Flutter in flow-limited collapsible tubes: a mechanism for generation of wheezes

We studied flutter in collapsible tubes as a possible mechanism for the generation of respiratory wheezes. The pressure-flow relationships and the wall oscillations of thick-walled [wall thickness (h)-to-lumen radius (r) ratio 1:1.7 to 1.3] self-supporting latex and Silastic tubes mounted between rigid pipes were measured. A high-impedance vacuum pump was connected to the downstream end. Upstream and downstream valves were used to control corresponding resistances. We found loud honking sounds and tube wall oscillations that occurred only when the tubes were buckled and flow limiting, i.e., when the flow became constant and independent of downstream driving pressure. The overall range of oscillatory frequencies was 260-750 Hz for airflow, presenting as sharp peaks of power on the frequency spectrum. The oscillatory frequencies (f) were higher at higher fluid velocities (u) and with narrower distance between opposing flattened walls (2b), resulting from increasing downstream suction pressure and the transmural pressure becoming more negative. The effect of u and b on f for a latex tube (h-to-r ratio 1:1.7) were found to be f = 228 + 0.021 (u/b). These relationships were valid throughout the range of oscillations in this tube (283-720 Hz) and with flow rates of 12-64 l/min. The experimental data were compared with predictions of the fluid dynamic flutter theory and the vortex-induced wall vibrations mechanism. We conclude that viscid flutter in soft tubes is the more probable mechanism for the generation of oscillations in the soft tube model and is a possible mechanism for the generation of respiratory wheezes.     

Separation of polystyrene microbeads using dielectrophoretic/gravitational field-flow-fractionation.

The characterization of a dielectrophoretic/gravitational field-flow-fractionation (DEP/G-FFF) system using model polystyrene (PS) microbeads is presented. Separations of PS beads of different surface functionalization (COOH and none) and different sizes (6, 10, and 15 microm in diameter) are demonstrated. To investigate the factors influencing separation performance, particle elution times were determined as a function of particle suspension conductivity, fluid flow rate, and applied field frequency and voltage. Experimental data were analyzed using a previously reported theoretical model and good agreement between theory and experiment was found. It was shown that separation of PS beads was based on the differences in their effective dielectric properties. Particles possessing different dielectric properties were positioned at different heights in a fluid-flow profile in a thin chamber by the balance of DEP and gravitational forces, transported at different velocities under the influence of the fluid flow, and thereby separated. To explore hydrodynamic (HD) lift effects, velocities of PS beads were determined as a function of fluid flow rate in the separation chamber when no DEP field was applied. In this case, particle equilibrium height positions were governed solely by the balance of HD lift and gravitational forces. It was concluded that under the experimental conditions reported here, the DEP force was the dominant factor in controlling particle equilibrium height and that HD lift force played little role in DEP/G-FFF operation. Finally, the influence of various experimental parameters on separation performance was discussed for the optimization of DEP/G-FFF.     

Frequency-dependent response of SI RA-class neurons to vibrotactile stimulation of the receptive field

Three types of experiment were carried out on anesthetized monkeys and cats. In the first, spike discharge activity of rapidly adapting (RA) SI neurons was recorded extracellularly during the application of different frequencies of vibrotactile stimulation to the receptive field (RF). The second used the same stimulus conditions to study the response of RA-I (RA) cutaneous mechanoreceptive afferents. The third used optical intrinsic signal (OIS) imaging and extracellular neurophysiological recording methods together, in the same sessions, to evaluate the relationship between the SI optical and RA neuron spike train responses to low- vs high-frequency stimulation of the same skin site. RA afferent entrainment was high at all frequencies of stimulation. In contrast, SI RA neuron entrainment was much lower on average, and was strongly frequency-dependent, declining in near-linear fashion from 6 to 200 Hz. Even at 200 Hz, however, unambiguous frequencyfollowing responses were present in the spike train activity of some SI RA neurons. These entrainment results support the "periodicity hypothesis" of Mountcastle et al. ( J Neurophysiol 32: 452-484, 1969) that the capacity to discriminate stimulus frequency over the range 5-50 Hz is attributable to the ability of SI RA pyramidal neurons to discharge action potentials in consistent temporal relationship to stimulus motion, and raise the possibility that perceptual frequency discriminative capacity at frequencies between 50 and 200 Hz might be accounted for in the same way. An increase in vibrotactile stimulus frequency within the range 6-200 Hz consistently resulted in an increase in RA afferent mean spike firing rate (M FR). SI RA neuron M FR also increased as frequency increased between 6 and 50 Hz, but declined as stimulus frequency was increased over the range 50-200 Hz. At stimulus frequencies > 100 Hz, and at positions in the RF other than the receptive field center (RF center ), SI RA neuron MFR declined sharply within 0.5-2s of stimulus onset and rebounded transiently upon stimulus termination. In contrast, when the stimulus was applied to the RF center, MFR increased with increasing frequency and tended to remain well maintained throughout the period of high-frequency stimulation. The evidence obtained in "combined" OIS imaging and extracellular microelectrode recording experiments suggests that SI RA neurons with an RF center that corresponds to the stimulated skin site occupy small foci within the much larger SI region activated by same-site cutaneous flutter stimulation, while for the RA neurons located elsewhere in the large SI region activated by a flutter stimulus, the stimulus site and RF center are different.     

Frequency-dependent contractile strength in mice over- and underexpressing the sarco(endo)plasmic reticulum calcium-ATPase

One of the prominent markers of end-stage heart failure at the molecular level is a decrease in function and/or expression of the sarcoplasmic reticulum ATPase protein [sarco(endo)plasmic reticulum calcium-ATPase, SERCA]. It has been often postulated that a decrease in SERCA pump activity can contribute in a major way to decreased cardiac function. To establish a functional relationship, we assessed how alterations in SERCA activity level affect basic contractile function in healthy myocardium devoid of other significant molecular changes. We investigated baseline contractile function, frequency-dependent activation, and beta-adrenergic response in ultrathin trabeculae isolated from hearts of mice overexpressing SERCA (transgenic, TG), underexpressing SERCA2a (heterozygous knockout, Het), and their respective wild-type (WT) littermates. At physiological temperature and frequency, compared with their respective WT littermates, SERCA1a mice displayed increased developed force at frequencies of 4-8 Hz ( approximately 90% increase at 4 Hz) and force equal to WT mice at 10-14 Hz. Force development at 4 Hz in presence of 1 muM isoproterenol was similar in TG and WT mice. In Het mice, developed force was nearly identical at the lower end of the frequency range (4-8 Hz) but slightly depressed at higher frequency (P < 0.05 at 14 Hz). In presence of 1 muM isoproterenol, developed force at 4 Hz was equal to that in WT mice. Compared with normal levels, increased SERCA activity enhanced force development only at subphysiological frequencies. A reduction in SERCA activity only showed a depression of force at the higher frequency range. Thus generalizations regarding the correlation between SERCA activity and contractility can be highly ambiguous, because this relationship is critically dependent on other factors including stimulation frequency.     

On the dynamics of a spherical scaffold in rotating bioreactors

We analyze the dynamics of a spherical scaffold in rotating bioreactors (or clinostats). The idealized clinostat environment consists of a purely rotational flow that is perpendicular to a gravitational field. We confirm through a detailed analytical study that lift effects considerably alter the position of the equilibrium point reached by the scaffolds in the (vertical) direction collinear to the gravitational field. This result holds for small particle and shear Reynolds numbers. Our analysis shows that the inertial lift effect is negligible in the horizontal direction. We show that for all rotations of practical interest, and for the range of particle Reynolds number smaller than unity, the vertical coordinate of the equilibrium point is strongly affected by consideration of lift effects. For light (heavy) particles, inclusion of lift in the formation forces the equilibrium position to be below (above) the horizontal plane that contains the axis of rotation. The equilibrium point for light particles is stable and therefore is observable experimentally. The equilibrium point for heavy particles is unstable. We also estimate the stress level applied to the scaffold and derive an algebraic expression that indicates that the stress level acting on the scaffold decreases with increasing shear Reynolds number.     

Flutter in collapsible tubes: a theoretical model of wheezes

A mathematical analysis of flow through a flexible channel is examined as a model of flow-induced flutter oscillations that pertain to the production of wheezing breath sounds. The model provides predictions for the critical fluid speed that will initiate flutter waves of the wall, as well as their frequency and wavelength. The mathematical results are separated into linear theory (small oscillations) and nonlinear theory (larger oscillations). Linear theory determines the onset of the flutter, whereas nonlinear theory determines the relationships between the fluid speed and both the wave amplitudes and frequencies. The linear theory predictions correlate well with data taken at the onset of flutter and flow limitation during experiments of airflow in thick-walled collapsible tubes. The nonlinear theory predictions correlate well with data taken as these flows are forced to higher velocities while keeping the flow rate constant. Particular ranges of the parameters are selected to investigate and discuss the applications to airway flows. According to this theory, the mechanism of generation of wheezes is based in the interactions of fluid forces and friction and wall elastic-restoring forces and damping. In particular, a phase delay between the fluid pressure and wall motion is necessary. The wave speed theory of flow limitation is discussed with respect to the specific data and the flutter model.     

Dependence of central airway resistance on frequency and tidal volume: a model study

The resistance of a hollow cast of human central airways was measured during true sinusoidal airflow oscillations over a wide range of frequencies (0.5-40 Hz) and for various flow amplitudes up to 8 l/s. Pressure and flow were measured in the trachea with high-performance transducers, digitized and averaged over 100 cycles. Data were studied at two points in the flow cycle: at peak inspiratory and expiratory flows and in the two neighborhoods around zero flow where airway resistance (Rv approximately equal to o) was taken as the average slope of the pressure-flow (P-V) curve in each zone. When data obtained near peak flow were plotted in terms of dimensionless pressure drop vs. peak Reynolds number (Rem) and compared with steady-state data, we found no difference up to 2 Hz as previously reported (Isabey and Chang, J. Appl. Physiol. 51: 1338-1348, 1981), a slight decay in pressure drop between 4 and 8 Hz, a frequency-dependent increase in peak flow resistance at high frequencies (10-40 Hz) governed by the Strouhal number alpha 2/Rem beyond alpha 2/Rem = 0.5. On the other hand RV approximately equal to o was found to increase relative to steady state as local acceleration increases, e.g., as peak flow increases at a fixed frequency; this differs from the classical linear theory of oscillatory flow in a long straight tube. To explain these results, we had to use, as in our previous study, an alternative expression for the Strouhal number, i.e., epsilon = L X A X (dV/dt)/V2 (where L and A are the length and cross-sectional area of the trachea and V is a constant flow range over which resistance around flow reversal was computed), which accurately reflects the ratio of local acceleration [d(V/A)/dt)] to convective acceleration [(V/A)2/L] in developing branching flow. Finally, to delineate the regions of dominance of each of the dimensionless parameters, we compiled frequency-tidal volume diagrams for peak flows as well as for reversal. Epsilon, which is negligible near peak flows, appeared to govern the oscillatory P-V relationship near flow reversal in a transitional region of the diagram located between regions of steadiness, or moderate unsteadiness, and a region of dominant unsteadiness governed by alpha.     

Design of a system for the accelerated loading of heart valve prostheses

In this paper an equipment is described for the loading of heart valve prostheses under physiological pressure conditions at a frequency of 10 Hz. The system consists essentially of two reservoirs between which a housing is mounted for holding the valve prosthesis. The reservoirs are partly filled with liquid. The physiological pressure variation across the valve is obtained by pressure control within the two reservoirs. A phase difference between the pressures in the two reservoirs compensates for the mass-inertia effects which normally occur at these high frequencies. The system without a valve has been analysed on the basis of simplified relationships between pressure and flow. The predicted values for the phase difference between the flow and the pressure curves within the valve housing, have been verified experimentally for various values of phase difference and amplitude ratios of the pressure variations within the reservoirs. The agreement between theory and experiment is fair. For the system with a valve the experimentally observed patterns closely resemble the theoretically predicted ones. From experiments with a Bj?rk-Shiley ( 21ABP ) and a Hancock (242-A21) valve prosthesis it is concluded that the valves open and close completely and that the pressure and flow patterns around the valves mimic the essential features of the in-vivo signals.     

Contractile parameters and occurrence of alternans in isolated rat myocardium at supra-physiological stimulation frequency

The cardiac refractory period prevents the heart from tetanic activation that is typically used in noncardiac striated muscle tissue. To what extent the refractory period prevents successive action potentials to activate the excitation-contraction coupling process and contractile machinery at supra-physiological rates, such as those present during ventricular fibrillation, is unknown. Using multicellular trabeculae isolated from rat hearts, we studied amplitude and kinetics of contraction at rates well above the normal in vivo rat heart range. We show that even at twice the maximal heart rate of the rat, little or no mechanical instability is observed; twitch contractions are at steady state, albeit with an elevated active diastolic force. Although the amplitude of contraction increased within in vivo heart rates (positive force-frequency response), at frequencies beyond the maximal heart rate (10-30 Hz) a steady decline of contractile amplitude is observed. Not until 30 Hz do the majority of the isolated muscle preparations show mechanical alternans, where strong and weak beats alternate. Interestingly, unlike striated limb skeletal muscle, fusing of twitch contractions did not cause a continuous increase in peak force: at frequencies of 10 Hz and above, systolic force declines with relatively little elevation in diastolic force. Contractile kinetics continued to accelerate, from 1 Hz up to 30 Hz, whereas the relative speed of contraction and relaxation remained closely coupled, reflected by a singular linear relationship between the maximal and minimal derivative of force (dF/dt). We conclude that cardiac muscle can produce mechanically stable steady-state contractions at supra-physiological pacing rates, while these contractions continue to decline in amplitude and increase in diastolic force past maximal heart rate.     

Tetanic force development of adductor pollicis muscle in anesthetized man.

The tetanic force development of the human adductor pollicis muscle was studied under light anesthesia with nitrous oxide, oxygen, and Demerol, by the use of tetanic stimulation of the ulnar nerve at frequencies ranging from 10 to 100 Hz. The time necessary for the tetanic contraction to reach a plateau was longest at frequencies between 15 and 20 Hz. Fusion of tetanus occurred between 40 and 45 Hz. The mean maximal force of 6.92 kg was developed at a mean frequency of approximately 75 Hz. The maximal force was well maintained up to a stimulation frequency of 100 Hz. The results indicate that in lightly anesthetized man, the maximal force is developed at higher stimulation frequencies than those observed in conscious man and that it is well sustained at higher frequencies.     

Force-frequency relationship and potentiation in mammalian skeletal muscle.

Repetitive activation of a skeletal muscle results in potentiation of the twitch contractile response. Incompletely fused tetanic contractions similar to those evoked by voluntary activation may also be potentiated by prior activity. We aimed to investigate the role of stimulation frequency on the enhancement of unfused isometric contractions in rat medial gastrocnemius muscles in situ. Muscles set at optimal length were stimulated via the sciatic nerve with 50-micros duration supramaximal pulses. Trials consisted of 8 s of repetitive trains [5 pulses (quintuplets) 2 times per second or 2 pulses (doublets) 5 times per second] at 20, 40, 50, 60, 70, and 80 Hz. These stimulation frequencies represent a range over which voluntary activation would be expected to occur. When the frequency of stimulation was 20, 50, or 70 Hz, the peak active force (highest tension during a contraction - rest tension) of doublet contractions increased from 2.2 +/- 0.2, 4.1 +/- 0.4, and 4.3 +/- 0.5 to 3.1 +/- 0.3, 5.6 +/- 0.4, and 6.1 +/- 0.7 N, respectively. Corresponding measurements for quintuplet contractions increased from 2.2 +/- 0.2, 6.1 +/- 0.5, and 8.7 +/- 0.7 to 3.2 +/- 0.3, 7.3 +/- 0.6, and 9.0 +/- 0.7 N, respectively. Initial peak active force values were 27 +/- 1 and 61.5 +/- 5% of the maximal (tetanic) force for doublet and quintuplet contractions, respectively, at 80 Hz. With doublets, peak active force increased at all stimulation frequencies. With quintuplets, peak active force increased significantly for frequencies up to 60 Hz. Twitch enhancement at the end of the 8 s of repetitive stimulation was the same regardless of the pattern of stimulation during the 8 s, and twitch peak active force returned to prestimulation values by 5 min. These experiments confirm that activity-dependent potentiation is evident during repeated, incompletely fused tetanic contractions over a broad range of frequencies. This observation suggests that, during voluntary motor unit recruitment, derecruitment or decreased firing frequency would be necessary to achieve a fixed (submaximal) target force during repeated isometric contractions over this time period.     

Less is more: high pass filtering, to remove up to 99% of the surface EMG signal power, improves EMG-based biceps brachii muscle force estimates.

It is generally assumed that raw surface EMG (sEMG) should be high pass filtered with cutoffs of 10-30 Hz to remove motion artifact before subsequent processing to estimate muscle force. The purpose of the current study was to explore the benefits of filtering out much of the raw sEMG signal when attempting to estimate accurate muscle forces. Twenty-five subjects were studied as they performed rapid static, anisotonic contractions of the biceps brachii. Biceps force was estimated (as a percentage of maximum) based on forces recorded at the wrist. An iterative approach was used to process the sEMG from the biceps brachii, using progressively greater high pass cutoff frequencies (20-440 Hz in steps of 30 Hz) with first and sixth order filters, as well as signal whitening, to determine the effects on the accuracy of EMG-based biceps force estimates. The results indicate that removing up to 99% of the raw sEMG signal power resulted in significant and substantial improvements in biceps force estimates. These findings challenge previous assumptions that the raw sEMG signal power between about 20 and 500 Hz should used when estimating muscle force. For the purposes of force prediction, it appears that a much smaller, high band of sEMG frequencies may be associated with force and the remainder of the spectrum has little relevance for force estimation.     

Reliability of parameter estimates from models applied to respiratory impedance data

Many previous studies have fit lumped parameter models to respiratory input (Zin) and transfer (Ztr) impedance data. For frequency ranges higher than 4-32 Hz, a six-element model may be required in which an airway branch (with a resistance and inertance) is separated from a tissue branch (with a resistance, inertance, and compliance) by a shunt compliance. A sensitivity analysis is applied to predict the effects of frequency range on the accuracy of parameter estimates in this model obtained from Zin or Ztr data. Using a parameter set estimated from experimental data between 4 and 64 Hz in dogs, both Zin and Ztr were simulated from 4 to 200 Hz. Impedance sensitivity to each parameter was also calculated over this frequency range. The simulation predicted that for Zin a second resonance occurs near 80 Hz and that the impedance is considerably more sensitive to several of the parameters at frequencies surrounding this resonance than at any other frequencies. Also, unless data is obtained at very high frequencies (where the model is suspect), Zin data provides more accurate estimates than Ztr data. After adding random noise to the simulated Zin data, we attempted to extract the original parameters by using a nonlinear regression applied to three frequency ranges: 4-32, 4-64, and 4-110 Hz. Estimated parameters were substantially incorrect when using only 4- to 32-Hz or 4- to 64-Hz data, but nearly correct when fitting 4- to 110-Hz data. These results indicate that respiratory system parameters can be more accurately extracted from Zin than Ztr, and to make physiological inferences from parameter estimates based on Zin impedance data in dogs, the data must include frequencies surrounding the second resonance.     

Effects of hypocalcemia on diaphragmatic strength generation

We studied the effects of hypocalcemia on diaphragmatic force and diaphragm blood flow (Qdi) in 12 anesthetized dogs. The diaphragm was electrically stimulated with intramuscular electrodes surgically implanted in the ventral surface of each hemidiaphragm. The transdiaphragmatic pressure (Pdi) during supramaximal (50 V) 2-s stimulations applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. A catheter was placed via the femoral vein into the left inferior phrenic vein, and Qdi was measured by timed volume collections of left inferior venous effluent. A catheter was introduced in a femoral artery to monitor blood pressure (BP). In five additional dogs, the force generated by the sartorius muscle during electrical stimulation was also studied concomitantly to diaphragmatic force. The animals were mechanically ventilated throughout the experiment, and the arterial blood gases and pH were maintained constant. Hypocalcemia was induced by a continuous infusion of EGTA (70 mg X kg-1 X h-1), which led to a progressive decrease (P less than 0.0001) of ionized calcium plasmatic level from 2.21 +/- 0.4 meq/1 during control to 1.69 +/- 0.06, 1.25 +/- 0.5, and 1.07 +/- 0.5 meq/1 after 30, 60, and 120 min, respectively. Hypocalcemia decreased progressively Pdi, which amounted to 84 +/- 3 (P less than 0.001) and 98 +/- 2% of control values for the low frequencies (10 and 20 Hz) and the high frequencies (50 and 100 Hz), respectively, after 30 min of EGTA infusion and to 74 +/- 5 and 79 +/- 6% for the low and high frequencies, respectively, after 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Role of Elytra in Beetle Flight: I. Generation of Quasi-Static Aerodynamic Forces

We conducted a comprehensive study to investigate the aerodynamic characteristics and force generation of the elytra of abeetle,Allomyrina dichotoma.Our analysis included wind tunnel experiments and three-dimensional computational fluiddynamics simulations using ANSYS-CFX software.Our first approach was a quasi-static study that considered the effect ofinduced flapping flow due to the flapping motion of the fore-wings (elytra) at a frequency of around 30 Hz to 40 Hz.The dihedralangle was varied to represent flapping motion during the upstroke and downstroke.We found that an elytron producespositive lift at 0° geometric angle of attack,negative lift during the upstroke,and always produces drag during both the upstrokeand downstroke.We also found that the lift coefficient of an elytron does not drop even at a very high geometric angle of attack.For a beetle with a body weight of 5 g,based on the quasi-static method,the fore-wings (elytra) can produce lift of less than 1%of its body weight.     

Dynamic cerebral autoregulation under sinusoidal gravitational loading

Dynamic cerebral autoregulation (CA) has been studied previously using spectral analysis of oscillations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). The dynamics of the CA can be modeled as a high-pass filter. The purpose of this study is to compare CA of blood pressure oscillations induced by gravitational loading to CA during resting conditions. We subjected twelve healthy subjects to repeated sinusoidal head-up (0 degrees - 60 degrees) tilts at several set frequencies (0.07 to 0.25 Hz) on a computer controlled tilt table while we recorded ABP (Finapres) and CBFV (transcranial Doppler ultrasound). We fitted the data sets to a high-pass filter model and computed an average time constant (T). Our results show similar phase leads of CBFV to ABPbrain in the rest recording and in sinusoidal tilting, in the studied frequency range. The transfer function gain of the resting spectra increased with increasing frequency, the gain of the tilting spectra did not. Fitting the phase responses of both data sets to a high pass filter model yielded similar time constants.     

Auditory frequency discrimination in the squirrel monkey

Four squirrel monkeys (Saimiri sciureus) were tested for their frequency discrimination capacity using an eyeblink classical conditioning procedure, with air puff against the eye as unconditioned stimulus and 600-ms pure tones as conditioned stimuli. Absolute frequency difference thresholds showed a minimum (20-41 Hz, mean 30 Hz) at 4,000-8,000 Hz and increased towards higher as well as lower frequencies (70-90 Hz, mean 80 Hz at 300 Hz; 44-120 Hz, mean 82 Hz at 16,000 Hz). Relative frequency difference thresholds increased from higher to lower frequencies, with values as low as 0.3-0.8% (mean 0.5%) at 16,000 Hz and as large as 24-30% (mean 27%) at 300 Hz. The squirrel monkey's frequency discrimination function thus shows a severe deviation from Weber's law. The frequency difference thresholds are comparable to human's in the 4,000-8,000 Hz range, but are 65-80 times higher in the 500- to 300-Hz range. Individuals with high auditory thresholds do not necessarily also have high frequency difference thresholds.     

Neural response to very low-frequency sound in the avian cochlear nucleus

Recordings were made in the chick cochlear nucleus from neurons that are sensitive to very low frequency sound. The tuning, discharge rate response and phase-locking properties of these units are described in detail. The principal conclusions are: 1. Low frequency (LF) units respond to sound frequencies between 10-800 Hz. Best thresholds average 60 dB SPL, and are occasionally as low as 40 dB SPL. While behavioral thresholds in this frequency range are not available for the domestic chick, these values are in good agreement with the pigeon behavioral audiogram (Kreithen and Quine 1979). 2. About 60% of the unit population displays tuning curves resembling low-pass filter functions with corner frequencies between 50-250 Hz. The remaining units have broad band-pass tuning curves. Best frequencies range from 50-300 Hz. 3. Spontaneous discharge rate was analyzed quantitatively for LF units recorded from nucleus angularis. The distribution of spontaneous rates for LF units is similar to that seen from higher CF units (300-5000 Hz) found in the same nucleus. However, the spontaneous firing of LF units is considerably more regular than that of their higher CF counterparts. 4. Low frequency units with low spontaneous rates (SR's less than 40 spikes/s) show large driven rate increases and usually saturate by discharging once or twice per stimulus cycle. Higher SR units often show no driven rate increases. 5. All LF units show strong phase-locking at all excitatory stimulus frequencies. Vector strengths as high as 0.98 have been observed at moderate sound levels. 6. The preferred phase of discharge (relative to the sound stimulus) increases with stimulus frequency in a nearly linear manner. This is consistent with the LF units being stimulated by a traveling wave. The slope of these phase-frequency relationships provides an estimate of traveling wave delay. These delays average 7.2 ms, longer than those seen for higher CF auditory brainstem units. These observations suggest that the peripheral site of low frequency sensitivity is the very distal region of the basilar papilla, an area whose morphology differs significantly from the rest of the chick basilar papilla. 7. LF units are described whose response to sound is inhibitory at frequencies above 50 Hz.     

Autonomic cardiovascular control in conscious mice

Autonomic cardiovascular control was characterized in conscious, chronically catheterized mice by spectral analysis of arterial pressure (AP) and heart rate (HR) during autonomic blockade or baroreflex modulation of autonomic tone. Both spectra were similar to those obtained in humans, but at approximately 10x higher frequencies. The 1/f relation of the AP spectrum changed to a more shallow slope below 0.1-0.2 Hz. Coherence between AP and HR reached 0.5 or higher below 0.3-0.4 Hz and also above 2.5 Hz. Muscarinic blockade (atropine) or beta-adrenergic blockade (atenolol) did not significantly affect the AP spectrum. Atropine reduced HR variability at all frequencies, but this effect waned above 1 Hz. beta-Adrenergic blockade (atenolol) slightly enhanced the HR variability only above 1 Hz. alpha-Adrenergic blockade (prazosin) reduced AP variability between 0.05 and 3 Hz, most prominently at 0. 15-0.7 Hz. A shift of the autonomic nervous tone by a hypertensive stimulus (phenylephrine) enhanced, whereas a hypotensive stimulus (nitroprusside) depressed AP variability at 1-3 Hz; other frequency ranges of the AP spectrum were not affected except for a reduction below 0.4 Hz after nitroprusside. Variability of HR was enhanced after phenylephrine at all frequencies and reduced after nitroprusside. As with atropine, the reduction with nitroprusside waned above 1 Hz. In conclusion, in mice HR variability is dominated by parasympathetic tone at all frequencies, during both blockade and physiological modulation of autonomic tone. There is a limitation for further reduction but not for augmentation of HR variability from the resting state above 1 Hz. The impact of HR on AP variability in mice is confined to frequencies higher than 1 Hz. Limits between frequency ranges are proposed as 0.15 Hz between VLF (very low frequency range) and LF (low frequency range) and 1.5 Hz between LF and HF (high frequency range).     

Spontaneous fluctuations in cerebral blood flow: insights from extended-duration recordings in humans

To determine the dependence of cerebral blood flow (CBF) on arterial pressure over prolonged time periods, we measured beat-to-beat changes in mean CBF velocity in the middle cerebral artery (transcranial Doppler) and mean arterial pressure (Finapres) continuously for 2 h in six healthy subjects (5 men and 1 woman, 18-40 yr old) during supine rest. Fluctuations in velocity and pressure were quantified by the range [(peak - trough)/mean] and coefficients of variation (SD/mean) in the time domain and by spectral analysis in the frequency domain. Mean velocity and pressure over the 2-h recordings were 60 +/- 7 cm/s and 83 +/- 8 mmHg, associated with ranges of 77 +/- 8 and 89 +/- 10% and coefficients of variation of 9.3 +/- 2.2 and 7.9 +/- 2.3%, respectively. Spectral power of the velocity and pressure was predominantly distributed in the frequency range of 0.00014-0.1 Hz and increased inversely with frequency, indicating characteristics of an inverse power law (1/f(alpha)). However, linear regression on a log-log scale revealed that the slope of spectral power of pressure and velocity was steeper in the high-frequency (0.02-0.5 Hz) than in the low-frequency range (0.002-0.02 Hz), suggesting different regulatory mechanisms in these two frequency ranges. Furthermore, the spectral slope of pressure was significantly steeper than that of velocity in the low-frequency range, consistent with the low transfer function gain and low coherence estimated at these frequencies. We conclude that 1) long-term fluctuations in CBF velocity are prominent and similar to those observed in arterial pressure, 2) spectral power of CBF velocity reveals characteristics of 1/f(alpha), and 3) cerebral attenuation of oscillations in CBF velocity in response to changes in pressure may be more effective at low than that at high frequencies, emphasizing the frequency dependence of cerebral autoregulation.