bluuebunny/crossref_metadata_2025 huggingface dataset:
Compensating for a bite block in /s/ and /t/ production: Palatographic, acoustic, and perceptual data
Authors: Flege James Emil , Fletcher Samuel G. , Homiedan Abdullah
Published: October 2005

Electropalatography was used to monitor linguapalatal contact patterns in /s/ and /t/. Talkers often compensated incompletely for a bite block, both immediately after its insertion (sample B1) and after 10 min of practice (sample B2). Significant differences in the number of sensors contacted were noted between normal and bite-block samples for both /s/ and /t/. Differences in length of constriction in /t/, and the A-P location and width of the groove in /s/ were also noted. The two native English subjects compensated better than three Arabic subjects, perhaps because English /s/ and /t/ are formed more posteriorily and with a smaller contact area than their Arabic counterparts. A significant correlation existed between the area and A-P location of linguapalatal contact. All five subjects formed a groove for /s/ in sample B2, but two often did not produce /t/ with complete constriction. This suggests a groove is critical for /s/, but complete constriction is not critical for /t/. The contact patterns in sample B2 more closely resembled normal speech than those in sample B1 in some instances, while in other instances the reverse was true. The conclusion that subjects sometimes overcompensated in sample B2 was supported by the results of detailed acoustic and perceptual analyses for one subject. Taken together, the results suggest that compensation for a bite block is not instananeous, and that specific parameter values may be encoded in central phonetic representations.
An explicit resonance condition for a rigid symmetric Nth-order branching network
Authors: Raphael David T.
Published: October 2005

A technique is presented for the derivation of an explicit resonance condition at the open end of a rigid, symmetrical, branching structure with an arbitrary number N of successive bifurcations resulting in 2N terminal closed branches. The resonance condition is exact and explicitly relates the branch lengths and areas to the angular frequency and the integral harmonic number. Unlike conventional recursive algorithms that interrelate successive nodal impedances, it is demonstrated herein that the sucessive internodal relationship can be replaced with an area-weighted trigonometric operator that operates on the overall effective length of all branches distal to the node under consideration. This approach allows formulation of all nodal impedances, inclusive of the open-end input impedance, in an explicit closed-form manner.
A new method for determining acoustoelastic constants and plane stresses in textured thin plates
Authors: Chatellier Jean-Yves , Touratier Maurice
Published: October 2005

The texture of the material is taken into account in the present analysis of polycrystalline structures, which means that at least the third-order terms must be considered in the elastic strain energy density function. An original method is discussed that determines the acoustoelastic constants directly so that the third-order elastic constants can be included without having to determine them explicitly. A special type of test specimen is used to simulate a perfectly plane stress state with a uniaxial tensile load. A texture is introduced by cold rolling the specimen and then annealing it to eliminate the residual stresses due to manufacturing. The plane stresses are then estimated from the propagation times of bulk ultrasonic waves polarized in three orthogonal directions. The small rotation induced by the texture is measured along with the stress of the shear wave polarization plane. A more in-depth characterization of the material is deemed necessary if the theory is to be applied in extenso to the plastic domain.
On Green’s functions for elastic waves in anisotropic media
Authors: Tverdokhlebov A. , Rose J.
Published: October 2005

The Green’s function, as a temporal Fourier transform of the point-source solution of the wave equation in an infinite medium, is obtained for the homogeneous, transversely isotropic solids, such as fiber composites or directionally solidificated steels of the columnar-grained polycrystalline structure. The surface integrals, representing the exact point-source solutions for the quasilongitudinal, quasitransverse, and purely transverse horizontally polarized shear waves, are approximated in terms of elementary functions, given that the elastic parameters characterizing the deviation of the solid from the isotropic medium are relatively small (weak anisotropy approximation). A brief discussion of the main features of the solution and a comparison to well-known eikonal (ray) approximations are presented.
Interpreting measures of frequency selectivity: Is forward masking special?
Authors: Lutfi Robert A.
Published: October 2005

In a previous article [Lutfi, J. Acoust. Soc. Am. 76, 1045–1050 (1984)], the following relation was used to predict measures of frequency selectivity obtained in forward masking from measures obtained in simultaneous masking: F(g)=G+H(g)−H(0), where, for a given masker level, F is the amount of forward masking (in dB) as a function of signal-masker frequency separation (g), H is the amount of simultaneous masking, and G is the amount of forward masking for g=0. In the present study, the relation was tested for a wider range of signal and masker frequencies, masker levels, and signal delays. The relation described thresholds from all conditions well with the inclusion of one free parameter λ corresponding to a constant frequency increment, F(g)=G+H(g+λ)−H(λ). The parameter λ was required to account for observed shifts in the frequency of maximum forward masking. It is argued that a single tuning mechanism can account for commonly observed differences between simultaneous- and forward-masked measures of frequency selectivity.
Bistatic measurement of target scattering at resonance
Authors: Tsui C. Y. , Reid G. N. , Gaunaurd Guillermo C.
Published: October 2005

The resonance scattering theory (RST) postulates, among several basic points, that the bistatic or differential scattering cross section (DSCS), which is measured through a proper time delay by sampling the echo returned by a cylindrical target at resonance, in its free ringing stage, displays a pattern governed by the simple function cos (nα). For a spherical target this function becomes Pn (cos α). This ‘‘rosetta pattern’’ is used to identify the modal order n of each resonance excited and labeled by the index pair (n, l). The index l is subsequently determined by the ranking or ordering of the resonance frequencies present for each given value of n. In the experimental measurement of these patterns, however, some discrepancies are observed when they are compared to the smooth, symmetrical, theoretically predicted patterns. The most notable ones are a deep notch and some modulated diffractive fluctuations at both opposite ends of the angular pattern (viz., at α=0 and π). These discrepancies are examined here, and explanations for their existence are presented.
Equivalent circuits for conical waveguides
Authors: Benade A. H.
Published: October 2005

The acoustical properties of a cone of length L and small-end radius a0 are shown to be representable via an equivalent circuit involving a pair of inertances, a transformer, and a nontapered duct that has the same length and small-end radius as the cone to be represented. This is shunted at the small end by an inertance proportional to x0, which is the distance from this end to the (projected) apex of the cone. At the large end, there is a similar inertance proportional to the apical distance xe=x0+L. This inertance has a negative sign. The nature and correctness of the representation are demonstrated and a number of illustrative examples are presented, including a transformation of a clarinet (which is cylindrical) by means of a vent hole that gives it the basic playing properties of a saxophone (which is conical). The equivalent circuits are easy to calculate with and speak well to the intuition to suggest properties of the cone that are not otherwise very apparent.
Acoustic radiation force experienced by a solid cylinder in a plane progressive sound field
Authors: Hasegawa Takahi , Saka Kyosuke , Inoue Naoki , Matsuzawa Kiichiro
Published: October 2005

The acoustic radiation force experienced by a solid cylinder suspended freely in a plane progressive sound field is calculated, taking into account the elasticity of the cylinder. The results of numerical calculations are presented, indicating the ways in which the form of the frequency dependence of the radiation force function YP for cylindrical targets is affected by variations in the material parameters of the cylinder. The results are compared with those for solid spherical targets.
Ray statistics in reverberation
Authors: Gilbert E. N.
Published: October 2005

Four simple approximate formulas (Sabine, Eyring, Millington, Kuttruff) give the reverberation time of a room. Just the common assumptions, that all four formulas share, are used here to derive a new approximate reverberation time by a queueing theory argument. The new approximation is exact for diffuse spheres but is inconvenient to use in general. The standard simpler formulas are obtained as approximations to the new one by making further assumptions. To compare these formulas, they are applied to diffusely reflecting ellipsoidal rooms. Kuttruff’s approximation requires the least drastic extra assumptions and is usually closest to the new one. However, the common assumptions, which the new approximation uses, can be so far from true that even Kuttruff’s formula is inaccurate in some examples.
Combined monaural and binaural masking release
Authors: Hall Joseph W. , Cokely Jeffrey A. , Grose John H.
Published: October 2005

Stimulus conditions were examined where both across-frequency [comodulation masking release (CMR)] and across-ear [binaural masking-level difference (BMLD)] cues were available, as well as conditions where only one of these cue types was available. The main goal of the study was to determine how the two types of cues combine. The effects of comodulation were assessed either by modulating a masking noise and manipulating its bandwidth (experiment 1) or by using two comodulated narrow bands of noise separated in frequency (experiment 2). The masker was always No, and the 500-Hz pure-tone signal was either So or Sπ. The effect of the frequency of modulation was examined either by changing the frequency of the modulating stimulus (experiment 1) or by changing the bandwidth of the comodulated narrow-band noise (experiment 2). Four of six subjects showed greater masking release when both BMLD and CMR cues were available than for either type of cue alone, whereas the other two subjects did not show an ability to combine the two cues for additional advantage. For the subjects who were able to combine the two types of cue, the additional advantage was greater for low frequencies of modulation. The results indicate that one component of CMR may be based upon across-frequency envelope comparisons at a stage of processing after binaural analysis.
First Born and Rytov approximations: Modeling and inversion conditions in a canonical example
Authors: Beydoun Wafik B. , Tarantola Albert
Published: October 2005

First Born and, more recently, first Rytov approximations are widely used for solving complex forward and inverse seismic scattering problems. The exact pressure-field response from a one-dimensional velocity slab included in an infinite constant velocity medium is expressed analytically. This solution is used for testing these two approximations in modeling and in inversion. Conditions of applicability and parameter estimates lead to the following results: The first Rytov approximation is best suited for modeling and inverting the transmitted, or forward scattered, part of the wave field, whereas the first Born approximation is best suited for modeling and inverting the primary reflected, or backscattered, part of the wave field. If the long wavelength condition holds, linearization of the field with respect to slowness squared is preferable over linearization with respect to slowness, allowing for a very large velocity contrast between the slab and the reference medium. However, if the weak heterogeneity condition holds (i.e., small velocity contrast), the linearization choice is reversed. Numerical examples show and display these differences quantitatively.
Propagation of sound in vibrationally excited N2/He, N2/H2, N2/CH4, and N2/H2O mixtures
Authors: Shields F. Douglas , Lafleur L. Dwynn
Published: October 2005

Previous measurements of resonant reverberation of sound in N2/H2 mixtures in a closed tube have shown an amplification of the sound following the rapid excitation of the gas by an electric discharge [F. D. Shields, J. Acoust. Soc. Am. 81, 87–92 (1987)]. These measurements have been extended in this article to include N2/He, N2/CH4, and N2/H2O mixtures. Some of the excessively large amplification previously observed in N2/H2 mixtures has now been attributed to nonlinearity in the microphone response. However, even after correcting this error, the amplification is much larger and lasts for a longer time than theoretically predicted. This discrepancy is still unexplained. The variation in the translational temperature following the discharge is monitored by measuring the sound velocity. Relaxation times determined from the temperature versus time curves differ only slightly in magnitude and/or temperature dependence from previously reported values.
NEW TRENDS IN TISSUE ENGINEERED CARTILAGE: MICROFLUID DYNAMICS IN 3-D ENGINEERED CELL SYSTEMS
Authors: BOSCHETTI FEDERICA , CIOFFI MARGHERITA , RAIMONDI MANUELA TERESA , MIGLIAVACCA FRANCESCO , DUBINI GABRIELE
Published: October 2005

Bioreactors allowing culture medium direct-perfusion overcome diffusion limitations associated with static culturing and provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed on chondrocytes will depend not only on the culture medium flow rate, but also on the scaffold three-dimensional (3D) micro-architecture. We performed computational fluid-dynamic (CFD) simulations of the flow of culture medium through a 3D porous scaffold, with the aim of predicting the shear stress acting on the cells as a function of parameters that can be set in a tissue-engineering experiment, such as the medium flow rate and the diameter of the perfused scaffold section. We developed two CFD models: the first model (Model 1) was built from micro-computed tomography reconstruction of the actual scaffold geometry, while the second model (Model 2) was based on a simplification of the actual scaffold microstructure. The two models showed comparable results in terms of the distribution of the shear stresses acting on the inner surfaces of the scaffold walls. Models 1 and 2 gave a median shear stress of 3 mPa at a flow rate of 0.5 cm3 min-1 through a 15 mm diameter scaffold. Our results provide a basis for the completion of more exhaustive quantitative studies to further assess the relationship between perfusion at known micro-fluid dynamic conditions and tissue growth in vitro.
BIOMECHANICAL MECHANISMS FOR DAMAGE: RETRIEVAL ANALYSIS AND COMPUTATIONAL WEAR PREDICTIONS IN TOTAL KNEE REPLACEMENTS
Authors: HARMAN MELINDA K. , BANKS SCOTT A. , FREGLY BENJAMIN J. , SAWYER W. GREGORY , HODGE W. ANDREW
Published: October 2005

Damage patterns on the articular surface of the proximal tibia, including cartilage degeneration in osteoarthritic knees and damage of polyethylene knee prostheses after total knee replacement, provide information related to knee joint biomechanics and damage mechanisms at the articular surface. This study reports articular damage patterns and knee kinematics assessed in the knees of older subjects, before and after total knee replacement. The damage patterns are used to evaluate computational dynamic contact and tribological models that predict polyethylene damage in a patient-specific total knee replacement model.
MULTIMODAL DISPLAY INTERFACE FOR PLANNING AND MONITORING COMPLEX SKELETAL RECONSTRUCTIONS
Authors: TADDEI FULVIA , TESTI DEBORA , VICECONTI MARCO , LEARDINI ALBERTO
Published: October 2005

The aim of the present work is to present the new software Multimod Data Manager and to show applications in the planning and monitoring of complex skeletal reconstructions in orthopedic oncology. The DataManager allows the full integration of different kind of data, particularly medical imaging data, both static as CT, SPECT or MRI, or time-varying as fluoroscopy or dynamic MRI, with motion analysis data, but also 3D computer and finite element models of bones, joints and also soft tissues. All the data can be visualized with highly interactive and specialized modalities and can be integrated to offer a complete representation of the patient anatomy. Several algorithms are implemented to allow registration and synchronization of the data. A fully 3D environment is offered to the surgeon to navigate inside the medical imaging dataset. To exemplify the use of the software we document in this paper the data processing used to investigate different specific clinical cases in the field of orthopedic oncology.
THE BIOMECHANICAL BEHAVIOR OF SPHINCTERS: HOW THE THEORY AND THE PRACTICE MISMATCH
Authors: ZANNOLI ROMANO , CORAZZA IVAN , DONNA MAGDA DI , LUGARESI MARIA LUISA , MATTIOLI SANDRO
Published: October 2005

Monitoring sphincter activity presents remarkable methodological and conceptual problems. The particular shape, structure and function of the sphincters require an accurate analysis of the objectives of diagnostic procedures and the physical concepts applied. Researchers have developed practical solutions to the description of the sphincter activity not always rigorous on a theoretical basis, and the measurement results are difficult to evaluate and compare, in the event that the contour conditions of the assumed descriptive model are not well defined. A practical solution is to "create" a constant curvature radius chamber by introducing a cylinder within the sphincter and measuring the pressure, linearly proportional to the tangential force strength of the wall. This paper analyzes the coherence between the theoretical basis and the practical solutions of the different methods of sphincter monitoring, to clarify some controversial aspects, highlight the limitations and to suggest possible alternative solutions.
SECOND CARDIAC SOUND ANALYSIS TECHNIQUES AND PERFORMANCE COMPARISON
Authors: DEBBAL S. M. , BEREKSI-REGUIG F.
Published: October 2005

This paper presents the applications of the spectrogram, Wigner distribution and wavelet transform analysis methods to the second cardiac sound S2 of the phonocardiogram signal (PCG). A comparison between these methods has shown the resolution differences between them. It is found that the spectrogram Short-Time Fourier Transform (STFT) cannot detect the two internals components of the second sound S2 (A2 and P2, atrial and pulmonary components respectively). The Wigner Distribution (WD) can provide time-frequency characteristics of the sound S2, but with insufficient diagnostic information as the two components (A2 and P2) are not accurately detected, appearing to be one component only. It is found that the wavelet transform (WT) is capable of detecting the two components, the aortic valve component A2 and pulmonary valve component P2, of the second cardiac sound S2. However, the standard Fourier transform can display these components in frequency but not the time delay between them. Furthermore, the wavelet transform provides more features and characteristics of the second sound S2 that will hemp physicians to obtain qualitative and quantitative measurements of the time-frequency characteristics.
DETERMINATIONS OF ANALOGUES OF GAUSS SUMS AND OTHER TRIGONOMETRIC SUMS
Authors: BECK MATTHIAS , BERNDT BRUCE C. , CHAN O-YEAT , ZAHARESCU ALEXANDRU
Published: October 2005

Explicit determinations of several classes of trigonometric sums are given. These sums can be viewed as analogues or generalizations of Gauss sums. In a previous paper, two of the present authors considered primarily sine sums associated with primitive odd characters. In this paper, we establish two general theorems involving both sines and cosines, with more attention given to cosine sums in the several examples that we provide.
SIMULTANEOUS APPROXIMATION BY CONJUGATE ALGEBRAIC NUMBERS IN FIELDS OF TRANSCENDENCE DEGREE ONE
Authors: ROY DAMIEN
Published: October 2005

We present a general result of simultaneous approximation to several transcendental real, complex or p-adic numbers ξ1, …, ξt by conjugate algebraic numbers of bounded degree over ℚ, provided that the given transcendental numbers ξ1, …, ξt generate over ℚ a field of transcendence degree one. We provide sharper estimates for example when ξ1, …, ξt form an arithmetic progression with non-zero algebraic difference, or a geometric progression with non-zero algebraic ratio different from a root of unity. In this case, we also obtain by duality a version of Gel'fond's transcendence criterion expressed in terms of polynomials of bounded degree taking small values at ξ1, …, ξt.
ON PERFECT POWERS IN LUCAS SEQUENCES
Authors: BUGEAUD YANN , LUCA FLORIAN , MIGNOTTE MAURICE , SIKSEK SAMIR
Published: October 2005

Let (un)n≥0be the binary recurrence sequence of integers given by u0= 0, u1= 1 and un+2= 2(un+1+ un). We show that the only positive perfect powers in this sequence are u1= 1 and u4= 16. We further discuss the problem of determining perfect powers in Lucas sequences in general.
ARITHMETICAL FUNCTIONS IN SEVERAL VARIABLES
Authors: ALKAN EMRE , ZAHARESCU ALEXANDRU , ZAKI MOHAMMAD
Published: October 2005

In this paper we investigate the ring Ar(R) of arithmetical functions in r variables over an integral domain R. We study a class of absolute values, and a class of derivations on Ar(R). We show that a certain extension of Ar(R) is a discrete valuation ring. We also investigate the metric structure of the ring Ar(R).
EXPONENTIAL SUMS AND THE DISTRIBUTION OF INVERSIVE CONGRUENTIAL PSEUDORANDOM NUMBERS WITH POWER OF TWO MODULUS
Authors: NIEDERREITER HARALD , WINTERHOF ARNE
Published: October 2005

Niederreiter and Shparlinski obtained a nontrivial discrepancy bound for sequences of inversive congruential pseudorandom numbers with odd prime-power modulus. Because of technical difficulties they had to leave open the case of greatest practical interest, namely where the modulus is a power of 2. In the present paper we successfully treat this case by using recent advances in the theory of exponential sums.
EVALUATING DOUBLE EULER SUMS OVER RATIONALLY DEFORMED SIMPLICES
Authors: EIE MINKING , ONG YAO LIN , YANG FU YAO
Published: October 2005

As a natural generalization of the classical Euler sum defined by [Formula: see text] we change the upper limit of the inner summation into kr, a fixed rational multiple of k, and obtain countable families of new sums which we call the extended Euler sums. We shall develop a systematic new method to evaluate these extended Euler sums as well as corresponding alternating sums in terms of values at non-negative integers of cosine and sine parts of the periodic zeta function when the weight p + q is odd.
Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase
Authors: Dai Xiaoling , Cao Xian , Kreulen David L.
Published: October 2005

Superoxide anion (O2−·) production is elevated in sympathetic ganglion neurons and in the vasculature of hypertensive animals; however, it is not known what enzymatic pathway(s) are responsible for O2−· production. To determine the pathway(s) of O2−· production in sympathetic neurons, we examined the presence of mRNA of NADPH oxidase subunits in sympathetic ganglionic neurons and differentiated PC-12 cells. The mRNAs for NADPH oxidase subunits p47 phox, p22 phox, gp91 phox, and NOX1 were present in sympathetic neurons and PC-12 cells, whereas the NOX4 homologue was present in sympathetic neurons but not PC-12 cells. Freshly dissociated celiac ganglion neurons from normal rats and PC-12 cells produced O2−· when treated with the PKC activator PMA; O2−· production increased by 317% and 254%, respectively. The PMA-evoked increases were reduced by pretreatment with the NADPH oxidase inhibitor apocynin. These findings indicate that NADPH oxidase is the primary source of O2−· in sympathetic ganglion neurons. When celiac ganglia from hypertensive rats were incubated with apocynin, O2−· levels were reduced to the same levels as normotensive animals, indicating that NADPH oxidase activity accounted for the elevated O2−· levels in hypertensive animals. To test this latter finding, we compared NADPH oxidase activity in extracts of prevertebral sympathetic ganglia of DOCA-salt hypertensive rats and sham-operated rats. NADPH oxidase activities were 49.9% and 78.6% higher in sympathetic ganglia of DOCA rats compared with normotensive controls when using β-NADH and β-NADPH as substrates, respectively. Thus elevated O2−· levels in hypertension may be a result of the increased activity of NADPH oxidase in postganglionic sympathetic neurons.
Renal interstitial fluid ATP responses to arterial pressure and tubuloglomerular feedback activation during calcium channel blockade
Authors: Nishiyama Akira , Jackson Keith E. , Majid Dewan S. A. , Rahman Matlubur , Navar L. Gabriel
Published: October 2005

A close relationship between changes in renal interstitial fluid (RIF) ATP concentrations and renal autoregulatory or tubuloglomerular feedback (TGF)-dependent changes in renal vascular resistance (RVR) has been demonstrated, but it has not been determined whether the changes in RIF ATP are a consequence or the cause of the changes in RVR. The present study was performed in anesthetized dogs to assess the changes in RIF ATP following changes in renal arterial pressure (RAP) or stimulation of the TGF mechanism under conditions where changes in RVR were prevented by nifedipine, a calcium channel blocker. RIF ATP levels were measured by using microdialysis probes. Intra-arterial infusion of nifedipine (0.36 μg·kg−1·min−1) increased renal blood flow (RBF: from 4.49 ± 0.27 to 5.34 ± 0.39 ml·min−1·g−1) and glomerular filtration rate (GFR: from 0.84 ± 0.07 to 1.09 ± 0.11 ml·min−1·g−1). Under conditions of nifedipine infusion, autoregulatory adjustments in RBF, GFR, and RVR were not observed during stepwise reductions in RAP within the autoregulatory range (from 135 ± 7 to 76 ± 1 mmHg, n = 7). Furthermore, stimulation of the TGF mechanism with intra-arterial infusion of acetazolamide (100 μg·kg−1·min−1) did not alter RBF, GFR, and RVR ( n = 7). During treatment with nifedipine, RIF ATP levels were significantly decreased in response to reductions in RAP (10.7 ± 0.7, 5.8 ± 0.7 and 2.8 ± 0.3 nmol/l at 135 ± 7, 101 ± 4, and 76 ± 1 mmHg, n = 7) and increased by acetazolamide infusion (from 8.8 ± 0.8 to 17.0 ± 1.8 nmol/l, n = 7). These results are similar to those that occurred in dogs not treated with nifedipine and thus demonstrate that the changes in RIF ATP can occur in the absence of autoregulatory or TGF-mediated changes in RVR. The data provide further support to the hypothesis that RIF ATP contributes to adjustments in RVR associated with renal autoregulation and changes in activity of the TGF mechanism.
Optical mapping of late myocardial infarction in rats
Authors: Mills William R. , Mal Niladri , Forudi Farhad , Popovic Zoran B. , Penn Marc S. , Laurita Kenneth R.
Published: October 2005

Late myocardial infarction (MI) is associated with ventricular arrhythmias and sudden cardiac death. The exact mechanistic relationship between abnormal cellular electrophysiology, conduction abnormalities, and arrhythmogenesis associated with late MI is not completely understood. We report a novel, rapid dye superfusion technique to enable whole heart, high-resolution optical mapping of late MI. Optical mapping of action potentials was performed in normal rats and rats with anterior MI 7 days after left anterior descending artery ligation. Hearts from normal rats exhibited normal action potentials and impulse conduction. With the use of programmed stimulation to assess arrhythmia inducibility, 29% of hearts with late MI had inducible sustained ventricular tachycardia, compared with 0% in normal rats. A causal relationship between the site of infarction, abnormal action potential conduction (i.e., block and slow conduction), and arrhythmogenesis was observed. Optical mapping techniques can be used to measure high-resolution action potentials in a whole heart model of late MI. This experimental model reproduces many of the electrophysiological characteristics (i.e., conduction slowing, block, and ventricular tachycardia) associated with MI in patients. Importantly, the results of this study can enhance our ability to understand the interplay between cellular heterogeneity, conduction abnormalities, and arrhythmogenesis associated with MI.
Dependence of acetylcholine and ADP dilation of pial arterioles on heme oxygenase after transfusion of cell-free polymeric hemoglobin
Authors: Rebel Annette , Cao Suyi , Kwansa Herman , Doré Sylvain , Bucci Enrico , Koehler Raymond C.
Published: October 2005

Polymers of cell-free hemoglobin have been designed for clinical use as oxygen carriers, but limited information is available regarding their effects on vascular regulation. We tested the hypothesis that the contribution of heme oxygenase (HO) to acetylcholine-evoked dilation of pial arterioles is upregulated 2 days after polymeric hemoglobin transfusion. Dilator responses to acetylcholine measured by intravital microscopy in anesthetized cats were blocked by superfusion of the HO inhibitor tin protoporphyrin-IX (SnPPIX) in a group that had undergone exchange transfusion with hemoglobin 2 days earlier but not in surgical sham and albumin-transfused groups. However, immunoblots from cortical brain homogenates did not reveal changes in expression of the inducible isoform HO1 or the constitutive isoform HO2 in the hemoglobin-transfused group. To test whether the inhibitory effect of SnPPIX was present acutely after hemoglobin transfusion, responses were measured within an hour of completion of the exchange transfusion. In control and albumin-transfused groups, acetylcholine responses were unaffected by SnPPIX but were blocked by addition of the nitric oxide synthase inhibitor Nω-nitro-l-arginine (l-NNA) to the superfusate. In hemoglobin-transfused groups, the acetylcholine response was blocked by either SnPPIX or l-NNA alone. The effect of another HO inhibitor, chromium mesoporphyrin (CrMP), was tested on ADP, another endothelial-dependent dilator, in anesthetized rats. Pial arteriolar dilation to ADP was unaffected by CrMP in controls but was attenuated 62% by CrMP in rats transfused with hemoglobin. It is concluded that 1) polymeric hemoglobin transfusion acutely upregulates the contribution of HO to acetylcholine-induced dilation of pial arterioles in cats, 2) this upregulation persists 2 days after transfusion when 95% of the hemoglobin is cleared from the circulation, and 3) this acute upregulation of HO signaling is ubiquitous in that similar effects were observed with a different endothelial-dependent agonist (i.e., ADP) in a another species (rat).
Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension
Authors: Rodriguez-Porcel Martin , Zhu Xiang-Yang , Chade Alejandro R. , Amores-Arriaga Beatriz , Caplice Noel M. , Ritman Erik L. , Lerman Amir , Lerman Lilach O.
Published: October 2005

Advanced hypertension (HT), associated with left ventricular hypertrophy (LVH), impairs myocardial microvascular function and structure and leads to increased myocardial hypoxia and growth factor activation. However, the effect of HT on microvascular architecture and its relation to microvascular function, before the development of LVH (early HT), remains unclear. By way of method, pigs were studied after 12 wk of renovascular HT ( n = 7) or control ( n = 7) animals. Myocardial microvascular function (blood volume and blood flow at baseline and in response to adenosine) was assessed by using electron beam computed tomography (CT). Microvascular architecture was subsequently studied ex vivo using micro-CT, and microvessels (diameter, <500 μm) were counted in situ in three-dimensional images (40-μm on-a-side cubic voxels). Myocardial expression of vascular endothelial growth factor, basic fibroblast growth factor, and hypoxia-inducible factor-1α were also measured. By way of results, left ventricular muscle mass was similar between the groups. The blood volume response to intravenous adenosine was attenuated in HT animals compared with normal animals (+7.4 ± 17.0 vs. +46.2 ± 12.3% compared with baseline, P = 0.48 and P = 0.01, respectively). Microvascular spatial density in HT animals was significantly elevated compared with normal animals (246 ± 26 vs. 125 ± 20 vessels/cm2, P < 0.05) and correlated inversely with the blood volume response to adenosine. Growth factors expression was increased in HT animals compared with control animals. In conclusion, early HT elicits changes in myocardial microvascular architecture, which are associated with microvascular dysfunction and precede changes in muscle mass. These observations underscore the direct and early effects of HT on the myocardial vasculature.
Cardiac sympathetic neuroprotective effect of desipramine in tachycardia-induced cardiomyopathy
Authors: Liang Chang-seng , Mao Weike , Iwai Chikao , Fukuoka Shuji , Stevens Suzanne Y.
Published: October 2005

Cardiac sympathetic transmitter stores are reduced in the failing heart. In this study, we proposed to investigate whether the reduction of cardiac sympathetic neurotransmitters was associated with increased interstitial norepinephrine (NE) and reactive oxygen species in congestive heart failure (CHF), using a microdialysis technique and salicylate to detect ·OH generation. Rabbits with and without rapid ventricular pacing (340 beats/min) were randomized to receive desipramine (10 mg/day) or placebo for 8 wk. Rapid pacing produced left ventricular dilation and systolic dysfunction. The failing myocardium also showed reduced tissue contents of NE and tyrosine hydroxylase protein and activity. In contrast, myocardial interstitial NE was increased in CHF (0.89 ± 0.11 ng/ml) compared with the sham-operated animals (0.26 ± 0.03 ng/ml). In addition, cardiac oxidative stress was increased in CHF animals as measured by myocardial interstitial ·OH radical, tissue oxidized glutathione, and oxidized mitochondrial DNA. Desipramine treatment produced significant NE uptake inhibition as evidence by an exaggerated pressor response and a greater increase of myocardial interstitial NE in response to intravenous NE infusion but no significant effects on cardiac function or hemodynamics in sham-operated or CHF animals. However, desipramine treatment attenuated the reductions of tissue NE and tyrosine hydroxylase protein and activity in CHF. Desipramine also prevented the reduction of tyrosine hydroxylase produced by NE in PC12 cells. Thus the reduction of cardiac sympathetic neurotransmitters is related to the increased interstitial NE and tissue oxidative stress in CHF. Also, normal neuronal uptake of NE is required for NE or its oxidized metabolites to exert their neurotoxic effects.
Complement activation-related cardiac anaphylaxis in pigs: role of C5a anaphylatoxin and adenosine in liposome-induced abnormalities in ECG and heart function
Authors: Szebeni János , Baranyi Lajos , Sávay Sándor , Bodó Michael , Milosevits János , Alving Carl R. , Bünger Rolf
Published: October 2005

Cardiac anaphylaxis is a severe, life-threatening manifestation of acute hypersensitivity reactions to allergens and drugs. Earlier studies highlighted an amplifying effect of locally applied C5a on the process; however, the role of systemic complement (C) activation with C5a liberation in blood has not been explored to date. In the present study, we used the porcine liposome-induced cardiopulmonary distress model for 1) characterizing and quantifying peripheral C activation-related cardiac dysfunction; 2) exploring the role of C5a in cardiac abnormalities and therapeutic potential of C blockage by soluble C receptor type 1 (sCR1) and an anti-C5a antibody (GS1); and 3) elucidating the role of adenosine and adenosine receptors in paradoxical bradycardia, one of the symptoms observed in this model. Pigs were injected intravenously with different liposomes [Doxil and multilamellar vesicles (MLV)], zymosan, recombinant human (rhu) C5a, and adenosine, and the ensuing hemodynamic and cardiac changes (hypotension, tachy- or bradycardia, arrhythmias, ST-T changes, ventricular fibrillation, and arrest) were quantified by ranking on an arbitrary scale [cardiac abnormality score (CAS)]. There was significant correlation between CAS and C5a production by liposomes in vitro, and the liposome-induced cardiac abnormalities were partially or fully reproduced with zymosan, rhuC5a, adenosine, and the selective adenosine A1receptor agonist cyclopentyl-adenosine. The use of C nonactivator liposomes or pretreatment of pigs with sCR1 or GS1 attenuated the abnormalities. The selective A1blocker cyclopentyl-xanthine inhibited bradycardia without influencing hypotension, whereas the A2blocker 4-(2-{7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino}ethyl)phenol (ZM-24135) had no such effect. These data suggest that 1) systemic C activation can underlie cardiac anaphylaxis, 2) C5a plays a causal role in the reaction, 3) adenosine action via A1receptors may explain paradoxical bradycardia, and 4) inhibition of C5a formation or action or of A1-receptor function may alleviate the acute cardiotoxicity of liposomal drugs and other intravenous agents that activate C.
Sex-specific differences in cerebral arterial myogenic tone in hypertensive and normotensive rats
Authors: Ibrahim Jamila , McGee Ann , Graham Delyth , McGrath John C. , Dominiczak Anna F.
Published: October 2005

Cerebral blood flow (CBF) is maintained constant despite changes in systemic blood pressure (BP) through multiple mechanisms of autoregulation such as vascular myogenic reactivity. Our aim was to determine myogenic characteristics of cannulated middle cerebral arteries (MCA) in male and female stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) at 12 wk of age under pressurised no-flow conditions. MCA pressure-diameter relationships (20–200 mmHg) were constructed in active (with calcium) and passive (without calcium) conditions, and myogenic and mechanical properties were determined. Myogenic reactivity in WKY ( P < 0.05) and SHRSP ( P < 0.05) males was impaired compared with their female counterparts. Comparison of SHRSP with WKY in males revealed similar myogenic reactivity, but in females SHRSP exhibited augmented myogenic reactivity ( P < 0.05). In both sexes, myogenic tone yielded at lower pressure in SHRSP compared with WKY vessels (120–140 vs. 140–180 mmHg). Stress-strain relationships and elastic moduli in WKY rats showed that vessels were stiffer in females than in males. Conversely, in SHRSP, male vessels were stiffer than female vessels. Comparison of strains in males indicated that stiffness was increased in SHRSP compared with WKY vessels, whereas the converse was observed in females. These findings demonstrate that MCA myogenic and distensibility characteristics exhibit significant sex- and strain-dependent differences. Inappropriate myogenic adaptation and augmented vascular stiffness, particularly in male SHRSP, are potential limiting factors in blood flow autoregulation and may increase the predisposition for stroke-related cerebrovascular events.
Selenium prevents diabetes-induced alterations in [Zn2+]iand metallothionein level of rat heart via restoration of cell redox cycle
Authors: Ayaz Murat , Turan Belma
Published: October 2005

Intracellular free zinc concentration ([Zn2+]i) is very important for cell functions, and its excessive accumulation is cytotoxic. [Zn2+]ican increase rapidly in cardiomyocytes because of mobilization of Zn2+from intracellular stores by reactive oxygen species (ROS). Moreover, ROS have been proposed to contribute to direct and/or indirect damage to cardiomyocytes in diabetes. To address these hypotheses, we investigated how elevated [Zn2+]iin cardiomyocytes could contribute to diabetes-induced alterations in intracellular free calcium concentration ([Ca2+]i). We also investigated its relationship to the changes of metallothionein (MT) level of the heart. Cardiomyocytes from normal rats loaded with fura-2 were used to fluorometrically measure resting [Zn2+]i(0.52 ± 0.06 nM) and [Ca2+]i(26.53 ± 3.67 nM). Fluorescence quenching by the heavy metal chelator N, N, N′, N′-tetrakis(2-pyridylmethyl)ethylenediamine was used to quantify [Zn2+]i. Our data showed that diabetic cardiomyocytes exhibited significantly increased [Zn2+]i(0.87 ± 0.05 nM ) and [Ca2+]i(49.66 ± 9.03 nM), decreased levels of MT and reduced glutathione, increased levels of lipid peroxidation and nitric oxide products, and decreased activities of superoxide dismutase, glutathione reductase, and glutathione peroxidase. Treatment (4 wk) of diabetic rats with sodium selenite (5 μmol·kg body wt−1·day−1) prevented these defects induced by diabetes. A comparison of present data with previously observed beneficial effects of selenium treatment on diabetes-induced contractile dysfunction of the heart can suggest that an increase in [Zn2+]imay contribute to oxidant-induced alterations of excitation-contraction coupling in diabetes. In addition, we showed that oxidative stress is involved in the etiology of diabetes-induced downregulation of heart function via depressed endogenous antioxidant defense mechanisms.
Dual effects of mesenteric lymph isolated from rats with burn injury on contractile function in rat ventricular myocytes
Authors: Yatani Atsuko , Xu Da-Zhong , Irie Keiichi , Sano Kazunori , Jidarian Anoush , Vatner Stephen F. , Deitch Edwin A.
Published: October 2005

Gut-derived factors in intestinal lymph have been shown to trigger myocardial contractile dysfunction. However, the underlying cellular mechanisms remain unclear. We examined the effects of physiologically relevant concentrations of mesenteric lymph collected from rats with 40% burn injury (burn lymph) on excitation-contraction coupling in rat ventricular myocytes. Burn lymph (0.1–5%), but not control mesenteric lymph from sham-burn animals, induced dual positive and negative inotropic effects depending on the concentrations used. At lower concentrations (<0.5%), burn lymph increased the amplitude of myocyte contraction (1.6 ± 0.3-fold; n = 12). At higher concentrations (>0.5%), burn lymph initially enhanced myocyte contraction, which was followed by a block of contraction. These effects were partially reversible on washout. The initial positive inotropic effect was associated with a prolongation of action potential duration (measured at 90% repolarization, 2.5 ± 0.6-fold; n = 10), leading to significant increases in the net Ca2+ influx (1.7 ± 0.1-fold; n = 8). There were no significant changes in the resting membrane potential. The negative inotropic effect was accompanied by a decrease in the action potential plateau (overshoot decrease by 69 ± 10%; n = 4) and membrane depolarization. Voltage-clamp experiments revealed that the positive inotropic effects of burn lymph were due to an inhibition of the transient outward K+ currents that prolong action potential duration, and the inhibitory effects were due to a concentration-dependent inhibition of Ca2+ currents that lead to a reduction of action potential plateau. These burn lymph-induced changes in cardiac myocyte Ca2+ handling can contribute to burn-induced contractile dysfunction and ultimately to heart failure.
Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs
Authors: Schwartz Lisa M. , Lagranha Claudia J.
Published: October 2005

Transient episodes of ischemic preconditioning (PC) render myocardium protected against subsequent lethal injury after ischemia and reperfusion. Recent studies indicate that application of short, repetitive ischemia only during the onset of reperfusion after the lethal ischemic event may obtain equivalent protection. We assessed whether such ischemic postconditioning (Postcon) is cardioprotective in pigs by limiting lethal injury. Pentobarbital sodium-anesthetized, open-chest pigs underwent 30 min of complete occlusion of the left anterior descending coronary artery and 3-h reflow. PC was elicited by two cycles of 5-min occlusion plus 10-min reperfusion before the 30-min occlusion period. Postcon was elicited by three cycles of 30-s reperfusion, followed by 30-s reocclusion, after the 30-min occlusion period and before the 3-h reflow. Infarct size (%area-at-risk using triphenyltetrazolium chloride macrochemistry; means ± SE) after 30 min of ischemia was 26.5 ± 5.2% ( n = 7 hearts/treatment group). PC markedly limited myocardial infarct size (2.8 ± 1.2%, n = 7 hearts/treatment group, P < 0.05 vs. controls). However, Postcon had no effect on infarct size (37.8 ± 5.1%, n = 7 hearts/treatment group). Within the subendocardium, Postcon increased phosphorylation of Akt (74 ± 12%) and ERK1/2 (56 ± 10%) compared with control hearts subjected only to 30-min occlusion and 15-min reperfusion ( P ≤ 0.05), and these changes were not different from the response triggered by PC ( n = 5 hearts/treatment group). Phosphorylation of downstream p70S6K was also equivalent in PC and Postcon groups. These data do not support the hypothesis that application of 30-s cycles of repetitive ischemia during reperfusion exerts a protective effect on pig hearts subjected to lethal ischemia, but this is not due to a failure to phosphorylate ERK and Akt during early reperfusion.
Constitutive activation of prosurvival signaling in alveolar mesenchymal cells isolated from patients with nonresolving acute respiratory distress syndrome
Authors: Horowitz Jeffrey C. , Cui Zongbin , Moore Thomas A. , Meier Tamara R. , Reddy Raju C. , Toews Galen B. , Standiford Theodore J. , Thannickal Victor J.
Published: October 2005

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by stereotypic host inflammatory and repair cellular responses; however, mechanisms regulating the resolution of ARDS are poorly understood. Here, we report the isolation and characterization of a novel population of mesenchymal cells from the alveolar space of ARDS patients via fiber-optic bronchoscopy with bronchoalveolar lavage (BAL). BAL was performed on 17 patients during the course of ARDS. Immunofluorescence staining and multiparameter flow cytometric analysis defined a population of alveolar mesenchymal cells (AMCs) that are CD45−/prolyl-4-hydroxylase+/α-smooth muscle actin+/−. AMCs proliferated in ex vivo cell culture for multiple passages; early passage (3–5) cells were subsequently analyzed in 13 patients. AMCs isolated from patients with persistent or nonresolving ARDS (ARDS-NR, n = 4) demonstrate enhanced constitutive activation of prosurvival signaling pathways involving PKB/Akt, FKHR, and BCL-2 family proteins compared with AMCs from patients with resolving ARDS (ARDS-R, n = 9). Exogenous transforming growth factor-β1 markedly induces PKB/Akt activation in AMCs from ARDS-R. ARDS-NR cells are more resistant to serum deprivation-induced apoptosis compared with ARDS-R. This study identifies a novel population of mesenchymal cells that can be isolated from the alveolar spaces of ARDS patients. AMCs in patients with ARDS-NR acquire an activational profile characterized by enhanced prosurvival signaling and an antiapoptotic phenotype. These findings support the concept that apoptosis of mesenchymal cells may be an essential component of normal repair and resolution of ARDS and suggest that dysregulation of this process may contribute to persistent ARDS.