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Comparison of the usefulness of Doppler-derived deceleration time versus plasma brain natriuretic peptide to predict left ventricular remodeling after mechanical revascularization in patients with ST-elevation acute myocardial infarction and left ventricular systolic dysfunction.

The correlation between Doppler deceleration time (DT) and brain natriuretic peptide (BNP) and their predictive value for detecting left ventricular (LV) remodeling in patients who are treated with primary percutaneous intervention for infarction and LV dysfunction are unknown. Fifty-six patients (64 +/- 12 years of age; 11 women) who had a first ST-segment elevation myocardial infarction and systolic dysfunction that was successfully treated with direct primary coronary intervention underwent 2-dimensional Doppler echocardiographic and plasma BNP evaluation at days 1 and 3 and 1 and 6 months after the index infarction. Repeat coronary angiograms were obtained at 1 and 6 months. Because of previous consistent evidence, 3 days after the index infarction was the time point of comparison between BNP and DT values. Echocardiographic LV remodeling was defined as an increase in end-diastolic volume index above baseline values of 2 x SD. Ventricular remodeling occurred in 20 patients (36%). Multivariate analyses that included BNP level, Doppler DT, echocardiographic measurements of systolic function, peak creatine kinase, and anterior infarct location showed Doppler DT to be the only predictor of LV remodeling (odds ratio 0.963, 95% confidence interval 0.936 to 0.990, p = 0.008). The optimal cutoff for DT in the prediction of 6-month LV remodeling was <136 ms (sensitivity 75%, specificity 97%, accuracy 81%, area under receiver-operating characteristic curve 0.90). Thus, in patients who have a first ST-segment elevation myocardial infarction and LV systolic dysfunction that is successfully treated with primary percutaneous coronary intervention, Doppler-derived DT 3 days after index infarction is more effective than BNP level in detecting patients who are at higher risk for 6-month LV remodeling.

Aged↗

Reduced coenzyme Q10 supplementation decelerates senescence in SAMP1 mice.

The SAMP1 strain is a mouse model for accelerated senescence and severe senile amyloidosis. We determined whether supplementation with coenzyme Q10 (CoQ10) could decelerate aging in SAMP1 mice and its potential role in aging. Plasma concentrations of CoQ10 and CoQ9 decreased with age in SAMP1 but not in SAMR1 mice. Supplementation with reduced CoQ10 (CoQH2, 250 mg/kg/day) for one week increased plasma CoQ10 concentrations, with an accompanying decrease in plasma CoQ9 concentrations. In two series of experiments, lifelong supplementation with CoQH2 decreased the senescence grading scores from 10 to 14 months, 7 to 15 months, and at 17 months of age. The body weight of female mice increased from 2 to 10 months of age versus controls in the second series of experiments. Lifelong CoQH2 supplementation did not prolong or shorten the lifespan, nor did it alter the murine senile amyloid (AApoAII) deposition rate or cancer incidence. In the second series of experiments, urinary levels of 8-hydroxydeoxyguanosine did not change with age or long-term supplementation with CoQH2. Urinary levels of acrolein (ACR)-lysine adduct increased significantly with age in SAMP1 mice; however, CoQH2 had no effect. Thus, lifelong dietary supplementation with CoQH2 decreased the degree of senescence in middle-aged SAMP1 mice.

Aging, Premature↗

Velamentous cord insertion and atypical variable decelerations with no accelerations.

OBJECTIVES: To examine intrapartum fetal heart rate (FHR) patterns in the presence of velamentous cord insertion (VCI). METHODS: The site of cord insertion was determined in 1460 women on antenatal ultrasonographic and postnatal examinations. Each of 24 women with pregnancies complicated with VCI was matched at the onset of labor with 10 women who had a normal pregnancy, and FHR patterns were analyzed for both cases and controls. RESULTS: Compared with controls, cases of variable decelerations with no accelerations (VDNA) during the first and second stages of labor were more frequent in women with VCI (first stage: 25% vs. 5.1%, second stage: 65.0% vs. 21.7%, P < 0.001). The adjusted odds ratio associated with VDNA occurrence in women with VCI was 3.83 (95% confidence interval [CI]: 1.51-9.72, P = 0.005). The mean odds ratio associated with length of aberrant vessels in women with VCI plus VDNA was 1.38 (95% CI: 1.04-1.83, P = 0.026). CONCLUSION: Pregnancies complicated with VCI are associated with a higher rate of VDNA.

Adult↗

Doppler-derived mitral deceleration time as a strong prognostic marker of left ventricular remodeling and survival after acute myocardial infarction: results of the GISSI-3 echo substudy.

OBJECTIVES: The goal of this study was to assess the impact of left ventricular (LV) diastolic filling on remodeling and survival after acute myocardial infarction (AMI). BACKGROUND: Little is known regarding the link between LV filling, its changes over time, and six-month remodeling and late survival in uncomplicated AMI. METHODS: Doppler mitral profile, end-diastolic volume index (EDVi) and end-systolic volume index (ESVi), ejection fraction (EF), and wall motion abnormalities (%WMA) were evaluated in 571 patients from the GISSI-3 Echo substudy at baseline, pre-discharge, and six months after AMI. Patients with baseline early mitral deceleration time (DT) 130 ms were assigned to the restrictive group (n = 147), and those with DT >130 ms to the nonrestrictive group (n = 424). RESULTS: Restrictive group patients had greater baseline ESVi and %WMA and lower EF than nonrestrictive group, and six-month greater LV dilation (EDVi, ESVi: p < 0.001 for EDVi and ESVi), smaller decrease in %WMA decrease (p < 0.01), and larger EF impairment (p < 0.008). Among the restrictive group, patients (n = 56) with pre-discharge persistent restrictive filling (n = 56) showed six-month greater LV enlargement (p < 0.001) and EF impairment (p < 0.009) than those (n = 91) with reversible restrictive filling. Baseline %WMA and EDVi, together with pre-discharge persistent restrictive filling, predicted severe (>20%) LV dilation. Four-year survival was 93% in nonrestrictive patients versus 88% in the restrictive group (p < 0.06), and 93% in pre-discharge reversible restrictive versus 79% in persistent restrictive (p < 0.0003). The single best predictor of mortality, by Cox analysis, was pre-discharge persistent restrictive filling (chi-square 14.88). CONCLUSIONS: Left ventricular dilation may occur even after uncomplicated AMI and may be paralleled by an improvement in LV filling. However, a baseline restrictive filling that persists at pre-discharge identifies more compromised patients at higher risk for six-month remodeling and four-year mortality.

Aged↗

Shortening of Doppler-derived deceleration time of early diastolic transmitral flow in the presence of pulmonary hypertension through ventricular interaction.

Deceleration time (DT) of the early transmitral flow velocity has recently been highlighted as a simple, noninvasive indicator of pulmonary arterial wedge pressure. In patients with pulmonary hypertension without left-sided heart disease, however, increased right ventricular pressure may result in an abnormal ventricular septal motion, which may impact on left ventricular (LV) early diastolic filling. We sought to determine if DT may be influenced by the severity of pulmonary hypertension in patients without left-sided heart disease. Doppler-derived transmitral flow and hemodynamic parameters were simultaneously assessed in 26 patients with pulmonary hypertension (primary pulmonary hypertension = 11; chronic thromboembolism = 15). Transmitral Doppler variables including DT were correlated with hemodynamics and LV deformity index measured in early diastole with 2-dimensional echocardiography. DT significantly correlated with the total pulmonary resistance (r = -0.70, p <0.001). Multivariate analysis revealed that DT was independently determined by total pulmonary resistance, but not by pulmonary arterial wedge pressure, heart rate, or patient's age in our study population. DT showed a correlation with LV deformity index (r = -0.74, p <0.001). These results indicate that DT may shorten in association with the severity of pulmonary hypertension and that the shortened DT in pulmonary hypertension may be attributable to right ventricular pressure overload which causes geometric changes.

Adult↗

Heart rate and blood pressure responses to umbilical cord compression in fetal lambs with special reference to the mechanism of variable deceleration.

We examined heart rate and blood pressure responses to umbilical cord compression in fetal lambs. Fetal heart rate (FHR) responses resembling variable deceleration occurred only after umbilical blood flow was reduced by at least 50%. These changes during partial cord occlusion varied directly with the reduced umbilical blood flow and were abolished by atropine; no significant changes in arterial pressure were observed. Complete cord occlusion caused severe bradycardia, a progressive increase in arterial pressure, and delayed recovery of FHR. With partial cord occlusion, the bradycardia was of chemoreceptor origin and was vagally mediated; with complete occlusion the bradycardia may have resulted from both chemoreceptor and baroreceptor stimulation. During prolonged partial cord occlusion, FHR decreased initially, then recovered to above control value; this occurred in the face of a significant acidosis. Thus, FHR responses to cord compression are dependent on the actual percentage of reduction in umbilical blood flow and on its duration.

Animals↗

Flash-induced turnover of the cytochrome bc1 complex in chromatophores of Rhodobacter capsulatus: binding of Zn2+ decelerates likewise the oxidation of cytochrome b, the reduction of cytochrome c1 and the voltage generation.

The effect of Zn2+ on the rates of electron transfer and of voltage generation in the cytochrome bc1 complex (bc1) was investigated under excitation of Rhodobacter capsulatus chromatophores with flashing light. When added, Zn2+ retarded the oxidation of cytochrome b and allowed to monitor (at 561-570 nm) the reduction of its high potential heme b(h) (in the absence of Zn2+ this reaction was masked by the fast re-oxidation of the heme). The effect was accompanied by the deceleration of both the cytochrome c(1) reduction (as monitored at 552-570 nm) and the generation of transmembrane voltage (monitored by electrochromism at 522 nm). At Zn2+ <100 microM the reduction of heme b(h) remained 10 times faster than other reactions. The kinetic discrepancy was observed even after an attenuated flash, when bc1 turned over only once. These observations (1) raise doubt on the notion that the transmembrane electron transfer towards heme b(h) is the main electrogenic reaction in the cytochrome bc1 complex, (2) imply an allosteric link between the site of heme b(h) oxidation and the site of cytochrome c1 reduction at the opposite side of the membrane, and (3) indicate that the internal redistribution of protons might account for the voltage generation by the cytochrome bc1 complex.

Bacterial Chromatophores↗

Decelerated degradation of short peptides by the 20S proteasome.

Based on a twelve residue master peptide comprising all five specific cleavage sites defined for the proteasome, a set of variant peptides was generated in order to probe specificity and to elucidate the mechanism which determines product size. It is shown that the rate of degradation by the 20S proteasome from Thermoplasma acidophilum depends critically on the length of the peptide substrate. Peptides of 14 residues and longer are degraded much faster than shorter peptides although the sites of cleavage remain unchanged. The decelerated degradation of peptides shorter than 14 residues explains the accumulation of products with an average length of seven to nine residues.

Amino Acid Sequence↗

Polylysine decelerates kinetics of negatively charged gramicidin channels as shown by sensitized photoinactivation.

Effect of a cationic polymer, poly(L-lysine), on the kinetic properties of ionic channels formed by neutral gramicidin A (gA) and its negatively charged analogue O-pyromellitylgramicidin (OPg) in a bilayer lipid membrane is studied using a method of sensitized photoinactivation. This newly developed method is based on the analysis of transmembrane current transients induced by a flash in the presence of a photosensitizer. It has been shown previously that the time course of the flash-induced current decrease in most cases follows a single exponential decay with an exponential factor (tau, the characteristic time of photoinactivation) that correlates well with the single-channel lifetime. Addition of polylysine does not affect tau for gA channels, but causes a substantial increase in tau for OPg channels. This effect is reversed by addition of polyacrylic acid. The deceleration of the photoinactivation kinetics is ascribed to electrostatic interaction of polylysine with OPg probably resulting in OPg clustering. The latter can stabilize the channel state by reducing the rotational and lateral mobility of OPg monomers and dimers, and thus increase the single channel lifetime.

Acrylic Resins↗

Cortical bone tissue resists fatigue fracture by deceleration and arrest of microcrack growth.

Knowledge of kinetics of fatigue crack growth of microcracks is important so as to understand the dynamics of bone adaptation, remodeling, and the etiology of fatigue-based failures of cortical bone tissue. In this respect, theoretical models (Taylor, J. Biomech., 31 (1998) 587-592; Taylor and Prendergast, Proc. Instn. Mech. Engrs. Part H 211 (1997) 369-375) of microcrack growth in cortical bone have predicted a decreasing microcrack growth rate with increasing microcrack length. However, these predictions have not been observed directly. This study investigated microcrack growth and arrest through observations of surface microcracks during cyclic loading (R=0.1, 50-80MPa) of human femoral cortical bone (male, n=4, age range: 37-40yr) utilizing a video microscopy system. The change in crack length and orientation of eight surface microcracks were measured with the number of fatigue cycles from four specimens. At the applied cyclic stresses, the microcracks propagated and arrested in generally less than 10,000 cycles. The fatigue crack growth rate of all microcracks decreased with increasing crack length following initial identification, consistent with theoretical predictions. The growth rate of the microcracks was observed to be in the range of 5x10(-5) to 5x10(-7)mmcycle(-1). In addition, many of the microcracks were observed not to grow beyond 150 microm and a cyclic stress intensity factor of 0.5MNm(-3/2). The results of this study suggest that cortical bone tissue may resist fracture at the microscale by deceleration of fatigue crack growth and arrest of microcracks.

Adaptation, Physiological↗

The relation between transmitral early filling wave deceleration time and the recovery of atrial contractility after electrical cardioversion of atrial fibrillation.

BACKGROUND: Electrical cardioversion of atrial fibrillation (AF) to sinus rhythm is associated with transient left atrial dysfunction and this phenomenon may lead to thrombus formation and embolic stroke. Delay of atrial mechanical function recovery may be related to ventricular diastolic function. OBJECTIVE: This study examined the effects of left ventricular diastolic function as well as the multiple clinical factors on the recovery of atrial systolic function after cardioversion for atrial fibrillation. METHODS: A total of 44 patients (28 male, 16 female, 61+/-18 years) with chronic AF (> or =1 month) underwent electrical cardioversion. Deceleration time of early filling wave (pre-CV EDT) on transmitral inflow obtained by using Doppler echocardiography before cardioversion and serial transmitral inflow Doppler variables were recorded through a 1 week study period in all patients. Various clinical (age, gender, the duration of AF) and echocardiographic variables (pre-CV EDT, left atrial dimension, left ventricular ejection fraction) were tested for an association with peak atrial filling wave velocity (VA) on day 1, 3 and 7 after cardioversion. RESULTS: EDT measured before cardioversion had a strong linear correlation with peak VA on every echocardiographic evaluation after cardioversion (Regression coefficient (R)=0.69, P<0.001; R=0.78, P<0.001 and R=0.83, P<0.001, on day 1, day 3 and day 7, respectively). The effect of left ventricular ejection fraction on peak VA was weaker than those of EDT. The duration of AF showed an inverse association with the recovery of atrial function, but this lost on multivariate analysis. None of the other parameters significantly correlated with peak VA after cardioversion. CONCLUSION: The recovery of atrial mechanical function after cardioversion, as assessed by peak VA on transthoracic Doppler echocardiography is mainly associated with the left ventricular diastolic function as measured by EDT, whereas the left ventricular systolic function relatively a small effect on this outcome. The duration of AF does not have any association with peak VA, possibly if it is chronic.

Analysis of Variance↗

[E wave deceleration time predicts left ventricular telediastolic pressure in acute myocardial infarction in patients with systolic dysfunction].

OBJECTIVES: Left ventricular end-diastolic pressure (LVEDP) is a useful parameter for the management of postinfarction patients. As the current methods of estimating LVEDP are invasive, the existence of non-invasive methods would be of great practical value. This study investigates the relation between LVEDP and Doppler parameters such as E wave deceleration time (EDT) and E/A ratio, at one month following an acute myocardial infarction. METHODS: Eighty-nine patients with a first acute myocardial infarction treated with thrombolytic agents were studied. Doppler-echocardiography at 29 +/- 3 days and cardiac catheterization at 30 +/- 4 days postinfarction were performed. According to the ejection fraction (EF), the patients were divided into group 1 (n = 17) with EF < 45%, and group 2 (n = 72) with EF > 45%. RESULTS: Overall, the E/A ratio showed a weak correlation with LVEDP (r = 0.32; p = 0.007), and EDT did not correlate with LVEDP. When patients from group 2 were analyzed, no correlation was found between LVEDP and either E/A or EDT. However, in patients from group 1, LVEDP strongly correlated with both EDT (r = -0.83; p = 0.00001) and E/A (r = 0.70; p = 0.003). Moreover, the sensitivity and specificity of an EDT of less than 150 ms in predicting a LVEDP > 20 mmHg was 100%. CONCLUSIONS: We conclude that at the first month after a myocardial infarction EDT provides a non-invasive and useful parameter for estimating LVEDP in patients with systolic dysfunction.

Aged↗

Decelerated rate of dendrite outgrowth from dopaminergic neurons in primary cultures from brains of hypoxanthine phosphoribosyltransferase-deficient knockout mice.

Lesch-Nyhan syndrome (LNS), caused by the complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT), is characterized by a neurological deficit, the etiology of which is still unclear. Evidence has accumulated indicating that it reflects dopamine deficiency associated with defective arborization of dopaminergic dendrites. We monitored the differentiation in vitro of dopaminergic neurons, cultured from HPRT-deficient knockout mice. The HPRT-deficient dopaminergic neurons exhibited a decelerated rate of outgrowth of dendrites in comparison to that of control neurons resulting, after 8 days in culture, in 32% smaller average total length of dendrites per neuron (P<0.025). The results suggest that the abnormal dendrite outgrowth in LNS reflects a defective developmental process.

Animals↗

Anticipation of oxidative damage decelerates aging in virgin female medflies: hypothesis tested by statistical modeling.

Empirical analysis of survival data obtained from large samples of Mediterranean fruit flies shows that the trajectory of the mortality rate for virgin females departs from that for females maintained in mixed sex cages. It increases, decelerates, reaches its maximum, declines and then increases again within the reproductive interval. Non-virgin females, however, display an early-age plateau instead of this dip. We assume that these deviations are produced by the interplay between changes in oxygen consumption associated with reproductive behavior and the antioxidant defense that acts against anticipated oxidative damage caused by reproduction. Since there are no data on antioxidant mechanisms in medflies available that explain the observed patterns of mortality, we develop a model of physiological aging based on oxidative stress theory, which describes age-related changes in oxygen consumption and in antioxidative capacity during the reproductive period. Using this model, we simulate virtual populations of 25,000 virgin and non-virgin flies, calculate the respective mortality rates and show that they practically coincide with those of experimental populations. We show that the hypothesis about the biological support of reproduction used in our model does not contradict experimental data. The model explains how the early-age dip and plateau might arise in the mortality rates of female medflies and why the male mortality pattern does not exhibit such deviations.

Aging↗

Decelerating flow ventilation effects in acute respiratory failure.

PURPOSE: The purpose of this article is to analyze the effect of a pressure-regulated volume-controlled ventilation mode on lung mechanics and gas exchange in patients with acute respiratory failure. MATERIALS AND METHODS: We ventilated 10 patients with two pressure-limited modes: pressure-controlled ventilation (PC) and pressure-regulated volume-controlled ventilation (PRVC) in random order, for 1 hour each. Patients were stabilized on volume-controlled ventilation (VC) for 30 minutes before, between, and at the end of PC and PRVC to reach baseline conditions. At the end of every VC period and at 30 and 60 minutes of PC and PRVC, respiratory mechanics, gasometrics, and hemodynamic parameters were collected. RESULTS: We found no significant differences between the three VC periods. Comparing VC with the two pressure-limited ventilation modes, peak pressure decreased from 29.4+/-9.1 cm H2O (VC) to 25.9+/-8.4 (PC 60 minutes) and 26.1+/-8.2 (PRVC 60 minutes), and PaCO2 decreased significantly from 38.6+/-3.1 mm Hg (VC) to 36.7+/-2.8 (PC 60 minutes) and 36.8+/-2.9 (PRVC 60 minutes). CONCLUSIONS: Pressure-limited ventilation allows mechanical ventilation for the same tidal volume as VC but results in a lower peak inspiratory pressure and a slightly lower PaCO2. The mechanism responsible for this gas exchange effect is unknown but is probably related to a better air distribution of the decelerated flow. The clinical relevance of this phenomenon remains to be established.

Acute Disease↗

Physiological significance of early deceleration time prolongation in asymptomatic elderly subjects.

BACKGROUND: Alterations in Doppler-derived diastolic filling patterns are common among elderly persons, but their physiological and prognostic significance remains uncertain, particularly in asymptomatic older persons without overt cardiac disease. This study was designed to determine whether early mitral inflow deceleration time (DT) prolongation is of physiological significance in asymptomatic elderly subjects. METHODS AND RESULTS: In 15 asymptomatic patients aged 60 to 93 years with no history of heart failure (HF) or edema, we performed two-dimensional and Doppler echocardiography and 60-minute head-out, isothermic water immersion to produce circulatory volume expansion. Plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured immediately before and after water immersion. Seven of 15 patients had a normal mitral early DT (160 to 240 milliseconds; group 1) and 8 of 15 patients had DT prolongation (> 240 milliseconds; group 2). Group 2 subjects had significantly smaller chamber sizes and increased relative wall thickness without increased left ventricular mass. Head-out water immersion produced greater increases in plasma ANP levels in group 2 subjects with longer DTs despite similar degrees of circulatory volume expansion in each group. In contrast, plasma BNP levels did not increase significantly with water immersion in either group. CONCLUSION: Early DT prolongation in asymptomatic elderly subjects is associated with increased relative wall thickness and enhanced ANP increments after central volume expansion. Such exaggerated responses suggest that, in the elderly, a prolonged DT has physiological significance and may represent a precursor to symptomatic diastolic HF, a condition known to be associated with advancing age.

Age Factors↗

Absence of cardiac deceleration in a signalled escape paradigm: a psychophysiological deficit in chronic schizophrenia.

Fourteen chronic male schizophrenic patients and six male control subjects were compared in an escape paradigm involving temporal warning of the presentation of an aversive tone stimulus to which an escape response was to be made. The characteristic heart rate deceleration shown immediately prior to the aversive stimulus by control subjects was absent in the schizophrenic group. Further features of this novel test paradigm distinguished the control and schizophrenic groups. This psychophysiological test procedure may be fruitful for schizophrenia research.

Acoustic Stimulation↗