Linear electrical properties of passive and active currents in spherical heart cell clusters.

Impedance studies were performed on small spherical clusters of embryonic chick heart cells grown in tissue culture. Each syncytial cluster was impaled with two microelectrodes; one injected low amplitude stochastic current and the other recorded the resulting perturbation of intracellular potential. The current and potential records were digitized, decomposed into their sinusoidal components, and the frequency domain impedance of the cluster was determined. The impedance data were compared with a theory for current flow in a spherical syncytium and values were derived for parameters describing the membranes and intercellular clefts of the tissue. The clusters were spontaneously active but usually became temporarily quiescent when impaled with two electrodes. The potential stabilized at a value close to -30 mV. At this depolarized potential, active slow currents, presumably present in the cardiac action potential, contributed noticeably to the linear impedance, producing a resonant peak in the magnitude of the impedance at a frequency of 1-3 Hz. The linearized impedance functions for these currents were characterized in the presence and absence of tetrodotoxin (TTX) and D-600. TTX had no noticeable effect on the impedance but D-600 essentially abolished the active currents. Although the ionic basis of these currents is not known, frequency domain analysis appears to be a viable technique for studying slow currents in heart muscle.     

Extracellular and intracellular components of the impedance of neural tissue

Electric phenomena in brain tissue can be measured using extracellular potentials, such as the local field potential, or the electro-encephalogram. The interpretation of these signals depends on the electric structure and properties of extracellular media, but the measurements of these electric properties are still debated. Some measurements point to a model in which the extracellular medium is purely resistive, and thus parameters such as electric conductivity and permittivity should be independent of frequency. Other measurements point to a pronounced frequency dependence of these parameters, with scaling laws that are consistent with capacitive or diffusive effects. However, these experiments correspond to different preparations, and it is unclear how to correctly compare them. Here, we provide for the first time, impedance measurements (in the 1–10 kHz frequency range) using the same setup in various preparations, from primary cell cultures to acute brain slices, and a comparison with similar measurements performed in artificial cerebrospinal fluid with no biological material. The measurements show that when the current flows across a cell membrane, the frequency dependence of the macroscopic impedance between intracellular and extracellular electrodes is significant, and cannot be captured by a model with resistive media. Fitting a mean-field model to the data shows that this frequency dependence could be explained by the ionic diffusion mainly associated with Debye layers surrounding the membranes. We conclude that neuronal membranes and their ionic environment induce strong deviations to resistivity that should be taken into account to correctly interpret extracellular potentials generated by neurons.     

Studies on magnetism and bioelectromagnetics for 45 years: from magnetic analog memory to human brain stimulation and imaging

Forty-five years of studies on magnetism and bioelectromagnetics, in our laboratory, are presented. This article is prepared for the d'Arsonval Award Lecture. After a short introduction of our early work on magnetic analog memory, we review and discuss the following topics: (1) Magnetic nerve stimulation and localized transcranial magnetic stimulation (TMS) of the human brain by figure-eight coils; (2) Measurements of weak magnetic fields generated from the brain by superconducting quantum interference device (SQUID) systems, called magnetoencephalography (MEG), and its application in functional brain studies; (3) New methods of magnetic resonance imaging (MRI) for the imaging of impedance of the brain, called impedance MRI, and the imaging of neuronal current activities in the brain, called current MRI; (4) Cancer therapy and other medical treatments by pulsed magnetic fields; (5) Effects of static magnetic fields and magnetic control of cell orientation and cell growth; and (6) Effects of radio frequency magnetic fields and control of iron ion release and uptake from and into ferritins, iron cage proteins. These bioelectromagnetic studies have opened new horizons in magnetism and medicine, in particular for brain research and treatment of ailments such as depression, Parkinson's, and Alzheimer's diseases.     

Currents induced in anatomic models of the human for uniform and nonuniform power frequency magnetic fields

We have used the quasi-static impedance method to calculate the currents induced in the nominal 2 x 2 x 3 and 6 mm resolution anatomically based models of the human body for exposure to magnetic fields at 60 Hz. Uniform magnetic fields of various orientations and magnitudes 1 or 0.417 mT suggested in the ACGIH and ICNIRP safety guidelines are used to calculate induced electric fields or current densities for the various glands and organs of the body including the pineal gland. The maximum 1 cm(2) area-averaged induced current densities for the central nervous system tissues, such as the brain and the spinal cord, were within the reference level of 10 mA/m(2) as suggested in the ICNIRP guidelines for magnetic fields (0.417 mT at 60 Hz). Tissue conductivities were found to play an important role and higher assumed tissue conductivities gave higher induced current densities. We have also determined the induced current density distributions for nonuniform magnetic fields associated with two commonly used electrical appliances, namely a hair dryer and a hair clipper. Because of considerably higher magnetic fields for the latter device, higher induced electric fields and current densities were calculated.     

Transcranial Extracellular Impedance Control (tEIC) Modulates Behavioral Performances

Electric brain stimulations such as transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), and transcranial alternating current stimulation (tACS) electrophysiologically modulate brain activity and as a result sometimes modulate behavioral performances. These stimulations can be viewed from an engineering standpoint as involving an artificial electric source (DC, noise, or AC) attached to an impedance branch of a distributed parameter circuit. The distributed parameter circuit is an approximation of the brain and includes electric sources (neurons) and impedances (volume conductors). Such a brain model is linear, as is often the case with the electroencephalogram (EEG) forward model. Thus, the above-mentioned current stimulations change the current distribution in the brain depending on the locations of the electric sources in the brain. Now, if the attached artificial electric source were to be replaced with a resistor, or even a negative resistor, the resistor would also change the current distribution in the brain. In light of the superposition theorem, which holds for any linear electric circuit, attaching an electric source is different from attaching a resistor; the resistor affects each active electric source in the brain so as to increase (or decrease in some cases of a negative resistor) the current flowing out from each source. From an electrophysiological standpoint, the attached resistor can only control the extracellular impedance and never causes forced stimulation; we call this technique transcranial extracellular impedance control (tEIC). We conducted a behavioral experiment to evaluate tEIC and found evidence that it had real-time enhancement and depression effects on EEGs and a real-time facilitation effect on reaction times. Thus, tEIC could be another technique to modulate behavioral performance.     

Impedance of goat lens as a function of frequency at DC voltages 0, 50, 100, 200 mV

Impedance characteristics of lens tissue has been studied using the AC impedance system (EG&G PARC, model 318) at different low voltage excitations using a Cole-Cole Plot. The extracellular resistance (Re), intracellular resistance (Ri), depressed angle (theta), total impedance (/Z/), and phase angle (phi) of the tissue were measured. The impedance locus between the real part (Z') and imaginary part (Z') of the complex impedance of lens was examined at discrete frequencies ranging from 10 mHz to 10 Hz. A decrease in extra-cellular resistance (Re) and increase in distribution of the factor (alpha) of 56.8 KOmega, 48.1 KOmega, 32.8 KOmega, 13.4 KOmega, and 0.40, 0.43, 0.46, 0.53 were found at 0 mV, 50 mV, 100 mV, and 200 mV, respectively. The total impedance (/Z/) and phase angle (phi) were also evaluated and the observed frequency dependent for the frequency range was tested as a function of excitation voltage. An attempt has been made to explain the effect of voltage stress on lens impedance.     

The feasibility of computational modelling technique to detect the bladder cancer

A numerical technique, finite element analysis (FEA) was used to model the electrical properties, the bio impedance of the bladder tissue in order to predict the bladder cancer. This model results showed that the normal bladder tissue have significantly higher impedance than the malignant tissue that was in opposite with the impedance measurements or the experimental results. Therefore, this difference can be explained using the effects of inflammation, oedema on the urothelium and the property of the bladder as a distensible organ. Furthermore, the different current distributions inside the bladder tissue (in histological layers) in normal and malignant cases and finally different applied pressures over the bladder tissue can cause different impedances for the bladder tissue. Finally, it is believed that further studies have to be carried out to characterise the human bladder tissue using the electrical impedance measurement and modelling techniques.     

A measuring device for calculating electrical impedance of the heart in clinical conditions]

Changes in the electrical impedance of tissue can indicate structural changes. This suggests a technique for the noninvasive detection of allograft rejection after heart transplantation. The direct electrical connection to the heart and the application of a measuring current to the myocardium requires a high standard of safety. A device was developed for measuring cardiac impedance using a sinusoidal current of 20 microA at a frequency of 15 kHz. The control logic ensures a slow current onset and also an immediate cessation in case of conductor fracture or excessive voltage. Initial results in patients with normal recovery after heart transplantation revealed a rapid drop in impedance to about 70% of the initial value in the 1st 48 hours and then a stable course. In the sole rejection episode observed so far, the impedance increased again to 85% of the initial value. This paper discusses the technical safety requirements and the design of the device, and presents initial results of clinical examinations.     

Effect of transplantation of embryonic neural tissue on the dynamics of brain edema following experimental craniocerebral trauma

The effect of transplantation of embryonic neural tissue (ENT) on the dynamics of brain edema following heavy craniocerebral trauma (CCT) made to the left parietotemporal area was studied in rats. The brain tissue impedance was measured in the damaged and contralateral hemispheres 1 to 30 days after the trauma in the animals of three groups: (i) without any procedures after the CCT, (ii) with surgical treatment of the damaged brain area, and (iii) with transplantation of 1–2 mm³ sensorimotor cortex fragments from 18-day-old rats grafted into the cavity created by this treatment. At the first day after CCT, the impedance in the damaged hemisphere decreased by 30–37%, while the impedance in the contralateral hemisphere decreased approximately by 20%, compared with the control, which was evidence of the development of intensive generalized edema. In the group of animals with the ENT transplantation, the edema involuted noticeably faster than in the other two groups: the mean impedance value reached 97.9% of the control value (before the damage) already by the 7th post-traumatic day. Complete recovery of the impedance by the 30th day was observed only in the animals with transplantation. The adequacy of an impedancemetric technique for investigation of the dynamics of water-electrolyte re-distribution in the brain tissue, and the mechanisms underlying corrective effect of ENT transplantation on the edema dynamics in the post-traumatic period are discussed.     

Impedance analysis of MDCK cells measured by electric cell-substrate impedance sensing.

Transepithelial impedance of Madin-Darby canine kidney cell layers is measured by a new instrumental method, referred to as electric cell-substrate impedance sensing. In this method, cells are cultured on small evaporated gold electrodes, and the impedance is measured in the frequency range 20-50,000 Hz by a small probing current. A model for impedance analysis of epithelial cells measured by this method is developed. The model considers three different pathways for the current flowing from the electrode through the cell layer: (1) in through the basal and out through the apical membrane, (2) in through the lateral and out through the apical membrane, and (3) between the cells through the paracellular space. By comparing model calculation with experimental impedance data, several morphological and cellular parameters can be determined: (1) the resistivity of the cell layer, (2) the average distance between the basal cell surface and substratum, and (3) the capacitance of apical, basal, and lateral cell membranes. This model is used to analyze impedance changes on removal of Ca2+ from confluent Mardin-Darby canine kidney cell layers. The method shows that reduction of Ca2+ concentration causes junction resistance between cells to drop and the distance between the basal cell surface and substratum to increase.     

聚3，4乙烯二氧噻吩修饰的新型碳纳米管纤维电极及其电化学性能评价

目的 植入式脑机接口在神经疾病的治疗方面已经得到了广泛应用，治疗的效果依赖于与神经组织接触的电极。与刚性材料制作的电极相比，碳基微纤维电极尺度小、生物兼容性好、组织炎症反应小，可以减少植入后的异物反应，改善神经记录信号的信噪比，可以长期保持稳定的电极特性。方法 本文设计了一种柔性碳纳米管（carbon nanotubes，CNTs）纤维电极的修饰方法，该方法采用电化学聚合的方式可以将聚3,4-乙烯二氧噻吩（poly（3,4-ethylenedioxythiophene），PEDOT）薄膜沉积到CNTs纤维电极上，作为微电极涂层。为了证明修饰涂层在电极表面具有良好的机械稳定性，对修饰电极进行了超声处理。此外，本文将PEDOT薄膜沉积到ITO玻璃上，评价了PEDOT薄膜的生物相容性。结果 恒电流方式在CNTs纤维电极表面沉积的PEDOT涂层降低了电极的电化学阻抗，提高了电极的电化学性能，且PEDOT沉积的时间越长阻抗减少的幅度越明显。对电极进行超声处理后，电极的电化学阻抗没有产生显著变化，说明超声处理后PEDOT涂层剥离较少，证明了修饰涂层在电极表面具有良好的机械稳定性。最后，细胞实验表明，PEDOT薄膜具有与ITO导电玻璃相当的细胞相容性。结论 PEDOT薄膜可以提高CNTs纤维电极的稳定性，有望提高脑机接口系统的寿命和可靠性，具有应用于长时间记录神经电信号的前景。     

Use of Electrical Impedance Tomography to Monitor Regional Cerebral Edema during Clinical Dehydration Treatment

Objective

Variations of conductive fluid content in brain tissue (e.g. cerebral edema) change tissue impedance and can potentially be measured by Electrical Impedance Tomography (EIT), an emerging medical imaging technique. The objective of this work is to establish the feasibility of using EIT as an imaging tool for monitoring brain fluid content.

Design

a prospective study.

Setting

In this study EIT was used, for the first time, to monitor variations in cerebral fluid content in a clinical model with patients undergoing clinical dehydration treatment. The EIT system was developed in house and its imaging sensitivity and spatial resolution were evaluated on a saline-filled tank.

Patients

23 patients with brain edema.

Interventions

The patients were continuously imaged by EIT for two hours after initiation of dehydration treatment using 0.5 g/kg intravenous infusion of mannitol for 20 minutes.

Measurement and Main Results

Overall impedance across the brain increased significantly before and after mannitol dehydration treatment (p = 0.0027). Of the all 23 patients, 14 showed high-level impedance increase and maintained this around 4 hours after the dehydration treatment whereas the other 9 also showed great impedance gain during the treatment but it gradually decreased after the treatment. Further analysis of the regions of interest in the EIT images revealed that diseased regions, identified on corresponding CT images, showed significantly less impedance changes than normal regions during the monitoring period, indicating variations in different patients'' responses to such treatment.

Conclusions

EIT shows potential promise as an imaging tool for real-time and non-invasive monitoring of brain edema patients.     

Microelectrode chip based real time monitoring of vital MCF-7 mamma carcinoma cells by impedance spectroscopy

Sensorchip based impedance spectroscopy can detect inhibitory effects of human neuropeptide Y (hNPY) on living cells in a non-invasive labelling free way in real time without the need of supporting reagents. Since the discovery that neoplasmatic transformations in breast cancer are correlated with a change of the receptor subtype expression of hNPY in the affected tissue, the hNPY receptor-ligand system has come to the fore of cancer research. Today there are different methods detecting hNPY receptor interactions like fluorescent and radioactive labelling or detecting hNPY-pathway activation like cyclic adenosine monophosphate (cAMP) and G protein-coupled receptor (GPCR)-assays. For all these assays it is necessary to either label related proteins with additional substances, which can affect the nature state of the cell, or the need of producing cell lysate which allows only a snapshot of the investigated cells. To overcome these problems we established a new method to detect hNPY-receptor interactions. Therefore, we monitor the complex electric resistance (impedance) of cells attached to a microelectrode over a wide frequency range. Cell alterations are detected as changes in the impedance spectra. After application of the adenylyl cyclase-stimulating reagent forskolin, impedance is decreased at 5kHz frequency within minutes. This effect can be inhibited by preincubating the cells with hNPY for a time range of 20min. The inhibitory effect of hNPY can be washed out and the same cells can be stimulated by forskolin again.     

Tracking of airway and tissue mechanics during TLC maneuvers in mice.

A tracking impedance estimation technique was developed to follow the changes in total respiratory impedance (Zrs) during slow total lung capacity maneuvers in six anesthetized and mechanically ventilated BALB/c mice. Zrs was measured with the wave-tube technique and pseudorandom forced oscillations at nine frequencies between 4 and 38 Hz during inflation from a transrespiratory pressure of 0-20 cmH2O and subsequent deflation, each lasting for approximately 20 s. Zrs was averaged for 0.125 s and fitted by a model featuring airway resistance (Raw) and inertance, and tissue damping and elastance (H). Lower airway conductance (Glaw) was linearly related to volume above functional residual capacity (V) between 0 and 75-95% maximum V, with a mean slope of dGlaw/dV = 13.6 +/- 4.6 cmH2O-1. s-1. The interdependence of Raw and H was characterized by two distinct and closely linear relationships for the low- and high-volume regions, separated at approximately 40% maximum V. Comparison of Raw with the highest-frequency resistance of the total respiratory system revealed a marked volume-dependent contribution of tissue resistance to total respiratory system resistance, resulting in the overestimation of Raw by 19 +/- 8 and 163 +/- 40% at functional residual capacity and total lung capacity, respectively, whereas the lowest frequency reactance was proportional to H; these findings indicate that single-frequency resistance values may become inappropriate as surrogates of Raw when tissue impedance is changing.     

Label-free impedimetric immunosensor for ultrasensitive detection of cancer marker Murine double minute 2 in brain tissue

The detection of cancer biomarkers is as important tool for the diagnosis and prognosis of cancer such as brain cancer. Murine double minute 2 (MDM2) has been widely studied as prognostic marker for brain tumor. Here we describe development of a new sensitive label free impedimetric immunosensor for the detection of MDM2 based on cysteamine self assembled monolayers on a clean polycrystalline Au electrode surface. The amine-modified electrodes were further functionalized with antibody using homobifunctional 1,4-phenylene diisothiocyanate (PDITC) linker. The assembly processes of the immunosensor had been monitored with cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques using Fe(CN)(6)(3-/4-) solution as redox probe. The impedance changes upon binding of MDM2 protein to the sensor surface was utilized for the detection of MDM2. The increase in relative electron-transfer resistance (ΔR/R(0)%) values was linearly proportional to the concentration of tumor marker MDM2 in the wide dynamic range of 1pg/ml-1μg/ml. The limit of detection was 0.29pg/ml in phosphate buffer saline (PBS) and 1.3pg/ml in mouse brain tissue homogenate, respectively. The immunosensor showed a good performance in comparison with ELISA for the analysis of the MDM2 in the cancerous mouse brain tissue homogenates. Moreover, the immunosensor had a good selectivity against epidermal growth factor receptor (EGFR) protein, long-storage stability and reproducibility. It might be become a promising assay for clinical diagnosis and early detection of tumors.     

Electrical Resonance in the θ Frequency Range in Olfactory Amygdala Neurons

The cortical amygdala receives direct olfactory inputs and is thought to participate in processing and learning of biologically relevant olfactory cues. As for other brain structures implicated in learning, the principal neurons of the anterior cortical nucleus (ACo) exhibit intrinsic subthreshold membrane potential oscillations in the θ-frequency range. Here we show that nearly 50% of ACo layer II neurons also display electrical resonance, consisting of selective responsiveness to stimuli of a preferential frequency (2–6 Hz). Their impedance profile resembles an electrical band-pass filter with a peak at the preferred frequency, in contrast to the low-pass filter properties of other neurons. Most ACo resonant neurons displayed frequency preference along the whole subthreshold voltage range. We used pharmacological tools to identify the voltage-dependent conductances implicated in resonance. A hyperpolarization-activated cationic current depending on HCN channels underlies resonance at resting and hyperpolarized potentials; notably, this current also participates in resonance at depolarized subthreshold voltages. KV7/KCNQ K⁺ channels also contribute to resonant behavior at depolarized potentials, but not in all resonant cells. Moreover, resonance was strongly attenuated after blockade of voltage-dependent persistent Na⁺ channels, suggesting an amplifying role. Remarkably, resonant neurons presented a higher firing probability for stimuli of the preferred frequency. To fully understand the mechanisms underlying resonance in these neurons, we developed a comprehensive conductance-based model including the aforementioned and leak conductances, as well as Hodgkin and Huxley-type channels. The model reproduces the resonant impedance profile and our pharmacological results, allowing a quantitative evaluation of the contribution of each conductance to resonance. It also replicates selective spiking at the resonant frequency and allows a prediction of the temperature-dependent shift in resonance frequency. Our results provide a complete characterization of the resonant behavior of olfactory amygdala neurons and shed light on a putative mechanism for network activity coordination in the intact brain.     

Optimal combination of electrodes and conductive gels for brain electrical impedance tomography

Background

Electrical impedance tomography (EIT) is an emerging imaging technology that has been used to monitor brain injury and detect acute stroke. The time and frequency properties of electrode–skin contact impedance are important for brain EIT because brain EIT measurement is performed over a long period when used to monitor brain injury, and is carried out across a wide range of frequencies when used to detect stroke. To our knowledge, no study has simultaneously investigated the time and frequency properties of both electrode and conductive gel for brain EIT.

Methods

In this study, the contact impedance of 16 combinations consisting of 4 kinds of clinical electrode and five types of commonly used conductive gel was measured on ten volunteers’ scalp for a period of 1 h at frequencies from 100 Hz to 1 MHz using the two-electrode method. And then the performance of each combination was systematically evaluated in terms of the magnitude of contact impedance, and changes in contact impedance with time and frequency.

Results

Results showed that combination of Ag⁺/Ag⁺Cl^? powder electrode and low viscosity conductive gel performed best overall (Ten 20^® in this study); it had a relatively low magnitude of contact impedance and superior performance regarding contact impedance with time (p?<?0.05) and frequency (p?<?0.05).

Conclusions

Experimental results indicates that the combination of Ag⁺/Ag⁺Cl^? powder electrode and low viscosity conductive gel may be the best choice for brain EIT.

     

Detection of viable Salmonella typhimurium by impedance measurement of electrode capacitance and medium resistance

Three-electrode electrochemical impedance technique was investigated for detection of Salmonella typhimurium by monitoring the growth of bacteria in selenite cystine (SC) broth supplemented with trimethylamine oxide hydrochloride (TMAO.HCl) and mannitol (M). The change in the system impedance during the growth of bacteria was studied using frequency spectral scanning. It was found that the impedance at low frequencies (<10 kHz) mainly came from the double-charged layer capacitance, reflecting the changes at the electrode interface and the adsorption on the electrode surface. While at high frequencies (>10 kHz), the system impedance mainly depended on the medium resistance. The adsorption of bacteria on the electrode surface was detected by measuring low frequency impedance, and verified with Faradic impedance spectroscopy. Enumeration of S. typhimurium using a low frequency (1 Hz) capacitance measurement and a high frequency (1 MHz) resistance measurement were compared. The detection times were determined for quantitative analysis based on the growth curves of bacteria referring to either the medium resistance or electrode capacitance. The regression equations for the detection times (t(d), h) and the initial cell number (N, cells.ml(-1)) were t(d)=-1.24logN+13.4 with R(2)=0.98 and t(d)=-1.40logN+14.46 with R(2)=0.97 for the medium resistance and electrode capacitance methods, respectively.     

Respiratory impedance to ambient pressure changes at low frequencies

Respiratory impedance may be studied by measuring airway flow (Vaw) when pressure is varied at the mouth (input impedance) or around the chest (transfer impedance). A third possibility, which had not been investigated so far, is to apply pressure variations simultaneously at the two places, that is to vary ambient pressure (Pam). This provides respiratory impedance to ambient pressure changes (Zapc = Vaw/Pam). In that situation airway impedance (Zaw) and tissue impedance (Zt) are mechanically in parallel, and both are in series with alveolar gas impedance (Zg): Zapc = Zaw + Zg + Zaw.Zg/Zt. We assessed the frequency dependence of Zapc from 0.05 to 2 Hz in nine normal subjects submitted to sinusoidal Pam changes of 2-4 kPa peak to peak. The real part of Zapc (Rapc) was of 6.2 kPa.1(-1).s at 0.05 Hz and decreased to 1.9 kPa.1(-1).s at 2 Hz. Similarly the effective compliance (Capc), computed from the imaginary part of Zapc, decreased from 0.045 1.kPa-1 at 0.05 Hz to 0.027 1.kPa-1 at 2 Hz. Breathing against an added resistance of 0.46 kPa.1(-1).s exaggerated the negative frequency dependence of both Rapc and Capc. When values of airway resistance and inertance derived from transfer impedance data were introduced, Zapc was used to compute effective tissue resistance (Rt) and compliance (Ct). Rt was found to decrease from 0.32 to 0.15 kPa.1(-1).s and Ct from 1.11 to 0.64 1.kPa-1 between 0.25 and 2 Hz. Ct was slightly lower with the added resistance. These results are in good agreement with the data obtained by other approaches.     

Respiratory transfer impedance and derived mechanical properties of conscious rats.

A setup is described for measuring the respiratory transfer impedance of conscious rats in the frequency range 16-208 Hz. The rats were placed in a restraining tube in which head and body were separated by means of a dough neck collar. The restraining tube was placed in a body chamber, allowing the application of pseudorandom noise pressure variations to the chest and abdomen. The flow at the airway opening was measured in a small chamber connected to the body chamber. The short-term reproducibility of the transfer impedance was tested by repeated measurements in nine Wistar rats. The mean coefficient of variation for the impedance did not exceed 10%. The impedance data were analyzed using different models of the respiratory system of which a three-coefficient resistance-inertance-compliance model provided the most reliable estimates of respiratory resistance (Rrs) and inertance (Irs). The model response, however, departed systematically from the measured impedance. A nine-coefficient model best described the data. Optimization of this model provided estimates of the respiratory tissue coefficients and upper and lower airway coefficients. Rrs with this model was 13.6 +/- 1.0 (SD) kPa.l-1.s, Irs was 14.5 +/- 1.3 Pa.l-1.s2, and tissue compliance (Cti) was 2.5 +/- 0.5 ml/kPa. The intraindividual coefficient of variation for Rrs and Irs was 11 and 18%, respectively. Because most of the resistance and inertance was located in the airways (85 and 81% of Rrs and Irs, respectively), the partitioning in tissue and upper and lower airway components was rather poor. Our values for Rrs and Irs of conscious rats were much lower and our values for Cti were higher than previously reported values for anesthetized rats.