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Atropine unmasks bed-rest effect: a spectral analysis of cardiac interbeat intervals.

Bed-rest deconditioning is suspected to reduce cardiac reserve, possibly by impairing autonomic function. Heart rate response in normal subjects reveals considerable variability, reflected by a relatively broadband interbeat interval power spectrum. A reduction in this autonomically modulated variability would be predicted to cause a narrowing of the spectrum. We retrospectively analyzed data from 10 aerobically conditioned men (age range 35-49 yr) who had undergone orthostatic tolerance testing with lower body negative pressure pre-bed rest and after 7-10 days of bed rest, while on placebo and after intravenous atropine. Spectra were derived by Fourier analysis of 128 interbeat interval data sets. Spectral power was estimated by computing the root-mean-square (rms) values (mean +/- SD) for the band encompassing the 2nd to 64th harmonics from subjects with a sufficient number of beats: placebo rms is 93 +/- 33 ms for pre-bed rest and 84 +/- 38 ms for bed rest (NS, n = 6); atropine rms is 63 +/- 24 ms for pre-bed rest and 40 +/- 23 ms for bed rest (P less than 0.01; n = 7). These data suggest that atropine "unmasks" a deconditioning effect of bed rest in athletic men, evidenced by a reduction in interbeat interval spectral power not apparent with placebo. Spectral analysis offers a useful means of quantitating the effects of bed-rest deconditioning and autonomic perturbations on cardiac dynamics.

Adult↗

Correlations between frequency-domain HRV indices and lagged Poincaré plot width in healthy and diabetic subjects.

The conventional Poincaré plot for heart rate variability (HRV) analysis is a scatterplot of successive (lag 1) pairs of RR intervals (intervals between heartbeats), and its width (SD1) is considered a measure of short-term variability. It has been shown that SD1 correlates better with HF than with LF (high- and low-frequency bands of the spectrum, respectively). Our aim was to assess how these correlations were affected when SD1 was obtained for longer lags. 10 min ECGs were used to construct Poincaré plots with lags of 1-10 heartbeats in two groups of subjects, one with normal HRV and the other with impaired HRV (control and diabetic groups respectively, N = 15 each). SD1 was quantified for these subjects and HRV spectral indices were estimated. The diabetic group had lower LF, HF and SD1 than the control group (p < 0.05). In both groups, SD1 tended to increase as the lag increased. In the control group, SD1 for lags 1 and 2 was highly correlated with HF (r(s) > 0.9), while SD1 for lags 4 correlated better with LF (r(s) 0.9) than with HF (0.65 <or= r(s) <or= 0.73). However, in the diabetic group, the correlation results did not change in that way for different lags (correlation results between HF and SD1: r(s) 0.95 for lags 1-10). In conclusion, the comparative strength of the correlations between lagged Poincaré widths and spectral indices might be useful to distinguish normal from pathological HRV.

Adult↗

Spectral shape discrimination by hearing-impaired and normal-hearing listeners.

The ability to discriminate between sounds with different spectral shapes was evaluated for normal-hearing and hearing-impaired listeners. Listeners discriminated between a standard stimulus and a signal stimulus in which half of the standard components were decreased in level and half were increased in level. In one condition, the standard stimulus was the sum of six equal-amplitude tones (equal-SPL), and in another the standard stimulus was the sum of six tones at equal sensation levels re: audiometric thresholds for individual subjects (equal-SL). Spectral weights were estimated in conditions where the amplitudes of the individual tones were perturbed slightly on every presentation. Sensitivity was similar in all conditions for normal-hearing and hearing-impaired listeners. The presence of perturbation and equal-SL components increased thresholds for both groups, but only small differences in weighting strategy were measured between the groups depending on whether the equal-SPL or equal-SL condition was tested. The average data suggest that normal-hearing listeners may rely more on the central components of the spectrum whereas hearing-impaired listeners may have been more likely to use the edges. However, individual weighting functions were quite variable, especially for the HI listeners, perhaps reflecting difficulty in processing changes in spectral shape due to hearing loss. Differences in weighting strategy without changes in sensitivity suggest that factors other than spectral weights, such as internal noise or difficulty encoding a reference stimulus, also may dominate performance.

Adult↗

Absorption spectra and linear dichroism of some amphibian photoreceptors.

Absorption spectra and linear dichroism of dark-adapted, isolated photoreceptors of mudpuppies, larval and adult tiger salamanders, and tropical toads were measured microspectrophotometrically. Spectral half-band width, dichroic ratio, and transverse specific density were determined using averaged polarized absorptance spectra and photomicrographs of seven types of rod outer segments. Two classes of cells were found, one with higher specific density and dichroic ratio, associable with the presence of rhodopsins, the other, lower in both quantities, associable with porphyropsins. Relationships were derived to calculate the product of molar concentration and extinction coefficient (CEmax) from specific density and dichroic ratio. By utilizing the hypothesis of invariance of oscillator strengths and measured half-band widths, Emax values were independently determined, permitting the calculation of C. The pigment concentration for all cells tested was about 3.5 mM. The broadness of green rod pigment spectra is correlated with reduced molar absorptivity and reduced cellular specific density. Estimation of physiological spectral sensitivities is discussed. Based on dichroic ratio considerations, a model is proposed for the orientation of retinals in situ which could account for the apparent degree of alignment of transition moments. In the chosen orientation, the ring portion of conjugation becomes primarily responsible for axial extinction. Reduced dichroism of dehydroretinal-bearing cells can thus result from the extended ring conjugation of chromophores. Some inferences derivable from the model are discussed.

Ambystoma↗

Position control of intravascular Doppler guidewire: concept of a tracking indicator and its clinical implications.

Intracoronary Doppler ultrasound guidewires (DGW) utilize a wide ultrasound beam combined with a measurement of the spectral peak velocity to estimate the spatial peak velocity within a blood vessel. However, the spectral peak velocity may underestimate the true spatial peak velocity if the DGW is not properly positioned. The purpose of this study was to find a Doppler-derived parameter that would aid in the optimal positioning of the DGW within the vessel lumen. We studied the relationship between the time-averaged, spectral-peak velocity (APV) and the normalized first Doppler moment (M1/M0) to develop a DGW position indicator and demonstrate its clinical utility. In vitro, heparinized, human whole blood with a hematocrit of 45% was directed from a reservoir via a roller pump into four serially connected straight silicone tubes of known diameter (2.5, 3.0, 3.5, 4.0 mm). A DGW was inserted into the tubes where simultaneous APV and M1/M0 measurements were obtained for flow rates ranging from 49 to 316 ml/min. Optimal positioning of the DGW was identified at the position where maximum APV and M1/M0 were obtained. With optimal positioning the correlation between APV and M1/M0 was good (APV = 1.62 M1/M0 + 5.0; R2 = 0.98). Importantly, this correlation showed no dependence on the tube diameter. In vivo, in four patients APV and M1/M0 measurements were obtained in 16 coronary artery segments in one left anterior descending, two circumflex, and two right coronary arteries. In 10 vessel segments, there was no discrepancy between the measured and expected M1/M0 after positioning the DGW with help of the Doppler signal quality only. In six vessel segments, repeat DGW positioning using M1/M0 was necessary, yielding an average increase of APV of 20% (7-38%). We conclude that DGW positioning can be optimized using the correlation between APV and M1/M0 as a reference. For any given APV value, there is a corresponding expected value for M1/M0 under the condition of optimal positioning. Any discrepancy between the measured and expected values for M1/M0 then indicates suboptimal positioning.

Blood Flow Velocity↗

An isotope labeling strategy for quantifying the degree of phosphorylation at multiple sites in proteins.

A procedure for determining the extent of phosphorylation at individual sites of multiply phosphorylated proteins was developed and applied to two polyphosphorylated proteins. The protocol, using simple chemical (Fischer methyl-esterification) and enzymatic (phosphatase) modification steps and an accessible isotopic labeling reagent (methyl alcohol-d(4)), is described in detail. Site-specific phosphorylation stoichiometries are derived from the comparison of chemically identical but isotopically distinct peptide species analyzed by microspray liquid chromatography-mass spectrometry (microLC-MS) using a Micromass Q-TOF2 mass spectrometer. Ten phosphorylation sites were unambiguously identified in tryptic digests of both proteins, and phosphorylation stoichiometries were determined for eight of the ten sites using the isotope-coded strategy. The extent of phosphorylation was also estimated from the mass spectral peak areas for the phosphorylated and unmodified peptides, and these estimates, when compared with stoichiometries determined using the isotope-coded technique, differed only marginally (within approximately 20%).

Amino Acid Sequence↗

Evaluation of the spectral fit algorithm as functions of frequency range and deltakaeff.

Considerable effort has been directed at quantifying the properties of the tissue microstructure (i.e., scatterer correlation length) to diagnose disease and monitor treatment. In vivo assessments have had limited success due to frequency-dependent attenuation along the propagation path (i.e., total attenuation) masking the frequency dependence of the scattering from the tissue microstructure. Previously, both total attenuation and scatterer correlation length, given by the effective radius, were solved simultaneously by a two-parameter minimization of the mean squared error between a reference spectrum, modified by the attenuation and scatterer effective radius, and the backscattered waveforms using an algorithm termed the spectral fit algorithm. Herein, the impact of frequency range (largest frequency minus smallest frequency) and deltakaeff (largest kaeff value minus smallest kaeff value; k is wave number and aeff is scatterer effective radius) used by the spectral fit algorithm on estimating the scatterer effective radius, and total attenuation was assessed by computer simulations while excluding frequencies of the backscattered power spectrum dominated by electronic noise. The simulations varied the effective radius of the scatterers (5 microm to 150 microm), the attenuation of the region (0 to 1 dB/cm-MHz), the bandwidth of the source, and the amount of electronic noise added to the radio frequency (rf) waveforms. The center frequency of the source was maintained at 8 MHz. Comparable accuracy and precision of the scatterer effective radius were obtained for all the simulations whenever the same deltakaeff was used to obtain the estimates. A deltakaeff of 1 gave an accuracy and precision of approximately 15% +/- 35%, and a width of 1.5 gave an accuracy and precision of approximately 5% +/- 15% consistently for all of the simulations. Similarly, the accuracy and precision of the total attenuation estimate were improved by increasing the frequency range used by the spectral fit algorithm.

Algorithms↗

Prevalence of spontaneous otoacoustic emissions in adults revisited.

The potential influence of spectral analysis factors on estimates of the prevalence of spontaneous otoacoustic emissions (SOAE) was explored. The detection of a SOAE was influenced by two spectral factors: (1) the frequency resolution of the spectrum, and (2) the number of spectral averages. For 15 different combinations of these two factors, the estimate of the prevalence of SOAEs for females ranged from 64 to 81% and, for males, from 39 to 55%. Combining across all 15 combinations, 83% of the females and 62% of the males were judged to have SOAEs. These results provide a context for understanding the inconsistencies in previous estimates of the prevalence of SOAEs and underscore the need to employ many different spectral analyses because some SOAEs are only detected when the spectral analyses are suitably tailored.

Adult↗

Solid state 13C NMR of unlabeled phosphatidylcholine bilayers: spectral assignments and measurement of carbon-phosphorus dipolar couplings and 13C chemical shift anisotropies.

The direct measurement of 13C chemical shift anisotropies (CSA) and 31P-13C dipolar splitting in random dispersions of unlabeled L alpha-phase phosphatidylcholine (PC) has traditionally been difficult because of extreme spectral boradening due to anisotropy. In this study, mixtures of dimyristoyl phosphatidylcholine (DMPC) with three different detergents known to promote the magnetic orientation of DMPC were employed to eliminate the powder-pattern nature of signals without totally averaging out spectral anisotropy. The detergents utilized were CHAPSO, Triton X-100, and dihexanoylphosphatidylcholine (DHPC). Using such mixtures, many of the individual 13C resonances from DMPC were resolved and a number of 13C-31P dipolar couplings were evident. In addition, differing line widths were observed for the components of some dipolar doublets, suggestive of dipolar/chemical shift anisotropy (CSA) relaxation interference effects. Oriented sample resonance assignments were made by varying the CHAPSO or DHPC to DMPC ratio to systematically scale overall bilayer order towards the isotropic limit. In this manner, peaks could be identified based upon extrapolation to their isotropic positions, for which assignments have previously been made (Lee, C.W.B., and R.G. Griffin. 1989. Biophys. J. 55:355-358; Forbes, J., J. Bowers, X. Shan, L. Moran, E. Oldfield, and M.A. Moscarello. 1988. J. Chem. Soc., Faraday, Trans. 1 84:3821-3849). It was observed that the plots of CSA or dipolar coupling versus overall bilayer order obtained from DHPC and CHAPSO titrations were linear. Estimates of the intrinsic dipolar couplings and chemical shift anisotropies for pure DMPC bilayers were made by extrapolating shifts and couplings from the detergent titrations to zero detergent. Both detergent titrations led to similar "intrinsic" CSAs and dipolar couplings. Results extracted from an oriented Triton-DMPC mixture also led to similar estimates for the detergent-free DMPC shifts and couplings. The results from these experiments were found to compare favorably with limited measurements made from pure L alpha PC. This detergent-based method for assigning spectra and for determining dipolar couplings and CSA in detergent-free systems should be extendable to other lipid systems. The resulting data set from this study may prove useful in future modeling of the structure and dynamics of DMPC bilayers. In addition, the fact that experiments utilizing each of the three detergents led to similar estimates for the spectral parameters of pure DMPC, and the fact that spectral parameter versus bilayer order plots were linear, indicate that the averaged conformation and dynamics of DMPC in the presence of the three detergents are very similar to those of pure L alpha DMPC.

Biophysical Phenomena↗

A statistical analysis of NMR spectrometer noise.

Estimation of NMR spectral parameters, using e.g. maximum likelihood methods, is commonly based on the assumption of white complex Gaussian noise in the signal obtained by quadrature detection. Here we present a statistical analysis with the purpose of discussing and testing the validity of this fundamental assumption. Theoretical expressions are derived for the correlation structure of the noise under various conditions, showing that in general the noise in the sampled signal is not strictly white, even if the thermal noise in the receiver steps prior to digitisation can be characterised as white Gaussian noise. It is shown that the noise correlation properties depend on the ratio between the sampling frequency and the filter cut-off frequency, as well as the filter characteristics. The theoretical analysis identifies conditions that are expected to yield non-white noise in the sampled signal. Extensive statistical characterisation of experimental noise confirms the theoretical predictions. The statistical methods outlined here are also useful for residual analysis in connection with validation of the model and the parameter estimates.

Magnetic Resonance Spectroscopy↗

Secondary structure and temperature behavior of the acetylcholine receptor by Fourier transform infrared spectroscopy.

Fourier transform infrared spectroscopy (FT-IR) was used to test the secondary structure of purified acetylcholine receptor membranes from Torpedo californica. The secondary structure was estimated using the spectral features observed in the structure sensitive region of amide I and amide I' (between 1600 and 1700 cm-1), taking advantage of Fourier self-deconvolution and second-derivative techniques along with least-squares band fitting procedures. At least six different amide I' band components could be resolved in D2O and were tentatively assigned to beta-structures (1680 and 1636 cm-1), alpha-helices (1657 cm-1), aperiodic structures and/or distorted helices (1646-1648 cm-1), and turns (1690 and 1668 cm-1), respectively. The beta-band around 1637 cm-1, in particular, turned out to be complex since it reproducibly exhibited weak features near 1630 and 1627 cm-1, thereby suggesting the presence of different chain interacting beta-structures. The band near 1657 cm-1 was assigned to alpha-helices which transverse the membrane bilayers, while 1646-1648-cm-1 component was tentatively attributed to aperiodic structures and alpha-helices localized within the "globular head" of the receptor protein protruding from the membrane surface into the surrounding water. Least-squares band fitting procedures were applied in order to estimate relative amounts of secondary structures. The results suggest 36-43%, 32-33%, 14-24%, and 18-19% for beta-, alpha-helical, turn, and "rest" structures, respectively. Additionally, the temperature- and time-dependent variations of the secondary structure was tested by evaluating the changes of amide I and amide II band components of receptor membranes dispersed in H2O and D2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Parameter estimation in a stochastic model of the tubuloglomerular feedback mechanism in a rat nephron.

A key parameter in the understanding of renal hemodynamics is the gain of the feedback function in the tubuloglomerular feedback mechanism. A dynamic model of autoregulation of renal blood flow and glomerular filtration rate has been extended to include a stochastic differential equations model of one of the main parameters that determines feedback gain. The model reproduces fluctuations and irregularities in the tubular pressure oscillations that the former deterministic models failed to describe. This approach assumes that the gain exhibits spontaneous erratic variations that can be explained by a variety of influences, which change over time (blood pressure, hormone levels, etc.). To estimate the key parameters of the model we have developed a new estimation method based on the oscillatory behavior of the data. The dynamics is characterized by the spectral density, which has been estimated for the observed time series, and numerically approximated for the model. The parameters have then been estimated by the least squares distance between data and model spectral densities. To evaluate the estimation procedure measurements of the proximal tubular pressure from 35 nephrons in 16 rat kidneys have been analyzed, and the parameters characterizing the gain and the delay have been estimated. There was good agreement between the estimated values, and the values obtained for the same parameters in independent, previously published experiments.

Animals↗

Estimation of frequency shift in cardiovascular variability signals.

Spectral analysis of heart rate (HR) and blood pressure (BP) oscillations has traditionally concentrated on spectral power, although a shift in spectral frequency characterises the variability better than power in some cases. Experimental data were obtained from 14 healthy males in control and pharmacological blockade conditions. When parasympathetic control was reduced, LF oscillations of HR and BP tend to shift towards lower frequencies. Three parameters were compared to estimate the spectral shift within the low frequency (LF, 0.04-0.15 Hz) band in HR and BP variability: mean (fmean), median (fmed), and central frequency (fc). Parameter variance (pSTD) and sensitivity to noise were also estimated using realistic HR, systolic BP (SBP) and diastolic BP (DBP) data. fmean showed the lowest parameter variance both for an autoregressive (AR) method (SBP pSTD 3.1 vs 4.8 vs 4.7 mHz for fmean, fmed and fc, respectively; p<0.001) and an FFT method (SBP pSTD 4.7 vs 7.7 mHz for fmean and fmed, respectively; p<0.001). Furthermore, fmean was least sensitive to noise. fc showed the poorest performance being especially sensitive to noise. To analyse the spectral shift, fmean is preferred, since it performs better than fc, which has been used in most previous studies. To quantify the frequency of oscillations in cardiovascular signals, the mean frequency is recommended, with analyses across different spectral bands.

Adrenergic beta-Antagonists↗

Confidence images for MR spectroscopic imaging.

Automated spectral analysis and estimation of signal amplitudes from magnetic resonance data generally constitutes a difficult nonlinear optimization problem. Obtaining a measure of the degree of confidence that one has in the estimated parameters is as important as the estimates themselves. This is particularly important if clinical diagnoses are to be based on estimated metabolite levels, as in applications of MR Spectroscopic Imaging for human studies. In this report, a standard method of obtaining confidence intervals for nonlinear estimation is applied to simulated data and short-TE clinical proton spectroscopic imaging data sets of human brain. So-called "confidence images" are generated to serve as visual indicators of how much trust should be placed in interpretation of spatial variations seen in images derived from fitted metabolite parameter estimates. This method is introduced in a Bayesian framework to enable comparison with similar techniques using Cramer-Rao bounds and the residuals of fitted results.

Bayes Theorem↗

Peculiar manifestation of the dipole-dipole interaction between non-Kramers paramagnetic centers as studied by tunable high-frequency EPR spectroscopy.

EPR spectral shape of non-Kramers paramagnetic centers (PCs) is theoretically analyzed under conditions of saturation. The analysis is performed in a model that includes the spectral diffusion process induced by a random modulation of the dipole-dipole interaction of the paramagnetic centers, by reorientations of magnetic moments. It is shown that around zero magnetic field, a 'hole' might appear in the EPR spectrum. We have also studied experimentally the saturation behavior of the EPR spectrum in Cr2+: Mg2SiO4. The experimental results are interpreted in the framework of the model considered. By comparing simulated and experimental spectra, the paramagnetic relaxation times and the characteristic rate of the spectral diffusion are estimated.

Journal Article↗

Water-suppressed one-dimensional 1H NMR chemical shift imaging of the heart before and after regional ischemia.

This study tests the hypothesis that brief periods of ischemia result in an increase in myocardial lipids during early reperfusion. We conducted 1H NMR spectroscopy to serially measure myocardial lipids before and after regional ischemia. Localized 1H NMR spectra (spatial resolution of 1.25 mm) were obtained using a one-dimensional chemical shift imaging technique. Two regions, the subendocardium and the subepicardium, were estimated by summing spectral areas from three slices (3.75 mm). Two groups of dogs that underwent a 45 min ischemia and 4 h reperfusion were studied: a group in which the myocardium beneath the surface coil underwent ischemia and reperfusion; and a group in which the ischemic event was distant from the tissue under the surface coil. Microsphere measurements showed significant blood flow reductions in the subepicardium and subendocardium in the ischemic zones during coronary occlusion. Flow returned to baseline values during reperfusion. In the ischemic zone group, the subendocardium, the triglyceride resonance areas decreased by 24% (p < 0.05) during reperfusion. However, subepicardial triglyceride areas were unchanged. Subendocardial creatine areas were also unchanged. The non-ischemic zone group subendocardial triglycerides decreased by 33% (p < 0.05) following ischemia and reperfusion in the remote region. In contrast to the ischemic group, the subepicardial triglyceride resonance areas decreased by 42% (p < 0.05). Subendocardial creatine areas were unchanged. These data show that triglycerides of the ischemic-reperfused subendocardium do not increase during 4 h of reperfusion. Furthermore, they show that the triglycerides resonance areas of the non-ischemic region decrease following remote ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The automated analysis of data from single ionic channels.

The development of single channel recording has brought with it the need to analyse enormous amounts of data. The data analysis is time consuming and subject to observer biases since the events are random in time and are contaminated with uncorrelated noise. We have developed a heuristic pattern recognition program which identifies with high precision single channel currents and rejects contaminating noise. The program interactively provides for a variety of amplitude and duration measures. Analysis is flexible and rapid: a file containing over 10,000 events can be analysed in under 2 h. Specific detection features include variable lowpass filtering, automatic baseline restoration, and adaptive amplitude thresholds. A record is analysed through duration histograms, binomial estimates of the number of active channels present, cross-correlation estimates between parameters, spectral analysis of events and background noise, and stationarity of mean channel current. The graphic output facilities can plot raw data (after filtering and baseline restoration) with the idealized signal superimposed or with detected events underlined. A batch processing facility has been included to allow processing of data during periods of low computer demand.

Animals↗

Cortical short-term fatigue effects assessed via rhythmic brain-muscle coherence.

This study is aimed at assessing the short-term effects of muscular fatigue on the sensorimotor areas organization in the left and right hemispheres. Magnetoencephalographic (MEG) and electromyographic (EMG) activities were simultaneously recorded during the execution of a non-fatiguing motor task, performed before and after a task known to induce muscle fatigue (Fatigue). Coherence between cerebral and muscular rhythms as well as cerebral and muscular rhythms spectral densities were estimated during this non-fatiguing task and at rest. The MEG-EMG coherence in the beta band (13-32 Hz) was higher after than before Fatigue. The background activity reduction during contraction with respect to rest (i.e. the cerebral reactivity) was less evident after than before Fatigue in the gamma (33-45 Hz) and beta bands. When differentiating subjects on the base of Fatigue endurance times, while a huge inter-subject variability was found, an evident intra-subject similarity was observed for left and right arms, suggesting that resistance to fatigue is more an individual ability than a motor skill differentiated for the dominant and non-dominant side. In conclusion, signs of a more selective neural recruitment, more coupled with muscular activity, appeared as short-term effects of muscular fatigue in primary sensorimotor cortical areas. Evidence suggested that the reduction of cortical recruitment and the increased cortico-muscular coupling are distinct mechanisms.

Adult↗