Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography - A comparison with contrast-enhanced magnetic resonance imaging

OBJECTIVES We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). BACKGROUND Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. METHODS Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, 75% of the wall thickness replaced by scar. RESULTS As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (50% were viable by SPECT. CONCLUSIONS Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar. (C) 2004 by the American College of Cardiology Foundation.

Prediction of subclinicial left ventricular dysfunction with strain rate imaging in patients with asymptomatic severe mitral regurgitation

This study sought the ability of strain rate imaging to detect subclinical left ventricular dysfunction, as evidenced by reduced contractile reserve (CR) in 32 asymptomatic patients with isolated severe mitral regurgitation. Compared with CR- patients (n = 10), CR+ patients (n = 22) had significantly higher end-systolic strain and peak systolic strain rate, but these parameters were not significantly different between CR+ patients and matched normal controls. (C) 2004 by Excerpta Medica, Inc.

Should we be evaluating the ventricle or the myocardium? Advances in tissue characterization

The assessment of left ventricular (LV) dysfunction has become the most frequent indication for echocardiography, a growth that has been driven by the epidemic of heart failure. The value of echocardiography for assessing LV dysfunction is unquestionable, the quantification of both LV systolic and diastolic dysfunction being a reliable indicator of mortality. 1,2 Nonetheless, whereas the ejection fraction and diastolic assessment are important clinical parameters, they are highly dependent on loading and may produce abnormal results under unusual loading conditions. Moreover, in a number of situations where the LV is evaluated, although the overall function is an important finding, the referring clinician is really requesting an assessment of the nature of the underlying myocardial tissue (Table 1). Indeed, in some situations (eg, among family members of patients with a cardiomyopathy) questions arise about the presence of pathology despite the presence of normal ventricular function. Traditionally, it has been difficult to obtain this information because of the lack of sufficiently sensitive parameters, but a number of new developments have shown such success in this area that the clinical application of tools to assess the myocardium in routine practice appears finally to be a realistic proposition.

Exercise ech predicts development of late post-operative left ventricular dysfunction and cardiac morbidity in asymptomatic severe mitral regurgitation

Objective: Mitral repair is increasingly performed in asymptomatic mitral regurgitation (MR). Previous work showed that pre-operative documentation of loss of contractile reserve (Cr) by exercise echo (ExE) may predict LV dysfunction early after repair. We sought the value of Cr in predicting late post-op LV dysfunction and clinical outcome. Methods: Pre-op ExE was performed in 41 pts with isolated MR without coronary disease undergoing repair. LV end-systolic and end-diastolic volumes were measured at rest and post-stress and EF was calculated using modified Simpson’s rule. Intact Cr was defined by >4% increment of stress compared with rest EF. During follow up (3±1 years), EF was serially assessed and occurrence of cardiac events was documented. Results: Cr was present in 19 pts (Cr+)(peak EF 76±7%) and absent in 22 pts (Cr-)(peak EF 56±11%, p

Reserve carbohydrates and lipids from the seeds of four tropical tree species with different sensitivity to desiccation

Considering the importance of water content for the conservation and storage of seeds, and the involvement of soluble carbohydrates and lipids for embryo development, a comparative study was carried out among the seeds of Inga vera (ingá), Eugenia uniflora (pitanga), both classified as recalcitrant, and Caesalpinia echinata (brazilwood) and Erythrina speciosa (mulungu), considered as orthodox seeds. Low concentrations of cyclitols (0.3-0.5%), raffinose family oligosaccharides (ca. 0.05%) and unsaturated fatty acids (0-19%) were found in the seeds of ingá and pitanga, while larger amounts of cyclitols (2-3%) and raffinose (4.6-13%) were found in brazilwood and mulungu, respectively. These results, in addition to higher proportions of unsaturated fatty acids (53-71%) in orthodox seeds, suggested that sugars and lipids played important role in water movement, protecting the embryo cell membranes against injuries during dehydration.

Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy

Background: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies. Methodology/Principal Findings: Myocardium homogenates from CCC (N = 5), IC (N = 5) and IDC (N = 5) patients, as well as from heart donors (N = 5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. Conclusions/Significance: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.

Bioinsecticidal activity of Talisia esculenta reserve protein on growth and serine digestive enzymes during larval development of Anticarsia gemmatalis

Plants synthesize a variety of molecules to defend themselves against an attack by insects. Talisin is a reserve protein from Talisia esculenta seeds, the first to be characterized from the family Sapindaceae. In this study, the insecticidal activity of Talisin was tested by incorporating the reserve protein into an artificial diet fed to the velvetbean caterpillar Anticarsia gemmatalis, the major pest of soybean crops in Brazil. At 1.5% (w/w) of the dietary protein, Talisin affected larval growth, pupal weight, development and mortality, adult fertility and longevity, and produced malformations in pupae and adult insects. Talisin inhibited the trypsin-like activity of larval midgut homogenates. The trypsin activity in Talisin-fed larvae was sensitive to Talisin, indicating that no novel protease-resistant to Talisin was induced in Talisin-fed larvae. Affinity chromatography showed that Talisin bound to midgut proteinases of the insect A. gemmatalis, but was resistant to enzymatic digestion by these larval proteinases. The transformation of genes coding for this reserve protein could be useful for developing insect resistant crops. (C) 2010 Elsevier Inc. All rights reserved.

Effects of data characteristics on the results of reserve selection algorithms

We tested the effects of four data characteristics on the results of reserve selection algorithms. The data characteristics were nestedness of features (land types in this case), rarity of features, size variation of sites (potential reserves) and size of data sets (numbers of sites and features). We manipulated data sets to produce three levels, with replication, of each of these data characteristics while holding the other three characteristics constant. We then used an optimizing algorithm and three heuristic algorithms to select sites to solve several reservation problems. We measured efficiency as the number or total area of selected sites, indicating the relative cost of a reserve system. Higher nestedness increased the efficiency of all algorithms (reduced the total cost of new reserves). Higher rarity reduced the efficiency of all algorithms (increased the total cost of new reserves). More variation in site size increased the efficiency of all algorithms expressed in terms of total area of selected sites. We measured the suboptimality of heuristic algorithms as the percentage increase of their results over optimal (minimum possible) results. Suboptimality is a measure of the reliability of heuristics as indicative costing analyses. Higher rarity reduced the suboptimality of heuristics (increased their reliability) and there is some evidence that more size variation did the same for the total area of selected sites. We discuss the implications of these results for the use of reserve selection algorithms as indicative and real-world planning tools.

Putative beta(4)-adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca2+: comparison with atrial receptors and relationship to (-)-[H-3]-CGP 12177 binding

1 We identified putative beta(4)-adrenoceptors by radioligand binding, measured increases in ventricular contractile force by (-)-CGP 12177 and (+/-)-cyanopindolol and demonstrated increased Ca2+ transients by (-)-CGP 12177 in rat cardiomyocytes. 2 (-)-[H-3]-CGP 12177 labelled 13-22 fmol mg(-1) protein ventricular beta(1), beta(2)-adrenoceptors (pK(D) similar to 9.0) and 50-90 fmol mg(-1) protein putative beta(4)-adrenoceptors (pK(D) similar to 7.3). The affinity values (PKi) for (beta(1),beta(2)-) and putative beta(4)-adrenoceptors, estimated from binding inhibition, were (-)-propranolol 8.4, 5.7; (-)-bupranolol 9.7, 5.8; (+/-)-cyanopindolol 10.0,7.4. 3 In left ventricular papillary muscle, in the presence of 30 mu M 3-isobutyl-1-methylxanthine, (-)CGP 12177 and (+/-)-cyanopindolol caused positive inotropic effects, (pEC(50) (-)-CGP 12177, 7.6; (+/-)-cyanopindolol, 7.0) which were antagonized by (-)-bupranolol (pK(B) 6.7-7.0) and (-)-CGP 20712A (pK(B) 6.3-6.6). The cardiostimulant effects of(-)-CGP 12177 in papillary muscle, left and right atrium were antagonized by (+/-)-cyanopindolol (pK(i), 7.0-7.4). 4 (-)-CGP 12177 (1 mu M) in the presence of 200 nM (-)-propranolol increased Ca2+ transient amplitude by 56% in atrial myocytes, but only caused a marginal increase in ventricular myocytes. In the presence of 1 mu M 3-isobutyl-1-methylxanthine and 200 nM (-)-propranolol, 1 mu M (-)-CGP 12177 caused a 73% increase in Ca2+ transient amplitude in ventricular myocytes. (-)-CGP 12177 elicited arrhythmic transients in some atrial and ventricular myocytes. 5 Probably by preventing cyclic AMP hydrolysis, 3-isobutyl-1-methylxanthine facilitates the inotropic function of ventricular putative beta(4)-adrenoceptors. suggesting coupling to G(s) protein-adenylyl cyclase. The receptor-mediated increases in contractile force are related to increases of Ca2+ in atrial and ventricular myocytes. The agreement of binding affinities of agonists with cardiostimulant potencies is consistent with mediation through putative beta(4)-adrenoceptors labelled with (-)-[H-3]-CGP 12177.

Heterogeneous distribution of isoactins in cultured vascular smooth muscle cells does not reflect segregation of contractile and cytoskeletal domains

We have previously demonstrated that or-smooth muscle (alpha -SM) actin is predominantly distributed in the central region and beta -non-muscle (beta -NM) actin in the periphery of cultured rabbit aortic smooth muscle cells (SMCs). To determine whether this reflects a special form of segregation of contractile and cytoskeletal components in SMCs, this study systematically investigated the distribution relationship of structural proteins using high-resolution confocal laser scanning fluorescent microscopy. Not only isoactins but also smooth muscle myosin heavy chain, alpha -actinin, vinculin, and vimentin were heterogeneously distributed in the cultured SMCs. The predominant distribution of beta -NM actin in the cell periphery was associated with densely distributed vinculin plaques and disrupted or striated myosin and ol-actinin aggregates, which may reflect a process of stress fiber assembly during cell spreading and focal adhesion formation. The high-level labeling of alpha -SM actin in the central portion of stress fibers was related to continuous myosin and punctate alpha -actinin distribution, which may represent the maturation of the fibrillar structures. The findings also suggest that the stress fibers, in which actin and myosin filaments organize into sar-comere-like units with alpha -actinin-rich dense bodies analogous to Z-lines, are the contractile vimentin structures of cultured SMCs that link to the network of vimentin-containing intermediate alpha -actinin filaments through the dense bodies and dense plaques.

Optimal reserve management and sovereign debt

Most models currently used to determine optimal foreign reserve holdings take the level of international debt as given. However, given the sovereign`s willingness-to-pay incentive problems, reserve accumulation may reduce sustainable debt levels. In addition, assuming constant debt levels does not allow addressing one of the puzzles behind using reserves as a means to avoid the negative effects of crisis: why do not sovereign countries reduce their sovereign debt instead? To study the joint decision of holding sovereign debt and reserves, we construct a stochastic dynamic equilibrium model calibrated to a sample of emerging markets. We obtain that the reserve accumulation does not play a quantitatively important role in this model. In fact, we find the optimal policy is not to hold reserves at all. This finding is robust to considering interest rate shocks, sudden stops, contingent reserves and reserve dependent output costs. (c) 2008 Elsevier B.V. All rights reserved.

Reserve price commitments in auctions

It is well known that the optimal auction-one that maximizes the seller's expected revenue-can be implemented using a standard auction format with a suitably chosen reserve price. This reserve price is above the seller's value of retaining the object and the mechanism requires a commitment not to sell the object below the reserve. This commitment is what makes the reserve valuable to the seller. However, in practice, a reserve price commits the seller to sell the object if the reserve is reached, but does not commit her to withhold the object from sale if bidding falls short of the reserve. In this note we investigate whether reserve prices remain valuable for the seller when she may negotiate with the highest bidder if the reserve is not met. We show that the value of the reserve price may be completely undermined if the seller is a sufficiently weak bargainer. (c) 2004 Elsevier B.V. All rights reserved.

Contractile activity per se induces transcriptional activation of SLC2A4 gene in soleus muscle: involvement of MEF2D, HIF-1a, and TR alpha transcriptional factors

Lima GA, Anhe GF, Giannocco G, Nunes MT, Correa-Giannella ML, Machado UF. Contractile activity per se induces transcriptional activation of SLC2A4 gene in soleus muscle: involvement of MEF2D, HIF-1a, and TR alpha transcriptional factors. Am J Physiol Endocrinol Metab 296: E132-E138, 2009. First published October 28, 2008; doi: 10.1152/ajpendo.90548.2008.-Skeletal muscle is a target tissue for approaches that can improve insulin sensitivity in insulin-resistant states. In muscles, glucose uptake is performed by the GLUT-4 protein, which is encoded by the SLC2A4 gene. SLC2A4 gene expression increases in response to conditions that improve insulin sensitivity, including chronic exercise. However, since chronic exercise improves insulin sensitivity, the increased SLC2A4 gene expression could not be clearly attributed to the muscle contractile activity per se and/or to the improved insulin sensitivity. The present study was designed to investigate the role of contractile activity per se in the regulation of SLC2A4 gene expression as well as in the participation of the transcriptional factors myocyte enhancer factor 2D (MEF2D), hypoxia inducible factor 1a (HIF-1a), and thyroid hormone receptor-alpha (TR alpha). The performed in vitro protocol excluded the interference of metabolic, hormonal, and neural effects. The results showed that, in response to 10 min of electrically induced contraction of soleus muscle, an early 40% increase in GLUT-4 mRNA (30 min) occurred, with a subsequent 65% increase (120 min) in GLUT-4 protein content. EMSA and supershift assays revealed that the stimulus rapidly increased the binding activity of MEF2D, HIF-1a, and TR alpha into the SLC2A4 gene promoter. Furthermore, chromatin immunoprecipitation assay confirmed, in native nucleosome, that contraction induced an approximate fourfold (P < 0.01) increase in MEF2D and HIF-1a-binding activity. In conclusion, muscle contraction per se enhances SLC2A4 gene expression and that involves MEF2D, HIF-1a, and TR alpha transcription factor activation. This finding reinforces the importance of physical activity to improve glycemic homeostasis independently of other additional insulin sensitizer approaches.

Abnormal chronotropic reserve and heart rate recovery in patients with SLE: a case-control study

Abnormal heart-rate (HR) response during or after a graded exercise test has been recognized as a strong and an independent predictor of all-cause mortality in healthy and diseased subjects. The purpose of the present study was to evaluate the HR response during exercise in women with systemic lupus erythematosus (SLE). In this case-control study, 22 women with SLE (age 29.5 perpendicular to 1.1 years) were compared with 20 gender-, BMI-, and age-matched healthy subjects (age 26.5 +/- 1.4 years). A treadmill cardiorespiratory test was performed and HR response during exercise was evaluated by the chronotropic reserve (CR). HR recovery (Delta HRR) was defined as the difference between HR at peak exercise and at both first (Delta HRR1) and second (Delta HRR2) minutes after exercising. SLE patients presented lower peak VO(2) when compared with healthy subjects (27.6 perpendicular to 0.9 vs. 36.7 perpendicular to 1.1 ml/kg/min, p = 0.001, respectively). Additionally, SLE patients demonstrated lower CR (71.8 +/- 2.4 vs. 98.2 +/- 2.6%, p = 0.001), Delta HRR1 (22.1 +/- 2.5 vs. 32.4 +/- 2.2%, p = 0.004) and Delta HRR2 (39.1 +/- 2.9 vs. 50.8 +/- 2.5%, p = 0.001) than their healthy peers. In conclusion, SLE patients presented abnormal HR response to exercise, characterized by chronotropic incompetence and delayed Delta HRR. Lupus (2011) 20, 717-720.