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Sample records for myocardial metabolic derangement

  1. Diabetes, perioperative ischaemia and volatile anaesthetics: consequences of derangements in myocardial substrate metabolism.

    PubMed

    van den Brom, Charissa E; Bulte, Carolien Se; Loer, Stephan A; Bouwman, R Arthur; Boer, Christa

    2013-01-01

    Volatile anaesthetics exert protective effects on the heart against perioperative ischaemic injury. However, there is growing evidence that these cardioprotective properties are reduced in case of type 2 diabetes mellitus. A strong predictor of postoperative cardiac function is myocardial substrate metabolism. In the type 2 diabetic heart, substrate metabolism is shifted from glucose utilisation to fatty acid oxidation, resulting in metabolic inflexibility and cardiac dysfunction. The ischaemic heart also loses its metabolic flexibility and can switch to glucose or fatty acid oxidation as its preferential state, which may deteriorate cardiac function even further in case of type 2 diabetes mellitus.Recent experimental studies suggest that the cardioprotective properties of volatile anaesthetics partly rely on changing myocardial substrate metabolism. Interventions that target at restoration of metabolic derangements, like lifestyle and pharmacological interventions, may therefore be an interesting candidate to reduce perioperative complications. This review will focus on the current knowledge regarding myocardial substrate metabolism during volatile anaesthesia in the obese and type 2 diabetic heart during perioperative ischaemia. PMID:23452502

  2. [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

  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. 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.

  5. 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

  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. Obesity-metabolic derangement exacerbates cardiomyocyte loss distal to moderate coronary artery stenosis in pigs without affecting global cardiac function.

    PubMed

    Li, Zi-Lun; Ebrahimi, Behzad; Zhang, Xin; Eirin, Alfonso; Woollard, John R; Tang, Hui; Lerman, Amir; Wang, Shen-Ming; Lerman, Lilach O

    2014-04-01

    Obesity associated with metabolic derangements (ObM) worsens the prognosis of patients with coronary artery stenosis (CAS), but the underlying cardiac pathophysiologic mechanisms remain elusive. We tested the hypothesis that ObM exacerbates cardiomyocyte loss distal to moderate CAS. Obesity-prone pigs were randomized to four groups (n = 6 each): lean-sham, ObM-sham, lean-CAS, and ObM-CAS. Lean and ObM pigs were maintained on a 12-wk standard or atherogenic diet, respectively, and left circumflex CAS was then induced by placing local-irritant coils. Cardiac structure, function, and myocardial oxygenation were assessed 4 wk later by computed-tomography and blood oxygenation level dependent (BOLD) MRI, the microcirculation with micro-computed-tomography, and injury mechanisms by immunoblotting and histology. ObM pigs showed obesity, dyslipidemia, and insulin resistance. The degree of CAS (range, 50-70%) was similar in lean and ObM pigs, and resting myocardial perfusion and global cardiac function remained unchanged. Increased angiogenesis distal to the moderate CAS observed in lean was attenuated in ObM pigs, which also showed microvascular dysfunction and increased inflammation (M1-macrophages, TNF-α expression), oxidative stress (gp91), hypoxia (BOLD-MRI), and fibrosis (Sirius-red and trichrome). Furthermore, lean-CAS showed increased myocardial autophagy, which was blunted in ObM pigs (downregulated expression of unc-51-like kinase-1 and autophagy-related gene-12; P < 0.05 vs. lean CAS) and associated with marked apoptosis. The interaction diet xstenosis synergistically inhibited angiogenic, autophagic, and fibrogenic activities. ObM exacerbates structural and functional myocardial injury distal to moderate CAS with preserved myocardial perfusion, possibly due to impaired cardiomyocyte turnover.

  8. First report of congenital or infantile cataract in deranged proteoglycan metabolism with released xylose

    PubMed Central

    Sulochana, K; Ramakrishnan, S; Vasanthi, S; Madhavan, H; Arunagiri, K; Punitham, R

    1997-01-01

    AIM—To investigate the chemical pathology in the blood and lens, in cases of congenital or infantile cataract in children excreting predominantly non-reducing carbohydrates in urine.
METHODS—Urine samples from children with congenital or infantile cataract, and age and sex-matched controls, were analysed for (i) inherited errors of metabolism, (ii) paper chromatography of sugars, (iii) spectrophotometric assay of glycosaminoglycans (GAG), (iv) cetyl trimethyl ammonium bromide test, (v) electrophoresis using Alcian blue, (vi) ion exchange chromatography with IR 120 resin, and (vii) HPLC for xylose. Blood and lens material were also tested for GAG fragments and xylose. β Glucuronidase was assayed in lymphocytes and urine.
RESULTS—Of 220 children of both sexes below 12 years of age, with congenital or infantile cataract treated in Sankara Nethralaya, Madras, India, during a period of 2 years, 145 excreted fragments of GAG (heparan and chondroitin sulphates) in their urine. There was no such excretion among the control group of 50 children. The same was found accumulated in the blood and lenses of affected children. In addition, xylose was present in small amounts in the urine and blood and xylitol was present in the lens. There was a significant elevation in the activity of β glucuronidase in lymphocytes and urine, when compared with normals. All the above findings suggest deranged proteoglycan metabolism. As the urine contained mostly GAG fragments and very little xylose, Benedict's reagent was not reduced. This ruled out galactosaemia.
CONCLUSION—An increase of β glucuronidase activity might have caused extensive fragmentation of GAG with resultant accumulation in the blood and lens and excretion in urine. Small amounts of xylose may have come from xylose links between GAG and core protein of proteoglycans. Owing to their polyanionic nature, GAG fragments in the lens might abstract sodium, and with it water, thereby increasing the hydration

  9. 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.

  10. 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

  11. Obesity and Altered Sleep: A Pathway to Metabolic Derangements in Children?

    PubMed Central

    Hakim, Fahed; Kheirandish-Gozal, Leila; Gozal, David

    2015-01-01

    Obstructive sleep apnea (OSA) is a frequent disorder in children and is primarily associated with adenotonsillar hypertrophy., The prominent increases in childhood overweight and obesity rates in the world even among youngest of children have translated into parallel increases in the prevalence of OSA, and such trends will undoubtedly be associated with deleterious global health outcomes and life expectancy. Even an obesity phenotype in childhood OSA, more close to the adult type, has been recently proposed. Reciprocal interactions between sleep in general, OSA, obesity, and disruptions of metabolic homeostasis have emerged in recent years. These associations have suggested the a priori involvement of complex sets of metabolic and inflammatory pathways all of which may underlie increased risk for increased orexigenic behaviors and dysfunctional satiety, hyperlipidemia, and insulin resistance that ultimately favor the emergence of metabolic syndrome. Here, we will review some of the critical evidence supporting the proposed associations between sleep disruption and the metabolism-obesity complex. In addition, we will describe the more recent evidence linking the potential interactive roles of OSA and obesity on metabolic phenotype. PMID:26072337

  12. Obesity and Altered Sleep: A Pathway to Metabolic Derangements in Children?

    PubMed

    Hakim, Fahed; Kheirandish-Gozal, Leila; Gozal, David

    2015-06-01

    Obstructive sleep apnea (OSA) is a frequent disorder in children and is primarily associated with adenotonsillar hypertrophy. The prominent increases in childhood overweight and obesity rates in the world even among youngest of children have translated into parallel increases in the prevalence of OSA, and such trends are undoubtedly associated with deleterious global health outcomes and life expectancy. Even an obesity phenotype in childhood OSA, more close to the adult type, has been recently proposed. Reciprocal interactions between sleep in general, OSA, obesity, and disruptions of metabolic homeostasis have emerged in recent years. These associations have suggested the a priori involvement of complex sets of metabolic and inflammatory pathways, all of which may underlie an increased risk for increased orexigenic behaviors and dysfunctional satiety, hyperlipidemia, and insulin resistance that ultimately favor the emergence of metabolic syndrome. Here, we review some of the critical evidence supporting the proposed associations between sleep disruption and the metabolism-obesity complex. In addition, we describe the more recent evidence linking the potential interactive roles of OSA and obesity on metabolic phenotype. PMID:26072337

  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. Proteasome inhibition in skeletal muscle cells unmasks metabolic derangements in type 2 diabetes.

    PubMed

    Al-Khalili, Lubna; de Castro Barbosa, Thais; Ostling, Jörgen; Massart, Julie; Cuesta, Pablo Garrido; Osler, Megan E; Katayama, Mutsumi; Nyström, Ann-Christin; Oscarsson, Jan; Zierath, Juleen R

    2014-11-01

    Two-dimensional difference gel electrophoresis (2-D DIGE)-based proteome analysis has revealed intrinsic insulin resistance in myotubes derived from type 2 diabetic patients. Using 2-D DIGE-based proteome analysis, we identified a subset of insulin-resistant proteins involved in protein turnover in skeletal muscle of type 2 diabetic patients, suggesting aberrant regulation of the protein homeostasis maintenance system underlying metabolic disease. We then validated the role of the ubiquitin-proteasome system (UPS) in myotubes to investigate whether impaired proteasome function may lead to metabolic arrest or insulin resistance. Myotubes derived from muscle biopsies obtained from people with normal glucose tolerance (NGT) or type 2 diabetes were exposed to the proteasome inhibitor bortezomib (BZ; Velcade) without or with insulin. BZ exposure increased protein carbonylation and lactate production yet impaired protein synthesis and UPS function in myotubes from type 2 diabetic patients, marking the existence of an insulin-resistant signature that was retained in cultured myotubes. In conclusion, BZ treatment further exacerbates insulin resistance and unmasks intrinsic features of metabolic disease in myotubes derived from type 2 diabetic patients. Our results highlight the existence of a confounding inherent abnormality in cellular protein dynamics in metabolic disease, which is uncovered through concurrent inhibition of the proteasome system.

  15. 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

  16. Glucose metabolism derangements in adults with the MELAS m.3243A>G mutation.

    PubMed

    El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W; Chanprasert, Sirisak; Jahoor, Farook; Scaglia, Fernando; Craigen, William J

    2014-09-01

    The m.3243A>G mutation in the mitochondrial gene MT-TL1 leads to a wide clinical spectrum ranging from asymptomatic carriers to MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) at the severe end. Diabetes mellitus (DM) occurs in mitochondrial diseases, with the m.3243A>G mutation being the most common mutation associated with mitochondrial DM. The pathogenesis of mitochondrial DM remains largely unknown, with previous studies suggesting that impaired insulin secretion is the major factor. In this study we used stable isotope infusion techniques to assess glucose metabolism in vivo and under physiological conditions in 5 diabetic and 11 non-diabetic adults with the m.3243A>G mutation and 10 healthy adult controls. Our results revealed increased glucose production due to increased gluconeogenesis in both diabetic and non-diabetic subjects with the m.3243A>G mutation. In addition, diabetic subjects demonstrated insulin resistance and relative insulin deficiency, resulting in an inability to increase glucose oxidation which can explain the development of DM in these subjects. Non-diabetic subjects showed normal insulin sensitivity; and therefore, they were able to increase their glucose oxidation rate. The ability to increase glucose utilization can act as a compensatory mechanism that explains why these subjects do not have DM despite the higher rate of glucose production. These results suggest that increased gluconeogenesis is not enough to cause DM and the occurrence of combined insulin resistance and relative insulin deficiency are needed to develop DM in individuals with the m.3243A>G mutation. Therefore, multiple defects in insulin and glucose metabolism are required for DM to occur in individuals with mitochondrial diseases. The results of this study uncover previously undocumented alterations in glucose metabolism in individuals with the m.3243A>G mutation that contribute significantly to our understanding of the pathogenesis

  17. Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier.

    PubMed

    Saheki, Takeyori; Kobayashi, Keiko; Iijima, Mikio; Moriyama, Mitsuaki; Yazaki, Masahide; Takei, Yo-Ichi; Ikeda, Shu-Ichi

    2005-10-01

    ratio. This follows inhibition of fatty acid oxidation. The peculiar fondness for food of CTLN2 patients who like protein and dislike carbohydrate and sweets may be related to their metabolic requirements. PMID:16199199

  18. 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...

  19. Impact of Gender on the Myocardial Metabolic Response to Obesity

    PubMed Central

    Peterson, Linda R.; Soto, Pablo F.; Herrero, Pilar; Mohammed, B. Selma; Avidan, Michael S.; Schechtman, Kenneth B.; Dence, Carmen; Gropler, Robert J.

    2010-01-01

    Objectives To determine the gender-specific effects of obesity on myocardial metabolism, work, and efficiency Background Myocardial metabolism abnormalities may contribute to the development of obesity-related heart failure. Increased myocardial oxygen consumption (MVO2) and fatty acid (FA) metabolism and decreased efficiency occur with obesity in women. It is unknown whether similar changes occur with obesity in men. Methods We quantified cardiac work, and efficiency, myocardial blood flow (MBF), MVO2, glucose, and FA metabolism, with echocardiography and positron emission tomography in nonobese and obese men and women (N=86). Results There were significant differences between the obese (N=35) and nonobese (N=51) in age, body composition, plasma lipids, and insulin resistance and differences between the men (N=30) and women (N=56) in body composition and plasma lipids. Female gender independently predicted increased cardiac work (p<.001). Female gender also related to lower efficiency (p<.05). Obesity and female gender independently predicted higher MBF (p<.01, p<.0005, respectively) and MVO2 (p<.0005, p<.0001). Myocardial glucose uptake was not different among the 4 subject groups, but obesity and gender interacted in predicting glucose uptake (p<.05). Lower myocardial glucose utilization was independently predicted by female gender (p<.05), and it independently predicted lower myocardial glucose utilization/plasma insulin (p<.05). Obesity and gender significantly interacted in the determination of glucose utilization/plasma insulin (p=.01). There were no differences in FA uptake among the 4 groups, and although increasing obesity correlated with higher myocardial FA utilization and oxidation; female gender (p<.005, <.01) and plasma triglycerides (p<.05, <.005) were their independent predictors. Conclusions Women’s and men’s myocardial metabolic response to obesity is not exactly the same. Obesity and gender modulate MBF and MVO2, are related to myocardial

  20. Extracellular brain pH with or without hypoxia is a marker of profound metabolic derangement and increased mortality after traumatic brain injury

    PubMed Central

    Timofeev, Ivan; Nortje, Jurgens; Al-Rawi, Pippa G; Hutchinson, Peter JA; Gupta, Arun K

    2013-01-01

    Cerebral hypoxia and acidosis can follow traumatic brain injury (TBI) and are associated with increased mortality. This study aimed to evaluate a relationship between reduced pHbt and disturbances of cerebral metabolism. Prospective data from 56 patients with TBI, receiving microdialysis and Neurotrend monitoring, were analyzed. Four tissue states were defined based on pHbt and PbtO2: 1—low PbtO2/pHbt, 2—low pHbt/normal PbtO2, 3—normal pHbt/low PbtO2, and 4—normal pHbt/PbtO2). Microdialysis values were compared between the groups. The relationship between PbtO2 and lactate/pyruvate (LP) ratio was evaluated at different pHbt levels. Proportional contribution of each state was evaluated against mortality. As compared with the state 4, the state 3 was not different, the state 2 exhibited higher levels of lactate, LP, and glucose and the state 1—higher LP and reduced glucose (P<0.001). A significant negative correlation between LP and PbtO2 (rho=−0.159, P<0.001) was stronger at low pHbt (rho=−0.201, P<0.001) and nonsignificant at normal pHbt (P=0.993). The state 2 was a significant discriminator of mortality categories (P=0.031). Decreased pHbt is associated with impaired metabolism. Measuring pHbt with PbtO2 is a more robust way of detecting metabolic derangements. PMID:23232949

  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.

  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. Effects of activation of endocannabinoid system on myocardial metabolism.

    PubMed

    Polak, Agnieszka; Harasim, Ewa; Chabowski, Adrian

    2016-01-01

    Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid storage. Long chain fatty acids are the main myocardial energy substrate. However, the heart exerts enormous metabolic flexibility emphasized by its ability to utilzation not only fatty acids, but also glucose, lactate and ketone bodies. Endocannabinoids can directly act on the cardiomyocytes through the CB1 and CB2 receptors present in cardiomyocytes. It appears that direct activation of CB1 receptors promotes increased lipogenesis, pericardial steatosis and bioelectrical dysfunction of the heart. In contrast, stimulation of CB2 receptors exhibits cardioprotective properties, helping to maintain appropriate amount of ATP in cardiomyocytes. Furthermore, the effects of endocannabinoids at both the central nervous system and peripheral tissues, such as liver, pancreas, or adipose tissue, resulting indirectly in plasma availability of energy substrates and affects myocardial metabolism. To date, there is little evidence that describes effects of activation of the endocannabinoid system in the cardiovascular system under physiological conditions. In the present paper the impact of metabolic diseases, i. e. obesity and diabetes, as well as the cardiovascular diseases - hypertension, myocardial ischemia and myocardial infarction on the deregulation of the endocannabinoid system and its effect on the metabolism are described. PMID:27333924

  4. 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...

  5. Inflammasome, mTORC1 activation, and metabolic derangement contribute to the susceptibility of diabetics to infections.

    PubMed

    Krakauer, Teresa

    2015-12-01

    The mechanisms leading to higher risks of infection in diabetics remain unknown despite recent advances in the understanding of associated immunological and metabolic aberrations. Hyperglycemia and hyperlipidemia in diabetics not only contribute to altered metabolism but glucose and free fatty acids can directly activate inflammation and the production of the proinflammatory cytokine interleukin 1β (IL-1β). Long-chain saturated fatty acids activate toll-like receptor 4 (TLR4), generating diacylglycerol and activating protein kinase C to upregulate the Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway. High glucose uptake switches cell metabolism from oxidative phosphorylation to glycolysis and deactivates AMP-activated protein kinase (AMPK), a critical sensor of nutrient and cellular energy, leading to mTORC1 activation. A deleterious consequence of mTORC1 activation is the suppression of autophagy which is a catabolic process for the lysosomal degradation of damaged organelles, protein aggregates and intracellular pathogens. In addition, high glucose concentration and fatty acids independently activate inflammasome, an intracellular multi-protein complex that promotes the proteolytic activation of caspase 1, leading to the processing and secretion of IL-1β. Other caspases induced by inflammasome can trigger apoptotic cell death. A common upstream signal for the activation of inflammasome and mTORC1 is oxidative stress, which generates reactive oxygen species (ROS) from dysregulated mitochondria. Increased flux of glucose and lipids activates stress kinases, enhances electron transport, and generates ROS in mitochondria. Mitochondrial stress arising from increased mitochondrial respiration and permeability damages mitochondria, activates caspases, which then induce apoptosis via the intrinsic cell death pathway releasing mitochondrial DNA. Normally apoptosis is down-regulated by autophagy as autophagy removes damaged organelles as a result of danger

  6. Hypoxia causes autophagic stress and derangement of metabolic adaptation in a cell model of amyotrophic lateral sclerosis.

    PubMed

    Cimini, Sara; Rizzardini, Milena; Biella, Gloria; Cantoni, Lavinia

    2014-05-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease that affects motor neurons. The recruitment of autophagy (macroautophagy) and mitochondrial dysfunction are documented in amyotrophic lateral sclerosis patients and experimental models expressing mutant forms of Cu, Zn superoxide dismutase (SOD1) protein, but their impact in the disease remains unclear. Hypoxia is a stress closely related to the disease in patients and mutant SOD1 mice; in individual cells, hypoxia activates autophagy and regulates mitochondrial metabolism as fundamental adaptive mechanisms. Our aim was to examine whether mutant SOD1 changed this response. Hypoxia (1% O2 for 22 h) caused greater loss of viability and more marked activation of caspase 3/7 in the motor neuronal NSC-34 cell line stably transfected with the G93A mutant human SOD1 (G93A-NSC) than in the one with the wild-type SOD1 (WT-NSC) or in untransfected NSC-34. In the G93A-NSC cells, there was a more marked accumulation of the LC3-II autophagy protein, attributable to autophagic stress; 3-methyladenine, which acts on initiation of autophagy, fully rescued G93A-NSC viability and reduced the activation of caspase 3/7 indicating this was a secondary event; the metabolic handling of hypoxia was inappropriate possibly contributing to the autophagic stress. Our findings evidentiate that the G93A mutation of SOD1 profoundly altered the adaptive metabolic response to hypoxia and this could increase the cell susceptibility to this stress. Hypoxia activates autophagy and modifies glycolysis and mitochondrial respiration as fundamental cell adaptive mechanisms. This stress is closely related to amyotrophic lateral sclerosis. The recruitment of autophagy and mitochondrial dysfunction are documented in patients and models expressing mutant Cu, Zn superoxide dismutase (SOD1) protein, but their impact in the disease remains unclear. G93ASOD1 cells were more susceptible to hypoxia than wild-type SOD1 cells and showed autophagic

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. 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

  12. Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment.

    PubMed

    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

    2010-08-01

    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 alpha-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 (13)C enrichment of glutamate when (13)C-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

  13. 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.

  14. Myocardial fatty acid metabolism and lipotoxicity in the setting of insulin resistance.

    PubMed

    Kok, Bernard P C; Brindley, David N

    2012-10-01

    Management of diabetes and insulin resistance in the setting of cardiovascular disease has become an important issue in an increasingly obese society. Besides the development of hypertension and buildup of atherosclerotic plaques, the derangement of fatty acid and lipid metabolism in the heart plays an important role in promoting cardiac dysfunction and oxidative stress. This review discusses the mechanisms by which metabolic inflexibility in the use of fatty acids as the preferred cardiac substrate in diabetes produces detrimental effects on mechanical efficiency, mitochondrial function, and recovery from ischemia. Lipid accumulation and the consequences of toxic lipid metabolites are also discussed. PMID:22999246

  15. 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.

  16. 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

  17. 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.

  18. 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

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

    PubMed Central

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

    2016-01-01

    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 (r2 = 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

  20. [Myocardial serotonin metabolism after local ischemia and ischemic precondition].

    PubMed

    Naumenko, S E; Latysheva, T V; Gilinskiĭ, M A

    2014-07-01

    To determine the effect of ischemic preconditioning upon myocardial serotonin and 5-hydroxyindolacetic acid (5-HIAA) dynamic in myocardial ischemia and reperfusion. 28 male Wistar rats anesthetized with urethane were randomly divided into 2 groups. In the control group (n = 13) rats were subjected to 30 min coronary occlusion and subsequent 120 min reperfusion. In the ex- perimental group (n = 15) ischemic preconditioning (3 x 3 min ischemia + 3 x 3 min reperfusion) before prolonged ischemia was used. Myocardial interstitial serotonin and 5-HIAA were measured using a microdialysis technique. Myocardial serotonin and 5-HIAA significantly increased af- ter ischemic preconditioning (p = 0.00298; p = 0.00187). In prolonged ischemia interstitial serotonin level was lower in the experimental group vs. control up to 20 min of ischemia (p < 0.05). We conclude that ischemic preconditioning increases interstitial myocardial serotonin, but inhibit serotonin increase in subsequent prolonged myocardial ischemia. After 20 minutes of reperfusion the lack of correlation between serotonin and 5-HIAA levels appeared which may be the evidence of serotonin uptake activation.

  1. Untargeted metabolic profiling reveals potential biomarkers in myocardial infarction and its application.

    PubMed

    Yao, Hong; Shi, Peiying; Zhang, Ling; Fan, Xiaohui; Shao, Qing; Cheng, Yiyu

    2010-06-01

    Although some important biomarkers for myocardial injury have been identified, there still lacks a systematic view of the development and progression of myocardial infarction, including enzymatic regulation, metabolite levels, fluxes, etc., which are pivotal to elucidate the physiological mechanism of disease. Here we present an untargeted analytical approach based on gas chromatography coupled with mass spectrometry (GC-MS) to map the temporal metabolic profilings in blood sera of myocardial infarction rat model prepared by left coronary artery ligation. Using XCMS software (http://metlin.scripps.edu/download/), data processing was simplified greatly. We identified the changes in circulating levels of 24 metabolites during the myocardial ischemia. By combination of previous proteomic results, it gives rise to a new insight view of energy metabolism changes referring to anaerobic glycolysis, citric acid cycle, fatty acid beta-oxidation, and some amino acids metabolism. With these altered metabolism pathways as possible drug targets, we validated a role for the presented metabonomic profiling in the systematic understanding of the action mechanism of component-complex medicine herbs, such as Radix Ophiopogonis, a widely-used anti-myocardial ischemia herbal medicine in Asia.

  2. 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

  3. Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.

    PubMed

    Park, Ju Yeon; Lee, Sang-Hak; Shin, Min-Jeong; Hwang, Geum-Sook

    2015-01-01

    Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.

  4. 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.

  5. Myocardial metabolism during hypoxia: Maintained lactate oxidation during increased glycolysis

    SciTech Connect

    Mazer, C.D.; Stanley, W.C.; Hickey, R.F.; Neese, R.A.; Cason, B.A.; Demas, K.A.; Wisneski, J.A.; Gertz, E.W. )

    1990-09-01

    In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. ({sup 14}C)lactate and ({sup 13}C)glucose tracers, or ({sup 13}C)lactate and ({sup 14}C)glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer-measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted {sup 14}C-lactate was accounted for by the appearance of {sup 14}CO{sub 2} in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia.

  6. Myocardial iron metabolism in the regulation of cardiovascular diseases in rats.

    PubMed

    Zhao, Na; Sun, Zhidan; Mao, Yuying; Hang, Pengzhou; Jiang, Xing; Sun, Lihua; Zhao, Jinlong; Du, Zhimin

    2010-01-01

    The iron homeostasis plays an important role in cardiac function. To understand how it acts in diabetic and ischemic myocardial injury, we studied the myocardial iron metabolism in diabetic and myocardial ischemic rats. Diabetic rats were induced by intraperitoneal injection of streptozocin (STZ) after intragastric administration of a high-fat diet while the ischemic rat hearts were subjected to coronary artery ligation for 0.5, 1, 6, 12 or 24 h, respectively. In STZ-induced diabetic rats, the contents of serum and myocardial iron were found elevated obviously accompany with the decrease of hepatic iron determined by the flame emission atomic absorption spectroscopy. The levels of superoxide dismutase (SOD), malonaldehyde (MDA) and serum ferritin were increased in diabetic rats. Moreover, protein level of divalent metal transporter 1 (DMT1) was decreased while that for transferrin receptor (TfR) and metal transporter protein 1 (MTP1) was increased. In contrast, no alteration of iron concentration was observed in the ischemic rats. The expression of DMT1, TfR and MTP1 has not changed after infraction. The findings suggested that diabetes mellitus (DM) induced the iron overload in the myocardium, at least in part by up-regulation of TfR. Meanwhile, down-regulation of DMT1 and up-regulation of MTP1 were induced to alleviate the excessive iron in the myocardium. However, myocardial infraction (MI) has not broken the balance of myocardial iron. In conclusion, the iron homeostasis reacts differently in DM and MI. PMID:20511703

  7. Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine.

    PubMed

    Stanley, W C; Hall, J L; Smith, K R; Cartee, G D; Hacker, T A; Wisneski, J A

    1994-01-01

    We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 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

  9. 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

  10. 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

  11. 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.

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

    PubMed

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

    2013-02-01

    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 [(13)C(6),(15)N]-L-leucine (3.7 mM) alone or with [2-(13)C]-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.

  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. 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

  16. 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.

  17. 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.

  18. The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics.

    PubMed

    Liu, Yue-tao; Jia, Hong-mei; Chang, Xing; Ding, Gang; Zhang, Hong-wu; Zou, Zhong-Mei

    2013-11-01

    Myocardial infarction (MI) is a leading cause of morbidity and mortality but the precise mechanism of its pathogenesis remains obscure. To achieve the most comprehensive screening of the entire metabolome related to isoproterenol (ISO) induced-MI, we present a tissue targeted metabonomic study using an integrated approach of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) and proton nuclear magnetic resonance (1H NMR). Twenty-two metabolites were detected as potential biomarkers related to the formation of MI, and the levels of pantothenic acid (), lysoPC(18:0) (), PC(18:4(6Z,9Z,12Z,15Z)/18:0) (), taurine (), lysoPC(20:3(8Z,11Z,14Z)) (), threonine (), alanine (), creatine (), phosphocreatine (), glucose 1-phosphate (), glycine (), xanthosine (), creatinine () and glucose () were decreased significantly, while the concentrations of histamine (), L-palmitoylcarnitine (), GSSG (), inosine (), arachidonic acid (), linoelaidic acid (), 3-methylhistamine () and glycylproline () were increased significantly in the MI rats compared with the control group. The identified potential biomarkers were involved in twelve metabolic pathways and achieved the most entire metabolome contributing to the injury of the myocardial tissue. Five pathways, including taurine and hypotaurine metabolism, glycolysis, arachidonic acid metabolism, glycine, serine and threonine metabolism and histidine metabolism, were significantly influenced by ISO-treatment according to MetPA analysis and suggested that the most prominent changes included inflammation, interference of calcium dynamics, as well as alterations of energy metabolism in the pathophysiologic process of MI. These findings provided a unique perspective on localized metabolic information of ISO induced-MI, which gave us new insights into the pathogenesis of MI, discovery of targets for clinical diagnosis and treatment.

  19. 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

  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.

  1. CD36 Protein Influences Myocardial Ca2+ Homeostasis and Phospholipid Metabolism

    PubMed Central

    Pietka, Terri A.; Sulkin, Matthew S.; Kuda, Ondrej; Wang, Wei; Zhou, Dequan; Yamada, Kathryn A.; Yang, Kui; Su, Xiong; Gross, Richard W.; Nerbonne, Jeanne M.; Efimov, Igor R.; Abumrad, Nada A.

    2012-01-01

    Sarcolemmal CD36 facilitates myocardial fatty acid (FA) uptake, which is markedly reduced in CD36-deficient rodents and humans. CD36 also mediates signal transduction events involving a number of cellular pathways. In taste cells and macrophages, CD36 signaling was recently shown to regulate store-responsive Ca2+ flux and activation of Ca2+-dependent phospholipases A2 that cycle polyunsaturated FA into phospholipids. It is unknown whether CD36 deficiency influences myocardial Ca2+ handling and phospholipid metabolism, which could compromise the heart, typically during stresses. Myocardial function was examined in fed or fasted (18–22 h) CD36−/− and WT mice. Echocardiography and telemetry identified conduction anomalies that were associated with the incidence of sudden death in fasted CD36−/− mice. No anomalies or death occurred in WT mice during fasting. Optical imaging of perfused hearts from fasted CD36−/− mice documented prolongation of Ca2+ transients. Consistent with this, knockdown of CD36 in cardiomyocytes delayed clearance of cytosolic Ca2+. Hearts of CD36−/− mice (fed or fasted) had 3-fold higher SERCA2a and 40% lower phospholamban levels. Phospholamban phosphorylation by protein kinase A (PKA) was enhanced after fasting reflecting increased PKA activity and cAMP levels in CD36−/− hearts. Abnormal Ca2+ homeostasis in the CD36−/− myocardium associated with increased lysophospholipid content and a higher proportion of 22:6 FA in phospholipids suggests altered phospholipase A2 activity and changes in membrane dynamics. The data support the role of CD36 in coordinating Ca2+ homeostasis and lipid metabolism and the importance of this role during myocardial adaptation to fasting. Potential relevance of the findings to CD36-deficient humans would need to be determined. PMID:23019328

  2. 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.

  3. 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

  4. 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

  5. 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

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

    PubMed

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

    2009-07-01

    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, Ppar alpha-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.

  7. 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

  8. 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

  9. GRK2 – A Link Between Myocardial Contractile Function and Cardiac Metabolism

    PubMed Central

    Woodall, Meryl C.; Ciccarelli, Michele; Woodall, Benjamin P.; Koch, Walter J.

    2014-01-01

    Heart failure (HF) causes a tremendous burden on the worldwide healthcare system, affecting more than 23 million people. There are many cardiovascular disorders that contribute to the development of HF and multiple risk factors that accelerate its occurrence, but regardless of its underlying cause, HF is characterized by a marked decrease in myocardial contractility and loss of pump function. One biomarker molecule consistently shown to be upregulated in human HF and several animal models is G protein-coupled receptor (GPCR) kinase 2 (GRK2), a kinase originally discovered to be involved in GPCR desensitization, especially β-adrenergic receptors (βARs). Indeed, higher levels of GRK2 can impair βAR-mediated inotropic reserve and its inhibition or molecular reduction has shown to improve pump function in several animal models including a pre-clinical pig model of HF. Recently, non-classical roles for GRK2 in cardiovascular disease have been described, including negative regulation of insulin signaling, a role in myocyte cell survival and apoptotic signaling, and it has been shown to be localized in/on mitochondria. These new roles of GRK2 suggest that GRK2 may be a nodal link in the myocyte, influencing both cardiac contractile function and cell metabolism and survival and contributing to HF independent of its canonical role on GPCR desensitization. In this review, classical and non-classical roles for GRK2 will be discussed, focusing on recently discovered roles for GRK2 in cardiomyocyte metabolism and the effects that these roles may have on myocardial contractile function and HF development. PMID:24812353

  10. The relationship between biventricular myocardial performance and metabolic parameters during incremental exercise and recovery in healthy adolescents.

    PubMed

    Pieles, Guido E; Gowing, Lucy; Forsey, Jonathan; Ramanujam, Paramanantham; Miller, Felicity; Stuart, A Graham; Williams, Craig A

    2015-12-15

    Background left ventricular (LV) and right ventricular (RV) myocardial reserve during exercise in adolescents has not been directly characterized. The aim of this study was to quantify myocardial performance response to exercise by using two-dimensional (2-D) speckle tracking echocardiography and describe the relationship between myocardial reserve, respiratory, and metabolic exercise parameters. A total of 23 healthy boys and girls (mean age 13.2 ± 2.7 yr; stature 159.1 ± 16.4 cm; body mass 49.5 ± 16.6 kg; BSA 1.47 ± 0.33 m(2)) completed an incremental cardiopulmonary exercise test (25 W · 3 min increments) with simultaneous acquisition of 2-D transthoracic echocardiography at rest, each exercise stage up to 100 W, and in recovery at 2 min and 10 min. Two-dimensional LV (LV Sl) and RV (RV Sl) longitudinal strain and LV circumferential strain (LV Sc) were analyzed to define the relationship between myocardial performance reserve and metabolic exercise parameters. Participants achieved a peak oxygen uptake (V̇o 2peak) of 40.6 ± 8.9 ml · kg(-1) · min(-1) and a work rate of 154 ± 42 W. LV Sl and LV Sc and RV Sl increased significantly across work rates (P < 0.05). LV Sl during exercise was significantly correlated to resting strain, V̇o 2peak, oxygen pulse, and work rate (0.530 ≤ r ≤ 0.784, P < 0.05). This study identifies a positive and moderate relationship between LV and RV myocardial performance and metabolic parameters during exercise by using a novel methodology. Relationships detected present novel data directly describing myocardial adaptation at different stages of exercise and recovery that in the future can help directly assess cardiac reserve in patients with cardiac pathology.

  11. Comparison of Components of Metabolic Syndrome in Premature Myocardial Infarction in an Iranian Population: A Case -Control Study

    PubMed Central

    Kazemi, Toba; Sharifzadeh, Gholamreza; Zarban, Asghar; Fesharakinia, Azita

    2013-01-01

    Background: Metabolic syndrome is a major risk factor for coronary artery disease (CAD). Aim: Aim of this study was to determine the prevalence of metabolic syndrome in patients with premature myocardial infarction (before 50 years of age). Methods: In this case–control study, we compared 98 consecutive patients who were hospitalized in Birjand with acute first myocardial infarction before the age of 50 years and 98 age- and sex-matched healthy controls without a history of coronary artery disease. The case and control groups were categorized according to the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) metabolic syndrome criteria [presence of ≥3 of the following: Fasting blood glucose ≥100 mg/dL, triglyceride (TG) level ≥150 mg/dL, low high density lipoprotein (HDL; <40 mg/dL in men and <50 mg/dL in women), blood pressure ≥130/85 mm Hg, and waist circumference >102 cm in men or 88 cm in women]. The data were collected and analyzed by t-test, χ2, and logistic regression in SPSS software 11.5. Results: Prevalence of metabolic syndrome was significantly higher in cases than in control group (34.7% in cases, 16.3% in controls, P=0.003). All components of metabolic syndrome except high waist circumstance in the cases group were significantly higher than in control. The most common component of metabolic syndrome was high TG and the least common component was low HDL. Conclusion: We conclude that prevalence of metabolic syndrome in patients with premature myocardial infarction is high; high TG is the most common component of metabolic syndrome. PMID:23411742

  12. Renin Inhibition and AT1R blockade improve metabolic signaling, oxidant stress and myocardial tissue remodeling

    PubMed Central

    Whaley-Connell, Adam; Habibi, Javad; Rehmer, Nathan; Ardhanari, Sivakumar; Hayden, Melvin R; Pulakat, Lakshmi; Krueger, Caroline; M Ferrario, Carlos; DeMarco, Vincent G; Sowers, James R

    2013-01-01

    Objective Strategies that block angiotensin II actions on its angiotensin type 1 receptor or inhibit actions of aldosterone have been shown to reduce myocardial hypertrophy and interstitial fibrosis in states of insulin resistance. Thereby, we sought to determine if combination of direct renin inhibition with angiotensin type 1 receptor blockade in vivo, through greater reductions in systolic blood pressure (SBP) and aldosterone would attenuate left ventricular hypertrophy and interstitial fibrosis to a greater extent than either intervention alone. Materials/Methods We utilized the transgenic Ren2 rat which manifests increased tissue expression of murine renin which, in turn, results in increased renin-angiotensin system activity, aldosterone secretion and insulin resistance. Ren2 rats were treated with aliskiren, valsartan, the combination (aliskiren+valsartan), or vehicle for 21 days. Results Compared to Sprague-Dawley controls, Ren2 rats displayed increased systolic blood pressure, elevated serum aldosterone levels, cardiac tissue hypertrophy, interstitial fibrosis and ultrastructural remodeling. These biochemical and functional alterations were accompanied by increases in the NADPH oxidase subunit Nox2 and 3-nitrotyrosine content along with increases in mammalian target of rapamycin and reductions in protein kinase B phosphorylation. Combination therapy contributed to greater reductions in systolic blood pressure and serum aldosterone but did not result in greater improvement in metabolic signaling or markers of oxidative stress, fibrosis or hypertrophy beyond either intervention alone. Conclusions Thereby, our data suggest that the greater impact of combination therapy on reductions in aldosterone does not translate into greater reductions in myocardial fibrosis or hypertrophy in this transgenic model of tissue renin overexpression. PMID:23352204

  13. Energetic myocardial metabolism and oxidative stress: let's make them our friends in the fight against heart failure.

    PubMed

    Scolletta, Sabino; Biagioli, Bonizella

    2010-03-01

    Heart failure (HF) is a syndrome causing a huge burden in morbidity and mortality worldwide. Current medical therapies for HF are aimed at suppressing the neurohormonal activation. However, novel therapies are needed for HF, independent of the neurohormonal axis, that can improve cardiac performance and prevent the progression of heart dysfunction. The modulation of cardiac metabolism may represent a new approach to the treatment of HF. The healthy heart converts chemical energy stored in fatty acids (FA) and glucose. Utilization of FA costs more oxygen per unit of ATP generated than glucose, and the heart gets 60-90% of its energy for oxidative phosphorylation from FA oxidation. The failing heart has been demonstrated to be metabolically abnormal, in both animal models and in patients, showing a shift toward an increased glucose uptake and utilization. The manipulation of myocardial substrate oxidation toward greater carbohydrate oxidation and less FA oxidation may improve ventricular performance and slow the progression of heart dysfunction. Impaired mitochondrial function and oxidative phosphorylation can reduce cardiac function by providing an insufficient supply of ATP to cardiomyocytes and by increasing myocardial oxidative stress. Although there are no effective stimulators of oxidative phosphorylation, several classes of drugs have been shown to open mitochondrial K(ATP) channels and, indirectly, to improve cardiac protection against oxidative stress. This article focuses on the energetic myocardial metabolism and oxidative status in the normal and failing heart, and briefly, it overviews the therapeutic potential strategies to improve cardiac energy and oxidative status in HF patients.

  14. 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.

  15. 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.

  16. 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

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

    PubMed

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

    2015-07-15

    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.

  18. 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

  19. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase.

    PubMed

    Constantin-Teodosiu, D; Greenhaff, P L; Gardiner, S M; Randall, M D; March, J E; Bennett, T

    1995-12-01

    1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.

  20. 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

  1. 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

  2. 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.

  3. Atorvastatin administered before myocardial infarction in rats improves contractility irrespective of metabolic changes.

    PubMed

    Lehnen, Tatiana Ederich; Lehnen, Alexandre Machado; Tavares, Angela Maria Vicente; Belló-Klein, Adriane; Markoski, Melissa Medeiros; Machado, Ubiratan Fabres; Schaan, Beatriz

    2014-12-01

    Statins have a beneficial effect after myocardial infarction, but the relationship between glucose transporters and their use before the event has not yet been studied. We assessed the effects of atorvastatin treatment pre- and post-myocardial infarction on cardiovascular function and glucose transporter 4 (GLUT4) in the heart. Wistar-Kyoto rats were treated with 20 mg/kg atorvastatin or vehicle for 14 days before coronary artery occlusion surgery (myocardial infarction) or sham surgery. Echocardiographic evaluations were carried out 48 h after myocardial infarction (protocol A) and after 7 days (protocol B), when atorvastatin was also administered. Plasma inflammatory markers and GLUT4 in the heart were also evaluated. Animals were divided into the following groups: sham-operated and vehicle (C), myocardial infarction and vehicle (I), sham-operated and atorvastatin (CAt) and myocardial infarction and atorvastatin (IAt). After 48 h, myocardial infarction induced higher left ventricular fractional shortening in IAt versus I (~ 60%, P = 0.036), and the ejection fraction was lower (protocol A ~ 37%; protocol B ~ 30%). Myocardial infarction was associated with a rise in plasma membrane GLUT4 after 48 h (~ 40%, P < 0.001), and a reduction in GLUT4 after 7 days (I 25%; IAt 49%, P < 0.001). Atorvastatin treatment for 48 h after the infarction did not change GLUT4 expression, and after 7 days it had an additional negative effect on GLUT4 content (~ 39%, P = 0.030). In conclusion, atorvastatin treatment pre- and post-myocardial infarction improved myocardial contractility after 48 h, but not after 7 days, and was not associated with an increase in GLUT4 expression.

  4. 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

  5. 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.

  6. 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

  7. Immunological Derangement in Hypocellular Myelodysplastic Syndromes

    PubMed Central

    Serio, B; Risitano, AM; Giudice, V; Montuori, N; Selleri, C

    2014-01-01

    Hypocellular or hypoplastic myelodysplastic syndromes (HMDS) are a distinct subgroup accounting for 10–15% of all MDS patients, that are characterized by the presence of bone marrow (BM) hypocellularity, various degree of dysmyelopoiesis and sometimes abnormal karyotype. Laboratory and clinical evidence suggest that HMDS share several immune-mediated pathogenic mechanisms with acquired idiopathic aplastic anemia (AA). Different immune-mediated mechanisms have been documented in the damage of marrow hematopoietic progenitors occurring in HMDS; they include oligoclonal expansion of cytotoxic T lymphocytes (CTLs), polyclonal expansion of various subtypes of T helper lymphocytes, overexpression of FAS-L and of the TNF–related apoptosis-inducing ligand (TRAIL), underexpression of Flice-like inhibitory protein long isoform (FLIPL) in marrow cells as well as higher release of Th1 cytokines, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). It has also been documented that some HMDS patients have higher frequency of polymorphisms linked both to high production of proinflammatory cytokines such as TNF-α and transforming growth factor-β and to the inhibition of T-cell mediated immune responses such as interleukin-10, further suggesting that immune-mediated mechanisms similar to those seen in AA patients may also operate in HMDS. Clinically, the strongest evidence for immune–mediated hematopoietic suppression in some HMDS is the response to immunosuppression including mainly cyclosporine, anti-thymocyte globulin and/or cyclosporine, or alemtuzumab. Here we review all these immune mechanisms as well as the influence of this deranged cellular and humoral immunologic mileau on the initiation and possible progression of MDS. All these observations are pivotal not only for a better understanding of MDS pathophysiology, but also for their immediate clinical implications, eventually leading to the identification of MDS patients who may benefit from

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Myocardial metabolism of 123I-BMIPP during low-flow ischaemia in an experimental model: comparison with myocardial blood flow and 18F-FDG.

    PubMed

    Hosokawa, R; Nohara, R; Fujibayashi, Y; Hirai, T; Fujita, M; Magata, Y; Tadamura, E; Konishi, J; Sasayama, S

    2001-11-01

    Risk stratification of coronary artery disease may provide a basis for selection of treatment to prevent myocardial events and to assist functional recovery. Iodine-123 (rho-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) is a radioiodinated fatty acid analogue for single-photon emission tomographic (SPET) imaging, and several reports have demonstrated that the abnormal uptake of 123I-BMIPP is associated with wall motion abnormality and severe coronary artery stenosis. Clarification of the contribution of fatty acids to myocardial metabolism would be highly valuable in recognising this critical condition. In this study, we investigated the myocardial uptake of 123I-BMIPP under low-flow ischaemia, and compared it with the uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). Using open chest dogs, the flow of the left anterior descending coronary artery was controlled using a pneumatic occluder in order to maintain a 30%-40% reduction of Doppler flow. 123I-BMIPP and 18F-FDG were injected into the left atrium after 90 min of ischaemia (protocols 1 and 3). Canine hearts were excised after 120 min of ischaemia for the measurement of radioactivity. In protocol 2, 123I-BMIPP alone was injected and hearts were excised 8 min after the injection. A time-course biopsy study was also performed at the same time (protocol 3). Wall thickening was evaluated using a wall tracker module. The uptake of 18F-FDG increased significantly in the ischaemic region (232%+/-135% vs non-ischaemic, P<0.05 in protocol 1) even on mild reduction of myocardial blood flow (MBF). The increased uptake of 18F-FDG did not correlate well with the severity of MBF. On the other hand, 123I-BMIPP uptake decreased gradually (78.9%+/-23.6%, P<0.05 in protocol 1, and 85.9%+/-24.3% in protocol 2) in the ischaemic region, specifically in the endocardium (64.0%+/-28.9%, P<0.05 in protocol 1, and 75.1%+/-28.8%, P<0.05 in protocol 2), and correlated strongly with MBF (r=0.93 in protocol 1 and r=0.97 in

  14. 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

  15. 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.

  16. 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.

  17. Biochemical rationale for the use of fatty acid analogs as agents for studying myocardial metabolism

    SciTech Connect

    Elmaleh D.R.; Livni E.; Brownell, G.L.; Strauss, H.W.

    1987-01-01

    Since fatty acids are the major energy source for myocardial contractile work, the rate of utilization of these substrates/unit work performed, should be an indicator of the health of the muscle. (1-C-11) palmitic acid has been shown to be useful as a myocardial imaging agent for positron tomography. The main limitations for the use of this substrate are the fast washout and translocation of the activity from the normal myocardium and the back diffusion in ischemia. Since alpha and omega oxidation are only present to a limited degree, branched chain fatty acids should have a prolonged residence time in the myocardium. The similarity in structure, chain length, solubility, and charge of the branched to the non-branched fatty acids should make these compounds behave in similar fashion in terms of their blood clearance and entry into tissues. 15 refs., 3 tabs.

  18. 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...

  19. 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.

  20. Temporal analysis of myocardial glucose metabolism by 2-( sup 18 F)fluoro-2-deoxy-D-glucose

    SciTech Connect

    Nguyen, V.T.; Mossberg, K.A.; Tewson, T.J.; Wong, W.H.; Rowe, R.W.; Coleman, G.M.; Taegtmeyer, H. )

    1990-10-01

    To assess kinetic changes of myocardial glucose metabolism after physiological interventions, we perfused isolated working rat hearts with glucose and 2-(18F)fluoro-2-deoxy-D-glucose (2-FDG). Tissue uptake of 2-FDG and the input function were measured on-line by external detection. The fractional rate of 2-FDG phosphorylation was determined by graphical analysis of time-activity curves. The steady-state uptake of 2-FDG was linear with time, and the tracer was retained predominantly in its phosphorylated form. Tissue accumulation of 2-FDG decreased with a reduction in work load and with the addition of competing substrates. Insulin caused a significant increase in 2-FDG accumulation in hearts from fasted but not from fed animals. We conclude that in the isolated working rat heart there is rapid adjustment of exogenous substrate utilization and that most interventions known to alter glucose metabolism induce parallel changes in 2-FDG uptake. Qualitative differences in the in vitro response to insulin may be affected by the presence of either endogenous insulin or glycogen.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Influence of GLP-1 on Myocardial Glucose Metabolism in Healthy Men during Normo- or Hypoglycemia

    PubMed Central

    Gejl, Michael; Lerche, Susanne; Mengel, Annette; Møller, Niels; Bibby, Bo Martin; Smidt, Kamille; Brock, Birgitte; Søndergaard, Hanne; Bøtker, Hans Erik; Gjedde, Albert; Holst, Jens Juul; Hansen, Søren Baarsgaard; Rungby, Jørgen

    2014-01-01

    Background and Aims Glucagon-like peptide-1 (GLP-1) may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake (MGU). We assessed the effects of GLP-1 on MGU in healthy subjects during normo- and hypoglycemia. Materials and Methods We included eighteen healthy men in two randomized, double-blinded, placebo-controlled cross-over studies. MGU was assessed with GLP-1 or saline infusion during pituitary-pancreatic normo- (plasma glucose (PG): 4.5 mM, n = 10) and hypoglycemic clamps (PG: 3.0 mM, n = 8) by positron emission tomography with 18fluoro-deoxy-glucose (18F-FDG) as tracer. Results In the normoglycemia study mean (± SD) age was 25±3 years, and BMI was 22.6±0.6 kg/m2 and in the hypoglycemia study the mean age was 23±2 years with a mean body mass index of 23±2 kg/m2. GLP-1 did not change MGU during normoglycemia (mean (+/− SD) 0.15+/−0.04 and 0.16+/−0.03 µmol/g/min, P = 0.46) or during hypoglycemia (0.16+/−0.03 and 0.13+/−0.04 µmol/g/min, P = 0.14). However, the effect of GLP-1 on MGU was negatively correlated to baseline MGU both during normo- and hypoglycemia, (P = 0.006, r2 = 0.64 and P = 0.018, r2 = 0.64, respectively) and changes in MGU correlated positively with the level of insulin resistance (HOMA 2IR) during hypoglycemia, P = 0.04, r2 = 0.54. GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia study. No differences in other circulating hormones or metabolites were found. Conclusions While GLP-1 does not affect overall MGU, GLP-1 induces changes in MGU dependent on baseline MGU such that GLP-1 increases MGU in subjects with low baseline MGU and decreases MGU in subjects with high baseline MGU. GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects. ClinicalTrials.gov registration numbers: NCT00418288

  8. Positron emission tomography demonstrates that coronary sinus retroperfusion can restore regional myocardial perfusion and preserve metabolism

    SciTech Connect

    O'Byrne, G.T.; Nienaber, C.A.; Miyazaki, A.; Araujo, L.; Fishbein, M.C.; Corday, E.; Schelbert, H.R. )

    1991-07-01

    Positron emission tomography was used to image blood flow and metabolic tracers in risk zone myocardium after left anterior descending coronary artery occlusion during synchronized coronary venous retroperfusion. Six control and seven intervention open chest dogs had occlusion of the mid left anterior descending coronary artery. Synchronized retroperfusion commenced 25 min later. Flow tracers (rubidium-82 and nitrogen-13 ammonia) were injected retrogradely. Three hours after coronary occlusion, fluorine-18 (F-18) deoxyglucose uptake in the control and treatment groups was compared. At 200 min of occlusion, infarct size was assessed. Retrograde flow tracer uptake was observed in the risk zone in the seven intervention dogs. Fluorine-18 deoxyglucose uptake in the risk zone was increased in five of the six intervention dogs but was reduced in five of the six control dogs. The risk zone to normal zone F-18 deoxyglucose count ratio was higher in the intervention than the control group (1.13 {plus minus} 0.39 vs. 0.59 {plus minus} 0.51; p less than 0.05). The endocardial subsegment risk zone to normal zone F-18 deoxyglucose count ratio was also significantly higher in the intervention group. Percent infarction in the risk zone was 70% lower in the group treated with synchronized retroperfusion than in the control group (18.4 {plus minus} 22.6% vs. 61.2 {plus minus} 25.4%; p less than 0.02). Thus, positron emission tomography revealed that retroperfusion could deliver oxygenated blood and maintain metabolism in risk zone myocardium. Infarct size was limited to 30% of that of control. In acute closure of the left anterior descending coronary artery, synchronized retroperfusion might be considered for maintaining viability of the jeopardized myocardium if the artery cannot be reopened rapidly.

  9. 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.

  10. General joint hypermobility and temporomandibular joint derangement in adolescents.

    PubMed Central

    Westling, L; Mattiasson, A

    1992-01-01

    Joint mobility was assessed in each member of an epidemiological sample of 96 girls and 97 boys, 17 years old, and graded by means of the hypermobility score of Beighton et al. Twenty two per cent of the girls and 3% of the boys could perform five or more of the nine manoeuvres. The prevalence of symptoms and signs of internal derangement in the temporomandibular joint was higher in adolescents with hypermobility of joints (score greater than or equal to 5/9). In subjects with a high mobility score oral parafunctions (overuse) correlated more strongly with several signs and symptoms of craniomandibular disorder than in those with a low score. PMID:1540046

  11. 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.

  12. Effects of substitution of Cx43 by Cx32 on myocardial energy metabolism, tolerance to ischaemia and preconditioning protection

    PubMed Central

    Rodríguez-Sinovas, Antonio; Sánchez, Jose A; González-Loyola, Alejandra; Barba, Ignasi; Morente, Miriam; Aguilar, Rio; Agulló, Esperanza; Miró-Casas, Elisatet; Esquerda, Neus; Ruiz-Meana, Marisol; García-Dorado, David

    2010-01-01

    Connexin 43 (Cx43) plays an important role in cardioprotective signalling by mechanisms at least in part independent of gap junctional communication. To investigate whether this role is related to specific properties of this connexin isoform, we used a knock-in mouse model in which the coding region of Cx43 is replaced by that of Cx32. Homozygous Cx43KI32 mice showed reduced cell-to-cell Lucifer Yellow transfer (P < 0.01), but QRS duration and left ventricular fractional shortening (echocardiography) were similar to those in wild-type animals. NMR spectroscopy detected reduced ATP and increased lactate content in myocardium from homozygous Cx43KI32 animals (P < 0.05). Despite this, isolated homozygous Cx43KI32 hearts showed smaller infarcts after ischaemia–reperfusion (40 min/60 min) as compared to hearts from heterozygous and wild-type animals (13 and 31% reduction, respectively, P < 0.05). Cardiac myocytes isolated from Cx43KI32 mouse hearts also showed a reduced rate of cell death after simulated ischaemia–reperfusion. In a separate series of experiments, both ischaemic (4 cycles of 3.5 min of ischaemia and 5 min of reperfusion) and pharmacological (50 μmol l−1 diazoxide, 10 min) preconditioning reduced infarct size in hearts from wild-type mice (by 24.84 and 26.63%, respectively, P < 0.05), but only ischaemic preconditioning was effective in hearts from heterozygous animals and both preconditioning strategies failed to protect Cx43KI32 homozygous hearts. These results demonstrate that Cx43 has an important and previously unknown modulatory effect in myocardial energy metabolism and tolerance to ischaemia, and plays a critical role in preconditioning protection, by mechanisms that are specific for this connexin isoform. PMID:20156849

  13. Myocardial metabolism of free fatty acids. Studies with /sup 14/C-labeled substrates in humans

    SciTech Connect

    Wisneski, J.A.; Gertz, E.W.; Neese, R.A.; Mayr, M.

    1987-02-01

    Free fatty acids are considered to be the major energy source for the myocardium. To investigate the metabolic fate of this substrate in humans, 24 subjects underwent coronary sinus and arterial catheterization. 13 subjects were healthy volunteers and 11 subjects had symptoms of ischemic heart disease. (1-/sup 14/C)oleate or (1-/sup 14/C)palmitate bound to albumin was infused at a constant rate of 25 microCi/h. Oxidation was determined by measuring the /sup 14/CO/sub 2/ production. The data demonstrated that a high percentage (84 +/- 17%) of the palmitate and oleate extracted by the myocardium underwent rapid oxidation. A highly significant correlation was present between the arterial level and the amount oxidized (r = 0.82, P less than 0.001 for palmitate; r = 0.77, P less than 0.001 for oleate). The isotope extraction ratio was greater than the chemical extraction ratio. This difference of 6 +/- 2 nmol/ml of blood in the young normal subjects was significantly less than the 12 +/- 4 nmol/ml observed in the ischemic heart disease patients (P less than 0.001).

  14. Phosphorylation at Connexin43 Serine-368 Is Necessary for Myocardial Conduction During Metabolic Stress.

    PubMed

    Nassal, Michelle M J; Werdich, Andreas A; Wan, Xiaoping; Hoshi, Malcolm; Deschênes, Isabelle; Rosenbaum, David S; Donahue, J Kevin

    2016-01-01

    Connexin43 (Cx43) phosphorylation alters gap junction localization and function. In particular, phosphorylation at serine-368 (S368) has been suggested to alter gap junctional conductance, but previous reports have shown inconsistent results for both timing and functional effects of S368 phosphorylation. The objective of this study was to determine the functional effects of isolated S368 phosphorylation. We evaluated wild-type Cx43 (AdCx43) and mutations simulating permanent phosphorylation (Ad368E) or preventing phosphorylation (Ad368A) at S368. Function was assessed by optical mapping of electrical conduction in patterned cultures of neonatal rat ventricular myocytes, under baseline and metabolic stress (MS) conditions. Baseline conduction velocity (CV) was similar for all groups. In the AdCx43 and Ad368E groups, MS moderately decreased CV. Ad368A caused complete conduction block during MS. Triton-X solubility assessment showed no change in Cx43 location during conduction impairment. Western blot analysis showed that Cx43-S368 phosphorylation was present at baseline, and that it decreased during MS. Our data indicate that phosphorylation at S368 does not affect CV under baseline conditions, and that preventing S368 phosphorylation makes Cx43 hypersensitive to MS. These results show the critical role of S368 phosphorylation during stress conditions.

  15. 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

  16. 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

    2016-07-26

    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.

  17. 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

  18. Theophylline produces an adverse effect on myocardial lactate metabolism at a therapeutic serum concentration: an effect blocked by verapamil.

    PubMed

    Bittar, G; Friedman, H S; Dominguez, A; Vorperian, V

    1991-04-01

    To assess the actions of theophylline on coronary blood flow and myocardial energetics, 1 mg/kg/min of this methylxanthine was infused i.v. in the dog for 15 min, producing an average concentration of 18 +/- 3 micrograms/ml. Heart rate increased by 20 +/- 7 min-1, P less than .05, but left ventricular (LV) systolic and end-diastolic pressures, cardiac output and LV peak dp/dt did not change. Although coronary vascular resistance decreased by 0.26 +/- 0.08 mm Hg/ml/min, P less than .05, coronary flow and myocardial oxygen consumption and extraction did not change. Myocardial lactate extraction decreased, from 22 +/- 2 to 1 +/- 5%, P less than .05. The decrement in lactate extraction was not related to heart rate, but to the change in LV peak dp/dt, r = 0.74, P less than .05. Furthermore, with verapamil, 0.2 mg/kg, pretreatment, and 0.2 mg/kg, during the theophylline infusion, reduction in lactate extraction was blocked and LV peak dp/dt increased by 843 +/- 311 mm Hg/sec, P less than .05. Thus, at therapeutic concentrations, theophylline reduces myocardial lactate extraction, an effect that is associated with the absence of the expected inotropic actions of theophylline. However, when verapamil is administered with theophylline, a reduction of myocardial extraction does not occur and myocardial inotropy is enhanced.

  19. N-Acetylcysteine Administration Prevents Nonthyroidal Illness Syndrome in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial

    PubMed Central

    Vidart, Josi; Wajner, Simone Magagnin; Leite, Rogério Sarmento; Manica, André; Schaan, Beatriz D.; Larsen, P. Reed

    2014-01-01

    Context: The acute phase of the nonthyroidal illness syndrome (NTIS) is characterized by low T3 and high rT3 levels, affecting up to 75% of critically ill patients. Oxidative stress has been implicated as a causative factor of the disturbed peripheral thyroid hormone metabolism. Objective: The objective of the study was to investigate whether N-acetylcysteine (NAC), a potent intracellular antioxidant, can prevent NTIS in patients with acute myocardial infarction. Design: This was a randomized, multicenter clinical trial. Settings: Consecutive patients admitted to the emergency and intensive care units of two tertiary hospitals in southern Brazil were recruited. Patients and intervention included 67 patients were randomized to receive NAC or placebo during 48 hours. Baseline characteristics and blood samples for thyroid hormones and oxidative parameters were collected. Main Outcome: Variation of serum T3 and rT3 levels was measured. Results: Baseline characteristics were similar between groups (all P > .05). T3 levels decreased in the placebo group at 12 hours of follow-up (P = .002) but not in NAC-treated patients (P = .10). Baseline rT3 levels were elevated in both groups and decreased over the initial 48 hours in the NAC-treated patients (P = .003) but not in the control group (P = .75). The free T4 and TSH levels were virtually identical between the groups throughout the study period (P > .05). Measurement of total antioxidant status and total carbonyl content demonstrated that oxidative balance was deranged in acute myocardial infarction patients, whereas NAC corrected these alterations (P < .001). Conclusions: NAC administration prevents the derangement in thyroid hormone concentrations commonly occurring in the acute phase of acute myocardial infarction, indicating that oxidative stress is involved in the NTIS pathophysiology. PMID:25148231

  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.

  1. 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

  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. Metabolomic profiling reveals distinct patterns of myocardial substrate utilization in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia-reperfusion

    PubMed Central

    Turer, Aslan T.; Stevens, Robert D.; Bain, James R.; Muehlbauer, Michael J.; van der Westhuizen, Johannes; Mathew, Joseph P.; Schwinn, Debra A.; Glower, Donald D.; Newgard, Christopher B.; Podgoreanu, Mihai V.

    2009-01-01

    Background Human myocardial metabolism has been incompletely characterized in the setting of surgical cardioplegic arrest and ischemia/reperfusion. Furthermore, the effect of pre-existing ventricular state on ischemia-induced metabolic derangements has not been established. Methods and Results We applied a mass spectrometry-based platform to profile 63 intermediary metabolites in serial paired peripheral arterial and coronary sinus blood effluents obtained from 37 patients undergoing cardiac surgery, stratified by presence of coronary artery disease (CAD) and left ventricular dysfunction (LVD). The myocardium was a net user of a number of fuel substrates before ischemia, with significant differences between patients with or without CAD. Following reperfusion, there were significantly lower extraction ratios of most substrates and significant release of two specific acylcarnitine species, acetyl-carnitine and 3-hydroxybutyryl-carnitine. These changes were especially evident in patients with impaired ventricular function, who exhibited profound limitations in extraction of all forms of metabolic fuels. Principal component analysis highlighted several metabolic groupings as potentially important in post-operative clinical course. Conclusions The pre-existing ventricular state is associated with significant differences in myocardial fuel uptake at baseline and following I/R. The dysfunctional ventricle is associated with global suppression of metabolic fuel uptake, and limited myocardial metabolic reserve and flexibility following global I/R stress associated with cardiac surgery. Altered metabolic profiles following I/R are associated with post-operative hemodynamic course, and suggest a role for perioperative metabolic monitoring and targeted optimization in cardiac surgical patients. PMID:19307475

  4. 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...

  5. Restoration of glucose metabolism in leptin-resistant mouse hearts after acute myocardial infarction through the activation of survival kinase pathways.

    PubMed

    Witham, William; Yester, Keith; O'Donnell, Christopher P; McGaffin, Kenneth R

    2012-07-01

    In the normal heart, leptin modulates cardiac metabolism. It is unknown, however, what effect leptin has on cardiac metabolism and outcomes in acute myocardial infarction (MI). This study was performed to test the hypothesis that leptin signaling increases glucose metabolism and attenuates injury in the acutely infarcted heart. Mice with (ObR(+/+)) and without (ObR(-/-)) cardiomyocyte specific expression of leptin receptor (ObR) were randomly assigned to experimental MI or sham procedure, and studied 3 days later. ObR(+/+) and ObR(-/-) sham mice were not significantly different in any measured outcome. However, after MI, ObR(-/-) mice had greater cardiac dysfunction, left ventricular dilation, and levels of oxidative stress. These worse indices of cardiac injury in ObR(-/-) mice were associated with attenuated signal transducer and activator of transcription (STAT) 3, phosphatidylinositol-3-kinase (PI3K), and Akt signaling, decreased malonyl CoA content, and reduced mitochondrial pyruvate dehydrogenase and electron transport Complex I, II and IV activities. Furthermore, ObR(-/-) mice maintained high rates of cardiac fatty acid oxidation after MI, whereas ObR(+/+) mice demonstrated a switch away from fatty acid oxidation to glucose metabolism. Restoration of cardiac STAT3, PI3K and Akt activity and mitochondrial function in ObR(-/-) mice post-MI was accomplished by ciliary neurotrophic factor (CNTF), an established STAT3 activator, administered immediately after MI. Moreover, CNTF therapy resulted in mitigation of cardiac structural and functional injury, attenuated levels of oxidative stress, and rescued glucose metabolism in the infarcted ObR(-/-) heart. These data demonstrate that impaired cardiac leptin signaling results in metabolic inflexibility for glucose utilization in the face of cardiac stress, and greater morbidity after MI. Further, these studies show that cardiac glucose metabolism can be restored in leptin-resistant hearts by CNTF-mediated activation

  6. /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.

  7. Application of time-resolved autofluorescence to label-free in vivo optical mapping of changes in tissue matrix and metabolism associated with myocardial infarction and heart failure

    PubMed Central

    Lagarto, João; Dyer, Benjamin T.; Talbot, Clifford; Sikkel, Markus B.; Peters, Nicholas S.; French, Paul M. W.; Lyon, Alexander R.; Dunsby, Chris

    2015-01-01

    We investigate the potential of an instrument combining time-resolved spectrofluorometry and diffuse reflectance spectroscopy to measure structural and metabolic changes in cardiac tissue in vivo in a 16 week post-myocardial infarction heart failure model in rats. In the scar region, we observed changes in the fluorescence signal that can be explained by increased collagen content, which is in good agreement with histology. In areas remote from the scar tissue, we measured changes in the fluorescence signal (p < 0.001) that cannot be explained by differences in collagen content and we attribute this to altered metabolism within the myocardium. A linear discriminant analysis algorithm was applied to the measurements to predict the tissue disease state. When we combine all measurements, our results reveal high diagnostic accuracy in the infarcted area (100%) and border zone (94.44%) as well as in remote regions from the scar (> 77%). Overall, our results demonstrate the potential of our instrument to characterize structural and metabolic changes in a failing heart in vivo without using exogenous labels. PMID:25780727

  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. Temporomandibular joint internal derangement type III: relationship to magnetic resonance imaging findings of internal derangement and osteoarthrosis. An intraindividual approach.

    PubMed

    Emshoff, R; Rudisch, A; Innerhofer, K; Bösch, R; Bertram, S

    2001-10-01

    The purpose of this study was to investigate whether in patients with a clinical unilateral temporomandibular joint (TMJ)-related finding of internal derangement type (ID)-III (disk displacement without reduction) in combination with TMJ-related pain, the intraindividual variable of 'unilateral TMJ ID-III pain' may be linked to subject-related magnetic resonance (MR) imaging findings of TMJ ID, and TMJ osteoarthrosis (OA). The study comprised 48 consecutive TMJ pain patients, who were assigned a clinical unilateral TMJ pain side-related diagnosis of ID-III. Bilateral sagittal and coronal MR images were obtained to establish the presence or absence of TMJ ID and/or OA. Comparison of the TMJ side-related data showed a significant relationship between the clinical finding of TMJ ID-III pain and the MR imaging diagnoses of TMJ ID (P=0.000) and TMJ ID type (P=0.000). There was no correlation between the clinical finding of TMJ ID-III pain and the MR imaging diagnosis of TMJ OA (P=0.217), nor between the MR imaging diagnosis of TMJ OA and that of TMJ ID (P=0.350). Regarding the diagnostic subgroups of TMJ ID, a significant relationship was found between the presence of TMJ OA and the MR imaging diagnoses of TMJ ID type(P=0.002). Use of the Kappa statistical test indicated a fair diagnostic agreement between the presence of TMJ ID-III pain and the MR imaging diagnosis of disk displacement without reduction (DDNR) (K=0.42). The results suggest that TMJ ID-III pain is related to TMJ-related MR imaging diagnoses of ID. Further, the data confirm the biological concept of 'DDNR and OA' as an underlying mechanism in the etiology of TMJ-related pain and dysfunction. PMID:11720040

  10. 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

  11. Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure

    PubMed Central

    Wang, Fang-Fang; Chen, Bao-Xia; Yu, Hai-Yi; Mi, Lin; Li, Zi-Jian; Gao, Wei

    2016-01-01

    Background Growth differentiation factor (GDF)-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure (HF). HF frequently develops after myocardial infarction (MI), contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF. Methods The study consists of a cohort of 179 patients, including stable angina pectoris patients (AP group, n = 50), old MI patients without HF (OMI group, n = 56), old MI patients with HF (OMI-HF group, n = 38) and normal Control group (n = 35). Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide (PINP), type I collagen carboxy-terminal peptide (ICTP), precollagen III N-terminal peptide (PIIINP) and GDF-15 were measured using an enzyme-linked inmunosorbent assay. Results The plasma GDF-15 level was higher in OMI-HF group (1373.4 ± 275.4 ng/L) than OMI group (1036.1 ± 248.6 ng/L), AP group (784.6 ± 222.4 ng/L) and Control group (483.8 ± 186.4 ng/L) (P < 0.001). The indicators of collagen turnover (ICTP, PINP, PIIINP) all increased in the OMI-HF group compared with Control group (3.03 ± 1.02 µg/L vs. 2.08 ± 0.95 µg/L, 22.2 ± 6.6 µg/L vs. 16.7 ± 5.1 µg/L and 13.2 ± 7.9 µg/L vs. 6.4 ± 2.1 µg/L, respectively; P < 0.01). GDF-15 positively correlated with ICTP and PIIINP (r = 0.302, P < 0.001 and r = 0.206, P = 0.006, respectively). GDF-15 positively correlated to the echocardiographic diastolic indicators E/Em and left atrial pressure (r = 0.349 and r = 0.358, respectively; P < 0.01), and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities (Sm) (r = −0.623 and r = −0.365, respectively; P < 0.01). Conclusion Plasma GDF-15 is associated with

  12. 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

  13. 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

  14. Myocardial Bridging

    PubMed Central

    Yuan, Shi-Min

    2016-01-01

    Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results. PMID:27074276

  15. Comparative studies of high performance swimming in sharks II. Metabolic biochemistry of locomotor and myocardial muscle in endothermic and ectothermic sharks.

    PubMed

    Bernal, D; Smith, D; Lopez, G; Weitz, D; Grimminger, T; Dickson, K; Graham, J B

    2003-08-01

    Metabolic enzyme activities in red (RM) and white (WM) myotomal muscle and in the heart ventricle (HV) were compared in two lamnid sharks (shortfin mako and salmon shark), the common thresher shark and several other actively swimming shark species. The metabolic enzymes measured were citrate synthase (CS), an index of aerobic capacity, and lactate dehydrogenase (LDH), an index of anaerobic capacity. WM creatine phosphokinase (CPK) activity, an index of rapid ATP production during burst swimming, was also quantified. Enzyme activities in RM, WM and HV were similar in the two lamnid species. Interspecific comparisons of enzyme activities at a common reference temperature (20 degrees C) show no significant differences in RM CS activity but higher CS activity in the WM and HV of the lamnid sharks compared with the other species. For the other enzymes, activities in lamnids overlapped with those of other shark species. Comparison of the HV spongy and compact myocardial layers in mako, salmon and thresher sharks reveals a significantly greater spongy CS activity in all three species but no differences in LDH activity. Adjustment of enzyme activities to in vivo RM and WM temperatures in the endothermic lamnids elevates CS and LDH in both tissues relative to the ectothermic sharks. Thus, through its enhancement of both RM and WM enzyme activity, endothermy may be an important determinant of energy supply for sustained and burst swimming in the lamnids. Although lamnid WM is differentially warmed as a result of RM endothermy, regional differences in WM CS and LDH activities and thermal sensitivities (Q(10) values) were not found. The general pattern of the endothermic myotomal and ectothermic HV muscle metabolic enzyme activities in the endothermic lamnids relative to other active, ectothermic sharks parallels the general pattern demonstrated for the endothermic tunas relative to their ectothermic sister species. However, the activities of all enzymes measured are lower in

  16. Assessment of myocardial metabolic rate of glucose by means of Bayesian ICA and Markov Chain Monte Carlo methods in small animal PET imaging

    NASA Astrophysics Data System (ADS)

    Berradja, Khadidja; Boughanmi, Nabil

    2016-09-01

    In dynamic cardiac PET FDG studies the assessment of myocardial metabolic rate of glucose (MMRG) requires the knowledge of the blood input function (IF). IF can be obtained by manual or automatic blood sampling and cross calibrated with PET. These procedures are cumbersome, invasive and generate uncertainties. The IF is contaminated by spillover of radioactivity from the adjacent myocardium and this could cause important error in the estimated MMRG. In this study, we show that the IF can be extracted from the images in a rat heart study with 18F-fluorodeoxyglucose (18F-FDG) by means of Independent Component Analysis (ICA) based on Bayesian theory and Markov Chain Monte Carlo (MCMC) sampling method (BICA). Images of the heart from rats were acquired with the Sherbrooke small animal PET scanner. A region of interest (ROI) was drawn around the rat image and decomposed into blood and tissue using BICA. The Statistical study showed that there is a significant difference (p < 0.05) between MMRG obtained with IF extracted by BICA with respect to IF extracted from measured images corrupted with spillover.

  17. 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

  18. 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

  19. [Comparison of myocardial metabolic effects of in subendocardial and subepicardial layers ischaemia and beta-adrenergic stimulation (author's transl)].

    PubMed

    Al Makdessi, S; Andrieu, J L; Tuduri, A; Timour Chah, Q; Faucon, G

    1982-01-01

    The influence of beta-adrenergic stimulation on myocardium carbohydrate and lipid metabolism has been compared with the influence of ischemia in anesthetized dog heart in situ. Transmural samples necessary to the repeated determination of tissular substrates were taken from left ventricular wall according to the "drill biopsy" technique: they were made possible by a total cardiopulmonary by-pass system. The beta-adrenergic stimulation was obtained by infusion of isoproterenol (1 microgram/kg/min.) and the ischemia by injection into left coronary artery before its division of a viscous mixture, reducing coronary flow by 40 to 70%. In both subendocardial and subepicardial layers, but mainly in the former: --beta-adrenergic stimulation lowers glycogen content and raises lactate content immediately, lowers free fatty acid concentration more progressively without modifying triglyceride concentration significantly; --ischemia decreases glycogen content and increases lactate content in the same way, but raises free fatty acid and triglyceride concentration. Consequently, beta-adrenergic stimulation and ischemia are likely to add their effects on anaerobic glycolysis, whereas they exert an opposite influence on lipid metabolism.

  20. Severe metabolic alkalosis in pregnancy

    PubMed Central

    Frise, Charlotte; Noori, Muna

    2013-01-01

    Summary Metabolic alkalosis is uncommon in pregnancy and is most often the result of severe vomiting. If this is present at the time of delivery, transient metabolic derangement in the fetus can occur, potentially requiring additional organ support. A 22-year-old woman is described, who presented at 37 weeks gestation with a severe metabolic alkalosis, vomiting and acute renal and hepatic impairment. The investigations, management options and maternal and fetal outcome are described. PMID:27708709

  1. 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.

  2. 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.

  3. 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

  4. [Ischemia-reperfusion myocardial injury].

    PubMed

    de Micheli, Alfredo; Chávez, Edmundo

    2003-01-01

    In this article, we present some considerations on the myocardial damage due to a deficit of oxygen supply. In fact, this damage properly constitutes a partial diastolic depolarization or injury, i.e., a moderate reduction of the rest transmembrane potential. This phenomenon is characteristic of the acute phase of the myocardial infarction syndrome and is responsible for the main electrical manifestations appearing in this phase: disorders of rhythm and conduction, as well as a reduced contractility of the involved myocardial fibers. All the mentioned phenomena are due to a defect of the myocardial energetic mechanisms, owing to the mitochondrial alterations in myocytes: early reduction of the nicotinamide adenine nucleotides, accumulation of calcium ("calcium overload") into mitochondria, and a drop in oxidative phosphorylation. These changes can present again, more exaggerated, in a following phase of evolution of the myocardial infarction due to myocardial reperfusion. Its severity is related to the duration of the initial ischemia period. Moreover, consequences of the oxidative stress can add producing cellular damage by liberation of reactive oxygen species. Oxidant stress causes also alterations in the mitochondrial DNA, i.e., mutations due to oxidation of nitrogenous bases. During the initial ischemia phase, as well as during reperfusion, metabolic therapy can be very useful as, for example, glucose-insulin-potassium solutions (G-I-K). These could act as scavengers of the free radicals derived from oxygen and avoid or reduce the myocardial damage due to reperfused myocytes. Metabolic drugs, as for example trimetazidine, antioxidants, etc, can also be used in the myocardial reperfusion phase.

  5. 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

  6. Internal derangements of the temporomandibular joint: A review of the anatomy, diagnosis, and management

    PubMed Central

    Young, Andrew L.

    2015-01-01

    Internal derangements of the temporomandibular joint are conditions in which the articular disc has become displaced from its original position the condylar head. Relevant anatomic structures and their functional relationships are briefly discussed. The displacement of the disc can result in numerous presentations, with the most common being disc displacement with reduction (with or without intermittent locking), and disc displacement without reduction (with or without limited opening). These are described in this article according to the standardized Diagnostic Criteria for Temporomandibular Disorders, as well as the less common posterior disc displacement. Appropriate management usually ranges from patient education and monitoring to splints, physical therapy, and medications. In rare and select cases, surgery may be necessary. However, in for the majority of internal derangements, the prognosis is good, particularly with conservative care. PMID:26929478

  7. 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.

  8. Effect of isoproterenol on myocardial perfusion, function, energy metabolism and nitric oxide pathway in the rat heart - a longitudinal MR study.

    PubMed

    Desrois, Martine; Kober, Frank; Lan, Carole; Dalmasso, Christiane; Cole, Mark; Clarke, Kieran; Cozzone, Patrick J; Bernard, Monique

    2014-05-01

    The chronic administration of the β-adrenoreceptor agonist isoproterenol (IsoP) is used in animals to study the mechanisms of cardiac hypertrophy and failure associated with a sustained increase in circulating catecholamines. Time-dependent changes in myocardial blood flow (MBF), morphological and functional parameters were assessed in rats in vivo using multimodal cardiac MRI. Energy metabolism, oxidative stress and the nitric oxide (NO) pathway were evaluated in isolated perfused rat hearts following 7 days of treatment. Male Wistar rats were infused for 7 days with IsoP or vehicle using osmotic pumps. Cine-MRI and arterial spin labeling were used to determine left ventricular morphology, function and MBF at days 1, 2 and 7 after pump implantation. Isolated hearts were then perfused, and high-energy phosphate compounds and intracellular pH were followed using ³¹P MRS with simultaneous measurement of contractile function. Total creatine and malondialdehyde (MDA) contents were measured by high-performance liquid chromatography. The NO pathway was evaluated by NO synthase isoform expression and total nitrate concentration (NO(x)). In IsoP-treated rats, left ventricular mass was increased at day 1 and maintained. Wall thickness was increased with a peak at day 2 and a tendency to return to baseline values at day 7. MBF was markedly increased at day 1 and returned to normal values between days 1 and 2. The rate-pressure product and phosphocreatine/adenosine triphosphate ratio in perfused hearts were reduced. MDA, endothelial NO synthase expression and NO(x) were increased. Sustained high cardiac function and normal MBF after 24 h of IsoP infusion indicate imbalance between functional demand and blood flow, leading to morphological changes. After 1 week, cardiac hypertrophy and decreased function were associated with impaired phosphocreatine, increased oxidative stress and up-regulation of the NO pathway. These results provide supplemental information on the

  9. 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: ...

  10. 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

  11. [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

  12. 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

  13. 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

  14. Impaired cognitive performance in neuronal nitric oxide synthase knockout mice is associated with hippocampal protein derangements.

    PubMed

    Kirchner, Liselotte; Weitzdoerfer, Rachel; Hoeger, Harald; Url, Angelika; Schmidt, Peter; Engelmann, Mario; Villar, Santiago Rosell; Fountoulakis, Michael; Lubec, Gert; Lubec, Barbara

    2004-12-01

    Nitric oxide is implicated in modulation of memory and pharmacological as well as genetic inhibition of neuronal nitric oxide synthase (nNOS) leads to impaired cognitive function. We therefore decided to study learning and memory functions and cognitive flexibility in the Morris water maze (MWM) in 1-month-old male mice lacking nNOS (nNOS KO). Hippocampal protein profiling was carried out to possibly link protein derangement to impaired cognitive function. Two-dimensional gel electrophoresis with in-gel digestion of spots and subsequent MALDI-TOF identification of proteins and quantification of proteins using specific software was applied. In the memory as well as in the relearning task of the MWM, most of the nNOS KO failed to find the submerged platform within a given time. Proteomic evaluation of hippocampus, the main anatomical structure computing cognitive functions, revealed aberrant expression of a synaptosomal associated protein of the exocytotic machinery (NSF), glycolytic enzymes, chaperones 78 kDa glucose-regulated protein, T-complex protein 1; the signaling structure guanine nucleotide-binding protein G(I)/G(S)/G(T) and heterogeneous nuclear ribonucleoprotein H of the splicing machinery. We conclude that nNOS knockout mice show impaired spatial performance in the MWM, a finding that may be either linked to direct effects of nNOS/NO and/or to specific hippocampal protein derangements.

  15. 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

  16. Cardiac BMIPP imaging in acute myocardial infarction.

    PubMed

    Nakata, T; Hashimoto, A; Eguchi, M

    1999-02-01

    Fatty acid metabolism functions as a major energy-producing system under aerobic conditions, but it is impaired immediately after myocardial ischaemia. This imaging can provide intracellular information which cannot be obtained by angiographical, perfusional or functional analysis. 123I-BMIPP and perfusion imagings in patients with acute myocardial infarction have demonstrated three different correlations between myocardial perfusion and fatty acid metabolism: concordant defects of perfusion and BMIPP which represent scar or non-viable tissue; lower BMIPP uptake relative to perfusion (perfusion-BMIPP mismatch) which implicates metabolically damaged, often dysynergic, but viable myocardium; and equivalently normal uptakes of perfusion and BMIPP in completely salvaged myocardium. Identification of these perfusion-metabolism correlations contributes to the detection of ischaemia-related myocardial injury in viable and non-viable myocardium, to the prediction of post-ischaemic or post-interventional functional recovery and to the identification of patients who have myocardium at ischaemic risk. Further clinical investigations might reveal more clearly the pathophysiological and prognostic implications of cardiac BMIPP imaging in patients with acute myocardial infarction.

  17. Myocardial abscess complicating healed myocardial infarction.

    PubMed Central

    Weisz, S.; Young, D. G.

    1977-01-01

    An isolated myocardial abscess due to Bacteroides fragilis developed in the scar of a myocardial infarction. Fever, chills and signs of pericarditis were the main clinical features. Mild enteritis 1 week prior to the onset of symptoms related to the abscess was the most likely cause of the bacteremia. The diagnosis was established at thoracotomy, performed because of cardiac tamponade. Thirteen other cases of isolated bacterial myocardial abscess accompanying myocardial infarction have been reported, but all the infarctions were recent. Surgical resection for a suspected myocardial abscess should be considered in view of the high mortality, largely from cardiac rupture. Images FIG. 1 PMID:861868

  18. 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

  19. Acute myocardial infarction in a young woman on isotretinoin treatment.

    PubMed

    Lorenzo, Natalia; Antuña, Paula; Dominguez, Lourdes; Rivero, Fernando; Bastante, Teresa; Alfonso, Fernando

    2015-02-15

    The use of isotretinoin has been associated with mild changes in the metabolic profile of adolescents. In very rare cases, a possible association with myocardial infarction, stroke and thromboembolic events has been reported. In this report we describe the potential association of isotretinoin with the occurrence of an acute myocardial infarction in a very young girl. OCT provided unique visualization of the culprit lesion.

  20. 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.

  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.

  2. 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

  3. 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

  4. 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

  5. Diabetes is associated with impaired myocardial performance in patients without significant coronary artery disease

    PubMed Central

    2010-01-01

    Background Patients with diabetes mellitus (DM) have high risk of heart failure. Whether some of the risk is directly linked to metabolic derangements in the myocardium or whether the risk is primarily caused by coronary artery disease (CAD) and hypertension is incompletely understood. Echocardiographic tissue Doppler imaging was therefore performed in DM patients without significant CAD to examine whether DM per se influenced cardiac function. Methods Patients with a left ventricular (LV) ejection fraction (EF) > 35% and without significant CAD, prior myocardial infarction, cardiac pacemaker, atrial fibrillation, or significant valve disease were identified from a tertiary invasive center register. DM patients were matched with controls on age, gender and presence of hypertension. Results In total 31 patients with diabetes and 31 controls were included. Mean age was 58 ± 12 years, mean LVEF was 51 ± 7%, and 48% were women. No significant differences were found in LVEF, left atrial end systolic volume, or left ventricular dimensions. The global longitudinal strain was significantly reduced in patients with DM (15.9 ± 2.9 vs. 17.7 ± 2.9, p = 0.03), as were peak longitudinal systolic (S') and early diastolic (E') velocities (5.7 ± 1.1 vs. 6.4 ± 1.1 cm/s, p = 0.02 and 6.1 ± 1.7 vs. 7.7 ± 2.0 cm/s, p = 0.002). In multivariable regression analyses, DM remained significantly associated with impairments of S' and E', respectively. Conclusion In patients without significant CAD, DM is associated with an impaired systolic longitudinal LV function and global diastolic dysfunction. These abnormalities are likely to be markers of adverse prognosis. PMID:20082690

  6. [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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Deranged jaw-neck motor control in whiplash-associated disorders.

    PubMed

    Eriksson, Per-Olof; Zafar, Hamayun; Häggman-Henrikson, Birgitta

    2004-02-01

    Recent findings of simultaneous and well coordinated head-neck movements during single as well as rhythmic jaw opening-closing tasks has led to the conclusion that 'functional jaw movements' are the result of activation of jaw as well as neck muscles, leading to simultaneous movements in the temporomandibular, atlanto-occipital and cervical spine joints. It can therefore be assumed that disease or injury to any of these joint systems would disturb natural jaw function. To test this hypothesis, amplitudes, temporal coordination, and spatiotemporal consistency of concomitant mandibular and head-neck movements during single maximal jaw opening-closing tasks were analysed in 25 individuals suffering from whiplash-associated disorders (WAD) using optoelectronic movement recording technique. In addition, the relative durations for which the head position was equal to, leading ahead of, or lagging behind the mandibular position during the entire jaw opening-closing cycle were determined. Compared with healthy individuals, the WAD group showed smaller amplitudes, and changed temporal coordination between mandibular and head-neck movements. No divergence from healthy individuals was found for the spatiotemporal consistency or for the analysis during the entire jaw opening-closing cycle. These findings in the WAD group of a 'faulty', but yet consistent, jaw-neck behavior may reflect a basic importance of linked control of the jaw and neck sensory-motor systems. In conclusion, the present results suggest that neck injury is associated with deranged control of mandibular and head-neck movements during jaw opening-closing tasks, and therefore might compromise natural jaw function.

  13. Relationship between temporomandibular joint pain and magnetic resonance imaging findings of internal derangement.

    PubMed

    Emshoff, R; Innerhofer, K; Rudisch, A; Bertram, S

    2001-04-01

    In terms of clinical decision-making in instances of temporomandibular disorders (TMD) and orofacial pain, there is controversy in the literature over the diagnostic significance of the temporomandibular joint (TMJ)-related variable disk-condyle relationship (DCR). The purpose of this study was to investigate whether in patients with TMJ-related pain, the variable of TMJ pain may be linked to magnetic resonance (MR) imaging findings of internal derangement (ID). The study comprised 163 consecutive TMJ pain patients. Criteria for including a patient were report of orofacial pain referred to the TMJ, and the presence of uni- or bilateral TMJ pain during palpation, during function, and/or during unassisted or assisted mandibular opening. Bilateral sagittal and coronal MR images were obtained to establish the prevalence of TMJ ID types. Analysis of the data revealed the presence of TMJ pain to be associated with significantly more MR imaging diagnoses of ID than an absence of ID (P<0.001), and disk displacement without reduction than disk displacement with reduction (P<0.001). Using chi-square analysis, the results showed a significant relationship between the presence of TMJ-related pain and the MR imaging diagnosis of TMJ ID (P=0.001), and TMJ ID type (P=0.000). Use of the Kappa statistical test indicated poor diagnostic agreement between the presence of TMJ pain and the MR imaging diagnosis of ID (K=0.16). The results suggest that the clinical variable of TMJ pain may have a significant effect on the prevalences of MR imaging diagnoses of TMJ ID. The data confirm the biological concept of DCR as a diagnostic approach in patients with signs and symptoms of TMJ-related pain.

  14. Metabolic asthma: is there a link between obesity, diabetes, and asthma?

    PubMed

    Perez, Miriam K; Piedimonte, Giovanni

    2014-11-01

    Childhood asthma and obesity have reached epidemic proportions worldwide, and the latter is also contributing to increasing rates of related metabolic disorders, such as diabetes. However, the relationship between asthma, obesity, and abnormal metabolism is not well understood nor has it been adequately explored in children. This article discusses the concept of metabolic asthma and the recent hypothesis that early derangement in lipid and glucose metabolism is independently associated with increased risk for asthma. PMID:25282290

  15. 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

  16. 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

  17. 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

  18. [Comparative studies of the tridosha theory in Ayurveda and the theory of the four deranged elements in Buddhist medicine].

    PubMed

    Endo, J; Nakamura, T

    1995-01-01

    It has been said that the tridosha theory in Ayurveda originated from the theory of the three elements of the universe. The names of these three doshas, which are roughly equivalent to humour, are vata (wind), pitta (bile), and Kapha (phlegm), corresponding to the three elements of the universe: air, fire, and water. On the other hand, Buddhist medicine which has a close relation to Ayurveda is based on the theory of the four elements of the universe which includes the earth as well as the three elements mentioned above. Greek medicine on the other hand, is founded on the theory of the four humours, i.e. blood, yellow bile, black bile, and phlegm. Furthermore, even in Ayurveda, like in "Sushruta Samhita", the theory of the four humours can be found: this includes the above-mentioned tridosha plus blood as the fourth humour. "Timaios" by Plato also mentions this. We compared these various theories and pointed out that the tridosha theory had its origin in the theory of the four elements of the universe. The process of the formation of the tridosha theory is considered as follows: (1) "Earth" was segregated from the four elements of the universe owing to its solid properties, and was rearranged into the seven elements of the body called "dhatu"; and the other three elements. "water", "fire", and "air", were integrated as the tridosha theory, namely, the theory of the three humours, owing to their properties of fluid; (2) "Blood", assigned to the element of "earth", was segregated from the tridosha because "blood" was considered to be comprised of the properties of every humour without having its own peculiar properties. Therefore, the diseases caused by deranged "blood" were regarded as an aggregate disease caused by the other three deranged humours. Then the category of the disease, caused by deranged "earth", did not appear.

  19. 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

  20. 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.

  1. 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

  2. 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.

  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.

  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. 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

  6. Transcriptomic Analysis of Myocardial Ischemia Using the Blood of Rat.

    PubMed

    Hou, Jincai; Fu, Jianhua; Li, Dan; Han, Xiao; Li, Lei; Song, Wenting; Yao, Mingjiang; Liu, Jianxun

    2015-01-01

    Myocardial ischemia is a pathological state of heart with reduced blood flow to heart and abnormal myocardial energy metabolism. This disease occurs commonly in middle aged and elderly people. Several studies have indicated that the rat was an appropriate animal model used to study myocardial ischemia. In this study, in order to gain insights into the pathogenesis of myocardial ischemia, we sequenced the transcriptomes of three normal rats as control and the same number of myocardial ischemia rats. We sequenced the genomes of 6 rats, including 3 cases (myocardial ischemia) and 3 controls using Illumina HiSeq 2000. Then we calculated the gene expression values and identified differentially expressed genes based on reads per kilobase transcriptome per million (RPKM). Meanwhile we performed a GO enrichment analysis and predicted novel transcripts. In our study, we found that 707 genes were up-regulated and 21 genes were down-regulated in myocardial ischemia rats by at least 2-fold compared with controls. By the distribution of reads and the annotation of reference genes, we found 1,703 and 1,552 novel transcripts in cases and controls, respectively. At the same time, we refined the structure of 9,587 genes in controls and 10,301 in cases. According to the results of GO term and pathway analysis of differentially expressed genes, we found that the immune response, stimulus response, response to stress and some diseases may be associated with myocardial ischemia. Since many diseases, especially immune diseases, are associated with myocardial ischemia, we should pay more attention to the complications which might result from myocardial ischemia.

  7. 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

  8. In vivo left ventricular assist induced coagulation derangements. Comparison of Sarns-3M and St. Jude Medical circuits.

    PubMed

    Curtis, J J; Wagner-Mann, C C; Mann, F A; Demmy, T L; Walls, J T; Schmaltz, R A

    1997-01-01

    An in vitro comparison of centrifugal pumping systems manufactured by Sarns-3M and St. Jude Medical revealed a difference in blood cell derangement. The purpose of this study was to compare in vivo the effects of 96 hr of left ventricular assist (LVA) on indexes of coagulopathy, hemolysis, and complement activation. Two groups of calves (each: n = 5) were instrumented with identical left atrial to thoracic aorta centrifugal pumping circuits using either Sarns-3M or St. Jude centrifugal pumps. Laboratory evaluations were performed pre-assist and at 1, 4, 24, 48, 72, and 96 hr during LVA. Platelet counts dropped significantly by 24 hr (Sarns-3M: 28%; St. Jude: 30%); no significant change in function was noted. Activated clotting time increased slightly (p > 0.05). Prothrombin time increased at 4 and 24 hr of LVA, returning to baseline by 96 hr (p < 0.05). Activated partial thromboplastin time increased with the St. Jude device from 24 to 96 hr on LVA (p < 0.05); the increase with the Sarns-3M device never reached significance. No significant changes in lactate dehydrogenase or plasma free hemoglobin were detected. Complement fraction C5a rose by 1 hr of LVA (p < 0.05), peaking at 4 hr and returning to baseline by 96 hr with both pumps. No significant difference was detected between pump groups for any of the parameters. It was concluded that 1) 96 hr Sarns-3M and St. Jude LVA caused coagulation derangement in calves, 2) neither pump demonstrated an advantage regarding coagulation and complement parameters, 3) hemolysis observed with the Sarns-3M pump in vitro was not evidenced in vivo, and 4) in vitro evidenced centrifugal pump differences may not be realized in vivo.

  9. Caffeine inhibits erythrocyte membrane derangement by antioxidant activity and by blocking caspase 3 activation.

    PubMed

    Tellone, Ester; Ficarra, Silvana; Russo, Annamaria; Bellocco, Ersilia; Barreca, Davide; Laganà, Giuseppina; Leuzzi, Ugo; Pirolli, Davide; De Rosa, Maria Cristina; Giardina, Bruno; Galtieri, Antonio

    2012-02-01

    The aim of this research was to investigate the effect of caffeine on band 3 (the anion exchanger protein), haemoglobin function, caspase 3 activation and glucose-6-phosphate metabolism during the oxygenation-deoxygenation cycle in human red blood cells. A particular attention has been given to the antioxidant activity by using in vitro antioxidant models. Caffeine crosses the erythrocyte membrane and interacts with the two extreme conformational states of haemoglobin (the T and the R-state within the framework of the simple two states allosteric model) with different binding affinities. By promoting the high affinity state (R-state), the caffeine-haemoglobin interaction does enhance the pentose phosphate pathway. This is of benefit for red blood cells since it leads to an increase of NADPH availability. Moreover, caffeine effect on band 3, mediated by haemoglobin, results in an extreme increase of the anion exchange, particularly in oxygenated erythrocytes. This enhances the transport of the endogenously produced CO(2) thereby avoiding the production of dangerous secondary radicals (carbonate and nitrogen dioxide) which are harmful to the cellular membrane. Furthermore caffeine destabilizes the haeme-protein interactions within the haemoglobin molecule and triggers the production of superoxide and met-haemoglobin. However this damaging effect is almost balanced by the surprising scavenger action of the alkaloid with respect to the hydroxyl radical. These experimental findings are supported by in silico docking and molecular dynamics studies and by what we may call the "caspase silence"; in fact, there is no evidence of any caspase 3 activity enhancement; this is likely due to the promotion of positive metabolic conditions which result in an increase of the cellular reducing power.

  10. 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

  11. 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

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

    PubMed

    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

  13. 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

  14. Derangements in bone mineral parameters and bone mineral density in south Indian subjects on antiepileptic medications

    PubMed Central

    Koshy, George; Varghese, Ron Thomas; Naik, Dukhabandhu; Asha, Hesargatta Shyamsunder; Thomas, Nihal; Seshadri, Mandalam Subramaniam; Alexander, Mathew; Thomas, Maya; Aaron, Sanjith; Paul, Thomas Vizhalil

    2014-01-01

    Background: Although there are reports describing the association of alternations of bone and mineral metabolism in epileptic patients with long-term anticonvulsant therapy, there are only limited Indian studies which have looked at this aspect. Objectives: This study was done to compare the prevalence of changes in bone mineral parameters and bone mineral density (BMD) in ambulant individuals on long-term anticonvulsant therapy with age- and body mass index (BMI)-matched healthy controls. Materials and Methods: There were 55 men (on medications for more than 6 months) and age- and BMI-matched 53 controls. Drug history, dietary calcium intake (DCI), and duration of sunlight exposure were recorded. Bone mineral parameters and BMD were measured. Results: The control group had a significantly higher daily DCI with mean ± SD of 396 ± 91 mg versus 326 ± 101 mg (P = 0.007) and more sunlight exposure of 234 ± 81 vs 167 ± 69 min (P = 0.05). BMD at the femoral neck was significantly lower in cases (0.783 ± 0.105 g/cm2) when compared to controls (0.819 ± 0.114 g/cm2). Majority of the patients (61%) had low femoral neck BMD (P = 0.04). There was no significant difference in the proportion of subjects with vitamin D deficiency (<20 ng/mL) between cases (n = 32) and controls (n = 37) (P = 0.234). Conclusions: Vitamin D deficiency was seen in both the groups in equal proportions, highlighting the existence of a high prevalence of this problem in India. Low femoral neck BMD found in cases may stress the need for supplementing calcium and treating vitamin D deficiency in this specific group. However, the benefit of such intervention has to be studied in a larger proportion of epileptic patients. PMID:25221394

  15. Depression after myocardial infarction.

    PubMed

    Ziegelstein, R C

    2001-01-01

    Depression is an independent risk factor for increased postmyocardial infarction morbidity and mortality, even after controlling for the extent of coronary artery disease, infarct size, and the severity of left ventricular dysfunction. This risk factor takes on added significance when one considers that almost half of patients recovering from a myocardial infarction have major or minor depression and that major depression alone occurs in about one in five of these individuals. Despite the well-documented risk of depression, questions remain about the mechanism of the relationship between mood disturbance and adverse outcome. The link may be explained by an association with lower levels of social support, poor adherence to recommended medical therapy and lifestyle changes intended to reduce the risk of subsequent cardiac events, disturbances in autonomic tone, enhanced platelet activation and aggregation, and systemic immune activation. Unfortunately, questions about the pathophysiologic mechanism of depression in this setting are paralleled by uncertainties about the optimal treatment of depression for patients recovering from a myocardial infarction and by a lack of knowledge about whether treating depression lowers the associated increased mortality risk. Ongoing research studies will help to determine the benefits of psychosocial interventions and of antidepressant therapy for patients soon after myocardial infarction. Although the identification of depression as a risk factor may by itself be a reason to incorporate a comprehensive psychological evaluation into the routine care of patients with myocardial infarction, this practice should certainly become standard if studies show that treating depression reduces the increased mortality risk of these patients.

  16. 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

  17. 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

  18. 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

  19. A cross-sectional study of the relationship between serum sexual hormone levels and internal derangement of temporomandibular joint.

    PubMed

    Madani, A S; Shamsian, A A; Hedayati-Moghaddam, M R; Fathi-Moghadam, F; Sabooni, M R; Mirmortazavi, A; Golmohamadi, M

    2013-08-01

    Temporomandibular disorders (TMD) are defined as clinical conditions that involve the masticatory muscles, temporomandibular joint (TMJ) or both. The aim of this study was to evaluate serum 17β-oestradiol and progesterone levels in menstruating women affected by internal derangement of the TMJ. A total of 142 women (mean age 30·2 ± 6·7) who referred to medical diagnostic laboratory of Iranian Academic Centre for Education, Culture and Research (ACECR), Mashhad Branch, were enrolled during 2007 and 2008. Forty-seven individuals had disc displacement with reduction (Group IIa) according to Research Diagnostic Criteria (RDC)/TMD Axis I diagnosis. Radioimmunoassay was used for the detection of serum 17β-oestradiol and progesterone levels in all 142 subjects. The mean progesterone level was significantly higher in control group (11·6 ± 10·4 ng mL(-1) ) compared to women with TMD (8·4 ± 6·8 ng mL(-1) , P = 0·03). No significant difference was found in two groups regarding 17β-oestradiol level. Lower progesterone level in women with TMD can suggest the more important role of this hormone in the development of the disorder.

  20. 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.

  1. 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

  2. [Assessing myocardial perfusion with positron emission tomography].

    PubMed

    vom Dahl, J

    2001-11-01

    Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to two indications: 1) The detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well-validated perfusion tracers, such as N-13 ammonia, Rb-82 rubidium chloride, or O-15 labeled water. 2) Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with high specificity, PET is today the best-validated available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows one to use PET perfusion imaging to detect subtle changes in the perfusion reserve for the detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial collaterals and, thus, imaging of several coronary distribution territories in one noninvasive

  3. Metabolic comorbidities in Cushing's syndrome.

    PubMed

    Ferraù, Francesco; Korbonits, Márta

    2015-10-01

    Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall. PMID:26060052

  4. 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

  5. Oxidative stress and myocardial injury in the diabetic heart

    PubMed Central

    Ansley, David M.; Wang, Baohua

    2013-01-01

    Reactive oxygen or nitrogen species play an integral role in both myocardial injury and repair. This dichotomy is differentiated at the level of species type, amount, duration of free radical generated. Homeostatic mechanisms designed to prevent free radical generation in the first instance, scavenge, or enzymatically convert them to less toxic forms and water, play crucial roles in maintenance of cellular structure and function. The outcome between functional recovery and dysfunction is dependent upon the inherent ability of these homeostatic antioxidant defenses to withstand acute free radical generation, in the order of seconds to minutes. Alternatively, pre-existent antioxidant capacity (from intracellular and extracellular sources) may regulate the degree of free radical generation. This converts reactive oxygen and nitrogen species to the role of second messenger involved in cell signalling. The adaptive capacity of the cell is altered by the balance between death or survival signal converging at the level of the mitochondria, with distinct pathophysiologic consequences that extends the period of injury from hours to days and weeks. Hyperglycemia, hyperlipidemia, and insulin resistance enhance oxidative stress in diabetic myocardium that cannot adapt to ischemia reperfusion. Altered glucose flux, mitochondrial derangements and nitric oxide synthase uncoupling in the presence of decreased antioxidant defense and impaired prosurvival cell signalling may render the diabetic myocardium more vulnerable to injury, remodelling and heart failure. PMID:23011912

  6. Protective effect of tetramethylpyrazine on myocardial ischemia-reperfusion injury.

    PubMed

    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 (Ca(2+)) overload and maintaining Ca(2+) 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

  7. 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

  8. 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

  9. Silent myocardial ischemia.

    PubMed

    Gutterman, David D

    2009-05-01

    Although much progress has been made in reducing mortality from ischemic cardiovascular disease, this condition remains the leading cause of death throughout the world. This might in part be due to the fact that over half of patients have a catastrophic event (heart attack or sudden death) as their initial manifestation of coronary disease. Contributing to this statistic is the observation that the majority of myocardial ischemic episodes are silent, indicating an inability or failure to sense ischemic damage or stress on the heart. This review examines the clinical characteristics of silent myocardial ischemia, and explores mechanisms involved in the generation of angina pectoris. Possible mechanisms for the more common manifestation of injurious reductions in coronary flow; namely, silent ischemia, are also explored. A new theory for the mechanism of silent ischemia is proposed. Finally, the prognostic importance of silent ischemia and potential future directions for research are discussed.

  10. Myocardial apoptosis and SIDS.

    PubMed

    Grasmeyer, Sarah; Madea, Burkhard

    2015-01-01

    Apoptosis mediates cardiac damage in severe forms of myocarditis. In fatal myocarditis, large amounts of cardiomyocytes show apoptotic DNA fragmentation, while in human controls, few apoptotic cardiomyocytes are found. In the present study the frequency of apoptosis in 88 SIDS cases (category 1b according to the San Diego Classification) and 15 control cases was investigated. In every case myocardial samples from 8 standard locations were collected. Detection of apoptotic cardiomyocytes was performed by TUNEL method. Furthermore the myocardial tissue was stained with HE and immunohistochemical methods (LCA, CD68, CD45-R0). More than 90% of the slides did not contain apoptotic cardiomyocytes at all. The detection rate of apoptotic cardiomyocytes was almost equal in control group (26.7%) and SIDS group (23.86%). A quantification of apoptotic cardiomyocytes per mm(2) revealed no significant difference between both groups either. Altogether there is no evidence for a higher rate of apoptosis in SIDS.

  11. Myocardial gene therapy

    NASA Astrophysics Data System (ADS)

    Isner, Jeffrey M.

    2002-01-01

    Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis using short-term gene expression may elicit functional improvement in affected individuals.

  12. Clinical decision-making in the management of cervical spine derangement: a case study survey using a patient vignette

    PubMed Central

    Hahn, Tracy; Kelly, Christina; Murphy, Erin; Whissel, Paul; Brown, Michael; Schenk, Ron

    2014-01-01

    Background: Neck pain is one of the most common, potentially disabling, and costly musculoskeletal conditions seen in outpatient physical therapy (PT). Clinical decision-making involves referral or the selection of intervention based on the results of the PT examination. Despite evidence that suggests that treatment based classification is most efficacious, it is hypothesized that examination and intervention may be heavily influenced by post-graduate training experiences. Purpose: The purpose of this study was to analyze which tests, measures, and interventions are most commonly selected by physical therapists (PTs) holding a credential from the McKenzie Institute and those holding the McKenzie credential plus the credential of Fellow of the American Academy of Orthopaedic Manual Physical Therapy (FAAOMPT). Their responses were based on a simulated case vignette involving a patient with a presentation of cervical spine disk derangement. Methods: A survey administered through Survey Monkey was sent to 714 members of the McKenzie Institute who are certified or hold a diploma in mechanical diagnosis and therapy (MDT) or these credentials with the addition of Fellowship credentialing (MDT+FAAOMPT). Of the 714 surveyed PTs, 83 completed the survey for a response rate of 11.6%. As the PTs were given further information regarding the patient, they were asked to progress through a clinical decision-making process by indicating their sequence of examination techniques, and then indicating which interventions would be performed based on the results of the examination. Results: A descriptive analysis was conducted to determine the most common sequences chosen by the PTs based on their training. To perform the analysis, only respondents who completed the survey were included: clinicians with MDT credentials, (n = 77), and clinicians with both the MDT and FAAOMPT credentials (MDT+FAAOMPT), (n = 6). Initially, the most common examination chosen regardless of credential

  13. Myocardial Tagging With SSFP

    PubMed Central

    Herzka, Daniel A.; Guttman, Michael A.; McVeigh, Elliot R.

    2007-01-01

    This work presents the first implementation of myocardial tagging with refocused steady-state free precession (SSFP) and magnetization preparation. The combination of myocardial tagging (a noninvasive method for quantitative measurement of regional and global cardiac function) with the high tissue signal-to-noise ratio (SNR) obtained with SSFP is shown to yield improvements in terms of the myocardium–tag contrast-to-noise ratio (CNR) and tag persistence when compared to the current standard fast gradient-echo (FGRE) tagging protocol. Myocardium–tag CNR and tag persistence were studied using numerical simulations as well as phantom and human experiments. Both quantities were found to decrease with increasing imaging flip angle (α) due to an increased tag decay rate and a decrease in myocardial steady-state signal. However, higher α yielded better blood–myocardium contrast, indicating that optimal α is dependent on the application: higher α for better blood–myocardium boundary visualization, and lower α for better tag persistence. SSFP tagging provided the same myocardium–tag CNR as FGRE tagging when acquired at four times the bandwidth and better tag– and blood–myocardium CNRs than FGRE tagging when acquired at equal or twice the receiver bandwidth (RBW). The increased acquisition efficiency of SSFP allowed decreases in breath-hold duration, or increases in temporal resolution, as compared to FGRE. PMID:12541254

  14. Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias.

    PubMed

    Kasumu, Adebimpe; Bezprozvanny, Ilya

    2012-09-01

    Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 30 autosomal-dominant genetic and neurodegenerative disorders. SCAs are generally characterized by progressive ataxia and cerebellar atrophy. Although all SCA patients present with the phenotypic overlap of cerebellar atrophy and ataxia, 17 different gene loci have so far been implicated as culprits in these SCAs. It is not currently understood how mutations in these 17 proteins lead to the cerebellar atrophy and ataxia. Several pathogenic mechanisms have been studied in SCAs but there is yet to be a promising target for successful treatment of SCAs. Emerging research suggests that a fundamental cellular signaling pathway is disrupted by a majority of these mutated genes, which could explain the characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. We propose that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells either as a result of an excitotoxic increase or a compensatory suppression of calcium signaling. We argue that disruptions in Purkinje cell calcium signaling lead to initial cerebellar dysfunction and ataxic sympoms and eventually proceed to Purkinje cell death. Here, we discuss a calcium hypothesis of Purkinje cell neurodegeneration in SCAs by primarily focusing on an example of spinocerebellar ataxia 2 (SCA2). We will also present evidence linking deranged calcium signaling to the pathogenesis of other SCAs (SCA1, 3, 5, 6, 14, 15/16) that lead to significant Purkinje cell dysfunction and loss in patients.

  15. 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.

  16. 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

  17. 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

  18. Perioperative myocardial infarction in patients undergoing myocardial revascularization surgery

    PubMed Central

    Pretto, Pericles; Martins, Gerez Fernandes; Biscaro, Andressa; Kruczan, Dany David; Jessen, Barbara

    2015-01-01

    Introduction Perioperative myocardial infarction adversely affects the prognosis of patients undergoing coronary artery bypass graft and its diagnosis was hampered by numerous difficulties, because the pathophysiology is different from the traditional instability atherosclerotic and the clinical difficulty to be characterized. Objective To identify the frequency of perioperative myocardial infarction and its outcome in patients undergoing coronary artery bypass graft. Methods Retrospective cohort study performed in a tertiary hospital specialized in cardiology, from May 01, 2011 to April 30, 2012, which included all records containing coronary artery bypass graft records. To confirm the diagnosis of perioperative myocardial infarction criteria, the Third Universal Definition of Myocardial Infarction was used. Results We analyzed 116 cases. Perioperative myocardial infarction was diagnosed in 28 patients (24.1%). Number of grafts and use and cardiopulmonary bypass time were associated with this diagnosis and the mean age was significantly higher in this group. The diagnostic criteria elevated troponin I, which was positive in 99.1% of cases regardless of diagnosis of perioperative myocardial infarction. No significant difference was found between length of hospital stay and intensive care unit in patients with and without this complication, however patients with perioperative myocardial infarction progressed with worse left ventricular function and more death cases. Conclusion The frequency of perioperative myocardial infarction found in this study was considered high and as a consequence the same observed average higher troponin I, more cases of worsening left ventricular function and death. PMID:25859867

  19. Nitric oxide synthase inhibitors in post-myocardial infarction cardiogenic shock--an update.

    PubMed

    Kaluski, Edo; Hendler, Alberto; Blatt, Alex; Uriel, Nir

    2006-11-01

    Cardiogenic shock (CS) in acute myocardial infarction, after successful coronary angioplasty, still carries a case fatality rate of 50%. These patients succumb to a systemic metabolic storm, superimposed on extensive myocardial necrosis and stunning. Nitric oxide (NO) overproduction contributes to the pathophysiology of this morbid state. Current data regarding the physiologic effects of NO and nitric oxide synthase (NOS) inhibitors on the cardiovascular system are reviewed. Clinical trials assessing the safety and efficacy of NOS inhibitors in CS are summarized.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. A life-threatening double gap metabolic acidosis.

    PubMed

    Tsao, Yu-Tzu; Tsai, Wei-Chi; Yang, Shih-Ping

    2008-03-01

    Double gap metabolic acidosis represents the high anion gap metabolic acidosis combined with raised serum osmolal gap due to retention of unmeasured osmole with accompanied metabolite. We describe a 62-year-old man diagnosed with community-acquired pneumonia undergoing continuous sedation in the context of asynchronous mechanical ventilation. High anion gap metabolic acidosis coupled with high plasma osmolal gap was noted with resultant severe bradyarrhythmia. D-Lactic acidosis and high serum concentration of propylene glycol (PG) eventually established the diagnosis of lorazepam-induced PG intoxication. Discontinuation of lorazepam followed by emergent long-extended hemodialysis effectively resolved the metabolic derangement without further recurrence. Serum osmolal gap is a sensitive and convenient surrogate for both early bedside detection and monitoring the therapeutic efficacy. Therefore, PG intoxication must be considered in the differential diagnosis of double gap metabolic acidosis. Early recognition with prompt hemodialysis intervention can avoid a life-threatening catastrophe.

  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. Myocardial fibre calcification.

    PubMed Central

    McClure, J; Pieterse, A S; Pounder, D J; Smith, P S

    1981-01-01

    Three cases of myocardial fibre calcification found at post-mortem examination are described. In one case there was antemortem hypercalcaemia and hyperphosphataemia and the case was clearly an example of metastatic calcification. In the other two cases there was ischaemic myocardial necrosis and calcification was seen in fibres which were not overtly necrotic, but which were both in proximity to (the majority) and remote from the necrotic zones. Since renal failure with hyperphosphataemia was present in both cases, these were considered to be examples of augmented (by the hyperphosphataemia) dystrophic calcification. The histological, histochemical and ultrastructural features were identical in the three cases. Hydroxyapatite formation was observed initially in mitochondria, followed by spillage of crystals into the cytosol and ultimately into the interstitium. It is suggested that the fundamental lesion is a dysfunction of the fibre membrane; the similarity of this reaction with the calcification seen in skeletal muscle fibres in various myopathies is noted and a unifying hypothesis of the mechanism of skeletal and cardiac muscle fibre calcification is thereby suggested. Images PMID:7309897

  7. 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

  8. Trauma induced myocardial infarction.

    PubMed

    Lolay, Georges A; Abdel-Latif, Ahmed K

    2016-01-15

    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.

  9. 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

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

    PubMed

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

    2014-10-23

    '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.

  11. Morin protects heart from beta-adrenergic-stimulated myocardial infarction: an electrocardiographic, biochemical, and histological study in rats.

    PubMed

    Pogula, Bharath Kumar; Maharajan, Mari Kannan; Oddepalli, Divya Rekha; Boini, Lavanya; Arella, Mounika; Sabarimuthu, Darlin Quine

    2012-09-01

    In recent years, polyphenols have attracted considerable attention as agents that protect cells or molecules from oxidative myocardial injury. The aim of the study was to prove the cardioprotective benefits of the flavonoid morin in isoproterenol-induced myocardial infarcted rats. Male Wistar rats are treated orally with morin (10 and 20 mg/kg) daily for a period of 21 days. After 21 days of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days to induce myocardial infarction. Electrocardiographical abnormalities and biomarkers were measured in normal and experimental rats. Isoproterenol-induced myocardial infarcted rats showed significant (p<0.05) increase in the levels of cardiac markers. Pretreatment with morin regulated the abnormalities in electrocardiograph and biomarkers. The lipid peroxidation products were increased and indicated the increased lipid peroxidation in isoproterenol-induced myocardial infarcted rats. The rats pretreated with morin significantly reduced lipid peroxidation. The altered lipid metabolism was observed in isoproterenol-induced myocardial infarcted rats and in pretreatment with morin-regulated lipid metabolism. Histopathological study evidenced that the pretreatment with morin inhibited myocardial damage. The results of this study proved the protective effect of morin as pretreatment and are rational to understand the beneficial effects of morin on cardioprotection against myocardial injury. Based on the results, the cardioprotective ability of morin on human beings can be studied in the future.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  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. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Rat myocardial protein degradation.

    PubMed

    Steer, J H; Hopkins, B E

    1981-07-01

    1. Myocardial protein degradation rates were determined by following tyrosine release from rat isolated left hemi-atria in vitro. 2. After two 20 min preincubations the rate of tyrosine release from hemi-atria was constant for 4 h. 3. Skeletal muscle protein degradation was determined by following tyrosine release from rat isolated hemi-diaphragm (Fulks, Li & Goldberg, 1975). 4. Insulin (10(-7) M) inhibited tyrosine release from hemi-atria and hemi-diaphragm to a similar extent. A 48 h fast increased tyrosine release rate from hemi-diaphragm and decreased tyrosine release rate from hemi-atria. Hemi-diaphragm tyrosine release was inhibited by 15 mmol/l D-glucose but a variety of concentrations of D-glucose (0, 5, 15 mmol/l) had no effect on tyrosine release from hemi-atria. Five times the normal plasma levels of the branched-chain amino acids leucine, isoleucine and valine had no effect on tyrosine release from either hemi-atria or hemi-diaphragm.

  6. Myocardial mechanics in cardiomyopathies.

    PubMed

    Modesto, Karen; Sengupta, Partho P

    2014-01-01

    Cardiomyopathies are a heterogeneous group of diseases that can be phenotypically recognized by specific patterns of ventricular morphology and function. The authors summarize recent clinical observations that mechanistically link the multidirectional components of left ventricular (LV) deformation with morphological phenotypes of cardiomyopathies for offering key insights into the transmural heterogeneity of myocardial function. Subendocardial dysfunction predominantly alters LV longitudinal shortening, lengthening and suction performance and contributes to the phenotypic patterns of heart failure (HF) with preserved ejection fraction (EF) seen with hypertrophic and restrictive patterns of cardiomyopathy. On the other hand, a more progressive transmural disease results in reduction of LV circumferential and twist mechanics leading to the phenotypic pattern of dilated cardiomyopathy and the clinical syndrome of HF with reduced (EF). A proper characterization of LV transmural mechanics, energetics, and space-time distributions of pressure and shear stress may allow recognition of early functional changes that can forecast progression or reversal of LV remodeling. Furthermore, the interactions between LV muscle and fluid mechanics hold the promise for offering newer mechanistic insights and tracking impact of novel therapies.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. Improved myocardial perfusion in chronic diabetic mice by the up-regulation of pLKB1 and AMPK signaling.

    PubMed

    Kusmic, Claudia; L'abbate, Antonio; Sambuceti, Gianmario; Drummond, George; Barsanti, Cristina; Matteucci, Marco; Cao, Jian; Piccolomini, Francesco; Cheng, Jennifer; Abraham, Nader G

    2010-04-01

    Previous studies related impaired myocardial microcirculation in diabetes to oxidative stress and endothelial dysfunction. Thus, this study was aimed to determine the effect of up-regulating pAMPK-pAKT signaling on coronary microvascular reactivity in the isolated heart of diabetic mice. We measured coronary resistance in wild-type and streptozotocin (STZ)-treated mice, during perfusion pressure changes. Glucose, insulin, and adiponectin levels in plasma and superoxide formation, NOx levels and heme oxygenase (HO) activity in myocardial tissue were determined. In addition, the expression of HO-1, 3-nitrotyrosine, pLKB1, pAMPK, pAKT, and peNOS proteins in control and diabetic hearts were measured. Coronary response to changes in perfusion pressure diverged from control in a time-dependent manner following STZ administration. The responses observed at 28 weeks of diabetes (the maximum time examined) were mimicked by L-NAME administration to control animals and were associated with a decrease in serum adiponectin and myocardial pLKB1, pAMPK, pAKT, and pGSK-3 expression. Cobalt protoporphyrin treatment to induce HO-1 expression reversed the microvascular reactivity seen in diabetes towards that of controls. Up-regulation of HO-1 was associated with an increase in adiponectin, pLKB1, pAKT, pAMPK, pGSK-3, and peNOS levels and a decrease in myocardial superoxide and 3-nitrotyrosine levels. In the present study we describe the time course of microvascular functional changes during the development of diabetes and the existence of a unique relationship between the levels of serum adiponectin, pLKB1, pAKT, and pAMPK activation in diabetic hearts. The restoration of microvascular function suggests a new therapeutic approach to even advanced cardiac microvascular derangement in diabetes.

  12. Myocardial contusion caused by a baseball.

    PubMed

    Morikawa, M; Hirose, K; Mori, T; Kusukawa, J; Tomioka, N; Watanabe, Y

    1996-10-01

    Myocardial contusion is a rare type of sports injury. We report a case of myocardial contusion caused by a baseball. In this patient, arrhythmias were induced by an exercise test 1 week after injury. That patients with myocardial contusion but without arrhythmias at rest need to be treated carefully is emphasized.

  13. 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.

  14. 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

  15. Morphological aspects of myocardial bridges.

    PubMed

    Lujinović, Almira; Kulenović, Amela; Kapur, Eldan; Gojak, Refet

    2013-11-01

    Although some myocardial bridges can be asymptomatic, their presence often causes coronary disease either through direct compression of the "tunnel" segment or through stimulation and accelerated development of atherosclerosis in the segment proximally to the myocardial bridge. The studied material contained 30 human hearts received from the Department of Anatomy. The hearts were preserved 3 to 5 days in 10% formalin solution. Thereafter, the fatty tissue was removed and arterial blood vessels prepared by careful dissection with special reference to the presence of the myocardial bridges. Length and thickness of the bridges were measured by the precise electronic caliper. The angle between the myocardial bridge fibre axis and other axis of the crossed blood vessel was measured by a goniometer. The presence of the bridges was confirmed in 53.33% of the researched material, most frequently (43.33%) above the anterior interventricular branch. The mean length of the bridges was 14.64 ± 9.03 mm and the mean thickness was 1.23 ± 1.32 mm. Myocardial bridge fibres pass over the descending blood vessel at the angle of 10-90 degrees. The results obtained on a limited sample suggest that the muscular index of myocardial bridge is the highest for bridges located on RIA, but that the difference is not significant in relation to bridges located on other branches. The results obtained suggest that bridges located on other branches, not only those on RIA, could have a great contractive power and, consequently, a great compressive force, which would be exerted on the wall of a crossed blood vessel.

  16. [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

  17. Acute myocardial infarction in rats.

    PubMed

    Wu, Yewen; Yin, Xing; Wijaya, Cori; Huang, Ming-He; McConnell, Bradley K

    2011-01-01

    With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial

  18. 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.

  19. Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis

    PubMed Central

    Carré, Jane E.; Parker, Nadeene; Curtin, Nancy A.; Duchen, Michael R.; Singer, Mervyn

    2015-01-01

    Muscle dysfunction is a common feature of severe sepsis and multiorgan failure. Recent evidence implicates bioenergetic dysfunction and oxidative damage as important underlying pathophysiological mechanisms. Increased abundance of uncoupling protein-3 (UCP3) in sepsis suggests increased mitochondrial proton leak, which may reduce mitochondrial coupling efficiency but limit reactive oxygen species (ROS) production. Using a murine model, we examined metabolic, cardiovascular, and skeletal muscle contractile changes following induction of peritoneal sepsis in wild-type and Ucp3−/− mice. Mitochondrial membrane potential (Δψm) was measured using two-photon microscopy in living diaphragm, and contractile function was measured in diaphragm muscle strips. The kinetic relationship between membrane potential and oxygen consumption was determined using a modular kinetic approach in isolated mitochondria. Sepsis was associated with significant whole body metabolic suppression, hypothermia, and cardiovascular dysfunction. Maximal force generation was reduced and fatigue accelerated in ex vivo diaphragm muscle strips from septic mice. Δψm was lower in the isolated diaphragm from septic mice despite normal substrate oxidation kinetics and proton leak in skeletal muscle mitochondria. Even though wild-type mice exhibited an absolute 26 ± 6% higher UCP3 protein abundance at 24 h, no differences were seen in whole animal or diaphragm physiology, nor in survival rates, between wild-type and Ucp3−/− mice. In conclusion, this murine sepsis model shows a hypometabolic phenotype with evidence of significant cardiovascular and muscle dysfunction. This was associated with lower Δψm and alterations in mitochondrial ATP turnover and the phosphorylation pathway. However, UCP3 does not play an important functional role, despite its upregulation. PMID:25714676

  20. 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.

  1. 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.

  2. Myocardial revascularization in Jehovah Witnesses.

    PubMed

    Seifert, P E; Auer, J E; Hohensee, P

    1989-04-01

    The refusal of certain patients to accept blood transfusions need not be a deterrent to surgery. We report on nine Jehovah's Witnesses who over a one-year period underwent myocardial revascularization without significant blood loss or decrease in hematocrit values. PMID:2786287

  3. [Myocardial infarction in young population].

    PubMed

    Shklovskii, B L; Prokhorchik, A A; Koltunov, A N; Lishchuk, A N; Ryzhman, N N; Ivanov, A V; Navaznov, V V; Baksheev, V I

    2015-03-01

    Description of clinical observation and literature review. Myocardial infarction in patients younger than 45 years is rare, but it is an important clinical, organizational and psychological problem. A case of myocardial infarction in 19-years old patient, who suffered since 6 years from kidney disease, is described. Transmural left-ventricular myocardial infarction has developed on the background of chronic glomerulonephritis, excessive exercise, and traditional risk factors for cardiovascular disease. Coronary venous bypass with the benefit-pleasing outcome is performed. When analysing the literature, the authors emphasize that in comparison with elderly patients, young people have different profiles of risk factors, clinical manfestations and prognosis of myocardial infarction. It is emphasized that kidney chronic disease, regardless the stage, worsen short-term and long-term outcomes of cardiovascular disease. Early stabilization is possible under the condition of risk stratification and-early revascularization, which leads to better clinical outcomes. Particular attention should be given to a comprehensive assessment, it prognostic criteria, risk factor modification, secondary prevention of major and associated diseases, clinical- and -dynamic observation, including patients with asymptomatic course of the disease.

  4. 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…

  5. Myocardial infarction following sternal surgery.

    PubMed Central

    Aggarwal, R. K.; Morrison, W. L.

    1996-01-01

    We report a case of myocardial infarction in a 32-year-old man undergoing sternal surgery. Thrombotic occlusion of the right coronary artery with no underlying atheromatous disease was demonstrated angiographically and successfully treated with intracoronary thrombolysis. Images Figure 1 Figure 2 PMID:8796219

  6. Androgen deficiency and metabolic syndrome in men

    PubMed Central

    Winter, Ashley G.; Zhao, Fujun

    2014-01-01

    Metabolic syndrome (MetS) is a growing health concern worldwide. Initially a point of interest in cardiovascular events, the cluster of HTN, obesity, dyslipidemia, and insulin resistance known as MetS has become associated with a variety of other disease processes, including androgen deficiency and late-onset hypogonadism (LOH). Men with MetS are at a higher risk of developing androgen deficiency, and routine screening of testosterone (T) is advised in this population. The pathophysiology of androgen deficiency in MetS is multifactorial, and consists of inflammatory, enzymatic, and endocrine derangements. Many options for the concomitant treatment of both disorders exist. Direct treatment of MetS, whether by diet, exercise, or surgery, may improve T levels. Conversely, testosterone replacement therapy (TRT) has been shown to improve MetS parameters in multiple randomized controlled trials (RTCs). PMID:26816752

  7. Biochemical Markers of Myocardial Damage

    PubMed Central

    2016-01-01

    Heart diseases, especially coronary artery diseases (CAD), are the leading causes of morbidity and mortality in developed countries. Effective therapy is available to ensure patient survival and to prevent long term sequelae after an acute ischemic event caused by CAD, but appropriate therapy requires rapid and accurate diagnosis. Research into the pathology of CAD have demonstrated the usefulness of measuring concentrations of chemicals released from the injured cardiac muscle can aid the diagnosis of diseases caused by myocardial ischemia. Since the mid-1950s successively better biochemical markers have been described in research publications and applied for the clinical diagnosis of acute ischemic myocardial injury. Aspartate aminotransferase of the 1950s was replaced by other cytosolic enzymes such as lactate dehydrogenase, creatine kinase and their isoenzymes that exhibited better cardiac specificity. With the availability of immunoassays, other muscle proteins, that had no enzymatic activity, were also added to the diagnostic arsenal but their limited tissue specificity and sensitivity lead to suboptimal diagnostic performance. After the discovery that cardiac troponins I and T have the desired specificity, they have replaced the cytosolic enzymes in the role of diagnosing myocardial ischemia and infarction. The use of the troponins provided new knowledge that led to revision and redefinition of ischemic myocardial injury as well as the introduction of biochemicals for estimation of the probability of future ischemic myocardial events. These markers, known as cardiac risk markers, evolved from the diagnostic markers such as CK-MB or troponins, but markers of inflammation also belong to these groups of diagnostic chemicals. This review article presents a brief summary of the most significant developments in the field of biochemical markers of cardiac injury and summarizes the most recent significant recommendations regarding the use of the cardiac markers in

  8. Myocardial disarray. A critical review.

    PubMed Central

    Becker, A E; Caruso, G

    1982-01-01

    Myocardial disarray or disorganisation is at present a contentious topic, not least because its value as a clinical marker for hypertrophic cardiomyopathy has changed considerably over the years. Initially observed as one of the features of asymmetric septal hypertrophy, disarray has since been promoted as its pathognomonic histological feature, regarded by some observers as the morphological manifestation of a genetically transmitted myocardial defect. Recently, however, it has become evident that myocardial disarray is not limited to hypertrophic cardiomyopathy, but is encountered in hearts with both congenital and acquired conditions, and is also observed in normal hearts. The specificity of disarray for hypertrophic cardiomyopathy is thus seriously questioned. Latterly, it has been suggested that disarray, judged from through-and-through sections of the ventricular midseptum is a highly specific and sensitive marker of hypertrophic cardiomyopathy when considered in quantitative rather than qualitative fashion. The present study sets out to answer the question whether disarray could be the histological expression of the normal but intricate fibre architecture of the heart, a consideration also initiated by debatable definitions of normality and abnormality of myocardial histology. Gross fibre dissections in five normal hearts showed that many sites occurred in which disarray was a natural phenomenon. In five more hearts it was found that the plane of section of a tissue block might profoundly influence the histology. In fact, tissue cubicles sampled from different faces showed a change in histology in the vast majority. Thus the diagnostic significance of myocardial disarray as a marker of hypertrophic cardiomyopathy in the clinical setting almost vanishes; a change in orientation of a tissue section may actually turn "normality" into "disarray". Images PMID:7044398

  9. Biochemical Markers of Myocardial Damage.

    PubMed

    Bodor, Geza S

    2016-04-01

    Heart diseases, especially coronary artery diseases (CAD), are the leading causes of morbidity and mortality in developed countries. Effective therapy is available to ensure patient survival and to prevent long term sequelae after an acute ischemic event caused by CAD, but appropriate therapy requires rapid and accurate diagnosis. Research into the pathology of CAD have demonstrated the usefulness of measuring concentrations of chemicals released from the injured cardiac muscle can aid the diagnosis of diseases caused by myocardial ischemia. Since the mid-1950s successively better biochemical markers have been described in research publications and applied for the clinical diagnosis of acute ischemic myocardial injury. Aspartate aminotransferase of the 1950s was replaced by other cytosolic enzymes such as lactate dehydrogenase, creatine kinase and their isoenzymes that exhibited better cardiac specificity. With the availability of immunoassays, other muscle proteins, that had no enzymatic activity, were also added to the diagnostic arsenal but their limited tissue specificity and sensitivity lead to suboptimal diagnostic performance. After the discovery that cardiac troponins I and T have the desired specificity, they have replaced the cytosolic enzymes in the role of diagnosing myocardial ischemia and infarction. The use of the troponins provided new knowledge that led to revision and redefinition of ischemic myocardial injury as well as the introduction of biochemicals for estimation of the probability of future ischemic myocardial events. These markers, known as cardiac risk markers, evolved from the diagnostic markers such as CK-MB or troponins, but markers of inflammation also belong to these groups of diagnostic chemicals. This review article presents a brief summary of the most significant developments in the field of biochemical markers of cardiac injury and summarizes the most recent significant recommendations regarding the use of the cardiac markers in

  10. Neuro-fuzzy systems for computer-aided myocardial viability assessment.

    PubMed

    Behloul, F; Lelieveldt, B P; Boudraa, A; Janier, M F; Revel, D; Reiber, J H

    2001-12-01

    This paper describes a multimodality framework for computer-aided myocardial viability assessment based on neuro-fuzzy techniques. The proposed approach distinguishes two main levels: the modality-independent inference level and the modality-dependent application level. This two-level distinction releases the hard constraint of multimodality image registration. An abstract description template is used to describe the different myocardial functions (contractile function, perfusion, metabolism). Parameters extracted from different image modalities are combined to derive a diagnostic image. The neuro-fuzzy techniques make our system transparent, adaptive and easily extendable. Its effectiveness and robustness are demonstrated in a positron emission tomography/magnetic resonance imaging data fusion application.

  11. [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

  12. High-fat feeding rapidly induces obesity and lipid derangements in C57BL/6N mice.

    PubMed

    Podrini, Christine; Cambridge, Emma L; Lelliott, Christopher J; Carragher, Damian M; Estabel, Jeanne; Gerdin, Anna-Karin; Karp, Natasha A; Scudamore, Cheryl L; Ramirez-Solis, Ramiro; White, Jacqueline K

    2013-06-01

    C57BL/6N (B6N) is becoming the standard background for genetic manipulation of the mouse genome. The B6N, whose genome is very closely related to the reference C57BL/6J genome, is versatile in a wide range of phenotyping and experimental settings and large repositories of B6N ES cells have been developed. Here, we present a series of studies showing the baseline characteristics of B6N fed a high-fat diet (HFD) for up to 12 weeks. We show that HFD-fed B6N mice show increased weight gain, fat mass, and hypercholesterolemia compared to control diet-fed mice. In addition, HFD-fed B6N mice display a rapid onset of lipid accumulation in the liver with both macro- and microvacuolation, which became more severe with increasing duration of HFD. Our results suggest that the B6N mouse strain is a versatile background for studying diet-induced metabolic syndrome and may also represent a model for early nonalcoholic fatty liver disease.

  13. 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

  14. 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

  15. Myocardial viability in patients with chronic coronary artery disease and previous myocardial infarction: comparison of myocardial contrast echocardiography and myocardial perfusion scintigraphy.

    PubMed

    Vernon, S; Kaul, S; Powers, E R; Camarano, G; Gimple, L W; Ragosta, M

    1997-11-01

    The aim of this study was to compare perfusion patterns on myocardial contrast echocardiography with those on myocardial perfusion scintigraphy for the assessment of myocardial viability in patients with previous myocardial infarction. Accordingly, perfusion scores with the two techniques were compared in 91 ventricular regions in 21 patients with previous (>6 weeks old) myocardial infarction. Complete concordance between the two techniques was found in 63 (69%) regions; 25 (27%) regions were discordant by only 1 grade, and complete discordance (2 grades) was found in only 3 (3%) regions. A kappa statistic of 0.65 indicated good concordance between the two techniques. Although the scores on both techniques demonstrated a relation with the wall motion score, the correlation between the myocardial contrast echocardiography and wall motion scores was closer (r = -0.63 vs r = -0.50, p = 0.05). It is concluded that myocardial contrast echocardiography provides similar information regarding myocardial viability as myocardial perfusion scintigraphy in patients with coronary artery disease and previous myocardial infarction.

  16. 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

  17. 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

  18. Chasing myocardial outcomes: perioperative myocardial infarction and cardiac troponin.

    PubMed

    Royo, Marc B; Fleisher, Lee A

    2016-02-01

    Perioperative myocardial infarction represents the most common cardiovascular complication following non-cardiac surgery, but frequently presents without the usual clinical signs and symptoms consistent with acute coronary syndrome. Given the silent nature of this event, a clinician's reliance on risk stratification tools and cardiac specific biomarkers to assist in the identification of at-risk individuals is heightened in the perioperative setting. Although cardiac troponin elevations following non-cardiac surgery have been consistently linked to increased mortality, uncertainty remains over how to clinically intervene to prevent harm. This decision is further complicated by the increasing sensitivity of the newest generation of cardiac biomarker immunoassays. In this narrative review, the growing body of evidence surrounding cardiac troponin elevations in the perioperative setting, how the evidence has been integrated into recent clinical practice guidelines, and its implications for the detection of perioperative myocardial infarction are discussed. PMID:26634279

  19. Metabolic comorbidities and psoriasis.

    PubMed

    Gisondi, Paolo; Ferrazzi, Anna; Girolomoni, Giampiero

    2010-01-01

    Psoriasis is a chronic inflammatory, immune-mediated skin disease, which affects 2%-3% of the population worldwide. Chronic plaque psoriasis is frequently associated with metabolic diseases including diabetes, obesity, dyslipidemia, metabolic syndrome and nonalcoholic fatty liver disease. Although the causal relationship between metabolic comorbidities and psoriasis has not yet been completely proven, it appears that shared genetic links, common environmental factors and/or common inflammatory pathways may underlie the development of psoriasis and comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardio-metabolic comorbidities, and may have important interactions with drugs commonly used by psoriatic patients. In contrast, the recent findings that the risk of myocardial infarction is reduced in patients with rheumatoid arthritis who respond to anti-TNF-α therapy compared to non-responders, supports the hypothesis that the anti-inflammatory effect of TNF-α blockers might reduce the cardiovascular risk potentially also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, and should be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit.

  20. Metabolic comorbidities and psoriasis.

    PubMed

    Gisondi, Paolo; Ferrazzi, Anna; Girolomoni, Giampiero

    2010-01-01

    Psoriasis is a chronic inflammatory, immune-mediated skin disease, which affects 2%-3% of the population worldwide. Chronic plaque psoriasis is frequently associated with metabolic diseases including diabetes, obesity, dyslipidemia, metabolic syndrome and nonalcoholic fatty liver disease. Although the causal relationship between metabolic comorbidities and psoriasis has not yet been completely proven, it appears that shared genetic links, common environmental factors and/or common inflammatory pathways may underlie the development of psoriasis and comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardio-metabolic comorbidities, and may have important interactions with drugs commonly used by psoriatic patients. In contrast, the recent findings that the risk of myocardial infarction is reduced in patients with rheumatoid arthritis who respond to anti-TNF-α therapy compared to non-responders, supports the hypothesis that the anti-inflammatory effect of TNF-α blockers might reduce the cardiovascular risk potentially also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, and should be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit. PMID:21251450

  1. [Arterial hypertension and metabolic syndrome].

    PubMed

    Christ, Michael; Klima, Theresia; Maisch, Bernhard

    2003-12-01

    BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic hypertension and insulin resistance. The prevalence of the metabolic syndrome has continuously grown in industrialized and developing countries during the last decades, and affects tens of millions of people in Germany and Europe. Particularly prominent as a risk factor for the development of insulin resistance is central obesity, which is causally involved in the pathogenesis of insulin resistance in addition to genetic predisposition. The metabolic syndrome can easily be diagnosed in clinical practice (guidelines of the WHO and ATP III panel), and immediate treatment of the metabolic syndrome is mandatory because those patients are at increased risk to develop overt diabetes mellitus, coronary artery disease and stroke. The high risk for cardiovascular diseases is supported by findings that the risk for myocardial infarction in patients with insulin resistance is as high as the risk of patients after their first myocardial infarction. Intentional weight reduction reduces abdominal obesity and beneficially modulates all features of the metabolic syndrome, while the benefits of aerobic exercise training are discussed controversially. Thus, weight reduction causally undoes essential features of the metabolic syndrome, but effects are often not enduring. Therefore, the treatment of cardiovascular risk factors such as hypertension and dislipidemia is essential. Of note, antihypertensive treatment is more effective than tight glucose control to reduce cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1 receptor antagonists are suggested as first line therapeutics. However, at least two antihypertensives are usually necessary to achieve the suggested goals of blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome is continuously growing. Due to its adverse impact

  2. [CHANGES OF GLOBAL AND LOCAL MYOCARDIAL CONTRACTILITY OF CHERNOBYL ACCIDENT CLEAN-UP WORKERS WITH STABLE ANGINA].

    PubMed

    Nastina, O

    2014-01-01

    Changes of global and local myocardial contractility of Chernobyl accident clean-up workers (ChA CW) with stable angina were investigated. There were discovered that regular long-term treatment of ChA CW with stable angina using of antiischemic and metabolic drugs promoted to stabilization of global and local myocardial contractility indexes. Ejection fraction, degree of contraction of front-rear systolic left ventricle size, systolic thickness of interventricular septum sufficiently increased. Step-by-step worsening of global and local myocardial contractility indexes in cases of non-regular treatment was taken place. Sufficient differences between indexes of ejection fraction, left ventricle end-diastolic volume, systolic thickness and excursion of interventricular septum in stable angina patients of general population and ChA CW were discovered. Results of global and local myocardial contractility monitoring in ChA CW with stable angina substantiate the advisability of long-term supporting treatment using evidence-based drugs.

  3. Myocardial tissue caveolae.

    PubMed

    Sanon, Vani P; Sawaki, Daigo; Mjaatvedt, Corey H; Jourdan-Le Saux, Claude

    2015-04-01

    Caveolae and their coat proteins, caveolins (Cav), are cave-like invaginations found in the plasma membrane of a variety of cells. These unique vesicles and their coat proteins, Cavs, have diverse effects on endothelial function, nitric oxide synthesis regulation, signal transduction, cholesterol metabolism, and apoptosis. Animal studies in Cav knockout mice demonstrate the vital role of these structural proteins on endothelial and vascular function. Genetic studies have proposed that beside neoplasia, Cavs may play a role in the development of atherosclerosis, cardiomyopathy, long QT syndrome, pulmonary fibrosis, and muscular dystrophy. The role of Cav expression in atherosclerotic disease is poorly understood and remains controversial. Interestingly, there is emerging evidence between low Cav-1 levels and the vulnerable plaque, which could potentially identify Cav-1 as a novel plaque biomarker. Cavs, through intricate biochemical pathways involving endothelial nitric oxide synthase and mitogen-activated protein kinase, are known to affect the cardiovascular system at multiple levels. In the present review, we aim to highlight the nature and types of caveolae, caveolar signaling mechanisms and regulation, and the pathophysiology of Cavs as it pertains to the cardiovascular system. Ongoing research is needed to clarify the diagnostic and prognostic role of these novel proteins and to determine how the effects of Cavs can translate into clinical medicine. PMID:25880516

  4. [Myocardial infarction caused by exertion].

    PubMed

    Bernard, F; Weber, S

    1997-01-01

    Myocardial infarction is the main cause of sudden death during physical exercise, particularly in subjects over 40 and may even occur in high-performance young athletes. Sports and physical activity have a beneficial effect in preventing cardiovascular diseases, but certain rules of prudence must be followed to avoid the risk of a severe coronary event. Myocardial infarction always occurs in particularly susceptible subjects with several risk factors, predominantly smoking, hypercholesterolemia, family history of atherosclerosis. Dietary factors, either before, during or after the exercise, are always found. Distribution of coronary lesions differs with age. Before 40 years, the coronary network is normal in 40% of the cases. The infarction is partially explained by platelet hyperaggregahility and coronary spasms at exercise or in the post-exercise period.

  5. Positron emission tomography for the assessment of myocardial viability

    SciTech Connect

    Schelbert, H.R. )

    1991-09-01

    The detection of viable myocardium or ischemically injured myocardium with a reversible impairment of contractile function remains clinically important but challenging. Detection of reversible dysfunction and distinction from irreversible tissue injury by positron emission tomography is based on identification of preserved or even enhanced glucose metabolism with F-18 2-fluoro 2-deoxyglucose. Regional patterns of myocardial glucose utilization and blood flow, defined as perfusion-metabolism mismatches or matches, on positron emission tomography in patients with chronic or even acute ischemic heart disease are highly accurate in predicting the functional outcome after interventional revascularization. Compared with thallium-201 redistribution scintigraphy, positron emission tomography appears to be diagnostically more accurate, especially in patients with severely impaired left ventricular function. While larger clinical trials are needed for further confirmation, positron emission tomography has already proved clinically useful for stratifying patients with poor left ventricular function to the most appropriate therapeutic approach.

  6. A comparative study of fluoride ingestion levels, serum thyroid hormone & TSH level derangements, dental fluorosis status among school children from endemic and non-endemic fluorosis areas.

    PubMed

    Singh, Navneet; Verma, Kanika Gupta; Verma, Pradhuman; Sidhu, Gagandeep Kaur; Sachdeva, Suresh

    2014-01-01

    The study was undertaken to determine serum/urinary fluoride status and comparison of free T4, free T3 and thyroid stimulating hormone levels of 8 to 15 years old children with and without dental fluorosis living in an endemic and non-endemic fluorosis area. A sample group of 60 male and female school children, with or without dental fluorosis, consuming fluoride-contaminated water in endemic fluoride area of Udaipur district, Rajasthan were selected through a school dental fluorosis survey. The sample of 10 children of same age and socio-economic status residing in non endemic areas who did not have dental fluorosis form controls. Fluoride determination in drinking water, urine and blood was done with Ion 85 Ion Analyzer Radiometer with Hall et al. method. The thyroid gland functional test was done by Immonu Chemiluminiscence Micropartical Assay with Bayer Centaur Autoanalyzer. The significantly altered FT3, FT4 and TSH hormones level in both group1A and 1B school children were noted. The serum and urine fluoride levels were found to be increased in both the groups. A significant relationship of water fluoride to urine and serum fluoride concentration was seen. The serum fluoride concentration also had significant relationship with thyroid hormone (FT3/FT4) and TSH concentrations. The testing of drinking water and body fluids for fluoride content, along with FT3, FT4, and TSH in children with dental fluorosis is desirable for recognizing underlying thyroid derangements and its impact on fluorosis.

  7. 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

  8. Pharmacology of myocardial calcium-handling.

    PubMed

    Vogler, Julia; Eckardt, Lars

    2012-07-01

    Disturbed myocardial calcium (Ca(+)) handling is one of the pathophysiologic hallmarks of cardiovascular diseases such as congestive heart failure, cardiac hypertrophy, and certain types of tachyarrhythmias. Pharmacologic treatment of these diseases thus focuses on restoring myocardial Ca(2+) homeostasis by interacting with Ca(2+)-dependent signaling pathways. In this article, we review the currently used pharmacologic agents that are able to restore or maintain myocardial Ca(2+) homeostasis and their mechanism of action as well as emerging new substances.

  9. Tombstoning ST-Elevation Myocardial Infarction

    PubMed Central

    Balci, Bahattin

    2009-01-01

    Tombstoning ST elevation myocardial infarction can be described as a STEMI characterized by tombstoning ST-segment elevation. This myocardial infarction is associated with extensive myocardial damage, reduced left ventricle function, serious hospital complications and poor prognosis. Tombstoning ECG pattern is a notion beyond morphological difference and is associated with more serious clinical results. Despite the presence of a few reports on tombstoning ST elevation, there is no report which reviews STEMI demonstrating this electrocardiographic pattern. PMID:21037844

  10. Echocardiographic assessment of myocardial strain.

    PubMed

    Gorcsan, John; Tanaka, Hidekazu

    2011-09-27

    Echocardiographic strain imaging, also known as deformation imaging, has been developed as a means to objectively quantify regional myocardial function. First introduced as post-processing of tissue Doppler imaging velocity converted to strain and strain rate, strain imaging has more recently also been derived from digital speckle tracking analysis. Strain imaging has been used to gain greater understanding into the pathophysiology of cardiac ischemia and infarction, primary diseases of the myocardium, and the effects of valvular disease on myocardial function, and to advance our understanding of diastolic function. Strain imaging has also been used to quantify abnormalities in the timing of mechanical activation for heart failure patients undergoing cardiac resynchronization pacing therapy. Further advances, such as 3-dimensional speckle tracking strain imaging, have emerged to provide even greater insight. Strain imaging has become established as a robust research tool and has great potential to play many roles in routine clinical practice to advance the care of the cardiovascular patient. This perspective reviews the physiology of myocardial strain, the technical features of strain imaging using tissue Doppler imaging and speckle tracking, their strengths and weaknesses, and the state-of-the-art present and potential future clinical applications.

  11. 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

  12. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    SciTech Connect

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium.

  13. Association between Myocardial Triglyceride Content and Cardiac Function in Healthy Subjects and Endurance Athletes

    PubMed Central

    Sai, Eiryu; Shimada, Kazunori; Yokoyama, Takayuki; Sato, Shuji; Miyazaki, Tetsuro; Hiki, Makoto; Tamura, Yoshifumi; Aoki, Shigeki; Watada, Hirotaka; Kawamori, Ryuzo; Daida, Hiroyuki

    2013-01-01

    Ectopic fat accumulation plays important roles in various metabolic disorders and cardiovascular diseases. Recent studies reported that myocardial triglyceride (TG) content measured by proton magnetic resonance spectroscopy (1H-MRS) is associated with aging, diabetes mellitus, and cardiac dysfunction. However, myocardial TG content in athletes has not yet been investigated. We performed 1H-MRS and cardiac magnetic resonance imaging in 10 male endurance athletes and 15 healthy male controls. Serum markers and other clinical parameters including arterial stiffness were measured. Cardiopulmonary exercise testing was also performed. There were no significant differences in clinical characteristics including age, anthropometric parameters, blood test results, or arterial stiffness between the two groups. Peak oxygen uptakes, end–diastolic volume (EDV), end–systolic volume (ESV), left ventricular (LV) mass, peak ejection rates and peak filling rates were significantly higher in the athlete group than in the control group (all P<0.02). Myocardial TG content was significantly lower in the athlete group than in the control group (0.60±0.20 vs. 0.89±0.41%, P<0.05). Myocardial TG content was negatively correlated with EDV (r = −0.47), ESV (r = −0.64), LV mass (r = −0.44), and epicardial fat volume (r = 0.47) (all P<0.05). In conclusion, lower levels of myocardial TG content were observed in endurance athletes and were associated with morphological changes related to physiological LV alteration in athletes, suggesting that metabolic imaging for measurement of myocardial TG content by 1H-MRS may be a useful technique for noninvasively assessing the “athlete’s heart”. PMID:23613879

  14. Cocaine, a risk factor for myocardial infarction.

    PubMed

    Galasko, G I

    1997-06-01

    Cocaine usage goes back thousands of years, to the times of the Incas. Over the past 20 years, its use has increased dramatically, especially in America, and adverse cardiovascular reactions to the drug have begun to be reported. The first report of myocardial infarction temporally related to the recreational use of cocaine appeared in 1982. Since then, myocardial infarction has become recognized as the drug's most common cardiovascular consequence, with over 250 cases now documented in the literature. This review discusses the history of cocaine use, its pharmacology, the possible pathological mechanisms underlying the pathogenesis of myocardial ischaemia and infarction, and current ideas on the management of cocaine-induced myocardial infarction.

  15. Energy-related metabolites during and after induced myocardial infarction with special emphasis on the reperfusion injury after extracorporeal circulation.

    PubMed

    Zemgulis, V; Ronquist, G; Bjerner, T; Henze, A; Waldenström, A; Thelin, S; Wikström, G

    2001-02-01

    In the clinical setting great efforts have been made with contradictory results to operate upon acutely myocardial ischaemic patients. The reasons for the absence of clear-cut results are not well understood nor are they scientifically explored. To resolve this problem further, we attempted to design an experimental in vivo model to mimic acute myocardial ischaemia followed by extracorporeal circulation (ECC) and reperfusion. One of the main targets of our protocol was monitoring of myocardial energy metabolism by microdialysis (MCD) during the periods of coronary occlusion (60 min), hypothermic (30 degrees C) ECC and cardioplegia (45 min), followed by reperfusion with (30 min) and without (60 min) ECC. In eight anaesthetized, open-chest pigs, myocardial lactate, pyruvate, adenosine, taurine, inosine, hypoxanthine and guanosine were sampled with MCD in both ischaemic and non-ischaemic areas. Myocardial area at risk and infarct size were quantified with the modified topographical evaluation methods. The principal finding with this experimental setup was a biphasic release pattern of lactate, adenosine, taurine, inosine, hypoxanthine and guanosine from ischaemic myocardium. Lactate levels were equally high in reperfused ischaemic and non-ischaemic myocardial tissue. Pyruvate demonstrated consistently higher values in non-ischaemic myocardium throughout the experiment. A pattern was discernible, lactate being a marker of compromised cell energy metabolism, and taurine being a marker of disturbed cell integrity. Of special interest was the increased level of pyruvate in microdialysates of non-ischaemic myocardium as compared with its ischaemic counterpart. In conclusion, we found disturbances in energy metabolism and cell integrity not only in ischaemic but also in non-ischaemic tissue during reperfusion implying that non-ischaemic myocardium demonstrated an unexpected accumulation of lactate and pyruvate. These new findings could at least partly be explicatory to the

  16. Metabolic Panel

    MedlinePlus

    A metabolic panel is a group of tests that measures different chemicals in the blood. These tests are usually ... kidneys and liver. There are two types: basic metabolic panel (BMP) and comprehensive metabolic panel (CMP). The ...

  17. Metabolic acidosis

    MedlinePlus

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys ... from the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known ...

  18. 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 ...

  19. Myocardial macronutrient transporter adaptations in the adult pregestational female intrauterine and postnatal growth-restricted offspring

    PubMed Central

    Abbasi, Afshan; Thamotharan, Manikkavasagar; Shin, Bo-Chul; Jordan, Maria C.; Roos, Kenneth P.; Stahl, Andreas

    2012-01-01

    Associations between exponential childhood growth superimposed on low birth weight and adult onset cardiovascular disease with glucose intolerance/type 2 diabetes mellitus exist in epidemiological investigations. To determine the metabolic adaptations that guard against myocardial failure on subsequent exposure to hypoxia, we compared with controls (CON), the effect of intrauterine (IUGR), postnatal (PNGR), and intrauterine and postnatal (IPGR) calorie and growth restriction (n = 6/group) on myocardial macronutrient transporter (fatty acid and glucose) -mediated uptake in pregestational young female adult rat offspring. A higher myocardial FAT/CD36 protein expression in IUGR, PNGR, and IPGR, with higher FATP1 in IUGR, FATP6 in PNGR, FABP-c in PNGR and IPGR, and no change in GLUT4 of all groups was observed. These adaptive macronutrient transporter protein changes were associated with no change in myocardial [3H]bromopalmitate accumulation but a diminution in 2-deoxy-[14C]glucose uptake. Examination of the sarcolemmal subfraction revealed higher basal concentrations of FAT/CD36 in PNGR and FATP1 and GLUT4 in IUGR, PNGR, and IPGR vs. CON. Exogenous insulin uniformly further enhanced sarcolemmal association of these macronutrient transporter proteins above that of basal, with the exception of insulin resistance of FATP1 and GLUT4 in IUGR and FAT/CD36 in PNGR. The basal sarcolemmal macronutrient transporter adaptations proved protective against subsequent chronic hypoxic exposure (7 days) only in IUGR and PNGR, with notable deterioration in IPGR and CON of the echocardiographic ejection fraction. We conclude that the IUGR and PNGR pregestational adult female offspring displayed a resistance to insulin-induced translocation of FATP1, GLUT4, or FAT/CD36 to the myocardial sarcolemma due to preexistent higher basal concentrations. This basal adaptation of myocardial macronutrient transporters ensured adequate fatty acid uptake, thereby proving protective against chronic

  20. 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

  1. 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

  2. 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

  3. 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...

  4. Automated laser spectrofluorimeter for monitoring of myocardial metabolism

    NASA Astrophysics Data System (ADS)

    Popov, A. Yu.; Salmin, V. V.; Fursov, A. A.; Stepanenko, A. V.; Sokolovich, A. G.; Salmina, A. B.; Rebenkova, A. A.; Makarov, R. A.; Provorov, A. S.

    2006-09-01

    Methods of optical biopsy have a series of advantages before other methods of clinical diagnostics. The high accuracy of received results enables registration even small change of concentration of substances, and the opportunity of remote registration makes methods optical biopsy by an optimum means for noninvasive methods of diagnostics in medicine. The method of the fluorescent analysis allows to investigate dynamics of changes of a functional condition of organs and tissue in norm and pathologies, called by the various factors (an inflammation, ischemia, degenerative changes). Bring the results of development of expiremental setup for the laser fluorescent analysis of physiological and functional condition of various organs and tissue of organism. In expiremental setup was used pulse UF nitric laser with length of wave generation = 337 nm. For delivery of radiation to tissue, and, also, collection of a radiation of fluorescence were used various optic fiber scheme. The expiremental setup includes automated tunable monochromator and ADC, receiving a signal from photomultiplier tube. Driving of all blocks and processing of results is realize on IBM-compatible computer with the appropriate software. Was used the synchronous detecting for reducing of a background signal. Myocard at surgical introoperation by an accompanied condition of sharp ischemia was researches on these expiremental setup. Spectrofluorimetric criteria of an estimation of a condition of viscus at peritonitis were development.

  5. Alcohol induced changes of carbohydrate metabolism [author's transl].

    PubMed

    Ishii, H; Okuno, F; Joly, J G; Tsuchiya, M

    1978-10-01

    It is evident that ethanol by itself or one of its metabolites produces alterations in transport, metabolism and disposition of carbohydrates. Ethanol acts via changes in the redox state of co-factors; e.g. ethanol-induced hypoglycemia is due, partly, to the inhibition of hepatic gluconeogenesis by ethanol as a consequence of the increased NADH2/NAD ratio in patients whose glycogen stores are already depleted. On the other hand, hyperglycemia has also been described in patients with alcoholism. Although its mechanism is still obscure, abnormal hormonal secretion of insulin, catecholamines and glucocorticoids has been incriminated. Finally, structural changes of the liver and pancreas such as cirrhosis and pancreatitis produced by chronic alcohol consumption should also be considered as pathogenetic factors in a variety of clinical states involving deranged carbohydrate metabolism.

  6. Association of metabolic syndrome with kidney function and histology in living kidney donors.

    PubMed

    Ohashi, Y; Thomas, G; Nurko, S; Stephany, B; Fatica, R; Chiesa, A; Rule, A D; Srinivas, T; Schold, J D; Navaneethan, S D; Poggio, E D

    2013-09-01

    The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

  7. 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.

  8. [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

  9. Usefulness of MRI to demonstrate the mechanisms of myocardial ischemia in hypertrophic cardiomyopathy with myocardial bridge.

    PubMed

    Thomson, Vivien; Botnar, Rene; Croisille, Pierre

    2007-01-01

    We present a case of symptomatic primary hypertrophic cardiomyopathy (HCM) associated with myocardial bridging of the left anterior descending (LAD) artery and suspected ischemia that could be related either to LAD artery compression or to microvascular perfusion abnormalities. MRI demonstrated the morphological appearance of myocardial hypertrophy, and coronary MR angiography evidenced the myocardial bridge and its functional consequences with stress MR perfusion. In conclusion, as a non-invasive comprehensive imaging technique, MRI should be considered in identifying the mechanisms of myocardial ischemia in HCM with myocardial bridge. PMID:16888385

  10. A case of acute myocardial infarction due to coronary spasm in the myocardial bridge.

    PubMed

    Fujibayashi, Daisuke; Morino, Yoshihiro; Ikari, Yuji

    2008-07-01

    A 68-year-old Japanese man with acute inferior myocardial infarction underwent emergent coronary angiography which showed a myocardial bridge, but no coronary stenosis, at the infarctrelated artery. A spasm provocation test using intracoronary acetylcholine revealed a total occlusion due to severe spasm at the site of the myocardial bridge. Thus, the myocardial ischemia in this case was caused by the coronary spasm, but not by the limited flow due to the myocardial bridge. Although a beta-blocker is usually the appropriate drug, it should be avoided for coronary spasm. The spasm provocation test is useful to determine the type of medication needed for treatment.

  11. Influence of dark phase restricted high fat feeding on myocardial adaptation in mice.

    PubMed

    Tsai, Ju-Yun; Villegas-Montoya, Carolina; Boland, Brandon B; Blasier, Zachary; Egbejimi, Oluwaseun; Gonzalez, Raquel; Kueht, Michael; McElfresh, Tracy A; Brewer, Rachel A; Chandler, Margaret P; Bray, Molly S; Young, Martin E

    2013-02-01

    Prolonged high fat feeding is associated with myocardial contractile dysfunction in rodents. However, epidemiological data do not necessarily support the concept that fat-enriched diets adversely affect cardiac function in humans. When fed in an ad libitum manner, laboratory rodents consume chow throughout the day. In contrast, humans typically consume food only during the awake phase. Discrepancies between rodent and human feeding behaviors led us to hypothesize that the time of day at which dietary lipids are consumed significantly influences myocardial adaptation. In order to better mimic feeding behavior in humans, mice were fed (either a control or high fat diet) only during the 12-hour dark phase (i.e., no food was provided during the light phase). We report that compared to dark phase restricted control diet fed mice, mice fed a high fat diet during the dark phase exhibit: 1) essentially normal body weight gain and energy balance; 2) increased fatty acid oxidation at whole body, as well as skeletal and cardiac muscle (in the presence of insulin and/or at high workloads) levels; 3) induction of fatty acid responsive genes, including genes promoting triglyceride turnover in the heart; 4) no evidence of cardiac hypertrophy; and 5) persistence/improvement of myocardial contractile function, as assessed ex vivo. These data are consistent with the hypothesis that ingestion of dietary fat only during the more active/awake period allows adequate metabolic adaptation, thereby preserving myocardial contractile function. This article is part of a Special Issue entitled "Focus on cardiac metabolism".

  12. 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.

  13. 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

  14. A Metabolic Signature of Mitochondrial Dysfunction Revealed through a Monogenic Form of Leigh Syndrome.

    PubMed

    Thompson Legault, Julie; Strittmatter, Laura; Tardif, Jessica; Sharma, Rohit; Tremblay-Vaillancourt, Vanessa; Aubut, Chantale; Boucher, Gabrielle; Clish, Clary B; Cyr, Denis; Daneault, Caroline; Waters, Paula J; Vachon, Luc; Morin, Charles; Laprise, Catherine; Rioux, John D; Mootha, Vamsi K; Des Rosiers, Christine

    2015-11-01

    A decline in mitochondrial respiration represents the root cause of a large number of inborn errors of metabolism. It is also associated with common age-associated diseases and the aging process. To gain insight into the systemic, biochemical consequences of respiratory chain dysfunction, we performed a case-control, prospective metabolic profiling study in a genetically homogenous cohort of patients with Leigh syndrome French Canadian variant, a mitochondrial respiratory chain disease due to loss-of-function mutations in LRPPRC. We discovered 45 plasma and urinary analytes discriminating patients from controls, including classic markers of mitochondrial metabolic dysfunction (lactate and acylcarnitines), as well as unexpected markers of cardiometabolic risk (insulin and adiponectin), amino acid catabolism linked to NADH status (?-hydroxybutyrate), and NAD(+) biosynthesis (kynurenine and 3-hydroxyanthranilic acid). Our study identifies systemic, metabolic pathway derangements that can lie downstream of primary mitochondrial lesions, with implications for understanding how the organelle contributes to rare and common diseases.

  15. Apoptosis in myocardial ischaemia and infarction.

    PubMed

    Krijnen, P A J; Nijmeijer, R; Meijer, C J L M; Visser, C A; Hack, C E; Niessen, H W M

    2002-11-01

    Recent studies indicate that, in addition to necrosis, apoptosis also plays a role in the process of tissue damage after myocardial infarction, which has pathological and therapeutic implications. This review article will discuss studies in which the role and mechanisms of apoptosis in myocardial infarction were analysed in vivo and in vitro in humans and in animals.

  16. [ST myocardial infarction with spontaneous coronary reperfusion].

    PubMed

    Uriel, Nir; Moravsky, Gil; Blatt, Alex; Vered, Zvi; Krakover, Ricardo; Kaluski, Edo

    2006-05-01

    ST elevation myocardial infarction continues to be a major medical problem even in the beginning of the 21st century. Treatment guidelines for these patients are based on multiple randomized clinical trials. In order to minimize myocardial damage, early patency of the infarct relating artery must be accomplished. This is the major difference in the treatment strategy between ST elevation myocardial infarction and other acute coronary syndromes. Primary percutaneous coronary intervention and fibrinolysis are the two treatment modalities for achieving myocardial reperfusion. The subgroup of ST elevation myocardial infarction with spontaneous coronary artery reperfusion carries a more favorable prognosis. This review addresses the clinical characteristics, natural history, prognosis and treatment strategies for this group, with special emphasis on the optimal timing for revascularization, and the role of glycoprotein IIb/IIIa inhibitors.

  17. 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.

  18. 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

  19. Macrophage Roles Following Myocardial Infarction

    PubMed Central

    Lambert, Jessica M.; Lopez, Elizabeth F.; Lindsey, Merry L.

    2010-01-01

    Following myocardial infarction (MI), circulating blood monocytes respond to chemotactic factors, migrate into the infarcted myocardium, and differentiate into macrophages. At the injury site, macrophages remove necrotic cardiac myocytes and apoptotic neutrophils; secrete cytokines, chemokines, and growth factors; and modulate phases of the angiogenic response. As such, the macrophage is a primary responder cell type that is involved in the regulation of post-MI wound healing at multiple levels. This review summarizes what is currently known about macrophage functions post-MI and borrows literature from other injury and inflammatory models to speculate on additional roles. Basic science and clinical avenues that remain to be explored are also discussed. PMID:18656272

  20. 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

  1. [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

  2. 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

  3. The iron-regulatory peptide hepcidin is upregulated in the ischemic and in the remote myocardium after myocardial infarction.

    PubMed

    Simonis, Gregor; Mueller, Katrin; Schwarz, Peggy; Wiedemann, Stephan; Adler, Guido; Strasser, Ruth H; Kulaksiz, Hasan

    2010-09-01

    Recent evidence suggests that iron metabolism contributes to the ischemic damage after myocardial infarction. Hepcidin, a recently discovered peptide hormone, regulates iron uptake and metabolism, protecting the body from iron overload. In this study we analyzed the regulation of hepcidin in the heart and blood of rats after myocardial infarction. To induce a myocardial infarction in the rats, left anterior descending coronary artery ligation was performed. After 1-24h, biopsies from the ischemic and the non-ischemic myocardium were taken. In these biopsies, the mRNA levels and the protein expression of hepcidin were analyzed by quantitative RT-PCR and immunoblot analysis, respectively. In parallel, the serum levels of prohepcidin were measured by ELISA. Six hours after myocardial infarction, the hepcidin mRNA expression was temporally upregulated in the ischemic and in the non-ischemic myocardium. The upregulation was specific for hepcidin, since other iron-related genes (hemojuvelin, IREG-1) remained unchanged. Furthermore, the alteration of the hepcidin protein expression in the ischemic area was connected to the level of hepcidin in the serum of the infarcted rats, where hepcidin also raised up. Angiotensin receptor blockade with candesartan did not influence the mRNA regulation of hepcidin. Together, these data show a particular upregulation of the iron-regulatory peptide hepcidin in the ischemic and the non-ischemic myocardium after myocardial infarction. It is speculated that upregulation of hepcidin may reduce iron toxicity and thus infarct size expansion in an infarcted heart.

  4. 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 ...

  5. Tetradecylthioacetic acid increases fat metabolism and improves cardiac function in experimental heart failure.

    PubMed

    Øie, Erik; Berge, Rolf K; Ueland, Thor; Dahl, Christen P; Edvardsen, Thor; Beitnes, Jan Otto; Bohov, Pavol; Aukrust, Pål; Yndestad, Arne

    2013-02-01

    Changes in myocardial metabolism, including a shift from fatty acid to glucose utilization and changes in fatty acid availability and composition are characteristics of heart failure development. Tetradecylthioacetic acid (TTA) is a fatty acid analogue lacking the ability to undergo mitochondrial β-oxidation. TTA promotes hepatic proliferation of mitochondria and peroxisomes and also decreases serum triglycerides and cholesterol in animals. We investigated the effect of TTA, in combination with a high-fat or regular diet, in a rat model of post-myocardial infarction heart failure. TTA had a beneficial effect on cardiac function in post-myocardial infarction heart failure without affecting myocardial remodeling. These effects of TTA on myocardial function were accompanied by decreased free fatty acids in plasma, increased myocardial proportion of n-3 polyunsaturated fatty acids (PUFA) and a decreased proportion of n-6 PUFA. Myocardial enzyme gene expression during TTA treatment suggested that the increase in n-3 PUFA could reflect increased n-3 PUFA synthesis and inadequately increased n-3 PUFA β-oxidation. Based on our data, it is unlikely that the changes are secondary to alterations in other tissues as plasma and liver showed an opposite pattern with decreased n-3 PUFA during TTA treatment. The present study suggests that TTA may improve myocardial function in heart failure, potentially involving its ability to decrease the availability of FFA and increase the myocardial proportion of n-3 PUFA. PMID:23266898

  6. 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

  7. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure.

    PubMed

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-12-14

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF.

  8. Dynamic genetic architecture of metabolic syndrome attributes in the rat.

    PubMed

    Seda, Ondrej; Liska, Frantisek; Krenova, Drahomira; Kazdova, Ludmila; Sedova, Lucie; Zima, Tomas; Peng, Junzheng; Pelinkova, Kveta; Tremblay, Johanne; Hamet, Pavel; Kren, Vladimir

    2005-04-14

    The polydactylous rat strain (PD/Cub) is a highly inbred (F > 90) genetic model of metabolic syndrome. The aim of this study was to analyze the genetic architecture of the metabolic derangements found in the PD/Cub strain and to assess its dynamics in time and in response to diet and medication. We derived a PD/Cub x BN/Cub (Brown Norway) F2 intercross population of 149 male rats and performed metabolic profiling and genotyping and multiple levels of genetic linkage and statistical analyses at five different stages of ontogenesis and after high-sucrose diet feeding and dexamethasone administration challenges. The interval mapping analysis of 83 metabolic and morphometric traits revealed over 50 regions genomewide with significant or suggestive linkage to one or more of the traits in the segregating PD/Cub x BN/Cub population. The multiple interval mapping showed that, in addition to "single" quantitative train loci, there are more than 30 pairs of loci across the whole genome significantly influencing the variation of particular traits in an epistatic fashion. This study represents the first whole genome analysis of metabolic syndrome in the PD/Cub model and reveals several new loci previously not connected to the genetics of insulin resistance and dyslipidemia. In addition, it attempts to present the concept of "dynamic genetic architecture" of metabolic syndrome attributes, evidenced by shifts in the genetic determination of syndrome features during ontogenesis and during adaptation to the dietary and pharmacological influences.

  9. [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.

  10. 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.

  11. 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.

  12. 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

  13. In vivo measurement of myocardial protein turnover using an indicator dilution technique

    SciTech Connect

    Revkin, J.H.; Young, L.H.; Stirewalt, W.S.; Dahl, D.M.; Gelfand, R.A.; Zaret, B.L.; Barrett, E.J. )

    1990-10-01

    We applied a nondestructive tracer technique, previously developed for measuring skeletal muscle protein turnover, to the measurement of myocardial protein turnover in vivo. During a continuous infusion of L-(ring-2,6-3H)phenylalanine to anesthetized, overnight-fasted dogs, we measured the uptake of radiolabeled phenylalanine from plasma and the release of unlabeled phenylalanine from myocardial proteolysis using arterial and coronary sinus catheterization and analytic methods previously applied to skeletal muscle. Using these measurements, together with a model of myocardial protein synthesis that assumes rapid equilibration of tracer specific activity between myocardial phenylalanyl-tRNA and circulating phenylalanine, we estimated the rates of heart protein synthesis and degradation. The rate of heart protein synthesis was also estimated directly from the incorporation of labeled phenylalanine into tissue protein. The use of (3H)phenylalanine was compared with L-(1-14C)leucine in the measurement of heart protein turnover in dogs given simultaneous infusion of both tracers. Leucine uptake and release by the myocardium exceeded that of phenylalanine by 3.1 +/- 0.4- and 1.7 +/- 0.3-fold, respectively, consistent with leucine's 2.4-fold greater abundance in heart protein and its metabolism via other pathways. Phenylalanine is the preferred tracer for use with this method because of its limited metabolic fate in muscle. One theoretical limitation to the method, slow equilibration of circulating labeled phenylalanine with myocardial phenylalanyl-tRNA, was resolved by comparison of these specific activities after a 30-minute infusion of labeled phenylalanine in the rat. A second, empirical limitation involves precision in the measurement of the small decrements in phenylalanine specific activity that occur with each pass of blood through the coronary circulation.

  14. 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

  15. Impact of hepatitis B virus infection on hepatic metabolic signaling pathway.

    PubMed

    Shi, Yi-Xian; Huang, Chen-Jie; Yang, Zheng-Gang

    2016-09-28

    A growing body of epidemiologic research has demonstrated that metabolic derangement exists in patients with hepatitis B virus (HBV) infection, indicating that there are clinical associations between HBV infection and host metabolism. In order to understand the complex interplay between HBV and hepatic metabolism in greater depth, we systematically reviewed these alterations in different metabolic signaling pathways due to HBV infection. HBV infection interfered with most aspects of hepatic metabolic responses, including glucose, lipid, nucleic acid, bile acid and vitamin metabolism. Glucose and lipid metabolism is a particular focus due to the significant promotion of gluconeogenesis, glucose aerobic oxidation, the pentose phosphate pathway, fatty acid synthesis or oxidation, phospholipid and cholesterol biosynthesis affected by HBV. These altered metabolic pathways are involved in the pathological process of not only hepatitis B, but also metabolic disorders, increasing the occurrence of complications, such as hepatocellular carcinoma and liver steatosis. Thus, a clearer understanding of the hepatic metabolic pathways affected by HBV and its pathogenesis is necessary to develop more novel therapeutic strategies targeting viral eradication. PMID:27688657

  16. Impact of hepatitis B virus infection on hepatic metabolic signaling pathway.

    PubMed

    Shi, Yi-Xian; Huang, Chen-Jie; Yang, Zheng-Gang

    2016-09-28

    A growing body of epidemiologic research has demonstrated that metabolic derangement exists in patients with hepatitis B virus (HBV) infection, indicating that there are clinical associations between HBV infection and host metabolism. In order to understand the complex interplay between HBV and hepatic metabolism in greater depth, we systematically reviewed these alterations in different metabolic signaling pathways due to HBV infection. HBV infection interfered with most aspects of hepatic metabolic responses, including glucose, lipid, nucleic acid, bile acid and vitamin metabolism. Glucose and lipid metabolism is a particular focus due to the significant promotion of gluconeogenesis, glucose aerobic oxidation, the pentose phosphate pathway, fatty acid synthesis or oxidation, phospholipid and cholesterol biosynthesis affected by HBV. These altered metabolic pathways are involved in the pathological process of not only hepatitis B, but also metabolic disorders, increasing the occurrence of complications, such as hepatocellular carcinoma and liver steatosis. Thus, a clearer understanding of the hepatic metabolic pathways affected by HBV and its pathogenesis is necessary to develop more novel therapeutic strategies targeting viral eradication.

  17. Impact of hepatitis B virus infection on hepatic metabolic signaling pathway

    PubMed Central

    Shi, Yi-Xian; Huang, Chen-Jie; Yang, Zheng-Gang

    2016-01-01

    A growing body of epidemiologic research has demonstrated that metabolic derangement exists in patients with hepatitis B virus (HBV) infection, indicating that there are clinical associations between HBV infection and host metabolism. In order to understand the complex interplay between HBV and hepatic metabolism in greater depth, we systematically reviewed these alterations in different metabolic signaling pathways due to HBV infection. HBV infection interfered with most aspects of hepatic metabolic responses, including glucose, lipid, nucleic acid, bile acid and vitamin metabolism. Glucose and lipid metabolism is a particular focus due to the significant promotion of gluconeogenesis, glucose aerobic oxidation, the pentose phosphate pathway, fatty acid synthesis or oxidation, phospholipid and cholesterol biosynthesis affected by HBV. These altered metabolic pathways are involved in the pathological process of not only hepatitis B, but also metabolic disorders, increasing the occurrence of complications, such as hepatocellular carcinoma and liver steatosis. Thus, a clearer understanding of the hepatic metabolic pathways affected by HBV and its pathogenesis is necessary to develop more novel therapeutic strategies targeting viral eradication. PMID:27688657

  18. Impact of hepatitis B virus infection on hepatic metabolic signaling pathway

    PubMed Central

    Shi, Yi-Xian; Huang, Chen-Jie; Yang, Zheng-Gang

    2016-01-01

    A growing body of epidemiologic research has demonstrated that metabolic derangement exists in patients with hepatitis B virus (HBV) infection, indicating that there are clinical associations between HBV infection and host metabolism. In order to understand the complex interplay between HBV and hepatic metabolism in greater depth, we systematically reviewed these alterations in different metabolic signaling pathways due to HBV infection. HBV infection interfered with most aspects of hepatic metabolic responses, including glucose, lipid, nucleic acid, bile acid and vitamin metabolism. Glucose and lipid metabolism is a particular focus due to the significant promotion of gluconeogenesis, glucose aerobic oxidation, the pentose phosphate pathway, fatty acid synthesis or oxidation, phospholipid and cholesterol biosynthesis affected by HBV. These altered metabolic pathways are involved in the pathological process of not only hepatitis B, but also metabolic disorders, increasing the occurrence of complications, such as hepatocellular carcinoma and liver steatosis. Thus, a clearer understanding of the hepatic metabolic pathways affected by HBV and its pathogenesis is necessary to develop more novel therapeutic strategies targeting viral eradication.

  19. Serum nickle estimation in acute myocardial infarction.

    PubMed

    Narang, N K; Goyal, R K; Gupta, A K; Balwani, S

    1989-11-01

    Serum nickle was estimated by atomic absorption spectrometer in 20 healthy controls and in 25 cases of acute myocardial infarction at 12 hourly intervals upto 48 hours, after the onset of chest pain. The mean serum nickel was 0.27 micrograms/dl in healthy controls and 0.40,050,049 and 0.30 micrograms/dl in patients of acute myocardial infarction. The serum nickel values were significantly (P less than 0.001) raised upto 36 hours in acute myocardial infarction when compared with controls.

  20. Nanog expression in heart tissues induced by acute myocardial infarction.

    PubMed

    Luo, Huanhuan; Li, Qiong; Pramanik, Jogen; Luo, Jiankai; Guo, Zhikun

    2014-10-01

    Nanog is a potential stem cell marker and is considered a regeneration factor during tissue repair. In the present study, we investigated expression patterns of nanog in the rat heart after acute myocardial infarction by semi-quantitative RT-PCR, immunohistochemistry and Western blot analyses. Our results show that nanog at both mRNA and protein levels is positively expressed in myocardial cells, fibroblasts and small round cells in different myocardial zones at different stages after myocardial infarction, showing a spatio-temporal and dynamic change. After myocardial infarction, the nanog expression in fibroblasts and small round cells in the infarcted zone (IZ) is much stronger than that in the margin zone (MZ) and remote infarcted zone (RIZ). From day 7 after myocardial infarction, the fibroblasts and small cells strongly expressed nanog protein in the IZ, and a few myocardial cells in the MZ and the RIZ and the numbers of nanog-positive fibroblasts and small cells reached the highest peak at 21 days after myocardial infarction, but in this period the number of nanog-positive myocardial cells decreased gradually. At 28 days after myocardial infarction, the numbers of all nanog-positive cells decreased into a low level. Therefore, our data suggest that all myocardial cells, fibroblasts and small round cells are involved in myocardial reconstruction after cardiac infarction. The nanog-positive myocardial cells may respond to early myocardial repair, and the nanog-positive fibroblasts and small round cells are the main source for myocardial reconstruction after cardiac infarction.

  1. Metabolic Syndrome

    MedlinePlus

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  2. [Characteristics of therapy of acute myocardial infarction in diabetes].

    PubMed

    Motz, W; Kerner, W

    2012-05-01

    Therapy of acute myocardial infarction (STEMI and NSTEMI) in diabetics does not principally differ from that of non-diabetic patients. Due to the higher mortality in diabetics reperfusion measures, such as direct percutaneous coronary intervention (PCI), should be rapidly performed. An intensive drug treatment with thrombocyte aggregation inhibitors, angiotensin-converting enzyme (ACE) inhibitors and beta-receptor blocking agents must be carried out according to the current guidelines. An important factor is the high risk of renal failure due to the contrast dye administered during PCI in the presence of pre-existing diabetic kidney damage which should be limited to 100 ml if possible. Direct PCI should be limited to the infarcted vessel. After stabilization a comprehensive strategy to cure coronary artery disease, whether with PCI or coronary artery bypass graft (CABG) should be finalized. If severe coronary 3-vessel disease is present, CABG should be favored in diabetic patients. After surviving an acute myocardial infarction differentiated metabolic monitoring is mandatory.

  3. 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

  4. A constant temperature perfusion system for myocardial energetics.

    PubMed

    Niesler, R A; Axon, D W; Eggert, M A

    1981-11-01

    A constant temperature perfusion system employing four heat exchangers has been developed in which perfusion fluid is heated from room temperature to 37 +/- 10 -4 degrees C for precision heat flow measurements on isolated working rat hearts. The temperature characteristics have been established and mathematical expressions developed to identify and quantify spurious thermal events. The system is a refinement of existing perfusion systems for metabolic and mechanical investigations which meets the complete requirements of myocardial energetics. It can also be used for experiments which include high precision temperature measurements on isolated working hearts or for thermal investigations on other isolated perfused organs where a highly stabilised temperature base line is required over perfusion flows from 0-100 cm3 min -1. PMID:7323145

  5. [Stem cell perspectives in myocardial infarctions].

    PubMed

    Aceves, José Luis; Archundia, Abel; Díaz, Guillermo; Páez, Araceli; Masso, Felipe; Alvarado, Martha; López, Manuel; Aceves, Rocío; Ixcamparij, Carlos; Puente, Adriana; Vilchis, Rafael; Montaño, Luis Felipe

    2005-01-01

    Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.

  6. Physiology and pharmacology of myocardial preconditioning.

    PubMed

    Raphael, Jacob

    2010-03-01

    Perioperative myocardial ischemia and infarction are not only major sources of morbidity and mortality in patients undergoing surgery but also important causes of prolonged hospital stay and resource utilization. Ischemic and pharmacological preconditioning and postconditioning have been known for more than two decades to provide protection against myocardial ischemia and reperfusion and limit myocardial infarct size in many experimental animal models, as well as in clinical studies (1-3). This paper will review the physiology and pharmacology of ischemic and drug-induced preconditioning and postconditioning of the myocardium with special emphasis on the mechanisms by which volatile anesthetics provide myocardial protection. Insights gained from animal and clinical studies will be presented and reviewed and recommendations for the use of perioperative anesthetics and medications will be given.

  7. 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

  8. Exosomes and cardiac repair after myocardial infarction.

    PubMed

    Sahoo, Susmita; Losordo, Douglas W

    2014-01-17

    Myocardial infarction is a leading cause of death among all cardiovascular diseases. The analysis of molecular mechanisms by which the ischemic myocardium initiates repair and remodeling indicates that secreted soluble factors are key players in communication to local and distant tissues, such as bone marrow. Recently, actively secreted membrane vesicles, including exosomes, are being recognized as new candidates with important roles in intercellular and tissue-level communication. In this review, we critically examine the emerging role of exosomes in local and distant microcommunication mechanisms after myocardial infarction. A comprehensive understanding of the role of exosomes in cardiac repair after myocardial infarction could bridge a major gap in knowledge of the repair mechanism after myocardial injury.

  9. Unexpectedly severe metabolic acidosis associated with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy.

    PubMed

    Selk, Natalie; Rodby, Roger A

    2011-01-01

    Calcific uremic arteriolopathy, formerly known as calciphylaxis is a devastating condition that primarily affects patients with end-stage renal disease. The lesions can progress to massive ulcerations of the subcutaneous tissue that are associated with a high degree of morbidity and mortality, usually related to sepsis. Although the pathophysiology of this condition is poorly understood, it appears to be related to a derangement in calcium-phosphate metabolism. Thus, treatments have focused on the treatment of hyperparathyroidism albeit with poor results. More recently, sodium thiosulfate (STS) has emerged as a promising therapy following multiple case reports of marked disease regression following its use. As STS is a strong acid, metabolic acidosis has been described following its administration, although relatively mild in degree. We report a case of a patient with calciphylaxis who repeatedly developed a severe anion gap metabolic acidosis following each dose of STS requiring a significant reduction in the dose.

  10. 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

  11. Intra-articular and muscle symptoms and subjective relief during TMJ internal derangement treatment with maxillary anterior repositioning splint or SVED and MORA splints: A comparison with untreated control subjects.

    PubMed

    Tecco, Simona; Caputi, Sergio; Teté, Stefano; Orsini, Giovanna; Festa, Felice

    2006-04-01

    Discomfort associated with wearing an intraoral splint represents a problem in the management of temporomandibular joint (TMJ) internal derangement. This study evaluated whether the use of a mandibular splint during the day and a maxillary splint at night could be more comfortable and therefore as efficacious in internal derangement treatment as a maxillary splint (AR splint). Fifty (50) patients (average age 28.8; range 14-63) with confirmed internal derangement in at least one TMJ were divided into three groups: 20 patients treated with AR splint (Group I); 20 patients treated with a SVED (Sagittal Vertical Extrusion Device) and a MORA (Mandibular Anterior Repositioning Splint) (Group II); and 10 patients who underwent no treatment (Control Group). Joint noise, pain intensity and its character (as constant or chewing/biting pain), muscular pain, and subjective relief were evaluated monthly before treatment began (T0) and for six months thereafter. The following results were found: 1. Subjects in Group I and Group II displayed a significant decrease in joint pain (p<0.001), constant pain (p<0.001), chewing/biting pain (p<0.001), joint noise and muscle pain from the beginning through the sixth month follow-ups; 2. At T1 and T2, subjects in Group II reported significantly lower discomfort associated with the devices than subjects in Group I. The use of two splints seems to be as efficacious as the use of an AR maxillary splint; however an AR splint is considered more comfortable by patients, especially during the first months of therapy.

  12. 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.

  13. Serotonin metabolism in children with kwashiorkor.

    PubMed

    Teotia, M; Teotia, S P

    1975-11-01

    Intestinal fat absorption, serum 5-hydroxytryptamine (5-HT) and 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) were studied in 13 children with kwashiorkor and 10 matched healthy controls. Eight out of 13 children with kwashiorkor who had steatorrhea also showed raised plasma serotonin levels in parallel with the high urinary excretion of 5-HIAA. In five children with kwashiorkor who showed normal intestinal fat absorption, the serum 5-HT and urinary 5-HIAA levels were comparable to controls. After therapy, concurrent with clinical and biochemical recovery, the intestinal absorption of fat improved, serum 5-HT concentration and the urinary excretion of 5-HIAA returned to normal range. This suggested that the deranged serotonin metabolism in our cases was secondary to the protein-calorie deficiency. The presence of defective metabolism of serotonin (5-HT) in children with kwashiorkor has been reported and its possible role in the etiopathogenesis of steatorrhea-diarrhea, skin lesions and psychomotor changes has been suggested for further work.

  14. [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

  15. Tachycardia induced myocardial dysfunction. A reversible phenomenon?

    PubMed Central

    McLaran, C J; Gersh, B J; Sugrue, D D; Hammill, S C; Seward, J B; Holmes, D R

    1985-01-01

    Four patients with myocardial dysfunction related to tachycardia underwent electrophysiological studies, which showed a re-entrant supraventricular tachycardia using an accessory atrioventricular connexion. Serial assessment of left ventricular function by echocardiography before and after control of the tachycardia indicated a variable degree of reversibility. Endomyocardial biopsy in two patients detected non-specific histological changes. Because of the possible role of ischaemia in this condition effective control of prolonged tachycardia is needed to prevent deterioration of myocardial function. Images PMID:3970789

  16. 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.

  17. The apoptotic effect and the plausible mechanism of microwave radiation on rat myocardial cells.

    PubMed

    Zhu, Wenhe; Cui, Yan; Feng, Xianmin; Li, Yan; Zhang, Wei; Xu, Junjie; Wang, Huiyan; Lv, Shijie

    2016-08-01

    Microwaves may exert adverse biological effects on the cardiovascular system at the integrated system and cellular levels. However, the mechanism underlying such effects remains poorly understood. Here, we report a previously uncharacterized mechanism through which microwaves damage myocardial cells. Rats were treated with 2450 MHz microwave radiation at 50, 100, 150, or 200 mW/cm(2) for 6 min. Microwave treatment significantly enhanced the levels of various enzymes in serum. In addition, it increased the malondialdehyde content while decreasing the levels of antioxidative stress enzymes, activities of enzyme complexes I-IV, and ATP in myocardial tissues. Notably, irradiated myocardial cells exhibited structural damage and underwent apoptosis. Furthermore, Western blot analysis revealed significant changes in expression levels of proteins involved in oxidative stress regulation and apoptotic signaling pathways, indicating that microwave irradiation could induce myocardial cell apoptosis by interfering with oxidative stress and cardiac energy metabolism. Our findings provide useful insights into the mechanism of microwave-induced damage to the cardiovascular system. PMID:27203380

  18. The apoptotic effect and the plausible mechanism of microwave radiation on rat myocardial cells.

    PubMed

    Zhu, Wenhe; Cui, Yan; Feng, Xianmin; Li, Yan; Zhang, Wei; Xu, Junjie; Wang, Huiyan; Lv, Shijie

    2016-08-01

    Microwaves may exert adverse biological effects on the cardiovascular system at the integrated system and cellular levels. However, the mechanism underlying such effects remains poorly understood. Here, we report a previously uncharacterized mechanism through which microwaves damage myocardial cells. Rats were treated with 2450 MHz microwave radiation at 50, 100, 150, or 200 mW/cm(2) for 6 min. Microwave treatment significantly enhanced the levels of various enzymes in serum. In addition, it increased the malondialdehyde content while decreasing the levels of antioxidative stress enzymes, activities of enzyme complexes I-IV, and ATP in myocardial tissues. Notably, irradiated myocardial cells exhibited structural damage and underwent apoptosis. Furthermore, Western blot analysis revealed significant changes in expression levels of proteins involved in oxidative stress regulation and apoptotic signaling pathways, indicating that microwave irradiation could induce myocardial cell apoptosis by interfering with oxidative stress and cardiac energy metabolism. Our findings provide useful insights into the mechanism of microwave-induced damage to the cardiovascular system.

  19. Cardiorespiratory fitness modifies the relationship between myocardial function and cerebral blood flow in older adults.

    PubMed

    Johnson, Nathan F; Gold, Brian T; Bailey, Alison L; Clasey, Jody L; Hakun, Jonathan G; White, Matthew; Long, Doug E; Powell, David K

    2016-05-01

    A growing body of evidence indicates that cardiorespiratory fitness attenuates some age-related cerebral declines. However, little is known about the role that myocardial function plays in this relationship. Brain regions with high resting metabolic rates, such as the default mode network (DMN), may be especially vulnerable to age-related declines in myocardial functions affecting cerebral blood flow (CBF). This study explored the relationship between a measure of myocardial mechanics, global longitudinal strain (GLS), and CBF to the DMN. In addition, we explored how cardiorespiratory affects this relationship. Participants were 30 older adults between the ages of 59 and 69 (mean age=63.73years, SD=2.8). Results indicated that superior cardiorespiratory fitness and myocardial mechanics were positively associated with DMN CBF. Moreover, results of a mediation analysis revealed that the relationship between GLS and DMN CBF was accounted for by individual differences in fitness. Findings suggest that benefits of healthy heart function to brain function are modified by fitness.

  20. 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

  1. Cardiorespiratory fitness modifies the relationship between myocardial function and cerebral blood flow in older adults.

    PubMed

    Johnson, Nathan F; Gold, Brian T; Bailey, Alison L; Clasey, Jody L; Hakun, Jonathan G; White, Matthew; Long, Doug E; Powell, David K

    2016-05-01

    A growing body of evidence indicates that cardiorespiratory fitness attenuates some age-related cerebral declines. However, little is known about the role that myocardial function plays in this relationship. Brain regions with high resting metabolic rates, such as the default mode network (DMN), may be especially vulnerable to age-related declines in myocardial functions affecting cerebral blood flow (CBF). This study explored the relationship between a measure of myocardial mechanics, global longitudinal strain (GLS), and CBF to the DMN. In addition, we explored how cardiorespiratory affects this relationship. Participants were 30 older adults between the ages of 59 and 69 (mean age=63.73years, SD=2.8). Results indicated that superior cardiorespiratory fitness and myocardial mechanics were positively associated with DMN CBF. Moreover, results of a mediation analysis revealed that the relationship between GLS and DMN CBF was accounted for by individual differences in fitness. Findings suggest that benefits of healthy heart function to brain function are modified by fitness. PMID:26032886

  2. Iodophenylpentadecanoic acid-myocardial blood flow relationship during maximal exercise with coronary occlusion

    SciTech Connect

    Caldwell, J.H.; Martin, G.V.; Link, J.M.; Krohn, K.A.; Bassingthwaighte, J.B. )

    1990-01-01

    Imaging {sup 123}I-labeled iodophenylpentadecanoic acid (IPPA) uptake and clearance from the myocardium following exercise has been advocated as a means of detecting myocardial ischemia because fatty acid deposition is enhanced and clearance prolonged in regions of low flow. However, normal regional myocardial blood flows are markedly heterogeneous, and it is not known how this heterogeneity affects regional metabolism or substrate uptake and thus image interpretation. In five instrumented dogs running at near maximal workload on a treadmill, {sup 131}I-labeled IPPA and 15-micron 46Sc microspheres were injected into the left atrium after 30 sec of circumflex coronary artery occlusion. Microsphere and IPPA activity were determined in 250 mapped pieces of myocardium of approximately 400 mg. Myocardial blood flows (from microspheres) ranged from 0.05 to 7.6 ml/min/g. Deposition of IPPA was proportional to regional flows (r = 0.83) with an average retention of 25%. The mean endocardial-epicardial ratio for IPPA (0.90 {plus minus} 0.43) was similar to that for microspheres (0.94 {plus minus} 0.47; p = 0.08). Thus, initial IPPA deposition during treadmill exercise increases in proportion to regional myocardial blood flow over a range of flows from very low to five times normal.

  3. 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.

  4. 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

  5. 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

  6. A somatic component to myocardial infarction.

    PubMed Central

    Nicholas, A S; DeBias, D A; Ehrenfeuchter, W; England, K M; England, R W; Greene, C H; Heilig, D; Kirschbaum, M

    1985-01-01

    Sixty two patients were randomised to be seen by osteopathic physicians for palpation of the thoracic paravertebral soft tissue, T1-T8. Twenty five patients had clinically confirmed acute myocardial infarction. Of the remainder, 22 without known cardiovascular disease served as controls and 15 were placed in an excluded group because of diagnosed cardiovascular disease other than myocardial infarction. Observations were described in predetermined standard terminology. The control group was found to have a low incidence of palpable changes throughout the thoracic dorsum, and these changes were uniformly distributed from T1 to T8. Examination of the group with myocardial infarction disclosed a significantly higher incidence of soft tissue changes (increased firmness, warmth, ropiness, oedematous changes, heavy musculature), confined almost entirely to the upper four thoracic levels. The 15 patients who were excluded from the experimental group because they had various cardiovascular diseases other than myocardial infarction also showed significantly different changes on palpation compared with the group with myocardial infarction. These findings suggest that myocardial infarction is accompanied by characteristic paravertebral soft tissue changes which are readily detected by palpation. PMID:3926040

  7. Novel adjunctive treatments of myocardial infarction

    PubMed Central

    Schmidt, Michael Rahbek; Pryds, Kasper; Bøtker, Hans Erik

    2014-01-01

    Myocardial infarction is a major cause of death and disability worldwide and myocardial infarct size is a major determinant of prognosis. Early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome, but reperfusion may induce further myocardial damage itself. Development of adjunctive therapies to limit myocardial reperfusion injury beyond opening of the coronary artery gains increasing attention. A vast number of experimental studies have shown cardioprotective effects of ischemic and pharmacological conditioning, but despite decades of research, the translation into clinical effects has been challenging. Recently published clinical studies, however, prompt optimism as novel techniques allow for improved clinical applicability. Cyclosporine A, the GLP-1 analogue exenatide and rapid cooling by endovascular infusion of cold saline all reduce infarct size and may confer clinical benefit for patients admitted with acute myocardial infarcts. Equally promising, three follow-up studies of the effect of remote ischemic conditioning (RIC) show clinical prognostic benefit in patients undergoing coronary surgery and percutaneous coronary intervention. The discovery that RIC can be performed noninvasively using a blood pressure cuff on the upper arm to induce brief episodes of limb ischemia and reperfusion has facilitated the translation of RIC into the clinical arena. This review focus on novel advances in adjunctive therapies in relation to acute and elective coronary procedures. PMID:24976915

  8. 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

  9. Effect of eating on thallium myocardial imaging

    SciTech Connect

    Wilson, R.A.; Sullivan, P.J.; Okada, R.D.; Boucher, C.A.; Morris, C.; Pohost, G.M.; Strauss, H.W.

    1986-02-01

    To determine if eating between initial and delayed thallium images alters the appearance of the delayed thallium scan, a prospective study was performed; 184 subjects sent for routine thallium imaging were randomized into two groups, those who ate a meal high in carbohydrates between initial and delayed thallium myocardial images (n = 106), and those who fasted (n = 78). The /sup 201/Tl images were interpreted in blinded fashion for global myocardial and pulmonary clearance of /sup 201/Tl myocardial defects. The eating group had a significantly lower incidence of transient myocardial defects compared to the noneating group (7 percent vs 18 percent, respectively; p less than 0.05). The time between initial and delayed images and the incidence of exercise-induced ischemic ST-segment depression or pathologic Q waves on the electrocardiogram were not significantly different between the two groups. These data suggest that eating a high-carbohydrate meal between initial and delayed /sup 201/Tl images causes increased /sup 201/Tl myocardial clearance rates and may alter /sup 201/Tl myocardial redistribution over time.

  10. Sensitive Troponin Assay and the Classification of Myocardial Infarction

    PubMed Central

    Shah, Anoop S.V.; McAllister, David A.; Mills, Rosamund; Lee, Kuan Ken; Churchhouse, Antonia M.D.; Fleming, Kathryn M.; Layden, Elizabeth; Anand, Atul; Fersia, Omar; Joshi, Nikhil V.; Walker, Simon; Jaffe, Allan S.; Fox, Keith A.A.; Newby, David E.; Mills, Nicholas L.

    2015-01-01

    Background Lowering the diagnostic threshold for troponin is controversial because it may disproportionately increase the diagnosis of myocardial infarction in patients without acute coronary syndrome. We assessed the impact of lowering the diagnostic threshold of troponin on the incidence, management, and outcome of patients with type 2 myocardial infarction or myocardial injury. Methods Consecutive patients with elevated plasma troponin I concentrations (≥50 ng/L; n = 2929) were classified with type 1 (50%) myocardial infarction, type 2 myocardial infarction or myocardial injury (48%), and type 3 to 5 myocardial infarction (2%) before and after lowering the diagnostic threshold from 200 to 50 ng/L with a sensitive assay. Event-free survival from death and recurrent myocardial infarction was recorded at 1 year. Results Lowering the threshold increased the diagnosis of type 2 myocardial infarction or myocardial injury more than type 1 myocardial infarction (672 vs 257 additional patients, P < .001). Patients with myocardial injury or type 2 myocardial infarction were at higher risk of death compared with those with type 1 myocardial infarction (37% vs 16%; relative risk [RR], 2.31; 95% confidence interval [CI], 1.98-2.69) but had fewer recurrent myocardial infarctions (4% vs 12%; RR, 0.35; 95% CI, 0.26-0.49). In patients with troponin concentrations 50 to 199 ng/L, lowering the diagnostic threshold was associated with increased healthcare resource use (P < .05) that reduced recurrent myocardial infarction and death for patients with type 1 myocardial infarction (31% vs 20%; RR, 0.64; 95% CI, 0.41-0.99), but not type 2 myocardial infarction or myocardial injury (36% vs 33%; RR, 0.93; 95% CI, 0.75-1.15). Conclusions After implementation of a sensitive troponin assay, the incidence of type 2 myocardial infarction or myocardial injury disproportionately increased and is now as frequent as type 1 myocardial infarction. Outcomes of patients with type 2 myocardial

  11. Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning.

    PubMed

    Mazzadi, Alejandro N; André-Fouët, Xavier; Costes, Nicolas; Croisille, Pierre; Revel, Didier; Janier, Marc F

    2006-12-01

    Patients with severe chronic coronary artery disease (CAD) exhibit a highly altered myocardial pattern of perfusion, metabolism, and mechanical performance. In this context, the diagnosis of stunning remains elusive not only because of methodological and logistic considerations, but also because of the pathophysiological characteristics of the myocardium of these patients. In addition, a number of alternative pathophysiological mechanisms may act by mimicking the functional manifestations usually attributed to stunning. The present review describes three mechanisms that could theoretically lead to reversible mechanical dysfunction in these patients: myocardial wall stress, the tethering effect, and myocardial expression and release of auto- and paracrine agents. Attention is focused on the role of these mechanisms in scintigraphically "normal" regions (i.e., regions usually showing normal perfusion, glucose metabolism, and cellular integrity as assessed by nuclear imaging techniques), in which stunning is usually considered, but these mechanisms could also operate throughout the viable myocardium. We hypothesize that reversion of these three mechanisms could partially explain the unexpected functional benefit after reperfusion recently highlighted by high-spatial-resolution imaging techniques. PMID:16861690

  12. Myocardial infarction caused by myocardial bridging in a male adolescent athlete.

    PubMed

    Zhu, Cheng-Gang; Liu, Jun; Liu, Wei-Dong; Xu, Yan-Lu; Wu, Na-Qiong; Guo, Yuan-Lin; Tang, Yi-Da; Jiang, Li-Xin; Li, Jian-Jun

    2012-02-01

    Myocardial bridging is a common congenital abnormality of a coronary artery, and is usually thought to be a benign anatomical variant. Although rare, previous studies have reported that patients with myocardial bridging may suffer from myocardial ischemia, myocardial infarction (MI), arrhythmias and even sudden death. Here we report the case of an 18-year-old adolescent athlete with myocardial bridging resulting in MI. Coronary angiography revealed 80% luminal narrowing by systolic compression in the proximal and mid segments of the left anterior descending coronary artery, which returned to normal during diastole. We considered that heavy sports might be a potential trigger for his MI attack. Therefore, special attention should be paid to this kind of athlete, especially if adolescent.

  13. 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.

  14. 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.

  15. 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.

  16. Phosphate Metabolism in CKD Stages 3–5: Dietary and Pharmacological Control

    PubMed Central

    Ketteler, Markus

    2011-01-01

    When compared to the available information for patients on dialysis (CKD stage 5D), data on the epidemiology and appropriate treatment of calcium and phosphate metabolism in the predialysis stages of chronic kidney disease (CKD) are quite limited. Perceptible derangements of calcium and phosphate levels start to become apparent when GFR falls below 30 mL/min in some, but not all, patients. However, hyperphosphatemia may be a significant morbidity and mortality risk predictor in predialysis CKD stages. The RIND study, evaluating progression of coronary artery calcification in incident hemodialysis patients, indirectly demonstrated that vascular calcification processes start to manifest in CKD patients prior to the dialysis stage, which may be closely linked to early and invisible derangements in calcium and phosphate homeostasis. Novel insights into the pathophysiology of calcium and phosphate handling such as the discovery of FGF23 and other phosphatonins suggest that a more complex assessment of phosphate balance is warranted, possibly including measurements of fractional phosphate excretion and phosphatonin levels in order to appropriately evaluate disordered metabolism in earlier stages of kidney disease. As a consequence, early and preventive treatment approaches may have to be developed for patients in CKD stages 3-5 to halt progression of CKD-MBD. PMID:21660261

  17. [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

  18. 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

  19. [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.

  20. Pediatric myocardial protection: an overview.

    PubMed

    Allen, B S; Barth, M J; Ilbawi, M N

    2001-01-01

    This article describes the experimental infrastructure and subsequent successful clinical application of a comprehensive bypass and cardioplegic strategy that limits intraoperative injury and improves postoperative outcomes in pediatric patients. The infant heart is at high risk of damage from poor protection because of preoperative hypertrophy, cyanosis, and ischemia. The background factors of vulnerability to damage caused by cyanosis and ischemia are discussed, together with studies of the infrastructure of strategies to use normoxia versus hyperoxia as bypass starts, white blood cell filtration, warm induction and reperfusion with substrate enhancements, multidose blood cardioplegia, and an integrated approach to allow ischemia only when vision is needed in pediatric surgeries. Data on cardioplegic management, including reducing calcium, increasing magnesium, and reducing perfusion pressure are shown, as used during this technique. These principles were applied to a consecutive series of 567 patients at the Heart Institute for Children and University of Illinois hospital over a 2-year period. Included also were 72 patients with hypoplastic left heart over a 4-year period with this myocardial management strategy. Application of these concepts may improve the safety of protection in infant hearts. PMID:11309728

  1. 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

  2. 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

  3. [Holiday effect in myocardial infarct].

    PubMed

    Otto, W; Hempel, W E; Goebel, H; Erkens, R

    1975-03-15

    Aimed measures of the organisation of the combat against infarction demand also the observation of temporary frequencies. On the basis of the evaluation of certificates of death of the month December of the years 1969 to 1973 of the GDR with differentiation according to so-called prehospital dead (persons who died at home and on the way to the hospital) and patients who died in the hospital with high significance an unwarrantedly high prehospital mortality during the period from Christmas to the end of the year (25th to 31st December) was established compared with the preceding week (18th to 24th December). Since in contrast to this the hospital cases and the cases "on the way" do not show any significant differences main tasks for the beginning of improvements concerning health policy may be deduced, all the more since the so-called holiday effect, expressed by a high home/clinic-relation of patients who died of myocardial infarction, could be restricted to 6 counties of the GDR on account of the analysis of further localities. From the results the tendency of a retrogression of the holiday effect is to be read off in the course of years. In the discussion an explantation of this peculiarity is attempted, and practicable conclusions for the removal and thus for the improvement the infarct situation are formulated.

  4. Metabolic and electrolyte disturbance after cardiac arrest: How to deal with it.

    PubMed

    Bellomo, Rinaldo; Märtensson, Johan; Eastwood, Glenn Matthew

    2015-12-01

    Cardiac arrest (CA) is a sudden, severe event that causes a cascade of metabolic and electrolyte disturbances throughout the body triggered by a loss of cardiac output. Metabolic disturbances are primarily in the form of mixed metabolic and respiratory acidosis; dysglycaemia; and states of deficiency or excess in potassium, calcium, magnesium and lactate. It is known that persistent metabolic disturbances are associated with poor patient outcome following resuscitation from CA, but this might simply be a reflection of the severity of illness. Moreover, contemporary evidence for the management of metabolic disturbances to improve outcomes in these patients is scarce. Moreover, metabolic disturbances during the early post-resuscitation period remain poorly understood in terms of severity, duration and the influence of their post-resuscitation care and treatment on outcome. Although sufficient data suggest that extreme metabolic disturbances such as hypoglycaemia, severe hyperglycaemia, severe hypokalaemia and hyperkalaemia and hypomagnesaemia likely have a devastating effect and should be avoided, randomised controlled trial evidence is clearly need for the management of metabolic and electrolyte derangements in resuscitated CA patients. PMID:26670818

  5. 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".

  6. Low-density lipoprotein subclass patterns and risk of myocardial infarction.

    PubMed

    Austin, M A; Breslow, J L; Hennekens, C H; Buring, J E; Willett, W C; Krauss, R M

    1988-10-01

    The association of low-density lipoprotein (LDL) subclass patterns with coronary heart disease was investigated in a case-control study of nonfatal myocardial infarction. Subclasses of LDL were analyzed by gradient gel electrophoresis of plasma samples from 109 cases and 121 controls. The LDL subclass pattern characterized by a preponderance of small, dense LDL particles was significantly associated with a threefold increased risk of myocardial infarction, independent of age, sex, and relative weight. Plasma levels of high-density lipoprotein cholesterol were decreased, and levels of triglyceride, very low-density lipoproteins, and intermediate-density lipoproteins were increased in subjects with this LDL subclass pattern. Multivariate logistic regression analyses showed that both high-density lipoprotein cholesterol and triglyceride levels contributed to the risk associated with the small, dense LDL subclass pattern. Thus, the metabolic trait responsible for this LDL subclass pattern results in a set of interrelated lipoprotein changes that lead to increased risk of coronary heart disease.

  7. 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.

  8. Myocardial perfusion and contraction in acute ischemia and chronic ischemic heart disease.

    PubMed

    Canty, John M; Suzuki, Gen

    2012-04-01

    A large body of evidence has demonstrated that there is a close coupling between regional myocardial perfusion and contractile function. When ischemia is mild, this can result in the development of a new balance between supply and energy utilization that allows the heart to adapt for a period of hours over which myocardial viability can be maintained, a phenomenon known as "short-term hibernation". Upon reperfusion after reversible ischemia, regional myocardial function remains depressed. The "stunned myocardium" recovers spontaneously over a period of hours to days. The situation in myocardium subjected to chronic repetitive ischemia is more complex. Chronic dysfunction can initially reflect repetitive stunning with insufficient time for the heart to recover between episodes of spontaneous ischemia. As the frequency and/or severity of ischemia increases, the heart undergoes a series of adaptations which downregulate metabolism to maintain myocyte viability at the expense of contractile function. The resulting "hibernating myocardium" develops regional myocyte cellular hypertrophy as a compensatory response to ischemia-induced apoptosis along with a series of molecular adaptations that while regional, are similar to global changes found in advanced heart failure. As a result, flow-function relations become independently affected by tissue remodeling and interventions that stimulate myocyte regeneration. Similarly, chronic vascular remodeling may alter flow regulation in a fashion that increases myocardial vulnerability to ischemia. Here we review our current understanding of myocardial flow-function relations during acute ischemia in normal myocardium and highlight newly identified complexities in their interpretation in viable chronically dysfunctional myocardium with myocyte cellular and molecular remodeling. This article is part of a Special Issue entitled "Coronary Blood Flow".

  9. Regional myocardial contractile function: multiparametric strain mapping.

    PubMed

    Cupps, Brian P; Taggar, Ajay K; Reynolds, Lina M; Lawton, Jennifer S; Pasque, Michael K

    2010-06-01

    Magnetic resonance imaging (MRI) with tissue tagging enables the quantification of multiple strain indices that can be combined through normalization into a single multiparametric index of regional myocardial contractile function. The aim of this study was to test the ability of multiparametric strain analysis to quantify regional differences in contractile function in an ovine model of myocardial injury. Regional variance in myocardial contractile function was induced in eight sheep by the ligation of the blood supply to the anterior and apical left ventricular (LV) myocardial walls. LV systolic strain was obtained from tissue tagged MRI images. A normal strain database (n=50) defines all parameters of systolic strain and allows normalization of regional function at 15,300 LV points by calculation of a z-score. Multiparametric systolic strain z-scores were therefore determined for 15,300 points in each injured sheep left ventricle. Multiparametric z-scores were found to vary significantly by region (P<0.001). z-Scores in regions remote to the infarct were found to be significantly smaller than those in the regions most likely to include infarcted myocardium. In this pre-clinical evaluation of MRI-based multiparametric strain analysis, it accurately quantified and visually defined regional differences in myocardial contractile function.

  10. Myocardial perfusion imaging with dual energy CT.

    PubMed

    Jin, Kwang Nam; De Cecco, Carlo N; Caruso, Damiano; Tesche, Christian; Spandorfer, Adam; Varga-Szemes, Akos; Schoepf, U Joseph

    2016-10-01

    Dual-energy CT (DECT) enables simultaneous use of two different tube voltages, thus different x-ray absorption characteristics are acquired in the same anatomic location with two different X-ray spectra. The various DECT techniques allow material decomposition and mapping of the iodine distribution within the myocardium. Static dual-energy myocardial perfusion imaging (sCTMPI) using pharmacological stress agents demonstrate myocardial ischemia by single snapshot images of myocardial iodine distribution. sCTMPI gives incremental values to coronary artery stenosis detected on coronary CT angiography (CCTA) by showing consequent reversible or fixed myocardial perfusion defects. The comprehensive acquisition of CCTA and sCTMPI offers extensive morphological and functional evaluation of coronary artery disease. Recent studies have revealed that dual-energy sCTMPI shows promising diagnostic accuracy for the detection of hemodynamically significant coronary artery disease compared to single-photon emission computed tomography, invasive coronary angiography, and cardiac MRI. The aim of this review is to present currently available DECT techniques for static myocardial perfusion imaging and recent clinical applications and ongoing investigations.

  11. Myocardial Factor Revisited: The Importance of Myocardial Fibrosis in Adults with Congenital Heart Disease

    PubMed Central

    Broberg, Craig S.; Burchill, Luke J.

    2015-01-01

    Pioneers in congenital heart surgery observed that exercise capacity did not return to normal levels despite successful surgical repair, leading some to cite a “myocardial factor” playing a role. They conjectured that residual alterations in myocardial function would be significant for patients’ long-term outlook. In fulfillment of their early observations, today’s adult congenital heart disease (ACHD) population shows well-recognized features of heart failure, even among patients without clear residual anatomic or hemodynamic abnormalities, demonstrating the vital role of the myocardium in their morbidity and mortality. Whereas the ‘myocardial factor’ was an elusive concept in the early history of congenital heart care, we now have imaging techniques to detect and quantify one such factor – myocardial fibrosis. Understanding the importance of myocardial fibrosis as a final common pathway in a variety of congenital lesions provides a framework for both the study and treatment of clinical heart failure in this context. While typical heart failure pharmacology should reduce or attenuate fibrogenesis, efforts to show meaningful improvements with standard pharmacotherapy in ACHD repeatedly fall short. This paper considers the importance of myocardial fibrosis and function, the current body of evidence for myocardial fibrosis in ACHD, and its implications for research and treatment. PMID:25897907

  12. Transient myocardial bridging of the left anterior descending coronary artery in acute inferior myocardial infarction.

    PubMed

    Kilic, Harun; Akdemir, Ramazan; Bicer, Asuman; Dogan, Mehmet

    2009-01-24

    We observed transient myocardial bridging of left anterior descending coronary artery (LAD) in 18.75% (12 of the total 64) of the patients during acute inferior myocardial infarction (MI). Myocardial bridging occurred only in the acute phase of inferior MI and not in the chronic phase. In the acute phase of inferior MI, compensatory hypercontraction of the anterior wall is assumed to occur in response to the decrease in the movement of the infarct-related walls. In the chronic phase, disappearance of the myocardial bridging observed due to the resolution of compensatory anterior wall hypercontraction, as a result of the reperfusion of infarct-related coronary artery. Most of the myocardial bridges seen in autopsy series are not seen angiographically. Variation at angiography may in part be attributable to small and thin bridges causing little compression. Adrenergic stimulation or afterload reduction by nitroglycerin facilitates diagnosis of myocardial bridging by increasing coronary compression. Both of these conditions are almost always present in acute MI. We concluded that transient myocardial bridging of LAD can be observed in some patients with acute inferior MI during acute stage. PMID:17920712

  13. 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

  14. 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.

  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. Association of stroke and myocardial infarction in children.

    PubMed

    Nakashima, M; Takashima, S; Hashimoto, K; Shiraishi, M

    1982-02-01

    A 9-year-old boy with cerebrovascular accident (CVA) and old myocardial infarction with mural thrombi is reported. The cause of the myocardial infarction was congenital coronary artery fistula originating from the left coronary artery and emptying into the right atrium. Although a common cause of strokes in adults, myocardial infarction has infrequently been reported as the source of emboli in children.

  17. [The perioperative myocardial infarction - an interdisciplinary task].

    PubMed

    Karatolios, Konstantinos; Rolfes, Caroline; Wulf, Hinnerk; Schieffer, Bernhard

    2016-09-01

    Cardiovascular complications, particularly perioperative myocardial infarction (PMI), are major contributors to mortaliyt after noncardiac surgery. PMI often occurs unnoticed without symptoms or ECG changes. Despite ist silent presentation, PMI is associated with increased mortality. The combination of high associated mortality and diagnostic challenges mandates increased awareness of PMI. Perioperative myocardial infarction may result from plaque rupture (PMI type I) or be caused by a myocardial supply-demand imbalance of oxygen without plaque rupture (PMI type II). Most PMIs occur within the first 3 days after surgery, highlighting the need for clinical monitoring in order to allow fast diagnosis and initiation of appropriate therapy. Measurement of cardiac troponin and 12-lead ECG are the diagnostic cornerstone. Therapy of PMI represents a challenge for physicians and requires a collaboration of surgeons, anesthesiologists and cardiologists. PMID:27631445

  18. Winter weather conditions and myocardial infarctions.

    PubMed

    Ohlson, C G; Bodin, L; Bryngelsson, I L; Helsing, M; Malmberg, L

    1991-03-01

    The daily number of cases of myocardial infarctions admitted to a hospital in middle Sweden over three winter seasons 1984-87 was correlated to the weather conditions on a day-to-day basis. The study encompassed 634 days and all cases younger than 70 years, living within the catchment area, in all 382 subjects. Information on temperature, wind force, precipitation and atmospheric pressure was obtained from the Swedish Institute of Meteorology and Hydrology. A low number of myocardial infarctions was seen on Saturdays and Sundays with a mild wind chill factor and on days with moderate snowfall and high atmospheric pressure. A high number was observed for workdays, especially Mondays, as day of diagnosis. Heterogeneity of the study population and a misclassification of the time relationships between dates of diagnosis and weather changes may have caused an underestimation of the impact of weather conditions. However, weather conditions do not seem to be a major triggering factor of myocardial infarctions in Sweden.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. Visualizing myocardial function using HARP MRI

    NASA Astrophysics Data System (ADS)

    Osman, Nael F.; Prince, Jerry L.

    2000-06-01

    Harmonic phase magnetic resonance imaging (HARP) is a new technique for measuring the motion of the left ventricle of the heart. HARP uses magnetic resonance tagging, Fourier filtering and special processing algorithms to calculate key indices of myocardial motion including Eulerian and Lagrangian strain. This paper presents several new methods for visualizing myocardial motion based on HARP. Quantities that are computed and visualized include motion grids, velocity fields, strain rates, pathlines, tracked Eulerian strain, and contraction angle. The computations are fast and fully automated and have the potential for clinical application.

  6. Rat cardiac myocyte adenosine transport and metabolism

    SciTech Connect

    Ford, D.A.; Rovetto, M.J.

    1987-01-01

    Based on the importance of myocardial adenosine and adenine nucleotide metabolism, the adenosine salvage pathway in ventricular myocytes was studied. Accurate estimates of transport rates, separate from metabolic fllux, were determined. Adenosine influx was constant between 3 and 60 s. Adenosine metabolism maintained intracellular adenosine concentrations < 10% of the extracellular adenosine concentrations and thus unidirectional influx could be measured. Myocytes transported adenosine via saturable and nonsaturable processes. A minimum estimate of the V/sub max/ of myocytic adenosine kinase indicated the saturable component of adenosine influx was independent of adenosine kinase activity. Saturable transport was inhibited by nitrobenzylthioinosine and verapamil. Extracellular adenosine taken up myocytes was rapidly phosphorylated to adenine taken up by myocytes was rapidly phosphorylated to adenine nucleotides. Not all extracellular adenosine, though, was phosphorylated on entering myocytes, since free, as opposed to protein-bound, intracellular adenosine was detected after digitonin extraction of cells in the presence of 1 mM ethylene-diaminetetraacetic acid.

  7. Metabolic encephalopathies.

    PubMed

    Angel, Michael J; Young, G Bryan

    2011-11-01

    Kinnier Wilson coined the term metabolic encephalopathy to describe a clinical state of global cerebral dysfunction induced by systemic stress that can vary in clinical presentation from mild executive dysfunction to deep coma with decerebrate posturing; the causes are numerous. Some mechanisms by which cerebral dysfunction occurs in metabolic encephalopathies include focal or global cerebral edema, alterations in transmitter function, the accumulation of uncleared toxic metabolites, postcapillary venule vasogenic edema, and energy failure. This article focuses on common causes of metabolic encephalopathy, and reviews common causes, clinical presentations and, where relevant, management.

  8. AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability

    PubMed Central

    Yang, Yoon Mee; Han, Chang Yeob; Kim, Yoon Jun; Kim, Sang Geon

    2010-01-01

    The adenosine monophosphate-activated protein kinase (AMPK) and p70 ribosomal S6 kinase-1 pathway may serve as a key signaling flow that regulates energy metabolism; thus, this pathway becomes an attractive target for the treatment of liver diseases that result from metabolic derangements. In addition, AMPK emerges as a kinase that controls the redox-state and mitochondrial function, whose activity may be modulated by antioxidants. A close link exists between fuel metabolism and mitochondrial biogenesis. The relationship between fuel metabolism and cell survival strongly implies the existence of a shared signaling network, by which hepatocytes respond to challenges of external stimuli. The AMPK pathway may belong to this network. A series of drugs and therapeutic candidates enable hepatocytes to protect mitochondria from radical stress and increase cell viability, which may be associated with the activation of AMPK, liver kinase B1, and other molecules or components. Consequently, the components downstream of AMPK may contribute to stabilizing mitochondrial membrane potential for hepatocyte survival. In this review, we discuss the role of the AMPK pathway in hepatic energy metabolism and hepatocyte viability. This information may help identify ways to prevent and/or treat hepatic diseases caused by the metabolic syndrome. Moreover, clinical drugs and experimental therapeutic candidates that directly or indirectly modulate the AMPK pathway in distinct manners are discussed here with particular emphasis on their effects on fuel metabolism and mitochondrial function. PMID:20698033

  9. Stimulating Myocardial Regeneration with Periostin Peptide in Large Mammals Improves Function Post-Myocardial Infarction but Increases Myocardial Fibrosis

    PubMed Central

    Ladage, Dennis; Yaniz-Galende, Elisa; Rapti, Kleopatra; Ishikawa, Kiyotake; Tilemann, Lisa; Shapiro, Scott; Takewa, Yoshiaki; Muller-Ehmsen, Jochen; Schwarz, Martin; Garcia, Mario J.; Sanz, Javier; Hajjar, Roger J.; Kawase, Yoshiaki

    2013-01-01

    Aims Mammalian myocardium has a finite but limited capacity to regenerate. Experimentally stimulating proliferation of cardiomyocytes with extracellular regeneration factors like periostin enhances cardiac repair in rodents. The aim of this study was to develop a safe method for delivering regeneration factors to the heart and to test the functional and structural effects of periostin peptide treatment in a large animal model of myocardial infarction (MI). Methods and Results We developed a controlled release system to deliver recombinant periostin peptide into the pericardial space. A single application of this method was performed two days after experimental MI in swine. Animals were randomly assigned to receive either saline or periostin peptide. Experimental groups were compared at baseline, day 2, 1 month and 3 months. Treatment with periostin peptide increased the EF from 31% to 41% and decreased by 22% the infarct size within 12 weeks. Periostin peptide-treated animals had newly formed myocardium strips within the infarct scar, leading to locally improved myocardial function. In addition the capillary density was increased in animals receiving periostin. However, periostin peptide treatment increased myocardial fibrosis in the remote region at one week and 12 weeks post-treatment. Conclusion Our study shows that myocardial regeneration through targeted peptides is possible. However, in the case of periostin the effects on cardiac fibrosis may limit its clinical application as a viable therapeutic strategy. PMID:23700403

  10. Assessment of Myocardial Fibrosis with Cardiac Magnetic Resonance

    PubMed Central

    Nathan, Mewton; Ying, Liu Chia; Pierre, Croisille; David, Bluemke; João, Lima

    2011-01-01

    Diffuse interstitial or replacement myocardial fibrosis are common features of a broad variety of cardiomyopathies. Myocardial fibrosis leads to impaired cardiac diastolic and systolic function and is related to adverse cardiovascular events. Cardiac magnetic resonance (CMR) may uniquely characterize the extent of replacement fibrosis and may have prognostic value in various cardiomyopathies. Myocardial T1 mapping is an emerging technique that could improve CMR’s diagnostic accuracy especially for interstitial diffuse myocardial fibrosis. As such, CMR could be integrated in the monitoring and the therapeutic management of a large number of patients. This review summarizes the advantages and limitations of CMR for the assessment of myocardial fibrosis. PMID:21329834

  11. Assessment of myocardial fibrosis with cardiovascular magnetic resonance.

    PubMed

    Mewton, Nathan; Liu, Chia Ying; Croisille, Pierre; Bluemke, David; Lima, João A C

    2011-02-22

    Diffuse interstitial or replacement myocardial fibrosis is a common feature of a broad variety of cardiomyopathies. Myocardial fibrosis leads to impaired cardiac diastolic and systolic function and is related to adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) may uniquely characterize the extent of replacement fibrosis and may have prognostic value in various cardiomyopathies. Myocardial longitudinal relaxation time mapping is an emerging technique that could improve CMR's diagnostic accuracy, especially for interstitial diffuse myocardial fibrosis. As such, CMR could be integrated in the monitoring and therapeutic management of a large number of patients. This review summarizes the advantages and limitations of CMR for the assessment of myocardial fibrosis. PMID:21329834

  12. Effect of cell hydration on metabolism.

    PubMed

    Lang, Florian

    2011-01-01

    Prerequisites for cell survival include avoidance of excessive cell volume alterations. Cell membranes are highly permeable to water, which follows osmotic gradients. Thus, cell volume constancy requires osmotic equilibrium across cell membranes. Cells accumulate osmotically active organic substances and compensate their osmolarity by lowering cytosolic Cl(-) concentrations. Following cell shrinkage, regulatory cell volume increase is accomplished by ion uptake (activation of Na(+), K(+), 2Cl(-) cotransport, Na(+)/H(+) exchange in - parallel to Cl(-)/HCO(-)(3) exchange and Na(+) channels), by cellular accumulation of organic osmolytes (e.g. myoinositol, betaine, phosphorylcholine, taurine) as well as by proteolysis leading to generation of amino acids and glycogenolysis generating glucose phosphate. Following cell swelling, cell volume is restored by ion exit (activation of K(+) channels and/ - or anion channels, KCl cotransport, parallel activation of K(+)/H(+) exchange and Cl(-)/HCO(-)(3) exchange), release or degradation of organic osmolytes as well as stimulation of protein synthesis and of glycogen synthesis. The activity of cell volume regulatory mechanisms is modified by hormones, transmitters and drugs, which thus influence protein and glycogen metabolism. Moreover, alterations of cell volume modify generation of oxidants and the sensitivity to oxidative stress. Deranged cell volume regulation significantly contributes to the pathophysiology of several disorders such as liver insufficiency, diabetic ketoacidosis, hypercatabolism, ischemia, and fibrosing disease. PMID:22301839

  13. [Effect of wall thickness of left ventricle on 201Tl myocardial SPECT images: myocardial phantom study].

    PubMed

    Koto, M; Namura, H; Kawase, O; Yamasaki, K; Kono, M

    1996-07-01

    201Tl myocardial SPECT is known for better sensitivity, specificity, and accuracy than planar images in detecting coronary artery disease and diagnosing myocardial viability. SPECT images are also superior to planar images in diagnostic sensitivity and anatomical orientation. However, as limitation of the spatial resolution of the machine, we often encounter poor SPECT plower image quality in patients with decreased wall thickness. To test the accuracy of SPECT images in patients with marked thinning of the left ventricular wall, as occurs in dilated cardiomyopathy, we performed a experimental study using myocardial phantom with 7 mm wall thickness. Tomographic image of the phantom images were rather heterogeneous, though no artificial defect was located. Dilated cardiomyopathy is thought to be characterized by patchy defects in the left ventricle. Careful attention should be given to elucidating myocardial perfusion in patients with a thin left ventricle wall, as there are technical limitations in addition to clinical features.

  14. 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

  15. 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 ...

  16. Metabolic Disorders

    MedlinePlus

    Metabolism is the process your body uses to get or make energy from the food you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system break the food parts down into sugars and acids, ...

  17. Delineation of myocardial oxygen utilization with carbon-11-labeled acetate

    SciTech Connect

    Brown, M.; Marshall, D.R.; Sobel, B.E.; Bergmann, S.R.

    1987-09-01

    Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man. Results of initial experiments with carbon-14-labeled acetate (/sup 14/C-acetate) indicated that the steady-state extraction fraction of acetate averaged 61.5 +/- 4.0% in control hearts (n = 4), 93.6 +/- 0.9% in hearts rendered ischemic (n = 4), and 54.8 +/- 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of /sup 14/C-acetate, assessed from the rate of efflux of /sup 14/CO/sub 2/ in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p less than .001). In addition, no significant differences were observed between rates of efflux of total /sup 14/C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of /sup 14/CO/sub 2/. Clearance of /sup 11/C-acetate, measured externally with gamma probes in normal and ischemic myocardium, correlated closely with clearance of /sup 14/C-acetate measured directly in the effluent (r = .99, p less than .001) and with overall myocardial oxygen consumption (r = .95, p less than .001). Accumulation and clearance of /sup 11/C-acetate from human myocardium with PET demonstrated kinetics comparable to those seen with radiolabeled acetate in vitro.

  18. Association of fragmented QRS complex with myocardial reperfusion in acute ST-elevated myocardial infarction.

    PubMed

    Erdem, Fatma Hizal; Tavil, Yusuf; Yazici, Hüseyin; Aygül, Nazif; Abaci, Adnan; Boyaci, Bülent

    2013-01-01

    In this study, we aimed to evaluate the relationship between TIMI myocardial perfusion (TMP) grade, as an indicator of myocardial reperfusion, and fragmented QRS (fQRS) in standard 12-lead electrocardiogram. Also, we evaluate fQRS is an additional indicator of myocardial reperfusion. One hundred patients admitted with first STEMI to Coronary Intensive Care Unit and who were used thrombolytic therapy was included in this retrospective study. Standard 12-lead electrocardiogram records of patients simultaneous with coronary angiography (second day) were assessed and analysed for the presence of fQRS. Also, coronary angiography images were analyzed to identify the infarct related artery, TIMI grade of infarct related artery and TMP grade of infarct related artery. The patients with fQRS demonstrated a significantly lower TMP grade, TIMI grade and ejection fraction compared with the non-fQRS patients (P = 0.004, P = 0.003, P = 0.02 respectively). The patients with inadequate myocardial reperfusion demonstrated a significantly higher fQRS compared with the adequate myocardial reperfusion patients. (56.9% versus 23.5%, P = 0.002 respectively). On correlation analysis, there was a significant negative correlation between fQRS and left ventricular ejection fraction (r = -232, P = 0.02) TMP grade and adequate myocardial reperfusion (TMP 3) showed significant negative correlation with fQRS (r = -0.370, P = 0.000; r = -0.318, P = 0.001 respectively). Presence of fragmented QRS in STEMI patients was associated with inadequate myocardial reperfusion and it can be used as a simple, noninvasive parameter to evaluate myocardial reperfusion.

  19. Relation of impaired Thrombolysis In Myocardial Infarction myocardial perfusion grades to residual thrombus following the restoration of epicardial patency in ST-elevation myocardial infarction.

    PubMed

    Kirtane, Ajay J; Weisbord, Aaron; Karmpaliotis, Dimitrios; Murphy, Sabina A; Giugliano, Robert P; Cannon, Christopher P; Antman, Elliott M; Ohman, E Magnus; Roe, Matthew T; Braunwald, Eugene; Gibson, C Michael

    2005-01-15

    Clinical and angiographic data were analyzed from 929 patients who had ST-elevation myocardial infarction and open epicardial arteries after fibrinolytic therapy. Residual angiographically evident thrombus was associated with more frequent Thrombolysis In Myocardial Infarction (TIMI) grade 2 flow (33.6% vs 26.8%, p = 0.03), higher corrected TIMI frame counts (34 vs 31 frames, p = 0.0003), and lower TIMI myocardial perfusion grades (43.0% vs 32.0% TIMI myocardial perfusion grades 0/1, p = 0.001) among all patients and among patients who had TIMI grade 3 flow (33.5% vs 26.0% TIMI myocardial perfusion grades 0/1, p = 0.043). In multivariate analyses, angiographically evident thrombus was associated with higher corrected TIMI frame counts and worsened myocardial perfusion independent of clinical and angiographic covariates, including TIMI grade 3 flow.

  20. [The effect of decimeter waves on the metabolism of the myocardium and its hormonal regulation in rabbits with experimental ischemia].

    PubMed

    Frenkel', I D; Zubkova, S M; Liubimova, N N; Popov, V I

    1992-01-01

    Biochemical and morphometric methods were employed to study the effect of decimetric waves (460 MHz, 10 and 120 mW/cm2) in cardiac and thyroid exposure on oxygen metabolism, myocardial microcirculation and contractility, thyroid and adrenal hormonal activity, kallikrein-kinin system activity in rabbits with experimental myocardial ischemia. Hypoxia discontinued in all the treatment regimens, but the exposure of the heart (field density 10 mW/sm2) had the additional effect on lipid peroxidation which reduced in the serum and normalized in the myocardium, on myocardial contractility, kallikrein-kinin system and on the adrenal and thyroid hormones.

  1. Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction.

    PubMed

    Hofmann, Ulrich; Frantz, Stefan

    2015-01-16

    A large body of evidence produced during decades of research indicates that myocardial injury activates innate immunity. On the one hand, innate immunity both aggravates ischemic injury and impedes remodeling after myocardial infarction (MI). On the other hand, innate immunity activation contributes to myocardial healing, as exemplified by monocytes' central role in the formation of a stable scar and protection against intraventricular thrombi after acute infarction. Although innate leukocytes can recognize a wide array of self-antigens via pattern recognition receptors, adaptive immunity activation requires highly specific cooperation between antigen-presenting cells and distinct antigen-specific receptors on lymphocytes. We have only recently begun to examine lymphocyte activation's relationship to adaptive immunity and significance in the context of ischemic myocardial injury. There is some experimental evidence that CD4(+) T-cells contribute to ischemia-reperfusion injury. Several studies have shown that CD4(+) T-cells, especially CD4(+) T-regulatory cells, improve wound healing after MI, whereas depleting B-cells is beneficial post MI. That T-cell activation after MI is induced by T-cell receptor signaling implicates autoantigens that have not yet been identified in this context. Also, the significance of lymphocytes in humans post MI remains unclear, primarily as a result of methodology. This review summarizes current experimental evidence of lymphocytes' activation, functional role, and crosstalk with innate leukocytes in myocardial ischemia-reperfusion injury, wound healing, and remodeling after myocardial infarction.

  2. 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.

  3. 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

  4. Myocardial infection due to Fusobacterium nucleatum.

    PubMed

    Storm, Jeremy C; Ford, Bradley A; Streit, Judy A

    2013-12-01

    Fusobacterium nucleatum is an anaerobic gram-negative bacillus, which inhabits the oropharynx, gastrointestinal tract, and female genital tract. Infections classically affect the head and neck. We report a patient with a myocardial mass due to F. nucleatum, initially thought to be a neoplasm, and discuss anaerobic cardiac infections.

  5. 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…

  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. [Myocardial infarction after conduction electrical weapon shock].

    PubMed

    Ben Ahmed, H; Bouzouita, K; Selmi, K; Chelli, M; Mokaddem, A; Ben Ameur, Y; Boujnah, M R

    2013-04-01

    Controversy persists over the safety of conducted electrical weapons, which are increasingly used by law enforcement agencies around the world. We report a case of 33-year-old man who had an acute inferior myocardial infarction after he was shot in the chest with an electrical weapon.

  8. [The effect of metformin on myocardial tolerance to ischemia in rats with diabetes mellitus type 2].

    PubMed

    Kravchuk, E N; Grineva, E N; Galagudza, M M; Bairamov, A A

    2013-01-01

    The effect of metformin on myocardial sensitivity to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion in the isolated perfused heart. Metformin administration had no effect on infarct size. At the same time, infarct size in T2DM was significantly lower than in controls, which is indicative of the phenomenon of metabolic preconditioning in T2DM. The protocol of metformin administration used in this study had not afforded a significant cardioprotective effect in animals with T2DM.

  9. On the plasmalogenation of myocardial choline glycerophospholipid during maturation of various vertebrates.

    PubMed

    Hack, M H; Helmy, F M

    1988-01-01

    1. The plasmalogen profiles of a series of hearts from fish to mammals were obtained by various TLC analyses. 2. All specimens (ventricular) contained ethanolamine plasmalogen and some choline plasmalogen, as well. 3. The distribution of these two plasmalogen species was relatable, in part, to (a) phylogeny and (b) ontogeny. 4. There were exceptions. 5. The appearance of choline plasmalogen was preceded by its alkylacyl precursor, suggesting plasmalogenation by a base-specific delta 1-alkyl desaturase. 6. From the data, we have raised some questions as to the metabolic role played by the plasmalogens and precursors as occupants of myocardial mitchondrial membranes.

  10. Type 2 diabetes mellitus and skeletal muscle metabolic function.

    PubMed

    Phielix, Esther; Mensink, Marco

    2008-05-23

    Type 2 diabetic patients are characterized by a decreased fat oxidative capacity and high levels of circulating free fatty acids (FFAs). The latter is known to cause insulin resistance, in particularly in skeletal muscle, by reducing insulin stimulated glucose uptake, most likely via accumulation of lipid inside the muscle cell. A reduced skeletal muscle oxidative capacity can exaggerate this. Furthermore, type 2 diabetes is associated with impaired metabolic flexibility, i.e. an impaired switching from fatty acid to glucose oxidation in response to insulin. Thus, a reduced fat oxidative capacity and metabolic inflexibility are important components of skeletal muscle insulin resistance. The cause of these derangements in skeletal muscle of type 2 diabetic patients remains to be elucidated. An impaired mitochondrial function is a likely candidate. Evidence from both in vivo and ex vivo studies supports the idea that an impaired skeletal muscle mitochondrial function is related to the development of insulin resistance and type 2 diabetes mellitus. A decreased mitochondrial oxidative capacity in skeletal muscle was revealed in diabetic patients, using in vivo 31-Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). However, quantification of mitochondrial function using ex vivo high-resolution respirometry revealed opposite results. Future (human) studies should challenge this concept of impaired mitochondrial function underlying metabolic defects and prove if mitochondria are truly functional impaired in insulin resistance, or low in number, and whether it represents the primary starting point of pathogenesis of insulin resistance, or is just an other feature of the insulin resistant state. PMID:18342897

  11. Metabolism and Action of the Hormone Vitamin D

    PubMed Central

    Coburn, Jack W.; Hartenbower, David L.; Norman, Anthony W.

    1974-01-01

    Extensive experimental evidence has established a significant role of calciferol in the maintenance of normal calcium homeostasis. Present knowledge indicates that vitamin D3 must first be converted to 25-OH-D3 and then to 1,25(OH)2D3, the most active known form of the steroid. Many of the factors regulating the rate of production of this last steroid from its precurser have been evaluated, and the concept that vitamin D functions as a steroid hormone seems to be well established. Deranged action of calciferol, caused by impaired metabolism of the steroid or through altered sensitivity of target tissues, may be involved in the pathophysiology of several disease states with abnormal calcium metabolism. It is noted that liver disease, osteomalacia due to anticonvulsant therapy, chronic renal failure, hypophosphatemic rickets, hypoparathyroidism, hyperparathyroidism, sarcoidosis and idiopathic hypercalciuria have possible relation to alterations in metabolism or action of vitamin D. The future clinical availability of 1,25(OH)2D3 and other analogs of this steroid may offer potential therapeutic benefit in the treatment of certain of the disease entities discussed. PMID:4365934

  12. Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction

    PubMed Central

    Joshi, Nikhil V; Toor, Iqbal; Shah, Anoop S V; Carruthers, Kathryn; Vesey, Alex T; Alam, Shirjel R; Sills, Andrew; Hoo, Teng Y; Melville, Adam J; Langlands, Sarah P; Jenkins, William S A; Uren, Neal G; Mills, Nicholas L; Fletcher, Alison M; van Beek, Edwin J R; Rudd, James H F; Fox, Keith A A; Dweck, Marc R; Newby, David E

    2015-01-01

    Background Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans. Methods and Results Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non–ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI. Conclusions The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization

  13. [Intraoperative myocardial protection with extracellular cardioplegic solutions in patients with cardiac valve diseases].

    PubMed

    Zhidkov, I L; Ivanov, V A; Kozhevnikov, V A; Charnaia, M A; Mukhamedzianova, A R; Trekova, N A

    2007-01-01

    A hundred patients operated on under extracorporeal circulation (EC) with bicaval cannulation in the moderate general hypothermia mode were intraoperatively examined. According to the used cardioplegic solution, all the patients were divided into three groups: 1) Konsol; 2) Konsol MF; 3) St. Thomas (a control group). All the groups were matched by age, gender, the duration of myocardial ischemia (MI) (37-128 min), that of EC (52-186 min), and the nature of surgical interventions, of which mitral valve replacement amounted to 72-78%. To prepare a modified solution, 20 ml of 40% glucose, 20 units of insulin, and 200 mg of creatine phosphate (Neoton) were added to a flask containing 400 ml of Konsol. The efficiency of myocardial protection was evaluated by the data characterizing cardiac arrest and cardiac performance resumption, as well as by heart rate and the use of inotropic support in the reperfusion period. The parameters of central hemodynamics and systemic coronary blood flow, the concentrations of glucose and lactate, the blood gas and electrolyte composition of the coronary sinus (CS), myocardial oxygen consumption and the oxygen-utilizing coefficient were monitored. The cardioplegic solutions Consol and Consol MF were found to have a more effective cardioprotective activity in patients with cardiac valvular disease, operated on under EC and moderate hypothermia that St. Thomas'solution. Modification of the Consol solution by adding glucose, creatine phosphate, and insulin improves the protective effect of the solution, promoting a rapider transition of the myocardium from anaerobic to aerobic metabolism.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Protective effect of taurine on myocardial antioxidant status in isoprenaline-induced myocardial infarction in rats.

    PubMed

    Shiny, K S; Kumar, S Hari Senthil; Farvin, K H Sabeena; Anandan, R; Devadasan, K

    2005-10-01

    We have examined the protective effect of taurine on the myocardial antioxidant defense system in isoprenaline (isoproterenol)-induced myocardial infarction in rats, an animal model of myocardial infarction in man. Levels of diagnostic marker enzymes in plasma, lipid peroxides and reduced glutathione, and the activity of glutathione-dependent antioxidant enzymes and anti-peroxidative enzymes in the heart tissue were determined. Intraperitoneal administration of taurine significantly prevented the isoprenaline-induced increases in the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine phosphokinase in the plasma of rats. Taurine exerted an antioxidant effect against isoprenaline-induced myocardial infarction by preventing the accumulation of lipid peroxides and by maintaining the level of reduced glutathione and the activity of glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase at near normality. The results indicated that the cardioprotective potential of taurine was probably due to the increase of the activity of the free radical enzymes, or to a counteraction of free radicals by its antioxidant nature, or to a strengthening of myocardial membrane by its membrane stabilizing property.

  1. 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.

  2. Structurally modified fatty acids - clinical potential as tracers of metabolism

    SciTech Connect

    Dudczak, R.; Schmoliner, R.; Angelberger, P.; Knapp, F.F.; Goodman, M.M.

    1985-01-01

    Recently 15-p-iodophenyl-betamethyl-pentadecanoic acid (BMPPA) was proposed for myocardial scintigraphy, as possible probe of metabolic processes other than ..beta..-oxidation. In 19 patients myocardial scintigraphy was done after i.v. BMPPA (2 to 4 mCi). Data were collected (LAO 45/sup 0//14; anterior/5) for 100 minutes in the fasted patients. From heart (H) and liver (L) organ to background (BG) ratios were calculated, and the elimination (E) behavior was analyzed from BG (V. cava region) corrected time activity curves. In 10 patients plasma and urine were examined. By CHCl/sub 3//MeOH extraction of plasma samples (90 min. pi) both in water and in organic medium soluble catabolites were found. TLC fractionation showed that those were co-migrating, compared to standards, with benzoic acid, BMPPA and triglycerides. In urine (0 to 2h pi: 4.1% dose) hippuric acid was found. It is concluded that BMPPA is a useful agent for myocardial scintigraphy. Its longer retention in the heart compared to unbranched radioiodinated fatty acids may facilitate SPECT studies. Rate of elimination and plasma analysis indicate the metabolic breakdown of BMPPA. Yet, the complexity of the supposed mechanism may impede curve interpretation in terms of specific metabolic pathways. 19 refs., 5 tabs.

  3. 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.

  4. Myocarditis confirmed by biopsy presenting as acute myocardial infarction.

    PubMed Central

    Costanzo-Nordin, M R; O'Connell, J B; Subramanian, R; Robinson, J A; Scanlon, P J

    1985-01-01

    Two cases of acute myocardial infarction occurred in association with myocarditis, which was confirmed by biopsy. The first patient suffered an anteroseptal and the second patient an inferior wall myocardial infarction shortly after an acute viral illness. In both patients, coronary angiography showed normal coronary arteries, and right ventricular endomyocardial biopsy confirmed myocarditis. Histological abnormalities attributable to ischaemic heart disease were absent. The first patient's condition became stable after immunosuppressive treatment. Myocarditis resolved spontaneously within three months in the second patient. Coronary artery spasm and myocardial involvement with a systemic disease were unlikely. Endomyocardial biopsy in patients with acute myocardial infarction and normal coronary arteries may be useful in identifying myocarditis associated with myocardial necrosis. Myocarditis in acute myocardial infarction in the absence of coronary artery obstruction has not previously been documented during life. Images PMID:3966948

  5. Multimodality Imaging of Myocardial Injury and Remodeling

    PubMed Central

    Kramer, Christopher M.; Sinusas, Albert J.; Sosnovik, David E.; French, Brent A.; Bengel, Frank M.

    2011-01-01

    Advances in cardiovascular molecular imaging have come at a rapid pace over the last several years. Multiple approaches have been taken to better understand the structural, molecular, and cellular events that underlie the progression from myocardial injury to myocardial infarction (MI) and, ultimately, to congestive heart failure. Multimodality molecular imaging including SPECT, PET, cardiac MRI, and optical approaches is offering new insights into the pathophysiology of MI and left ventricular remodeling in small-animal models. Targets that are being probed include, among others, angiotensin receptors, matrix metalloproteinases, integrins, apoptosis, macrophages, and sympathetic innervation. It is only a matter of time before these advances are applied in the clinical setting to improve post-MI prognostication and identify appropriate therapies in patients to prevent the onset of congestive heart failure. PMID:20395347

  6. Matrix metalloproteinases: drug targets for myocardial infarction

    PubMed Central

    Yabluchanskiy, Andriy; Li, Yaojun; Chilton, Robert J.; Lindsey, Merry L.

    2013-01-01

    Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide. Rapid advances in the treatment of acute MI have significantly improved short-term outcomes in patient, due in large part to successes in preventing myocardial cell death and limiting infarct area during the time of ischemia and subsequent reperfusion. Matrix metalloproteases (MMPs) play key roles in post-MI cardiac remodeling and in the development of adverse outcomes. This review highlights the importance of MMPs in the injury and remodeling response of the left ventricle and also discusses their potential as therapeutic targets Additional pre-clinical and clinical research is needed to further investigate and understand the cardioprotective effects of MMPs inhibitors. PMID:23316962

  7. 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

  8. Stimulation-dependent myocardial calcium uptake into slowly exchangeable compartments

    SciTech Connect

    Fintel, M.; Langer, G.A.

    1986-03-01

    Myocardial calcium uptake into slowly exchangeable sites was increased in response to beating following a period of prolonged quiescence (> 1 hr). Net calcium uptake was measured in rabbit interventricular septa using the /sup 45/Ca washout technique. The maximal increment of slowly exchangeable calcium induced by beating was 20 +/- 2% of calcium uptake during quiescence. The increment in calcium uptake induced by 282 beats in 10 minutes did not differ from the increment induced by 60 beats but was significantly greater than the increment induced by 35 and 15 beats. The total number of beats rather than the frequency of stimulation appeared to be the most critical factor which determined the increment in calcium uptake. Based on the increment of 0.12 +/- 0.02 mmoles/kg dry weight obtained when 15 beats occurred in 10 minutes, the minimum amount of calcium which entered slowly exchangeable sites per beat was calculated to be 1 ..mu..mol/kg wet weight. The increment in slowly exchangeable calcium induced by beating was not affected by ryanodine but was inhibited by the metabolic inhibitor CCCP. In conclusion, a net increment in slowly exchangeable calcium occurs when beating is resumed following a period of prolonged quiescence. This suggests that calcium influx exceeds efflux transiently, under these conditions, and that slowly exchangeable sites represent an important mechanism by which a fraction of incoming calcium is buffered.

  9. 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

  10. Myocardial contractile function and intradialytic hypotension.

    PubMed

    Owen, Paul J; Priestman, William S; Sigrist, Mhairi K; Lambie, Stewart H; John, Stephen G; Chesterton, Lindsay J; McIntyre, Christopher W

    2009-07-01

    Dialysis-induced hypotension remains a significant problem in hemodialysis (HD) patients. Numerous factors result in dysregulation of blood pressure control and impaired myocardial reserve in response to HD-induced cardiovascular stress. Episodic intradialytic hypotension may be involved in the pathogenesis of evolving myocardial injury. We performed an initial pilot investigation of cardiovascular functional response to pharmacological cardiovascular stress in hypotension-resistant (HR) and hypotension-prone (HP) HD patients. We studied 10 matched chronic HD patients (5 HP, 5 HR). Dobutamine-atropine stress (DAS) was performed on a nondialysis short interval day, with noninvasive pulse-wave analysis using the Finometer to continuously measure hemodynamic variables. Baroreflex sensitivity was assessed at rest and during DAS. Baseline hemodynamic variables were not significantly different. The groups had differing hemodynamic responses to DAS. The Mean arterial pressure was unchanged in the HR group but decreased in HP patients (-13.6 +/- 3.5 mmHg; P<0.001). This was associated with failure to significantly increase cardiac output in the HP group (cf. increase in cardiac output in the HR group of +33.4 +/- 6%; P<0.05), and a reduced response in total peripheral resistance (HP -10.3 +/- 6.8%, HR -22.7 +/- 2.9%, P=NS). Baroreflex sensitivity was not significantly different between groups at baseline or within groups with increasing levels of DAS; however, the mean baroreflex sensitivity was higher in HR cf. HP subjects throughout pharmacological stress (P<0.05). Hypotension-prone patients appear to have an impaired cardiovascular response to DAS. The most significant abnormality is an impaired myocardial contractile reserve. Early identification of these patients would allow utilization of therapeutic strategies to improve intradialytic tolerability, potentially abrogating aggravation of myocardial injury.

  11. Myocardial infarction due to lightning strike.

    PubMed

    Karadas, Sevdegul; Vuruskan, Ertan; Dursun, Recep; Sincer, Isa; Gonullu, Hayriye; Akkaya, Emre

    2013-09-01

    Cardiac events due to lightning strike and their severity vary according to the strength of the electric current and the duration of exposure. The electrophysiological effects of lightning on the heart can result in ventricular fibrillation, asystole, QT prolongation, supraventricular tachycardia, and non-specific ST-T wave changes. In this report, a case of a patient who suffered myocardial infarction due to lightning strike is presented, which is a rare complication. PMID:24601203

  12. 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

  13. Transmural Myocardial Mechanics During Isovolumic Contraction

    PubMed Central

    Ashikaga, Hiroshi; van der Spoel, Tycho I. G.; Coppola, Benjamin A.; Omens, Jeffrey H.

    2010-01-01

    OBJECTIVES We sought to resolve the 3-dimensional transmural heterogeneity in myocardial mechanics observed during the isovolumic contraction (IC) phase. BACKGROUND Although myocardial deformation during IC is expected to be little, recent tissue Doppler imaging studies suggest dynamic myocardial motions during this phase with biphasic longitudinal tissue velocities in left ventricular (LV) long-axis views. A unifying understanding of myocardial mechanics that would account for these dynamic aspects of IC is lacking. METHODS We determined the time course of 3-dimensional finite strains in the anterior LV of 14 adult mongrel dogs in vivo during IC and ejection with biplane cineradiography of implanted transmural markers. Transmural fiber orientations were histologically measured in the heart tissue postmortem. The strain time course was determined in the subepicardial, midwall, and subendocardial layers referenced to the end-diastolic configuration. RESULTS During IC, there was circumferential stretch in the subepicardial layer, whereas circumferential shortening was observed in the midwall and the subendocardial layer. There was significant longitudinal shortening and wall thickening across the wall. Although longitudinal tissue velocity showed a biphasic profile; tissue deformation in the longitudinal as well as other directions was almost linear during IC. Subendocardial fibers shortened, whereas subepicardial fibers lengthened. During ejection, all strain components showed a significant change over time that was greater in magnitude than that of IC. Significant transmural gradient was observed in all normal strains. CONCLUSIONS IC is a dynamic phase characterized by deformation in circumferential, longitudinal, and radial directions. Tissue mechanics during IC, including fiber shortening, appear uninterrupted by rapid longitudinal motion created by mitral valve closure. This study is the first to report layer-dependent deformation of circumferential strain

  14. 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

  15. 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.

  16. Myocardial infarction due to lightning strike.

    PubMed

    Karadas, Sevdegul; Vuruskan, Ertan; Dursun, Recep; Sincer, Isa; Gonullu, Hayriye; Akkaya, Emre

    2013-09-01

    Cardiac events due to lightning strike and their severity vary according to the strength of the electric current and the duration of exposure. The electrophysiological effects of lightning on the heart can result in ventricular fibrillation, asystole, QT prolongation, supraventricular tachycardia, and non-specific ST-T wave changes. In this report, a case of a patient who suffered myocardial infarction due to lightning strike is presented, which is a rare complication.

  17. 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.

  18. Myocardial infarction association with the Riley-Day syndrome.

    PubMed

    Reshef, R; Aderka, D; Suprun, H; Manelis, G; Manelis, J

    1977-10-01

    The "sudden death" of a 23-year-old Ashkenazy Jew, suffering from "familial dysautonomia" was probably caused by an arrhythmia accompanying a myocardial infarction. Such a report is unique. Diffuse coronary atherosclerosis and direct myocardial "catecholamine cardiomyopathy" seem responsible for the myocardial damage. However, diversion of the endocardial blood flow toward dpicardium and a "coronary steal" phenomenon, both the result of a sudden catecholamine discharge, could aggravate the ischemic injury.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. The Role of Uncoupling Protein 2 During Myocardial Dysfunction in a Canine Model of Endotoxin Shock.

    PubMed

    Wang, Xiaoting; Liu, Dawei; Chai, Wenzhao; Long, Yun; Su, Longxiang; Yang, Rongli

    2015-03-01

    To explore the role of uncoupling protein 2 (UCP2) during myocardial dysfunction in a canine model of endotoxin shock, 26 mongrel canines were randomly divided into the following four groups: A (control group; n = 6), B2 (shock after 2 h; n = 7), B4 (shock after 4 h; n = 7), and B6 (shock after 6 h; n = 6). Escherichia coli endotoxin was injected into the canines via the central vein, and hemodynamics were monitored. Energy metabolism, UCP2 mRNA and protein expression, and UCP2 localization were analyzed, and the correlation between energy metabolism changes, and UCP2 expression was determined. After the canine endotoxin shock model was successfully established, the expression of UCP2 mRNA and protein was found to increase, with later time points showing significant increases (P < 0.05). Immunofluorescence assays of UCP2 in heart tissue showed that UCP2 was localized in the cytoplasm, and its expression pattern was the same as that found in the mRNA and protein analyses. The energy metabolism results revealed that the ADP levels increased, but the ATP and phosphocreatine (PCr) levels and ATP/ADP and PCr/ATP ratios decreased in the model. In particular, the PCr/ATP ratio was significantly different from that of the control group 6 h after shock (P < 0.05). Furthermore, correlation analysis showed that the UCP2 protein and mRNA levels were negatively correlated with myocardial energy levels. In summary, decreased energy synthesis can occur in the myocardium during endotoxin shock, and UCP2 may play an important role in this process. The negative correlation between UCP2 expression and energy metabolism requires further study, as the results might contribute to the treatment of sepsis with heart failure.

  4. 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

  5. Myocardial uptake of digoxin in chronically digitalized dogs.

    PubMed Central

    Steiness, E; Valentin, N

    1976-01-01

    1 The time course of myocardial uptake of digoxin, increase in contractility and changes in myocardial potassium concentration was studied for 90 min following an intravenous digoxin dose to long-term digitalized dogs. 2 Nineteen dogs were investigated by the use of a biopsy technique which allowed sampling before and after administration of digoxin. 3 Ten minutes after administration of digoxin the myocardial concentration increased from 60 to 306 nmol/kg tissue, the myocardial concentration of digoxin was significantly lower (250 nmol/kg tissue) after 30 min and then increased again. 4 The transmural myocardial distribution of digoxin was uniform before and 90 min after administration of digoxin in long-term digitalized dogs but at 10 min after administration, both the subepicardial and the subendocardial concentration of digoxin were significantly lower than that of the mesocardial layer. 5 During the first 10 min the dp/dtmax increased to 135% of the control level. The increase remained unchanged during the rest of the study. 6 Myocardial potassium decreased throughout the study. 7 The M-configuration of the myocardial uptake curve and the non-uniformity of myocardial distribution of digoxin observed at 10 min after administrating digoxin to long-term digitalized dogs indicate that the distribution of myocardial blood flow may be changed during chronic digitalization. PMID:1000132

  6. Reduced apoptosis after acute myocardial infarction by simvastatin.

    PubMed

    Luo, Ke-qin; Long, Hui-bao; Xu, Bing-can

    2015-03-01

    To observe the effect of simvastatin in patients with acute myocardial infarction in rabbits against myocardial apoptosis, and to explore its possible mechanism. Male New Zealand white rabbits were randomized into three groups, including the myocardial infarction group (12 rabbits), the simvastatin treatment group (15 rabbits), and the sham group (12 rabbits). In the simvastatin treatment and myocardial infarction groups, the rabbits received myocardial infarction surgeries. While in the sham group, loose knots were tied in the left anterior descending coronary artery branches. The simvastatin treatment group was given simvastatin by oral gavage 24 h after surgery. Parameters, which included left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, and left ventricular mass index, were recorded in these three groups. Edge myocardial infarction and myocardial cell apoptosis were analyzed using TUNEL assay, and Bcl-2, Bax, and Caspase-3 protein levels were detected by Western blot. Acute myocardial infarction model was successfully established in rabbits by ligation of the left anterior descending coronary artery. Compared with the myocardial infarction group, left ventricular end-diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly reduced and left ventricular ejection fraction (LVEF) increased in the simvastatin treatment group. Compared with the sham group, LVEDD and LVESD were significantly increased and LVEF decreased in the simvastatin treatment group. All the differences were statistically significant (P < 0.05). Left ventricular mass index in the simvastatin treatment group was statistically lower than the myocardial infarction group. Compared with the sham group, left ventricular mass index in both the simvastatin treatment and myocardial infarction groups was significantly increased. The differences of the above comparisons were statistically

  7. Features of adenosine metabolism of mouse heart.

    PubMed

    Deussen, Andreas; Weichsel, Johannes; Pexa, Annette

    2006-11-01

    Adenosine metabolism and transport were evaluated in the isolated perfused mouse heart and compared with the well-established model of isolated perfused guinea pig heart. Coronary venous release of adenosine under well-oxygenated conditions in the mouse exceeds that in the guinea pig threefold when related to tissue mass. Total myocardial adenosine production rate under this condition was approximately 2 nmol/min per gramme and similar in both species. Coronary resistance vessels of mice are highly sensitive to exogenous adenosine, and the threshold for adenosine-induced vasodilation is approximately 30 nmol/l. Adenosine membrane transport was largely insensitive to nitrobenzyl-thioinosine (NBTI) in mouse heart, which is in contrast to guinea pig and several other species. This indicates the dominance of NBTI-insensitive transporters in mouse heart. For future studies, the assessment of cytosolic and extracellular adenosine metabolism and its relationship with coronary flow will require the use of more effective membrane transport blockers.

  8. Effects of creatinol-O-phosphate (COP) on haemodynamics and cardiac metabolism in conscious and anaesthetized dogs.

    PubMed

    Marchetti, G; Merlo, L

    1978-01-01

    The effects of creatinol-O-phosphate (COP, Aplodan) have been studied on haemodynamics and cardiac metabolism of virtually normal heart (conscious dogs with electromagnetic probes chronically implanted) and progressively failing heart (open chest anaesthetized dogs). The results obtained show that COP in both series of experiments increased cardiac work and improved some myocardial metabolic parameters (delta redox potential across the heart, lactate/pyruvate ratio, excess lactate) probably by enhancing the myocardial O2 supply-consumption ratio, and consequently increasing the amount of O2 available for energetic reactions in the cardiac muscle and possibly in other tissues as well.

  9. Depressive Symptoms Are Associated with Mental Stress-Induced Myocardial Ischemia after Acute Myocardial Infarction

    PubMed Central

    Wei, Jingkai; Pimple, Pratik; Shah, Amit J.; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon A.; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Objectives Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI. Methods We studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores. Results There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress. Conclusion Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress. PMID:25061993

  10. 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).

  11. Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of /sup 99m/Tc pyrophosphate and gallium

    SciTech Connect

    Forman, M.B.; Sandler, M.P.; Sacks, G.A.; Kronenberg, M.W.; Powers, T.A.

    1983-03-01

    A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, /sup 201/Tl, /sup 67/Ga, and /sup 99m/Tc pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.

  12. 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

  13. 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.

  14. Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction (EXAMI): study protocol for a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Myocardial infarction causes irreversible loss of cardiomyocytes and may lead to loss of ventricular function, morbidity and mortality. Infarct size is a major prognostic factor and reduction of infarct size has therefore been an important objective of strategies to improve outcomes. In experimental studies, glucagon-like peptide 1 and exenatide, a long acting glucagon-like peptide 1 receptor agonist, a novel drug introduced for the treatment of type 2 diabetes, reduced infarct size after myocardial infarction by activating pro-survival pathways and by increasing metabolic efficiency. Methods The EXAMI trial is a multi-center, prospective, randomized, placebo controlled trial, designed to evaluate clinical outcome of exenatide infusion on top of standard treatment, in patients with an acute myocardial infarction, successfully treated with primary percutaneous coronary intervention. A total of 108 patients will be randomized to exenatide (5 μg bolus in 30 minutes followed by continuous infusion of 20 μg/24 h for 72 h) or placebo treatment. The primary end point of the study is myocardial infarct size (measured using magnetic resonance imaging with delayed enhancement at 4 months) as a percentage of the area at risk (measured using T2 weighted images at 3-7 days). Discussion If the current study demonstrates cardioprotective effects, exenatide may constitute a novel therapeutic option to reduce infarct size and preserve cardiac function in adjunction to reperfusion therapy in patients with acute myocardial infarction. Trial registration ClinicalTrials.gov: NCT01254123 PMID:22067476

  15. 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

  16. Differential diagnosis of nongap metabolic acidosis: value of a systematic approach.

    PubMed

    Kraut, Jeffrey A; Madias, Nicolaos E

    2012-04-01

    Nongap metabolic acidosis is a common form of both acute and chronic metabolic acidosis. Because derangements in renal acid-base regulation are a common cause of nongap metabolic acidosis, studies to evaluate renal acidification often serve as the mainstay of differential diagnosis. However, in many cases, information obtained from the history and physical examination, evaluation of the electrolyte pattern (to determine if a nongap acidosis alone or a combined nongap and high anion gap metabolic acidosis is present), and examination of the serum potassium concentration (to characterize the disorder as hyperkalemic or hypokalemic in nature) is sufficient to make a presumptive diagnosis without more sophisticated studies. If this information proves insufficient, indirect estimates or direct measurement of urinary NH(4)(+) concentration, measurement of urine pH, and assessment of urinary HCO(3)(-) excretion can help in establishing the diagnosis. This review summarizes current information concerning the pathophysiology of this electrolyte pattern and the value and limitations of all of the diagnostic studies available. It also provides a systematic and cost-effective approach to the differential diagnosis of nongap metabolic acidosis.

  17. 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

  18. Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation

    PubMed Central

    Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

    2016-01-01

    Purpose: The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. Methods: A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Results: Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Conclusions: Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease.

  19. 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 ...

  20. 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

  1. 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

  2. Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population

    PubMed Central

    Srikanthan, Krithika; Feyh, Andrew; Visweshwar, Haresh; Shapiro, Joseph I.; Sodhi, Komal

    2016-01-01

    Introduction: Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia. Methods: A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1). Results: According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-α), markers of pro-oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster. Conclusion: Based on the evidence presented within the literature, the

  3. Metabolic supplementation with orotic acid and magnesium orotate.

    PubMed

    Rosenfeldt, F L

    1998-09-01

    Orotic acid (OA), a naturally occurring substance, is a key intermediate in the biosynthetic pathway of pyrimidines. Previous investigations in the heart suggest that orotate can protect recently infarcted hearts against a further ischemic stress and may be beneficial in certain types of experimental cardiomyopathy. At the Hamburg symposium on magnesium orotate, a number of studies of this form of metabolic supplementation were presented that indicate orotic acid and its magnesium salt have a modest beneficial effect on the myocardium under conditions of stress ranging from myocardial infarction to severe physical exercise. The following conclusions can be drawn: (1) Orotic acid can improve the energy status of the recently infarcted myocardium (rat hearts). (2) Orotic acid may improve myocardial purine and pyrimidine levels by stimulating hepatic release of uridine into the bloodstream, which in turn augments depleted myocardial pyrimidines and purines (rat heart). (3) Orotic acid improves the tolerance of the recently infarcted heart to global ischemia (rats). (4) Magnesium orotate may reduce the severity of chronic myocardial dysfunction and structural damage in cardiomyopathy (cardiomyopathic hamsters). (5) Magnesium orotate may improve exercise tolerance in patients with coronary artery disease and in trained athletes (humans). (6) Magnesium orotate has only a weak inotropic effect, if any, on normal hearts (rats). (7) Further clinical testing is indicated to determine if the effects described could be of significant clinical benefit in the treatment of heart disease. PMID:9794088

  4. Positron Emission Tomography for the Assessment of Myocardial Viability

    PubMed Central

    2010-01-01

    ) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%. Cardiac Magnetic Resonance Imaging Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery. Cardiac Positron Emission Tomography Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG). During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite

  5. Low High-Density Lipoprotein and Risk of Myocardial Infarction

    PubMed Central

    Ramirez, A.; Hu, P. P.

    2015-01-01

    Low HDL is an independent risk factor for myocardial infarction. This paper reviews our current understanding of HDL, HDL structure and function, HDL subclasses, the relationship of low HDL with myocardial infarction, HDL targeted therapy, and clinical trials and studies. Furthermore potential new agents, such as alirocumab (praluent) and evolocumab (repatha) are discussed. PMID:26692765

  6. Low High-Density Lipoprotein and Risk of Myocardial Infarction.

    PubMed

    Ramirez, A; Hu, P P

    2015-01-01

    Low HDL is an independent risk factor for myocardial infarction. This paper reviews our current understanding of HDL, HDL structure and function, HDL subclasses, the relationship of low HDL with myocardial infarction, HDL targeted therapy, and clinical trials and studies. Furthermore potential new agents, such as alirocumab (praluent) and evolocumab (repatha) are discussed. PMID:26692765

  7. Prognostic value of radionuclide exercise testing after myocardial infarction

    SciTech Connect

    Schocken, D.D.

    1984-08-01

    Abnormal systolic ventricular function and persistent ischemia are sensitive indicators of poor prognosis following myocardial infarction. The use