of myocardial infarction

    PubMed Central

    Taruttis, Adrian; Wildgruber, Moritz; Kosanke, Katja; Beziere, Nicolas; Licha, Kai; Haag, Rainer; Aichler, Michaela; Walch, Axel; Rummeny, Ernst; Ntziachristos, Vasilis

    2012-01-01

    Objectives To investigate the feasibility of a high resolution optical imaging strategy for myocardial infarction. Background Near-infrared approaches to imaging cardiovascular disease enable visualization of disease-associated biological processes in vivo. However, even at the scale of small animals, the strong scattering of light prevents high resolution imaging after the first 1–2 mm of tissue, leading to degraded signal localization. Methods Multispectral optoacoustic tomography (MSOT) was used to non-invasively image myocardial infarction (MI) in a murine model of coronary artery ligation at resolutions not possible with current deep-tissue optical imaging methods. Post-MI imaging was based on resolving the spectral absorption signature of a dendritic polyglycerol sulfate-based (dPGS) near-infrared imaging agent targeted to P- and L-selectin. Results In vivo imaging succeeded in detection of the agent in the injured myocardium after intravenous injection. The high anatomic resolution (<200 μm) achieved by the described method allowed signals originating in the infarcted heart to be distinguished from uptake in adjacent regions. Histological analysis found dPGS signal in infarcted areas, originating from leukocytes and endothelial cells. Conclusions MSOT imaging of myocardial infarction provides non-invasive visualization of optical contrast with a high spatial resolution that is not degraded by the scattering of light. PMID:25327410

  18. PARP inhibition and postinfarction myocardial remodeling.

    PubMed

    Halmosi, Robert; Deres, Laszlo; Gal, Roland; Eros, Krisztian; Sumegi, Balazs; Toth, Kalman

    2016-08-01

    Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt-1/GSK-3β, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling. PMID:27392900

  19. Myocardial perfusion echocardiography and coronary microvascular dysfunction

    PubMed Central

    Barletta, Giuseppe; Del Bene, Maria Riccarda

    2015-01-01

    Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking. PMID:26730291

  20. Myocardial infarction: management of the subacute period.

    PubMed

    Mercado, Michael G; Smith, Dustin K; McConnon, Michael L

    2013-11-01

    Optimal management of myocardial infarction in the subacute period focuses on improving the discharge planning process, implementing therapies early to prevent recurrent myocardial infarction, and avoiding hospital readmission. Evidence-based guidelines for the care of patients with acute coronary syndrome are not followed up to 25% of the time. Antiplatelet therapy, renin-angiotensin-aldosterone system inhibitors, beta blockers, and statins constitute the foundation of medical therapy. Early noninvasive stress testing is an important risk assessment tool, especially in patients who do not undergo revascularization. Discharge preparation should include a review of medications, referral for exercise-based cardiac rehabilitation, activity recommendations, education about lifestyle modification and recognition of cardiac symptoms, and a clear follow-up plan. Because nonadherence to medications is common in patients after a myocardial infarction and is associated with increased mortality risk, modifiable factors associated with medication self-discontinuation should be addressed before discharge. Structured discharge processes should be used to enhance communication and facilitate the transition from the hospital to the family physician's care. PMID:24364634

  1. Myocardial perfusion echocardiography and coronary microvascular dysfunction.

    PubMed

    Barletta, Giuseppe; Del Bene, Maria Riccarda

    2015-12-26

    Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking. PMID:26730291

  2. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

    PubMed Central

    van Dijk, Gertjan; van Heijningen, Steffen; Reijne, Aaffien C.; Nyakas, Csaba; van der Zee, Eddy A.; Eisel, Ulrich L. M.

    2015-01-01

    Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by “systems biology” approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework. PMID:26041981

  3. Combretastatin A4 disodium phosphate-induced myocardial injury

    PubMed Central

    Tochinai, Ryota; Nagata, Yuriko; Ando, Minoru; Hata, Chie; Suzuki, Tomo; Asakawa, Naoyuki; Yoshizawa, Kazuhiko; Uchida, Kazumi; Kado, Shoichi; Kobayashi, Toshihide; Kaneko, Kimiyuki; Kuwahara, Masayoshi

    2016-01-01

    Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner.

  4. Quantitation of Acute Necrosis After Experimental Myocardial Infarction

    PubMed Central

    Yeap, Xin-Yi; Dehn, Shirley; Adelman, Jeremy; Lipsitz, Jeremy; Thorp, Edward B.

    2016-01-01

    Myocardial infarction (MI) is death and necrosis of myocardial tissue secondary to ischemia. MI is associated with adverse cardiac remodeling, progressive heart chamber dilation, ventricular wall thinning, and loss of cardiac function. Myocardial necrosis can be experimentally induced in rodents to simulate human MI by surgical occlusion of coronary arteries. When induced in knockout or transgenic mice, this model is useful for the identification of molecular modulators of cell death, cardiac remodeling, and preclinical therapeutic potential. Herein we outline in tandem, methods for microsurgical ligation of the left anterior descending artery followed by quantitation of myocardial necrosis. Necrosis is quantified after staining the heart with triphenyltetrazolium chloride. PMID:23733573

  5. Combretastatin A4 disodium phosphate-induced myocardial injury.

    PubMed

    Tochinai, Ryota; Nagata, Yuriko; Ando, Minoru; Hata, Chie; Suzuki, Tomo; Asakawa, Naoyuki; Yoshizawa, Kazuhiko; Uchida, Kazumi; Kado, Shoichi; Kobayashi, Toshihide; Kaneko, Kimiyuki; Kuwahara, Masayoshi

    2016-07-01

    Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner. PMID:27559241

  6. PET: Is myocardial flow quantification a clinical reality?

    PubMed

    Saraste, Antti; Kajander, Sami; Han, Chunlei; Nesterov, Sergey V; Knuuti, Juhani

    2012-10-01

    Positron emission tomography (PET) enables quantitative measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Recent developments and improved availability of PET technology have resulted in growing interest in translation of quantitative flow analysis from mainly a research tool to routine clinical practice. Quantitative PET measurements of absolute MBF and MFR have potential to improve accuracy of myocardial perfusion imaging in diagnosis of multivessel coronary artery disease as well as definition of the extent and functional importance of stenoses. This article reviews recent advances and experience in the quantitative myocardial perfusion imaging together with issues that need to be resolved for quantitative analysis to become clinical reality. PMID:22733534

  7. Internal countershock produces myocardial damage and lactate production without myocardial ischemia in anesthetized dogs

    SciTech Connect

    Gaba, D.M.; Maxwell, M.S.; Merlone, S.; Smith, C.

    1987-04-01

    The global myocardial extraction of lactate was measured in 13 halothane anesthetized dogs to assess the effect of electric countershock applied directly to the heart. Seven animals received two countershocks of 30 delivered joules each, while six animals were not shocked but were atrially paced to a rate of 190-200, both with and without occlusion of the vena cava to produce a mean arterial pressure of 40-50 mmHg. All animals had substantially positive lactate extraction in the baseline state (36 +/- 10% for countershock group vs. 41 +/- 3% for pacing group). Myocardial lactate extraction reached a markedly negative nadir 2.5 min after countershock (-19 +/- 15%), but returned toward normal by 6 min (10 +/- 6%). Lactate extraction was not significantly changed from baseline in the pacing group. The relationship between changes in regional myocardial blood flow (radiolabeled microspheres) and post-countershock myocardial damage (technetium pyrophosphate uptake) was assessed in six dogs shocked as above. Mean myocardial blood flow was increased minimally immediately after countershock (0.78 +/- 0.08 ml X min-1 X g-1 vs. 1.16 +/- 0.3), but there was no difference in blood flow between damaged and undamaged tissue at either time point. The epicardial-to-endocardial ratio of blood flow was unchanged after countershock (0.97 +/- 0.05 vs. 0.99 +/- 0.08). There was no relationship between myocardial damage and either the absolute amount of blood flow after countershock (r = -0.03) or the change in blood flow compared with the pre-shock period (r = 0.01).

  8. Depressive Symptom