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Biomedical subjects

C E Hahn

Publications and source records attributed to C E Hahn.

At least 19 recordsLinked to original sources

Laminated microelectrodes: a simple approach to the construction of inexpensive microelectrodes with a variety of geometries.

Designs for reusable microelectrodes, which are easy to assemble and so do not require special technical skills or services for their construction, are presented. Three types of microelectrodes are fabricated by lamination of metal foil, wire, and wire grids, producing microband, microdisk, and a linear array of microdisk geometries. The electrodes themselves do not need to be polished prior to their use but are observed to be slightly recessed from the surrounding insulating surface. Good agreement is observed between experimental steady-state voltammetric results in nonaqueous solutions and the relevant analytical theory for the voltammetric current.

Journal Article↗

Modelling inert gas exchange in tissue and mixed-venous blood return to the lungs.

Inert gas exchange in tissue has been almost exclusively modelled by using an ordinary differential equation. The mathematical model that is used to derive this ordinary differential equation assumes that the partial pressure of an inert gas (which is proportional to the content of that gas) is a function only of time. This mathematical model does not allow for spatial variations in inert gas partial pressure. This model is also dependent only on the ratio of blood flow to tissue volume, and so does not take account of the shape of the body compartment or of the density of the capillaries that supply blood to this tissue. The partial pressure of a given inert gas in mixed-venous blood flowing back to the lungs is calculated from this ordinary differential equation. In this study, we write down the partial differential equations that allow for spatial as well as temporal variations in inert gas partial pressure in tissue. We then solve these partial differential equations and compare them to the solution of the ordinary differential equations described above. It is found that the solution of the ordinary differential equation is very different from the solution of the partial differential equation, and so the ordinary differential equation should not be used if an accurate calculation of inert gas transport to tissue is required. Further, the solution of the PDE is dependent on the shape of the body compartment and on the density of the capillaries that supply blood to this tissue. As a result, techniques that are based on the ordinary differential equation to calculate the mixed-venous blood partial pressure may be in error.

Anesthesia↗

Some factors affecting oxygen uptake by red blood cells in the pulmonary capillaries.

In this study we investigate the equations governing the transport of oxygen in pulmonary capillaries. We use a mathematical model consisting of a red blood cell completely surrounded by plasma within a cylindrical pulmonary capillary. This model takes account of convection and diffusion of oxygen through plasma, diffusion of oxygen through the red blood cell, and the reaction between oxygen and haemoglobin molecules. The velocity field within the plasma is calculated by solving the slow flow equations. We investigate the effect on the solution of the governing equations of: (i) mixed-venous blood oxygen partial pressure (the initial conditions); (ii) alveolar gas oxygen partial pressure (the boundary conditions); (iii) neglecting the convection term; and (iv) assuming an instantaneous reaction between the oxygen and haemoglobin molecules. It is found that: (a) equilibrium is reached much more rapidly for high values of mixed-venous blood and alveolar gas oxygen partial pressure; (b) the convection term has a negligible effect on the time taken to reach a prescribed degree of equilibrium; and (c) an instantaneous reaction may be assumed. Explanations are given for each of these results.

Capillaries↗

A tidal breathing model of the inert gas sinewave technique for inhomogeneous lungs.

The tidal breathing model conservation of mass equations for the sinewave technique have been described for a homogeneous alveolar compartment by Gavaghan and Hahn, 1996 [Gavaghan, D.J., Hahn, C.E.W., 1996. A tidal breathing model of the forced inspired gas sinewave technique. Respir. Physiol. 106, 209-221]. We develop these equations first to a multi-discrete alveolar compartment lung model and then to a lung model with a continuous distribution of volume, ventilation and perfusion. The effect on the output parameters of a multi-compartment model is discussed, and the results are compared to those derived from the conventional continuous-ventilation model. Using the barely soluble gas argon as the tracer gas, an empirical index of alveolar inhomogeneity is presented which uses the end-expired and mixed-expired partial pressures on each breath. This index distinguishes between a narrow unimodal distribution of ventilation-volume, a wide unimodal distribution of ventilation-volume and a bimodal distribution of ventilation-volume. By using Monte Carlo simulations, this index is shown to be stable to experimental error of realistic magnitude.

Argon↗

A method of reconstruction of clinical gas-analyzer signals corrupted by positive-pressure ventilation.

The use of sidestream infrared and paramagnetic clinical gas analyzers is widespread in anesthesiology and respiratory medicine. For most clinical applications, these instruments are entirely satisfactory. However, their ability to measure breath-by-breath volumetric gas fluxes, as required for measurement of airway dead space, oxygen uptake, and so on, is usually inferior to that of the mass spectrometer, and this is thought to be due, in part, to their slower response times. We describe how volumetric gas analysis with the Datex Ultima analyzer, although reasonably accurate for spontaneous ventilation, gives very inaccurate results in conditions of positive-pressure ventilation. We show that this problem is a property of the gas sampling system rather than the technique of gas analysis itself. We examine the source of this error and describe how cyclic changes in airway pressure result in variations in the flow rate of the gas within the sampling catheter. This results in the phenomenon of "time distortion," and the resultant gas concentration signal becomes a nonlinear time series. This corrupted signal cannot be aligned or integrated with the measured flow signal. We describe a method to correct for this effect. With the use of this method, measurements required for breath-by-breath gas-exchange models can be made easily and reliably in the clinical setting.

Algorithms↗

The effect of inspired oxygen concentration on the ventilation-perfusion distribution in inhomogeneous lungs.

The coupled conservation of mass equations for oxygen, carbon dioxide and nitrogen are written down for a lung model consisting of two homogeneous alveolar compartments (with different ventilation-perfusion ratios) and a shunt compartment. As inspired oxygen concentration and oxygen consumption are varied, the flux of oxygen, carbon dioxide and nitrogen across the alveolar membrane in each compartment varies. The result of this is that the expired ventilation-perfusion ratio for each compartment becomes a function of inspired oxygen concentration and oxygen consumption as well as parameters such as inspired ventilation and alveolar perfusion. Another result is that the "inspired ventilation-perfusion ratio and the "expired ventilation-perfusion ratio differ significantly, under some conditions, for poorly ventilated lung compartments. As a consequence, we need to distinguish between the "inspired ventilation-perfusion distribution, which is independent of inspired oxygen concentration and oxygen consumption, and the "expired ventilation-perfusion distribution, which we now show to be strongly dependent on inspired oxygen concentration and less dependent oxygen consumption. Since the multiple inert gas elimination technique (MIGET) estimates the "expired ventilation-perfusion distribution, it follows that the distribution recovered by MIGET may be strongly dependent on inspired oxygen concentration.

Administration, Intranasal↗

An IBM PC-based system for the assessment of cardio-respiratory function using oscillating inert gas forcing signals.

OBJECTIVE: An IBM PC-based real-time data acquisition, monitoring and analysis system was developed for the assessment of cardio-respiratory function, i.e. airway dead space, alveolar volume and pulmonary blood flow, using oscillating inert inspired gas forcing signals. METHODS: The forcing gas mixture was generated by an in-house sinusoid gas delivery unit. The system interfaced with a mass spectrometer and an airway flow transducer, and performed real-time tracking of the breath-by-breath end-inspired, end-expired and mixed-expired concentrations. It calculated the cardiorespiratory parameters using two, i.e. continuous and tidal, in-house mathematical models of the lungs. The system's performance was evaluated using a mechanical bench lung, laboratory subjects and awake adults breathing spontaneously. Its predictive accuracy was compared with the measured volumes of the bench lung; single breath CO2 test for airway dead space and N2 washout for alveolar volume in laboratory subjects and awake adults; and thermal dilution technique for pulmonary blood flow in laboratory subjects. RESULTS: Close agreements were found between the true and predicted airway dead space, i.e. mean differences of -12.39%, 14.47% and -17.49%, respectively, and that of alveolar volume, i.e. -8.03%, -3.62% and 7.22%, respectively, in the bench lung, laboratory subject and awake adult studies; and that of pulmonary blood flow (-23.81%) in the laboratory subjects using the continuous lung model. Even closer agreements were observed for airway dead space (-5.8%) and alveolar volume (-4.01%) of the bench lung and for pulmonary blood flow (-8.47%) in the laboratory subjects using the tidal lung model. CONCLUSIONS: A system was developed to deliver, monitor and analyse on-line, and in real-time, output data from the sinusoid forcing technique. The technique was administered using the system in various subjects, and produced favourable predictions.

Adult↗

Within-breath arterial PO2 oscillations in an experimental model of acute respiratory distress syndrome.

Tidal ventilation causes within-breath oscillations in alveolar oxygen concentration, with an amplitude which depends on the prevailing ventilator settings. These alveolar oxygen oscillations are transmitted to arterial oxygen tension, PaO2, but with an amplitude which now depends upon the magnitude of venous admixture or true shunt, QS/QT. We investigated the effect of positive end-expiratory pressure (PEEP) on the amplitude of the PaO2 oscillations, using an atelectasis model of shunt. Blood PaO2 was measured on-line with an intravascular PaO2 sensor, which had a 2-4 s response time (10-90%). The magnitude of the time-varying PaO2 oscillation was titrated against applied PEEP while tidal volume, respiratory rate and inspired oxygen concentration were kept constant. The amplitude of the PaO2 oscillation, delta PaO2, and the mean PaO2 value varied with the level of PEEP applied. At zero PEEP, both the amplitude and the mean were at their lowest values. As PEEP was increased to 1.5 kPa, both delta PaO2 and the mean PaO2 increased to a maximum. Thereafter, the mean PaO2 increased but delta PaO2 decreased. Clear oscillations of PaO2 were seen even at the lowest mean PaO2, 9.5 kPa. Conventional respiratory models of venous admixture predict that these PaO2 oscillations will be reduced by the steep part of the oxyhaemoglobin dissociation curve if a constant pulmonary shunt exists throughout the whole respiratory cycle. The facts that the PaO2 oscillations occurred at all mean PaO2 values and that their amplitude increased with increasing PEEP suggest that QS/QT, in the atelectasis model, varies between end-expiration and end-inspiration, having a much lower value during inspiration than during expiration.

Animals↗

Response-time enhancement of a clinical gas analyzer facilitates measurement of breath-by-breath gas exchange.

Tidal ventilation gas-exchange models in respiratory physiology and medicine not only require solution of mass balance equations breath-by-breath but also may require within-breath measurements, which are instantaneous functions of time. This demands a degree of temporal resolution and fidelity of integration of gas flow and concentration signals that cannot be provided by most clinical gas analyzers because of their slow response times. We have characterized the step responses of the Datex Ultima (Datex Instrumentation, Helsinki, Finland) gas analyzer to oxygen, carbon dioxide, and nitrous oxide in terms of a Gompertz four-parameter sigmoidal function. By inversion of this function, we were able to reduce the rise times for all these gases almost fivefold, and, by its application to real on-line respiratory gas signals, it is possible to achieve a performance comparable to the fastest mass spectrometers. With the use of this technique, measurements required for non-steady-state and tidal gas-exchange models can be made easily and reliably in the clinical setting.

Algorithms↗

The effect of the width of the ventilation-perfusion distribution on arterial blood oxygen content.

We investigate the effect of the width of ventilation-perfusion distributions on arterial blood oxygen content. We assume that the perfusion within the alveolar volume is a continuous function of ventilation-perfusion ratio, known as the continuous ventilation-perfusion distribution, and then write down the conservation of mass equations in the lung incorporating the nonlinear relationship between oxygen concentration in the gas phase and blood oxygen content. We solve these equations for various unimodal and bimodal ventilation-perfusion distributions believed to occur in practice and calculate the arterial blood oxygen content in each case. When a subject has a unimodal ventilation-perfusion distribution we show that the fraction of cardiac output to that mode (i.e. the fraction of non-shunted blood) has a large effect on arterial oxygen blood content. However, the width of the distribution has only a negligible effect on arterial oxygen blood content. For a bimodal ventilation-perfusion distribution the location and fraction of cardiac output to each mode has a large effect on arterial oxygen blood content. Again, the width of each mode of the distribution has little effect on arterial oxygen blood content. As a result there is little point, from a clinical perspective, in developing techniques for investigating the width of modes of these distributions since all relevant clinical information is contained in the nature (i.e. unimodal or bimodal) and in the location of the modes.

Arteries↗

A tidal breathing model for the multiple inert gas elimination technique.

The tidal breathing lung model described for the sine-wave technique (D. J. Gavaghan and C. E. W. Hahn. Respir. Physiol. 106: 209-221, 1996) is generalized to continuous ventilation-perfusion and ventilation-volume distributions. This tidal breathing model is then applied to the multiple inert gas elimination technique (P. D. Wagner, H. A. Saltzman, and J. B. West. J. Appl. Physiol. 36: 588-599, 1974). The conservation of mass equations are solved, and it is shown that 1) retentions vary considerably over the course of a breath, 2) the retentions are dependent on alveolar volume, and 3) the retentions depend only weakly on the width of the ventilation-volume distribution. Simulated experimental data with a unimodal ventilation-perfusion distribution are inserted into the parameter recovery model for a lung with 1 or 2 alveolar compartments and for a lung with 50 compartments. The parameters recovered using both models are dependent on the time interval over which the blood sample is taken. For best results, the blood sample should be drawn over several breath cycles.

Humans↗

A mathematical evaluation of the multiple breath nitrogen washout (MBNW) technique and the multiple inert gas elimination technique (MIGET).

We consider two and 50 compartment lung models for use with two techniques used to investigate the efficiency of the lungs: the Multiple Breath Nitrogen Washout (MBNW) technique used for investigating the ventilation-volume distribution; and the Multiple Inert Gas Elimination Technique (MIGET) used for investigating the ventilation-perfusion distribution. In each of these techniques pulmonary respiratory gas exchange is described by conservation of mass equations which may be written in identical form, and in each the underlying distributions of ventilation to volume and ventilation to perfusion are assumed to be continuous functions (usually assumed to be a linear sum of log-normal distributions). The mathematical models used to describe the lung have predominantly used a collection of discrete compartments to approximate these continuous distributions. The most commonly used models have used one, two or 50 compartments. In this paper, we begin by showing that in the limit as the width of the peaks of the distribution tend to zero, the continuous distributions may be replaced by a single discrete compartment placed at each peak of the distribution. We investigate the various methods used previously for parameter recovery, and show that one commonly used method for the MBNW is not suitable and suggest a modification to this recovery technique. Using simulated error-free data, we show that both the two compartment model and the 50 compartment model contain information about the ventilation-volume (or ventilation-perfusion) distribution, and investigate the extent to which this information can be used to recover the parameters which define these distributions. We go on to use Monte-Carlo methods to investigate the stability of the recovery process.

Breath Tests↗

Pulmonary blood flow measured by inspiratory inert gas concentration forcing oscillations.

The aim of this study was to discover if the forced inspired inert gas sinewave technique could be used to measure pulmonary blood flow, using nitrous oxide as the indicator gas, following inotropic stimulation of the heart by dobutamine, in the presence of a constant alveolar ventilation. Cardiac output (range 1-4.5 L min(-1)) was measured in six dogs by thermodilution and by calculation from the sinusoidal expired partial pressures of argon and nitrous oxide using: (i) analytical equations and a conventional continuous ventilation three-compartment lung model, which did not include recirculation; and (ii) a digital simulation tidal ventilation lung model (Gavaghan and Hahn, 1996. Respir. Physiol. 106, 209-221) which was adapted to include nitrous oxide mixed-venous recirculation from a combined single viscera compartment. The continuous ventilation model calculations always underestimated thermodilution cardiac output, with the bias error increasing to almost -1 L min(-1) at the longest forcing periods, 4-5 min. In contrast, the tidal ventilation model calculations were in close agreement to thermodilution cardiac output, with biases of -0.04 and -0.26 L min(-1) at forcing periods of 2 and 3 min, respectively.

Administration, Inhalation↗

Electrochemical analysis of clinical blood-gases, gases and vapours.

This tutorial review charts the development of electrochemical sensors for the analysis of blood-gases, gases and vapours in clinical medicine over the past four decades. The development of each sensor is set in its historical and clinical context, and the first part of the review concentrates on aqueous electrolyte electrochemistry and on those sensors which have made a major impact on the clinical measurement of the partial pressures of oxygen and carbon dioxide in the blood. The electrochemical interference effects of anaesthetic agents on these measurements are also described. Those electrochemical sensors which have failed, in the past, to make a clear impact in this area are not considered, but the few attempts to devise aqueous electrolyte electrochemical sensors for anaesthetic agent measurement are reviewed. The second part of the review describes the chequered history of the development of non-aqueous solvent electrochemical sensors to measure the partial pressures of oxygen and carbon dioxide, in both the presence and absence of each other, in the gas phase. The last part of the review examines various attempts, using non-aqueous solvent electrochemistry, to measure the concentration of inhalational anaesthetic vapours in the gas phase. These sensors have yet to make an impact on clinical practice. Throughout this tutorial review, theoretical models of membrane-covered electrochemical sensors are described where appropriate. This review represents a personal view of the development of electrochemical sensors for clinical measurement, and it is therefore necessarily selective in its approach and emphasis.

Anesthetics↗

A reconciliation of continuous and tidal ventilation gas exchange models.

Continuous-ventilation mathematical gas exchange models are widely used since their analytical equations are amenable to physiological interpretation. They describe qualitatively the respiratory system's response to changing physiological conditions, but do not calculate accurate values for respiratory parameters when experimental tidal ventilation expired gas data are inserted into their analytical expressions. A simple mathematical expression is presented to reconcile continuous and tidal ventilation gas exchange models. Tidal ventilation experimental data can then be inserted into conventional continuous ventilation equations to produce more accurate measures of lung volume. This hypothesis is tested with controlled experimental tidal ventilation tracer gas data obtained from both wash-out and forced inspired sinusoid experiments, using a mechanical lung model with known volume; tidal volume, VT; and series 'airway' dead space VD. We show that the subtraction of 1/2 (VT + VD) from the lung volume calculated from the continuous ventilation theory can produce lung volume measurements which agree with the true lung volume to within +/-5%, for physiological lung volume values, for both wash-out and forced sinusoid techniques.

Argon↗

Oxygen transport with oscillations of inspired oxygen concentration.

A theoretical model predicts that forced inspiratory oxygen concentration oscillations can be used to recover cardiorespiratory data and elicit information about the oxygen transport system (Hahn, 1996). The effects of hypoxia on the penetration of these generated oxygen oscillations into arterial and venous blood were explored in dogs exposed to a graded severity of hypoxia. Continuously recorded sinusoidal oxygen oscillations in the respired partial pressure, blood tension and mixed-venous saturation show that the transmission of forced oxygen oscillations from the lungs to the arterial blood depends on the mean arterial saturation. When mean inspired oxygen is high enough to fully saturate arterial haemoglobin, an inspired oscillation can only be transmitted in the blood as an oscillation in oxygen tension. However, in the presence of arterial hypoxaemia, oscillations in both the oxygen saturation and partial pressure of arterial blood are observed. Under these conditions, the oxygen saturation and partial pressure oscillations are also transmitted to mixed-venous blood. Our data illustrates that the link between the arterial and mixed-venous oscillations is non-linear and dependent on the sigmoidal binding relationship between oxygen and haemoglobin.

Animals↗

Alveolar and dead space volume measured by oscillations of inspired oxygen in awake adults.

Forced sinusoidal oscillations in the inspired concentration of a low-solubility inert gas can be used to measure airways dead space and alveolar volume. When inspired oxygen is oscillated about its mean value in the same way, the ratio between the amplitudes of the resulting end-expired and inspired oxygen oscillations is the same as that of an inert gas such as argon. Thus, oxygen forcing oscillations can be used to measure lung volume. In nine healthy spontaneously breathing adults, the FIO2 (mean FIO2 = 0.26, mean minute volume = 8.5 L/min) was forced to sinusoidally oscillate with an amplitude of +/- 0.04. The mean airways dead space measured using FIO2 oscillations with a forcing period of 3 min was 0.17 +/- 0.04 L, and the airways dead space measured by a single-breath C02 technique was no different at 0.19 +/- 0.03 L. An oxygen oscillation of the same period measured the mean end-expired alveolar volume at 3.1 +/- 0.7 L. Adding together the airways dead space and end-expired alveolar volume, obtained by the oxygen oscillation technique, provided a measure of FRC that at 3.3 +/- 0.7 L matched the FRC of 3.3 +/- 0.8 L measured by whole-body plethysmography. A third measure of FRC using a multiple-breath nitrogen washout technique gave a smaller volume of 3.00 +/- 0.85 L. The advantage of using FIO2 oscillations is that accurate FRC measurements can be made continuously, without interfering with the subject's natural breathing rhythm.

Adult↗