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PubMed1998

Changes in patterns of left ventricular diastolic filling revealed by Doppler echocardiography in infants with ventricular septal defect.

To evaluate left ventricular diastolic filling in infants with ventricular septal defect, which has yet to be documented, we measured various Doppler echocardiographic indexes from transmitral flow in the following groups: 10 infants with ventricular septal defect without pulmonary hypertension; 10 infants with ventricular septal defect with pulmonary hypertension; and 9 normal infants to serve as controls. The peak A, total velocity time integral, E area, and A area in patients without pulmonary hypertension were all significantly larger than those in controls. The peak ratio E/A, and 1/3 filling fraction, in patients without pulmonary hypertension were significantly lower than in controls. The peak A, A area, and deceleration time in patients with pulmonary hypertension were significantly larger than in patients without pulmonary hypertension and controls. The peak E/A, area E/A, and 1/3 filling fraction in patients with pulmonary hypertension were significantly lower than in those without pulmonary hypertension and controls. The index of left ventricular mass, as well as the index of end-diastolic left ventricular wall thickness, correlated strongly with peak A, A area, and deceleration time. The ratio between the systolic pulmonary and systemic pressures correlated strongly with peak A, A area, peak E/A, area E/A, and 1/3 filling fraction. These results demonstrated that the patterns of left ventricular filling in infants with ventricular septal defect were different from those in normal infants, and suggested that the abnormal patterns may indicate the insufficiency of adaptation of left ventricle (increase of left ventricular compliance) for volume overload in the presence of a ventricular septal defect.

Cardiac Catheterization↗
PubMed1995

Analysis of high-mass biomolecules using electrostatic fields and matrix-assisted laser desorption/ionization in a Fourier transform mass spectrometer.

A new decelerating technique that places dc potentials on the orthogonal excitation and receiver plates as well as the rear trapping plate (conductance limit) of the source cell of a dual cubic cell has been applied to the standard matrix-assisted laser desorption/ionization Fourier transform mass spectrometry technique. When this five-plate trapping method is applied, high-mass ions with large translational kinetic energies can be trapped efficiently and detected. Using this approach, low-resolution spectra of carbonic anhydrase (MW = 29,000), egg albumin (MW = 45,000), and bovine albumin (MW = 66,000) have been obtained. Because the new decelerating method requires no modification to the existing cell, it is also possible to obtain high-resolution spectra for compounds with masses of ca. 14,000 Da and lower. Utilizing the five-plate trapping method, a bovine insulin spectrum with a resolving power of 20,000 was obtained. It is not yet possible to obtain higher resolution for the higher mass proteins. The reasons for this difficulty are currently being investigated.

Animals↗
PubMed1995

Rate-limiting mechanisms of exchange reactions in the cardiac sarcolemma Na(+)-Ca2+ exchanger.

The effects of temperature, pH, voltage and K+ were tested on Na(+)-Ca2+ and Ca(2+)-Ca2+ exchanges with a goal to elucidate the rate-limiting mechanisms. The initial rates (t = 1 s) of Nai- and Cai-dependent 45Ca uptakes were measured in the sarcolemma vesicles. At pH 7.4 the Ca(2+)-Ca2+ exchange shows a bell-shaped temperature curve with a maximum at 27-29 degrees C. This effect is not caused by irreversible inactivation of the exchanger. The increase of pH from pH 6.0 to 7.4 in the K(+)-free medium decelerates the Ca(2+)-Ca2+ exchange 1.5-2.0-fold, while the addition of K+ accelerates the Ca(2+)-Ca2+ exchange 2.0-3.0-fold. Therefore, the accelerating effect of K+ opposes the decelerating effect of deprotonation. Temperatures increase (6-45 degrees C) in the K(+)-free medium (pH 7.4) elevates the Na(+)-Ca2+/Ca(2+)-Ca2+ exchange ratio from 0.8 to 5.0. With varying temperatures (6-37 degrees C) and pH 5.0-9.7, K+ has no considerable effect on Na(+)-Ca2+ exchange but accelerates the Ca(2+)-Ca2+ exchange 2-3-fold. At 6-45 degrees C and fixed pH 7.4, the inside-positive potential (delta psi > or = +200 mV) accelerates the Na(+)-Ca2+ exchange 1.7-2.0-fold, suggesting that the same rate-limiting reaction controls the Na(+)-Ca2+ exchange at various temperatures. It is concluded that (a) At pH > 6.5 (6-45 degrees C and 0-100 mM K+) the voltage-sensitive Na+ efflux limits the Na(+)-Ca2+ exchange, while the Ca2+ efflux limits the Ca(2+)-Ca2+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Electron and proton transfer in the arginine-54-methionine mutant of cytochrome c oxidase from Paracoccus denitrificans.

Arginine 54 in subunit I of cytochrome c oxidase from Paracoccus denitrificans interacts with the formyl group of heme a. Mutation of this arginine to methionine (R54M) dramatically changes the spectral properties of heme a and lowers its midpoint redox potential [Kannt et al. (1999) J. Biol. Chem. 274, 37974-37981; Lee et al. (2000) Biochemistry 39, 2989-2996; Riistama et al. (2000) Biochim. Biophys. Acta 1456, 1-4]. During anaerobic reduction of the mutant enzyme, a small fraction of heme a is reduced first along with heme a(3), while most of heme a is reduced later. This suggests that electron transfer is impaired thermodynamically due to the low redox potential of heme a but that it still takes place from Cu(A) via heme a to the binuclear site as in wild-type enzyme, with no detectable bypass from Cu(A) directly to the binuclear site. Consistent with this, the proton translocation efficiency is unaffected at 1 H(+)/e(-) in the mutant enzyme, although turnover is strongly inhibited. Time-resolved electrometry shows that when the fully reduced enzyme reacts with O(2), the fast phase of membrane potential generation during the P(R )()--> F transition is unaffected by the mutation, whereas the slow phase (F --> O transition) is strongly decelerated. In the 3e(-)-reduced mutant enzyme heme a remains oxidized due to its lowered midpoint potential, whereas Cu(A) and the binuclear site are reduced. In this case the reaction with O(2) proceeds via the P(M) state because transfer of the electron from Cu(A) to the binuclear site is delayed. The single phase of membrane potential generation in the 3e(-)-reduced mutant enzyme, which thus corresponds to the P(M)--> F transition, is decelerated, but its amplitude is comparable to that of the P(R)--> F transition. From this we conclude that the completely (4e(-)) reduced enzyme is fully capable of proton translocation.

Arginine↗
PubMed1988

Kinetics of accumulation and depletion of soluble newly synthesized histone in the reciprocal regulation of histone and DNA synthesis.

Procedures are presented which permit the identification and analysis of cellular histone that is not bound to chromatin. This histone, called soluble histone, could be distinguished from that bound to chromatin by the state of H4 modification and the lack of H2A ubiquitination. Changes in the levels of newly synthesized soluble histone were analyzed with respect to the balance between histone and DNA synthesis in hamster ovary cells. Pulse-chase protocols suggested that the chase of newly synthesized histone from the soluble fraction into chromatin may have two kinetic components with half-depletion times of about 1 and 40 min. When protein synthesis was inhibited, the pulse-chase kinetics of newly synthesized histone from the solubl fraction into chromatin were not significantly altered from those of the control. However, in contrast to the control, when protein synthesis was inhibited, DNA synthesis was also inhibited with kinetics similar to those of the chase of newly synthesized histone from the soluble fraction. There was a rapid decrease in the rate of DNA synthesis with a half-deceleration time of 1 min down to about 30% of the control rate, followed by a slower decrease with an approximate half-deceleration time of 40 min. When DNA synthesis was inhibited, newly synthesized histone accumulated in the soluble fraction, but H2A and H2B continued to complex with chromatin at a significant rate. Soluble histone in G1 cells showed the same differential partitioning of H4/H3 and H2A/H2B between the soluble and chromatin-bound fractions as was found in cycling cells with inhibited DNA synthesis. These results support a unified model of reciprocal regulatory mechanisms between histone and DNA synthesis in the assembly of chromatin.

Animals↗
PubMed2003

Role of an N-terminal loop in the secondary structural change of photoactive yellow protein.

Photoactive yellow protein (PYP) is photoconverted to its putative active form (PYP(M)) with global conformational change(s). The changes in the secondary structure were studied by far-UV circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy using PYP, which lacks N-terminal 6, 15, or 23 amino acid residues (T6, T15, and T23, respectively). Irradiation of truncated PYPs induced the loss of the CD signal, where the maximal difference was located at 222 nm. The reduction of the CD signal was significantly larger than the calculated CD of the N-terminal helices, indicating that it is mainly accounted for by the unfolding and/or structural change of the helices located outside the N-terminal region. The difference FTIR spectra between dark and photosteady states recorded using the solution samples demonstrated that large absorbance changes in the amide mode of the beta-sheet were reduced and downshifted by truncation. The structural change of the beta-sheet is therefore closely correlated with the N-terminal loop. NaCl decelerates the decay of intact PYP(M) and T6(M) at low concentrations (<500 mM) but accelerates decay at high concentrations (>1000 mM). For T15(M) and T23(M), NaCl accelerates their decay at >100 mM but never decelerates their decay, suggesting that the electrostatic interaction, which plays an important role for the recovery of PYP from PYP(M), is lost by removing positions 7-15. The electrostatic interaction between this region and the beta-scaffold is likely to promote the conformational change of PYP(M) for recovery of PYP.

Bacterial Proteins↗
PubMed2004

The effect of the "inert" counteranions in the deprotonation of the dihydrogen complex trans-[FeH(eta 2-H2)(dppe)2]+: kinetic and theoretical studies.

Kinetic studies indicate that trans-[FeH(H2)(dppe)2]+ reacts with an excess of NEt3 to form cis-[FeH2(dppe)2] in a single kinetic step. The second-order rate constant is strongly affected by the presence of added salts, an acceleration being observed with BF4- and PF6- salts and a deceleration with BPh4-. Theoretical calculations indicate that the role of the accelerating anions consists of the formation of ion pairs that provide a more effective reaction pathway for deprotonation. However, for the ion pair with the bulky BPh4- anion, steric crowding in the proximities of the dihydrogen ligand hinders the approach of the base, and the reaction is decelerated.

Journal Article↗
PubMed2005

Neutron scattering study on dynamics of water molecules in MCM-41. 2. Determination of translational diffusion coefficient.

Quasielastic neutron scattering (QENS) spectra of water-filled MCM-41 samples (pore diameters: 21.4 and 28.4 Angstrom) were measured over the temperature range 238-298 K and the momentum transfer range 0.31-0.99 A(-1) to investigate the dynamics of confined water molecules. The spectra, which consist mainly of contributions from the translational diffusion of water molecules, were analyzed by using the Lorentzian and the stretched exponential functions. Comparison of the fits indicated that the latter analysis is more reliable than the former one. The fraction of immobile water molecules located in the vicinity of the pore walls, which give an elastic component, was found to be 0.044-0.061 in both pores. The stretch exponent beta was determined as 0.66-0.80. It was shown that the translational diffusion of water molecules in the pores is decelerated by confinement and that the deceleration becomes marked with a decrease in pore size. The ratios of the translational diffusion coefficient D(T) of confined water to that of bulk water at room temperature were within a range of 0.47-0.63.

Absorption↗
PubMed1997

Prediction of the changes in cardiac output in association with preload reduction therapy in patients with hypertensive heart failure.

In treating patients with acute hypertensive heart failure we often try preload-reduction therapy using diuretics or vasodilators, but this may frequently produce a considerable decrease in cardiac output, particularly in hypertensive patients with diastolic dysfunction. Therefore, it is important from the clinical standpoint to predict the change in cardiac output following preload-reduction therapy. The objective of this study was to assess whether the change in cardiac output in association with preload-reduction therapy is predictable before treatment by analysis of mitral flow velocity patterns in patients with hypertensive heart failure. Changes in left ventricular volumes and cardiac output in association with preload-reduction therapy and Doppler echocardiographic parameters of the mitral flow velocity pattern before treatment were studied in 18 patients with hypertensive heart failure. Cardiac output increased in six patients with systolic dysfunction (fractional shortening < 25%). In the other 12 patients (those with normal systolic function), the changes in cardiac output were homogenous among the patients. In this subset there was a greater decrease in cardiac output in patients with a shorter deceleration time. Thus, analysis of deceleration time of the early diastolic filling wave before treatment may be useful in estimating the change in cardiac output following preload reduction in patients with hypertensive heart failure due to diastolic dysfunction.

Adult↗
PubMed1999

The effect of verapamil on left ventricular remodelling and diastolic function after acute myocardial infarction (the Verapamil Infarction Study on Remodelling and Relaxation--VISOR).

The VISOR is a double blind, randomized, placebo-controlled study aimed to assess the effects of early and prolonged administration of verapamil on the left ventricular geometry and diastolic function in patients with anterior acute myocardial infarction treated with thrombolysis. Patients with heart failure or ejection fraction < 45% were excluded. Within 12 hours from starting thrombolysis, 70 patients were given verapamil (5 mg/hour intravenously for the first 24 hours, followed by 120 mg t.i.d. perorally for 6 months) or equivalent placebo. Echocardiograms were performed on admittance, before discharge, after 3 months and 6 months. The following parameters were calculated: left ventricular volumes, ejection fraction, sphericity index, early (E) and late (A) transmitral peak flow velocities and time-velocity integrals with their ratios, deceleration time and half-time of E, isovolumic relaxation time (IVRT), and non-invasive time constant of ventricular relaxation (tau). The basal and the last available parameters were considered for statistical analysis. The effects of the treatment on the left ventricular volumes, ejection fraction, and sphericity index were not statistically relevant. Conversely, a reduction of E/A ratio (P < .05) and increases of A integral (P < .01), deceleration time and half-time of E, IVRT and tau (P < .05) were found in the placebo group and not in the verapamil group. No significant changes in the blood pressure, heart rate, PQ interval, and biochemical parameters were observed in the two groups. In conclusion, in patients with a thrombolysed anterior acute myocardial infarction and preserved systolic function, verapamil can prevent alterations of the diastolic function in absence of effect on ventricular remodelling, and has a good safety profile.

Calcium Channel Blockers↗
PubMed2001

Stabilizing and solubilizing effects of sulfobutyl ether beta-cyclodextrin on prostaglandin E1 analogue.

PURPOSE: Parent cyclodextrins are known to accelerate the degradations such as dehydration and isomerization of E-type prostaglandins in neutral and alkaline solutions. The objective of this study was to attempt the stabilization and solubilization of E1-type prostaglandin analogue in aqueous solution by biocompatible cyclodextrin derivatives. METHODS: The interaction of an E1-type prostaglandin, methyl 7-[(1R,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-4-(m-methoxymethylphenyl)1-butenyl]-5-oxocyclopentyl]-5-thiaheptanoate (MEester) with cyclodextrins (CyDs) was studied by spectroscopies and the solubility method. The degradation of MEester was monitored by high-performance liquid chromatography. RESULTS: 1H-nuclear magnetic resonance spectroscopic studies indicated that MEester forms 1:1 inclusion complexes with alpha-, beta-, and gamma-CyDs in solutions, where alpha-CyD interacts with the a-side chain containing methyl ester moiety of the drug, whereas beta- and gamma-CyDs preferentially include around the five-membered ring and both side chains of the drug. Parent alpha-CyD and hydrophilic derivatives, such as 2-hydoxypropyl-alpha- and -beta-CyDs, sulfobutyl ether beta-CyD (SBE-beta-CyD) and maltosyl beta-CyD showed higher solubilizing abilities against MEester over parent beta- and gamma-CyDs. SBE-beta-CyD and 2,6-dimethyl-beta-CyD (DM-beta-CyD) significantly decelerated the degradation of MEester, particularly the base-catalyzed dehydration, in neutral and alkaline solutions, whereas other CyDs accelerated the degradation. The acid-catalyzed degradation of MEester (pH < 3) was decelerated by the addition of CyDs, especially alpha-CyD. CONCLUSIONS: SBE-beta-CyD with low hemolytic activity and low toxicity is useful as a pharmaceutical carrier for the preparation of injectable MEester, because of its higher stabilizing and solubilizing effects on MEester. Furthermore, SBE-beta-CyD can be useful as a stabilizing agent for drugs, that are subject to base-catalyzed degradations, probably because of the electric repulsion between anionic charges of the sulfobutyl moiety and catalytic anionic species such as hydroxide ion.

Alprostadil↗
PubMed2002

Mechanisms involved in heart rate turbulence.

Proper understanding of the mechanisms involved in heart rate turbulence (HRT) may offer an explanation of why it is such a potent postinfarction risk stratifier. This article reviews the physiological background of ventriculophasic sinus arrhythmia-a phenomenon which shares some underlying physiological features with HRT including cardiac autonomic regulation. It is now believed that HRT is principally triggered by a transient loss of vagal efferent activity in response to the missed baroreflex afferent input due to ventricular premature beat-induced haemodynamically inefficient ventricular contraction. Studies are summarized which support more or less directly this hypothesis. The physiology of early acceleration and late deceleration of heart rate after a ventricular premature beat is discussed. Qualitatively different but otherwise quantitatively uniform postectopic dynamics of systolic blood pressure after ventricular premature beats is demonstrated in subjects with normal and abnormal left ventricular function. It is concluded that the slope of late deceleration of heart rate after ventricular premature beats can serve as a reasonable surrogate for baroreflex sensitivity.

Arrhythmia, Sinus↗
PubMed2000

Modeling prevention program effects on growth in substance use: analysis of five years of data from the Adolescent Alcohol Prevention Trial.

The efficacy of prevention programs is typically determined through analysis of covariance. To date, a growth curve modeling approach is not used extensively in program evaluation. However, for longitudinal data there are several advantages to using this approach as compared to methods comparing means at two time points in a piecemeal fashion. In this study, latent growth curve models were used to evaluate the effect of a program on the average level of drug use, rate of change (growth) of drug use, and acceleration or deceleration in the rate of change of drug use. The study relied on data from the Adolescent Alcohol Prevention Trial, a randomized longitudinal drug use prevention program. The program consists of drug use information, resistance skills training, and normative education components. Data regarding cigarette and alcohol use were collected over a 5-year period, grade 7 to grade 11. Students receiving the normative education program had significantly lower average levels of reported cigarette and alcohol use, lower rates of growth for reported cigarette and alcohol use, and less deceleration of reported levels of cigarette and alcohol use as compared with the control group. Growth curve analysis is a powerful and effective tool with which to model change and program efficacy.

Adolescent↗
PubMed2004

Impact of flow level on coronary flow velocity pattern. A doppler flow study in patients with first acute myocardial infarction.

Analysis of coronary flow velocity pattern has been used to assess microvascular function post acute myocardial infarction (AMI). This study sought to analyze whether the flow level has an impact on parameters of coronary flow velocity pattern. Parameters of coronary flow velocity pattern were determined at baseline and during increased flow due to maximal hyperemia induced by adenosine in 25 patients after PTCA for first AMI using Doppler flow wires. Patients were divided into those with depressed (global wall motion index (GWMI) > or = 1.5; n = 14) and those with preserved (GWMI < 1.5; n = 11) left ventricular (LV) function at 4 weeks. Coronary flow velocity pattern at rest was different between patients with depressed and patients with preserved LV function at follow-up. A difference in flow pattern between the groups remained at increased flow level. However, increase of flow altered parameters of flow pattern. Diastolic deceleration rate (DSR) increased for patients with preserved LV function (53.7+/-25.6 at baseline vs. 67.0+/-29.8 cm/s2 with adenosine) and depressed LV function (95.3+/-58.6 vs. 110.7+/-61.4 cm/s2, respectively, p = 0.0012). Induction of hyperemia resulted also in increased systolic and diastolic peak flow velocity and diastolic deceleration time (DDT). Higher flow had no impact on early systolic retrograde flow, systolic flow duration and diastolic-systolic velocity ratio (DSVR). The coronary flow velocity pattern allows prediction of LV function at 4 weeks after AMI. However, it should be considered that some parameters of the flow velocity pattern are affected by the coronary flow level.

Acute Disease↗
PubMed1993

Time-to-contact judgment in the locomotion of adults and preschool children.

The hypothesis of Lee (1976)--that approach and deceleration toward a surface can be controlled through the rate of change of the optic variable tau--was examined for natural human locomotion. In Experiment 1, 12 adults were asked to perform locomotor tasks that required running at speed and then decelerating so that either the hand or head made a controlled contact with a door. In Experiment 2, 12 preschool children performed a relay-running task that required similar control. In Experiment 3, 12 children and 12 adults ran with a stick as an extension to their arm length and performed the same task. The results supported Lee's hypothesis for the initial phase of approach, but subjects switched to a separate adjustment phase 2 to 3 arm lengths from the target. Children did not adopt an appropriate tau strategy for collision avoidance and appeared unable to modify their approach strategy to allow for a hand-held stick.

Acceleration↗
PubMed1985

Intraseptal scopolamine has differential effects on Pavlovian eye blink and heart rate conditioning.

The effects of intraseptal scopolamine hydrobromide injections on Pavlovian (classical) conditioning were evaluated, with tones used as the conditioned stimulus (CS) and a periorbital electric shock train as the unconditioned stimulus (UCS). Eye blink (EB) and heart rate (HR) conditioned responses were concomitantly recorded. Although injections of scopolamine into the medial septum impaired the acquisition of the Pavlovian conditioned eyelid reflex, these injections enhanced the magnitude of accompanying Pavlovian conditioned HR decelerations. However, scopolamine applied to the lateral septal area had no effect on EB conditioning, relative to the vehicle, but, like medial injections, enhanced the magnitude of the accompanying HR decelerations. These results are compatible with those of previous investigations: Medial septal dysfunction impairs somatomotor conditioning but leaves autonomic conditioning intact, and septal dysfunction produces a parasympathetic bias of the cardiovascular system.

Animals↗
PubMed1985

Dissociation of autonomic and behavioral components of conditioned fear during development in the rat.

Classical conditioning of heart rate (HR) was examined in unrestrained preweanling and weanling (16-, 19-, 21-, 25-, and 28-day-old) rats, with tone and light as the conditioned stimuli (CS) and electric shock as the unconditioned stimulus. The conditioned cardiac response was a sustained deceleration in HR which did not emerge until Day 21 for the tone CS and until Day 28 for the light CS. In contrast, when suppression of a behavioral response (running in a straight alley for dry suckling as reward) was used as the index of conditioning, the suppressive effects of the CS were evident around Day 16 for the tone and around Day 19 for the light. These findings indicate that during ontogenesis (a) the behavioral and autonomic responses to the same conditioned stimulus do not develop at the same pace, (b) the emergence of conditioned responses to tone and light stimuli parallel the sequential order in which the relevant sensory modalities achieve maturity (first audition, next vision), and (c) there is no clear-cut interdependence between development of the HR orienting response and conditionability of HR because unconditioned cardiac deceleration to both auditory and visual stimuli first appears about Day 16 in the developing rat, well before conditioned HR responses can be established to either stimulus.

Aging↗
PubMed1975

Cardiac activity and information processing: the effects of stimulus significance, and detection and response requirements.

In two experiments, measures of heart rate and electromyographic activity were obtained from 40 male undergraduates while they performed two series of trials involving a sequential information processing task. Each trial consisted of a warning light, three successive tones, and a responded light, separated by 6-sec intervals. In Experiment 1, subjects responded only if the three tones were of different frequencies. Acclerative heart-rate responses to the last tone increased as a function of the significance of that tone. Subsequent cardiac decelerations were only observed if the subject was preparing to make a response. These results were replicated in Experiment 2, in which subjects responded only if two of the preceding tones were of the same frequency. Electromyographic activity was not significantly affected by stimulus significance or response anticipation. The data indicate that cardiac acceleration and deceleration reflect two independent psychological processes, associated with information-processing and decision-making activity on the one hand, and preparatory activity on the other.

Adolescent↗