Association of severe coronary stenosis with subclinical left ventricular dysfunction in the absence of infarction

Background. Regional left ventricular (LV) dysfunction may occur in patients with coronary artery disease (CAD) in the absence of infarction, but the causes of this phenomenon are unclear. We sought to identify whether changes in regional LV function were related to stenosis severity, using sensitive new ultrasound markers of function. Methods: We studied 67 individuals with no history of infarction and with normal LV systolic function: 49 patients with CAD and 18 control subjects without CAD. All patients underwent color Doppler tissue imaging, integrated backscatter (IB), anatomic M-mode echocardiography, and strain rate imaging to detect changes in structure and function. Peak early and late diastolic myocardial velocity, cyclic variation of IB, wall thickness, and percent wall thickening were measured in each basal and mid segment. Strain rate and peak systolic strain were calculated in each wall. CAD was defined as greater than or equal to 50% diameter stenosis. Normokinetic segments (n = 354) subtended by CAD were divided according to stenosis severity into 3 groups: group 1 (subtended by 50%-69% stenosis); group 2 (subtended by 70%-98% stenosis); and group 3 (subtended by greater than or equal to99% stenosis). Each parameter in each group was compared with that in 216 segments from control subjects. Results: Segments subtended by significant CAD showed lower peak early and late diastolic myocardial velocity compared with control segments. Group 3 showed significantly lower myocardial velocities than group 2 for both peak early (4.8 +/- 1.8 vs 6.0 +/- 2.0 cm/s, P

Oxidative stress is responsible for deficient survival and dendritogenesis in Purkinje neurons from ataxia-telangiectasia mutated mutant mice

Atm gene-disrupted mice recapitulate the majority of characteristics observed in patients with the genetic disorder ataxia-telangiectasia (A-T). However, although they exhibit defects in neuromotor function and a distinct neurological phenotype, they do not show the progressive neurodegeneration seen in human patients, but there is evidence that ataxia-telangiectasia mutated ( Atm)-deficient animals have elevated levels of oxidized macromolecules and some neuropathology. We report here that in vitro survival of cerebellar Purkinje cells from both Atm knock-out and Atm knock-in mice was significantly reduced compared with their wild-type littermates. Although most of the Purkinje neurons from wild-type mice exhibited extensive dendritic elongation and branching under these conditions, most neurons from Atm-deficient mice had dramatically reduced dendritic branching. An antioxidant ( isoindoline nitroxide) prevented Purkinje cell death in Atm-deficient mice and enhanced dendritogenesis to wild-type levels. Furthermore, administration of the antioxidant throughout pregnancy had a small enhancing effect on Purkinje neuron survival in Atm gene-disrupted animals and protected against oxidative stress in older animals. These data provide strong evidence for a defect in the cerebellum of Atm-deficient mice and suggest that oxidative stress contributes to this phenotype.

Relationship of ventricular longitudinal function to contractile reserve in patients with mitral regurgitation

Background Latent left ventricular (LV) dysfunction in patients with valvular or myocardial disease may be identified by loss of contractile reserve (CR) at exercise echocardiography. Contraction in the LV longitudinal axis may be more sensitive than radial contraction to minor disturbances of LV function. We sought to determine whether tissue Doppler measurement of longitudinal function could be used to identify CR. Methods Exercise echocardiography was performed in 86 patients (20 women, age 53 +/- 18 years), 72 with asymptomatic or minimally symptomatic mitral regurgitation, and 14 normal controls. Pulsed-wave tissue Doppler imaging (DTI) was used to measure maximum annular systolic velocity at rest and stress. Inducible ischemia was excluded by analysis of wall motion by an experienced observer. CR was defined by greater than or equal to5% improvement of stress compared with rest ejection fraction (EF). Exercise capacity was assessed from expired gas analysis. Results CR was present in 34 patients with mitral regurgitation (47%); peak EF in patients with and without CR was 74% +/- 11% versus 54% +/- 15% (P

Usefulness of myocardial tissue Doppler echocardiography to evaluate left ventricular dyssynchrony before and after biventricular pacing in patients with idiopathic dilated cardiomyopathy

Tissue Doppler imaging allows assessment of left ventricular dyssynchrony and resynchronization after biventricular pacing.

Ventricular dysfunction in early diabetic heart disease: detection, mechanisms and significance

The detection of preclinical heart disease is a new direction in diabetes care. This comment describes the study by Vinereanu and co-workers in this issue of Clinical Science in which tissue Doppler echocardiography has been employed to demonstrate subtle systolic and diastolic dysfunction in Type 11 diabetic patients who had normal global systolic function and were free of coronary artery disease. The aetiology of early ventricular dysfunction in diabetes relates to complex intramyocardial and extramyocardial mechanisms. The initiating event may be due to insulin resistance, and involves abnormal myocardial substrate utilization and uncoupling of mitochondrial oxidative phosphorylation. Dysglycaemia plays an important role via the effects of oxidative stress, protein kinase C activation and advanced glycosylation end-products on inflammatory signalling, collagen metabolism and fibrosis. Extramyocardial mechanisms involve peripheral endothelial dysfunction, arterial stiffening and autonomic neuropathy. The clinical significance of the ventricular abnormalities described is unknown. Confirmation of their prognostic importance for cardiac disease in diabetes would justify routine screening for presymptomatic ventricular dysfunction, as well as clinical trials of novel agents for correcting causal mechanisms. These considerations could also have implications for patients with obesity and the metabolic syndrome.

A Sco homologue plays a role in defence against oxidative stress in pathogenic Neisseria

Sco proteins are found in mitochondria and in a variety of oxidase positive bacteria. Although Sco is required for the formation of the Cu-A centre in a cytochrome oxidase of the aa(3) type, it was observed that oxidases with a Cu-A centre are not present in many bacteria that contain a Sco homologue. Two bacteria of this type are the pathogens Neisseria meningitidis and Neisseria gonorrhoeae. The sco genes of N. gonorrhoeae strain 1291 and N. meningitidis strain MC58 were cloned, inactivated by inserting a kanamycin resistance cassette and used to make knockout mutants by allelic exchange. Both N. gonorrhoeae and N. meningitidis sco mutants were highly sensitive to oxidative killing by paraquat, indicating that Sco is involved in protection against oxidative stress in these bacteria. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

Method for determining the shear stress in cylindrical systems

We develop a method for determining the elements of the pressure tensor at a radius r in a cylindrically symmetric system, analogous to the so-called method of planes used in planar systems [B. D. Todd, Denis J. Evans, and Peter J. Daivis, Phys. Rev. E 52, 1627 (1995)]. We demonstrate its application in determining the radial shear stress dependence during molecular dynamics simulations of the forced flow of methane in cylindrical silica mesopores. Such expressions are useful for the examination of constitutive relations in the context of transport in confined systems.

A yield architecture framework to explain adaptation of pearl millet to environmental stress

Functional knowledge of the physiological basis of crop adaptation to stress is a prerequisite for exploiting specific adaptation to stress environments in breeding programs. This paper presents an analysis of yield components for pearl millet, to explain the specific adaptation of local landraces to stress environments in Rajasthan, India. Six genotypes, ranging from high-tillering traditional landraces to low-tillering open-pollinated modern cultivars, were grown in 20 experiments, covering a range of nonstress and drought stress patterns. In each experiment, yield components (particle number, grain number, 100 grain mass) were measured separately for main shoots, basal tillers, and nodal tillers. Under optimum conditions, landraces had a significantly lower grain yield than the cultivars, but no significant differences were observed at yield levels around 1 ton ha(-1). This genotype x environment interaction for grain yield was due to a difference in yield strategy, where landraces aimed at minimising the risk of a crop failure under stress conditions, and modem cultivars aimed at maximising yield potential under optimum conditions. A key aspect of the adaptation of landraces was the small size of the main shoot panicle, as it minimised (1) the loss of productive tillers during stem elongation; (2) the delay in anthesis if mid-season drought occurs; and (3) the reduction in panicle productivity of the basal tillers under stress. In addition, a low investment in structural panicle weight, relative to vegetative crop growth rate, promoted the production of nodal tillers, providing a mechanism to compensate for reduced basal tiller productivity if stress occurred around anthesis. A low maximum 100 grain mass also ensured individual grain mass was little affected by environmental conditions. The strategy of the high-tillering landraces carries a yield penalty under optimum conditions, but is expected to minimise the risk of a crop failure, particularly if mid-season drought stress occurs. The yield architecture of low-tillering varieties, by contrast, will be suited to end-of-season drought stress, provided anthesis is early. Application of the above adaptation mechanisms into a breeding program could enable the identification of plant types that match the prevalent stress patterns in the target environments. (C) 2003 E.J. van Oosterom. Published by Elsevier Science B.V. All rights reserved.

Relationships and estimates of longitudinal growth stress in Eucalyptus dunnii at different ages

O objetivo desse trabalho foi obter estimativas da tensão de crescimento longitudinal em árvores vivas e verificar a sua relação com algumas características da madeira de Eucalyptus dunnii Maiden aos oito, treze, quinze e dezenove anos de idade. O material foi proveniente da Empresa Procopiak Compensados e Embalagens S.A., localizada no Município de Canoinhas, Santa Catarina. Os níveis de tensão longitudinal de crescimento foram mensurados indiretamente pelo método do "CIRAD-Forêt", na árvore viva, e estimados a partir do módulo de elasticidade dinâmico e do módulo de elasticidade obtido no ensaio de tração paralela à grã. A deformação residual longitudinal (DRL) e as estimativas das tensões de crescimento longitudinais apresentaram tendência de aumento, na média, com a idade do material. A DRL apresentou correlação, positiva e significativa, com todas as estimativas das tensões de crescimento longitudinais, sendo de maior magnitude aos 13, 15 e 19 anos de idade. A densidade básica apresentou maiores correlações, positivas e significativas, com o módulo de elasticidade dinâmico, estimado no sentido longitudinal, para a madeira na condição de saturação e a 12% de umidade, em todas as idades avaliadas. Todas as estimativas das tensões de crescimento longitudinais apresentam elevadas correlações, positivas e significativas, entre si.

The left ventricular contractility of the rat heart is modulated by changes in flow and a1-adrenoceptor stimulation

Myocardial contractility depends on several mechanisms such as coronary perfusion pressure (CPP) and flow as well as on a1-adrenoceptor stimulation. Both effects occur during the sympathetic stimulation mediated by norepinephrine. Norepinephrine increases force development in the heart and produces vasoconstriction increasing arterial pressure and, in turn, CPP. The contribution of each of these factors to the increase in myocardial performance needs to be clarified. Thus, in the present study we used two protocols: in the first we measured mean arterial pressure, left ventricular pressure and rate of rise of left ventricular pressure development in anesthetized rats (N = 10) submitted to phenylephrine (PE) stimulation before and after propranolol plus atropine treatment. These observations showed that in vivo a1-adrenergic stimulation increases left ventricular-developed pressure (P<0.05) together with arterial blood pressure (P<0.05). In the second protocol, we measured left ventricular isovolumic systolic pressure (ISP) and CPP in Langendorff constant flow-perfused hearts. The hearts (N = 7) were perfused with increasing flow rates under control conditions and PE or PE + nitroprusside (NP). Both CPP and ISP increased (P<0.01) as a function of flow. CPP changes were not affected by drug treatment but ISP increased (P<0.01). The largest ISP increase was obtained with PE + NP treatment (P<0.01). The results suggest that both mechanisms, i.e., direct stimulation of myocardial a1-adrenoceptors and increased flow, increased cardiac performance acting simultaneously and synergistically.

Stress affects theta activity in limbic networks and impairs novelty-induced exploration and familiarization

Exposure to a novel environment triggers the response of several brain areas that regulate emotional behaviors. Here, we studied theta oscillations within the hippocampus (HPC)-amygdala (AMY)-medial prefrontal cortex (mPFC) network in exploration of a novel environment and subsequent familiarization through repeated exposures to that same environment; in addition, we assessed how concomitant stress exposure could disrupt this activity and impair both behavioral processes. Local field potentials were simultaneously recorded from dorsal and ventral hippocampus (dHPC and vHPC respectively), basolateral amygdala (BLA) and mPFC in freely behaving rats while they were exposed to a novel environment, then repeatedly re-exposed over the course of 3 weeks to that same environment and, finally, on re-exposure to a novel unfamiliar environment. A longitudinal analysis of theta activity within this circuit revealed a reduction of vHPC and BLA theta power and vHPC-BLA theta coherence through familiarization which was correlated with a return to normal exploratory behavior in control rats. In contrast, a persistent over-activation of the same brain regions was observed in stressed rats that displayed impairments in novel exploration and familiarization processes. Importantly, we show that stress also affected intra-hippocampal synchrony and heightened the coherence between vHPC and BLA. In summary, we demonstrate that modulatory theta activity in the aforementioned circuit, namely in the vHPC and BLA, is correlated with the expression of anxiety in novelty-induced exploration and familiarization in both normal and pathological conditions.