In vivo experiments with a pH-ISFET electrode

The_{in vivo} stability and pH sensitivity of 19 intravascular pH electrodes for continuous monitoring have been investigated. The sensors were mounted in indwelling vascular catheters (7F) which were inserted into the arteries of seven anaesthetised and mechanically ventilated dogs. Variations in arterial pH, ranging from 6·82 to 7·72, were obtained by infusion of sodium bicarbonate and hydrochloric acid and by hyper/ hypoventilation with various volume fractions of carbon dioxide in the inspiratory gas mixture. The pH sensor output potential was compared within vitro pH determinations of arterial blood samples. After an initial stabilisation period following their introduction into the arterial blood, the electrodes showed an average long-term drift of 2·3 mVh⁻¹. When this drift was taken into account, a typical pH sensitivity of 50 mV per pH was found. The relationship between the electrode potentials and thein vitro pH values was linear and in almost all cases the correlation coefficient (r) was above 0·9. The electrodes responded rapidly enough to reflect breath-to-breath oscillations in pH.     

Analysis of small discrete samples of gas with a respiratory mass spectrometer

A technique is described for analysing small discrete samples of gas (about 100 μl) by injecting them into a stream of carrier gas being continuously sampled by a ‘respiratory’ mass spectrometer. This involves interrupting the normal respiratory monitoring use of the mass spectrometer for only 20s per sample. The theory for calculating the composition is given for the case when the carrier gas is totally different from the discrete sample, and for the case when it is air and the discrete sample may contain air. Allowance is made for difference of viscosity between sample and carrier and for different response times to different components of the sample. The method was developed for the analysis of gas bubbles equilibrated with blood. When tested on a mixture of 1·2% halothane and 5% CO₂ in 50/50 N₂O/O₂, with air as the carrier, the standard deviation between repeat determinations was about 0·5% of the actual concentration of each component.     

Spectrophotometric monitoring of arterial oxygen saturation in the fingertip

A noninvasive oximeter that analyses the oxygen saturation of arterial blood in the fingertip is described. The light, after attenuating the infrared portion to avoid thermal injury, is applied to the fingertip through an optical transmitter made of glass fibres. The transmitted light is transferred to an optical reception system where a spectrophotometric determination of oxygen saturation is performed. The determination is performed by considering only the change in the attenuation of light caused by the inflow of arterial blood into the fingertip. The correlation between the oxygen saturation measured with the present instrument (y) and that with the blood-gas method (x), was y=0·907x+8·592 with a standard deviation and a correlation coefficient of 0·135% and 0·983, respectively. The reproducibility was assessed in a healthy subject by measuring the oxygen saturation repeatedly 60 times. The mean saturation was 95·82±0·675% (mean±standard deviation). The instrument has been useful in monitoring arterial oxygenation in patients with respiratory failure in our intensive-care unit. One of the disadvantages of the instrument is that the measurement is interrupted when the fingertip changes its position against the light beam.     

A new method for noninvasive bedside determination of pulmonary blood flow

A method is presented for determining the pulmonary blood flow from measurements of the time-averaged end-tidal pCO₂ and the CO₂ output. The novel technique is based on a formula that is derived from Fick's principle in such a way that it allows a direct calculation of the lung perfusion from simultaneously measured changes in end-tidal pCO₂ and CO₂ output. These changes are induced by altering the ventilation pattern of the patient for short (30s) periods of time. Different ways of doing this are discussed and it is shown that a bidirectional change in ventilation, involving hyper- and hypoventilation patterns, most adequately corresponds to the formula derived. The method has been validated by comparison with cardiac output data obtained by thermodilution. Forty-two measurements were performed during mechanical ventilation on five dogs and six patients with essentially healthy lungs. Lung perfusion was in the range 0·4–6·5l/min. We found that Q_{CO 2}=0·97 Q_thermo with a s.d.=18%. The reproducibility of individual measurements was better than 0·3l/min.     

System for long-term measurement of cerebral blood and tissue oxygenation on newborn infants by near infra-red transillumination

The technique of near-infra-red spectroscopy allows safe continuous monitoring of changes in blood and tissue oxygenation on an intact organ. This is made possible by observing spectral changes in the tissues caused by oxygenated haemoglobin [HbO₂], deoxygenated haemoglobin [Hb] and cytochrome aa₃ [Cyt aa₃]. The paper describes the design and performance of an instrument that has been developed to apply this technique to the monitoring of the brain in newborn infants. The instrument monitors optical transmission changes across a newborn infant's brain at four wavelengths. A standard deviation in error of 1 per cent (0·01 optical density OD) is achieved on measurements of transmission changes at 20s intervals. This performance is obtained at a mean attenuation of 10 OD, the approximate attenuation across a term infant's head. Long-term monitoring is possible as instrumental drift is less than 0·004 OD per hour.     

Saline conductivity method for measuring cardiac output simplified

Although hypertonic saline was the first indicator used for the determination of cardiac output, the saline conductivity method has never been clinically practicable because of the difficulty of calibrating it. For a conductivity cell we have used a standard bipolar pacing wire placed in the pulmonary artery and have excited the a.c. Wheatstone bridge circuit with an 8·9 kHz sinewave.In vitro we have shown that there is a linear change in the impedance of the blood between the electrodes following the injection of unit volumes of hypertonic saline into a litre of blood. The amount of this change is dependent on haematocrit (H) and is largely independent of flow and of temperature. Using the calibration factor we derived (0·57×e^0·0396×H×(1−H/100) μ/ml 7·2% NaCl/litre of blood), the saline conductivity method correlated well (r=0·92, n=88) with the indocyanine green technique for measuring cardiac output in three dogs.     

In vivo assessment of catheter-tip PO2 sensor: sampling lumen fabrication

Fabrication of the sampling lumen of an intra-arterial PO₂ sensor is performed in standard catheters mechanically or by laser. Clinical evaluation is performed with respect to catheter insertion, complications, accuracy of oxygen sensor data and fibrin deposition on the catheter surface. The success rate for catheter insertion is 57% for 138 standard and 50% for 74 laser-cut catheters studied. The proportion of catheter failures (blocked or non-reading) is 14% in laser-cut compared with 30% in standard. These differences are not statistically significant at the 5% level. There is no clinically significant difference in sensor accuracy, with 37·5% of results within ±0·0.5 kPa and 80% within ±2·0 kPa of simultaneous blood gas values. Drift is within ±0·3 kPa h⁻¹ for 78% of monitoring time. Significant errors of recalibration occur in 6% of calibrations. Scanning electron micrographs demonstrate a much smaller sampling lumen in the laser-cut group, but no reduction in fibrin deposition at the site of the sampling hole. The low success rate for catheter insertion is a problem because of cost implications. The accuracy of the system is usually sufficient for clinical purposes, provided the calibration is checked every 4 h.     

Dose-related elevations in venous pH with citrate ingestion do not alter 40-km cycling time-trial performance

The purpose of the current investigation was to determine whether sodium citrate enhances endurance cycling performance and, if so, what dosage(s) produces this effect. Eight trained [peak power output: 362 (48) W; power:weight: 5.1 (0.4) W · kg⁻¹, mean (SD)] male cyclists were requested to complete four, 40-km time-trials, each separated by 3–7 days, on their own bicycles, mounted on a Kingcycle ergometer. To mimic the stochastic nature of cycle road races, the time-trials included four 500-m, four 1-km and two 2-km sprints. The experimental conditions involved the ingestion of three dosages of sodium citrate dissolved in 400 ml water: 0.2 g · kg⁻¹, 0.4 g · kg⁻¹ and 0.6 g · kg⁻¹ body mass (b.m.) and a placebo (calcium carbonate, 0.1 g · kg⁻¹ b.m.). Subjects were asked to complete both the sprints and total distance in the fastest time possible. Venous blood samples were collected before, as well as at 10-km intervals during the trials for the analysis of plasma lactate and glucose concentrations and for the measurement of blood pH and PCO₂ levels. Immediately before, as well as during exercise, pH was significantly higher in the group ingesting the highest citrate dose (range 7.36–7.45) compared to the placebo (range 7.31–7.39) and the two lower citrate dosages. Despite this, no significant differences in power output (P=0.886) or time taken to complete the 40 km (P=0.754) were measured between the four trials. The average performance times (in min:s, with SD in parentheses) and average power output (in W) for the 40-km time-trials were: 58:46 (5:06) [265 (62) W], 60:24 (6:07) [251 (59) W], 61:47 (5:07) [243 (44) W] and 60:02 (5.05) [255 (55) W] for the 0.2, 0.4, 0.6 g · kg⁻¹ b.m. sodium citrate and placebo trials, respectively. There were also no significant differences measured between treatments in terms of time, power output, speed or heart rate during the 500-m, 1-km and 2-km sprints. The ingestion of increasing sodium citrate dosages before exercise produced dose-dependent changes in pH, base excess and HCO⁻ ₃ concentrations before and during the 40-km time-trial. However, these changes influenced neither the time-trial time nor the sprinting performance times. Accepted: 7 June 2000     

In vivo evaluation of signal processors for laser Doppler tissue flowmeters

The performance of different signal processors for laser Doppler tissue flowmeters was evaluated by the use of a well defined flow model comprising a segment of the feline intestinal wall. The processor that, apart from being based on the calculation of the first moment of the power spectral density, also takes into account the effect of multiple scattering in a number of blood cells gave an output signal that was linearly related to the intestinal wall perfusion as recorded independently by a drop-counting technique. At a recording bandwidth of 12 kHz, this linear relationship was valid for the entire flow range 0–300 ml min⁻¹ 100 g⁻¹ (r=0·98). The processor based on the first moment of the power spectral density alone under-estimated the highest flow rates by about 35 per cent, while within the flow range 0–100 ml min⁻¹ 100 g⁻¹ this processor also gave an output signal linearly related to flow at a recording bandwidth of 12 kHz (r=0·96). When the bandwidth was limited to 4 kHz, the output signals from both processors were linearly related to flow only within the range 0–100 ml min⁻¹ 100 g⁻¹ (r=0·90). The output signals recorded with the 4 kHz systems were, however, generally only about 65 per cent of those recorded with the 12 kHz systems.     

Effects of active recovery on power output during repeated maximal sprint cycling

The effects of active recovery on metabolic and cardiorespiratory responses and power output were examined during repeated sprints. Male subjects (n = 13) performed two maximal 30-s cycle ergometer sprints, 4 min apart, on two separate occasions with either an active [cycling at 40 (1)% of maximal oxygen uptake; mean (SEM)] or passive recovery. Active recovery resulted in a significantly higher mean power output ( ) during sprint 2, compared with passive recovery [ ] 603 (17) W and 589 (15) W, P < 0.05]. This improvement was totally attributed to a 3.1 (1.0)% higher power generation during the initial 10 s of sprint 2 following the active recovery (P < 0.05), since power output during the last 20 s sprint 2 was the same after both recoveries. Despite the higher power output during sprint 2 after active recovery, no differences were observed between conditions in venous blood lactate and pH, but peak plasma ammonia was significantly higher in the active recovery condition [205 (23) vs 170 (20) μmol · 1⁻¹;P < 0.05]. No differences were found between active and passive recovery in terms of changes in plasma volume or arterial blood pressure throughout the test. However, heart rate between the two 30-s sprints and oxygen uptake during the second sprint were higher for the active compared with passive recovery [148 (3) vs 130 (4) beats · min⁻¹;P < 0.01) and 3.3 (0.1) vs 2.8 (0.1) 1 · min⁻¹;P < 0.01]. These data suggest that recovery of power output during repeated sprint exercise is enhanced when low-intensity exercise is performed between sprints. The beneficial effects of an active recovery are possibly mediated by an increased blood flow to the previously exercised muscle.     

The importance of blood resistivity in the measurement of cardiac output by the thoracic impedance method

Twenty simultaneous pairs of cardiac output values from patients who did not have valvular abnormalities were obtained by the radioisotope method and the electrical-impedance method of Kubicek et al. (1966). If a standard value of 150Ω-cm was assumed for the resistivity of each patient's blood, the mean value for the impedance cardiac output was 14·5% high compared with the mean radioisotope value. In this study the patient's haematocrits ranged from 20 to 48%. Inserting the appropriate value of the resistivity for each patient into the stroke volume equation of Kubicek from the data of Geddes and Sadler (1973) made the mean impedance value 10·3% low compared with the mean isotope value. The use of our measured resistivity data made the mean impedance cardiac output value 21·5% lower than the mean isotope value. The correlation coefficient between the impedance and isotope techniques was 0·61 for the standard value of resistivity of 150Ω-cm. Using the resistivity data of Geddes and Sadler (1973) the correlation became 0·87, and with our data it was 0·88.     

In vitro,in vivo and numerical assessment of the working principle of the truCCOMS™ continuous cardiac output catheter system

The truCCOMS? cardiac output monitor system provides a continuous and instantaneous measurement of cardiac output, derived from the amount of energy required for heating a filament to maintain a fixed 2 °C blood temperature difference between two thermistors located distally on a pulmonary artery catheter. Clinical studies, however, reported relatively poor accuracy of the cardiac output estimation, possibly due to linearly assumed power–cardiac output relationship used for calibration of the catheters. We experimentally studied the shape of the truCCOMS? calibration relationship (i) in a hydraulic bench model of the right heart and (ii) in vivo intact animal model. The results showed a nonlinear relationship between the power input into the heating element and the cardiac output; which could satisfactorily be described with an exponential relationship. Comparison of the performance of the same catheters in vitro and in vivo showed that the in vitro determined calibration relationship should not be used for in vivo measurements. Finally, we also simulated the working principle of the catheter using a simplified numerical model of the blood flow and heat transfer around the catheter. The computed results also suggested a pronounced nonlinear relationship between power and cardiac output in pulsatile conditions. We conclude that the observed over- and underestimation of high- and low flows, respectively, by the current truCCOMS? system is likely to arise from its linear calibration relationship. An appropriate calibration scheme accounting for the intrinsic nonlinear power–cardiac output relationship and the difference between in vitro and in vivo conditions should improve the clinical performance of the system.     

Forearm oxygen uptake during maximal forearm dynamic exercise

Summary This study was undertaken in an attempt to determine the maximal oxygen uptake in a small muscle group by measuring directly the oxygen expenditure of the forearm. Five healthy medical students volunteered. The subjects' maximal forearm work capacity was determined on a spring-loaded hand ergometer. Exercise was continued until exhaustion by pain or fatigue. Two weeks later intra-arterial and intravenous catheters were placed in the dominant arm. Blood samples for measurement of oxygen concentration were collected via the catheters. Forearm blood flow was measured by means of the indicator dilution technique. Oxygen uptake was determined according to the Fick principle. The forearm oxygen uptake attained at maximal work loads was a mean of 201 (SD±56) μmol · min⁻¹ · 100 ml⁻¹. It was impossible at maximal exercise to discern a plateau of the oxygen uptake curve in relation to work output. It is suggested that a plateau in the oxygen uptake curve is not a useful criterion for maximal oxygen uptake in a small muscle group. Skeletal muscle may have an unused capacity for oxygen consumption even at maximal exercise intensity where muscle work cannot be continued due to muscle pain and fatigue.     

Cytosolic pH buffering during exercise and recovery in skeletal muscle of patients with McArdle’s disease

Cellular pH control is important in muscle physiology, and for interpretation of ³¹P magnetic resonance spectroscopy (MRS) data. Cellular acidification in exercise results from coupled glycolytic ATP production mitigated by cytosolic buffering, ‘consumption’ of H⁺ by phosphocreatine (PCr) breakdown, and membrane transport processes. Ex vivo methods for cytosolic buffer capacity are vulnerable to artefact, and MRS methods often require assumptions. ³¹P MRS of early exercise, when pH increases unopposed by glycolysis, is conceptually simple, but limited in normal muscle by time resolution and signal-to-noise. A therapeutic trial (Martinuzzi A et al. Musc Nerve 37: 350–357, 2007) in McArdle’s disease (glycogen phosphorylase deficiency), where pH does not decrease with exercise, offered the opportunity to test ³¹P MRS data obtained throughout incremental plantar flexion exercise and recovery in ten McArdle’s patients against the simple model of cellular pH control. Changes in pH, [Pi] and [PCr] throughout exercise and recovery were quantitatively consistent with mean ± SEM buffer capacity of 10 ± 1 mM/(pH unit), which was not significantly different from the control subjects under the initial-exercise conditions where the comparison could be made. The simple model of cellular acid–base balance therefore gives an adequate account of cellular pH changes during both exercise and recovery in McArdle’s disease.     

Force—velocity relations of nine load-moving skeletal muscles

The relationship between maximal velocity and load was studied in nine muscles of the cat’s hind limb using a technique in which the initial and final muscle lengths are determined by equilibrium of a suspended mass and the muscle’s passive and active forces elicited by tetanic stimulation. The maximal veloities of shortening during contraction under each of various loads was used to fit a Hill model using the least-squares method. It was shown that different muscles varied significantly in their ability to generate maximal velocity over a range of loads. The tibialis anterior muscle generate the highest velocity (28·4 cms⁻¹), whereas the tibialis posterior generated the lowest maximal velocity (4·2 cms⁻¹). In general, muscles with predominantly fast twitch fibres and with the largest elongation/shortening range displaced the load at the highest velocities, as compared with muscles with predominantly slow twitch and short excursion range which respond with low velocities. The a/P₀ ratio of Hill’s equation, which defines the curvature of the force velocity, also varied widely, being most monotonic (0·927) for the soleus and the steepest (0·067) for the extesor digitorum longus, further suggesting that fibre composition is also highly influential on the force—velocity relations of the muscle.     

In vitro performance test system for pulse oximeters

An in vitro system was developed capable of testing the accuracy and reproducibility of pulse oximeter readings. The pulse oximeter probe receives signals through a pulsating blood cuvette. The development of the design of the cuvette is described. Using the final design (or ‘model finger’), a comparison is made between readings from a Datex Satlite pulse oximeter (SpO₂) and saturation values obtained by use of a multiwavelength bench oximeter (SaO₂). Linear regression analysis of the data gives SpO₂=0·88 SaO₂+11·2 (r=0·979, p<0·001).     

Hydrogel basedin vivo reference electrode catheter

A hydrogel basedin vivo reference electrode catheter has been developed. A simple diffusion model of ion transport was applied to study chloride ion transport through polyhydroxyethylmethacrylate (pHEMA) membranes. Based on an experimentally derived effective diffusion coefficient of D_eff=4·04±0·5×10⁻⁸ cm²s⁻¹, a reference electrode catheter was fabricated featuring a dimensionally appropriate pHEMA porous liquid junction, a gelled Ringer's solution internal electrolyte compartment and a Ag/AgCl internal half cell. The reference electrode potential is not a function of pH from pH6 to pH9 and is linearly related to temperature by 0·33 m V^oC⁻¹. In animal trials, the intravascular catheter electrodes exhibit an average stability of ±0·92mV for 6–8h. Stability in blood can be attributed to the haemocompatibility and transport properties of pHEMA.     

Microcomputer-controlled sampling capnometer

The paper introduces the design and implementation of a new capnometer. It was developed to alleviate the problems with presently available instruments. The small sampling tube which is a trouble spot is avoided in this capnometer. The autocalibration method of the instrument eliminates the need for unwieldy gas cylinders. The instrument is easy to use in a monitoring application because the complex compensation routines are performed by the instrument rather than by the operator. The instrument’s accuracy is around 0·1 per cent.     

Noninvasive automatic determination of mean arterial pressure

A new instrument for the indirect noninvasive measurement of mean arterial pressure (m.a.p.) has been constructed and evaluated in man. The instrument does not require an external microphone or transducer and determines m.a.p. rather than systolic and diastolic pressure. Instead, the method employs the point of maximal oscillations as an indicator of m.a.p. The instrument automatically inflates a standard blood pressure cuff and determines the m.a.p. by measuring the cuff pressure oscillations as the cuff pressure is reduced by discrete increments. Cuff deflation in discrete increments, instead of continuously, allows the oscillation data obtained at each cuff pressure to be tested for artefacts and averaged, greatly enhancing artefact-rejection ability. The m.a.p. is selected as the lowest cuff pressure at which the oscillation amplitude is a maximum. The instrument was tested on the bicep and ankle in a series of 28 studies involving 17 human subjects with intra-arterial catheters. Averaging the mean errors from each of the 28 studies, there was an overall mean error of — 0·23 mmHg, with a standard deviation of 4·21 mmHg. The correlation coefficient was 0·98. The instrument was found to give good results in a wide variety of clinical subjects and physiologic states.     

Effect of compliance mismatch on flow disturbances in a model of an arterial graft replacement

Flow disturbances in a model of an interposition graft in an arterial segment were measured using an ultrasound Doppler velocimeter. The effect of the degree of compliance mismatch between a stiff ‘graft’ and compliant ‘arterial’ segments was investigated. In steady flow, disturbances were detected when the compliance ratio (stiff to compliant segments) was ≤0·1 and the Reynolds number ≥2200. A recirculation zone just downstream of the distal anastomosis was observed at a Reynolds number ≥2400. Disturbances were also measured under pulsatile flow which consisted of a time-varying component superimposed on a steady flow component. The time-varying flow component was either quasiphysiological or sinusoidal in shape. The Reynolds number was 500 but the frequency parameter varied from 4·2 to 8·5. Significant disturbances were observed for conduits with compliance ratio ≤0·19. The disturbance intensity tended to increase as the compliance ratio decreased and the frequency parameter increased. The magnitude of the disturbance was also greater with the quasiphysiological than the sinusoidal input flow waveform.