Continuous monitoring of blood glucose

Continuous blood glucose monitoring aims to: better evaluate glycaemic variations; better detect hypoglycaemia; and, ultimately, automatize insulin delivery (artificial beta cell). The sensors can be fully implantable, with the challenge of constructing durable systems to avoid repeated implantations. In-dwelling needle-like electrodes and microdialysis fibres with a pump that brings the dialysate to the glucose sensor are inserted in the subcutaneous tissue through the skin. The GlucoWatch is an almost non-invasive technique that extracts the extracellular fluid by iontophoresis. In these systems, the glucose oxidase generates the electrical signal, proportional to the glucose concentration. Non-invasive techniques aim at measuring the glucose concentration without breaching the skin, using absorption of light in the infrared spectrum. These techniques have not reached the necessary reliability for use as glycaemic alarms, and even less as artificial beta cells. Currently, glucose sensors are mainly used as glycaemic holters to help in the management of insulin therapy.     

Continuous monitoring of right ventricular volume changes using a conductance catheter in the rabbit.

To assess the reliability of conductance (G) catheter for evaluating right ventricular (RV) volume changes, a miniature (3.5F) six-electrode catheter was developed and tested in 11 New Zealand rabbit hearts. In five animals the heart was excised; in six it was left in the thorax. RV conductance was recorded while the RV was filled with blood in 0.25-ml steps at different left ventricular (LV) volumes. Linear correlation of measured conductance vs. reference volumes was computed. RV conductance was highly correlated with reference volume [correlation coefficient (r) ranging from 0.991 to 0.999]. Slope of regression lines was not significantly affected by LV volume variations in 1-ml steps or by acute conductance changes of structures surrounding the heart, whereas the intercept was affected only by the 0- to 1-ml LV volume change. In four rabbits, RV conductance changes during a cardiac cycle [stroke volume- (SV) G] were compared in vivo with electromagnetic flow probe-derived estimates of SV (SVem) as stroke volume was varied by graded inferior vena caval occlusion. SV-G correlated well with SVem (r ranging from 0.92 to 0.96). This correlation persisted after the thorax was filled with saline; however, significant differences were found in individual slopes (P < 0.001). These results show that the conductance catheter has a potential to reliably monitor in vivo relative RV volume changes in small-animal hearts.     

Continuous cardiac output monitoring in humans by invasive and noninvasive peripheral blood pressure waveform analysis.

We present an evaluation of a novel technique for continuous (i.e., automatic) monitoring of relative cardiac output (CO) changes by long time interval analysis of a peripheral arterial blood pressure (ABP) waveform in humans. We specifically tested the mathematical analysis technique based on existing invasive and noninvasive hemodynamic data sets. With the former data set, we compared the application of the technique to peripheral ABP waveforms obtained via radial artery catheterization with simultaneous thermodilution CO measurements in 15 intensive care unit patients in which CO was changing because of disease progression and therapy. With the latter data set, we compared the application of the technique to noninvasive peripheral ABP waveforms obtained via a finger-cuff photoplethysmography system with simultaneous Doppler ultrasound CO measurements made by an expert in 10 healthy subjects during pharmacological and postural interventions. We report an overall CO root-mean-squared normalized error of 15.3% with respect to the invasive hemodynamic data set and 15.1% with respect to the noninvasive hemodynamic data set. Moreover, the CO errors from the invasive and noninvasive hemodynamic data sets were only mildly correlated with mean ABP (rho = 0.41, 0.37) and even less correlated with CO (rho = -0.14, -0.17), heart rate (rho = 0.04, 0.19), total peripheral resistance (rho = 0.38, 0.10), CO changes (rho = -0.26, -0.20), and absolute CO changes (rho = 0.03, 0.38). With further development and successful prospective testing, the technique may potentially be employed for continuous hemodynamic monitoring in the acute setting such as critical care and emergency care.     

Continuous intra-arterial blood gas monitoring in rats

Studies on lung injury and its treatment options are often performed on small animals like rats. Because conventional blood gas analyses may not detect rapid changes in gas exchange during respiratory distress syndrome and intermittent blood withdrawal can result in hypo-volaemia and anaemia, we tested the applicability and accuracy of a continuous intravascular blood gas monitor (Paratrend 7+). Anaesthetized and ventilated rats with a body weight of 398 +/-45 g (n =22) had a 20-gauge cannula inserted in both carotid arteries. A photochemical blood gas sensor for continuous measurement (Paratrend 7+) was advanced into the aorta via the left carotid artery. Blood was sampled for intermittent blood gas analysis by means of the right carotid artery. Arterial pO(2) was varied by applying different inspiratory oxygen concentrations, and arterial pCO(2) by applying different respiratory rates. Paired blood gas measurements (n =136) were analysed over a wide range of pO(2) values (5.3-76.8 kPa). We found an acceptable correlation for pO(2) (r(2)=0.98), pCO(2) (r(2)=0.96) and pH (r(2)=0.92). The calculated bias and imprecision for pO(2) was -1.0 +/- 3.3 kPa, for pCO(2) 0.04 +/- 0.28 kPa and for hydrogen ion concentration -0.05 +/-2.2 nmol/l. We conclude that in rats, continuous blood gas monitoring with a photochemical blood gas sensor provides pO(2), pCO(2) and pH measurements with acceptable accuracy.     

Continuous monitoring of urea in blood during dialysis

Urease was immobilized to porous glass and used in combination with a conductivity meter for determining urea in standard solutions as well as in blood from a patient undergoing dialysis. The sampling unit involves a possibility for heparinization at the sampling point and a dialysis step prior to exposure to the enzyme column. The unit operates in a linear mode in the concentration range 5-50 mM. Monitoring of dialysis process gave good correlation with off-line analyses.     

Continuous blood gas and lactate monitoring during exercise

An improved computer method for continuous monitoring of arterial blood gases synchronized with an analysis of ventilatory variables was developed. Lactate was determined every 30 s. Sixteen healthy male volunteers who exercised regularly were included in this study. To evaluate the different transients of ventilation and metabolism, a gradual increase in the work load was used, starting with 40 W and increasing the load by 20 W every 2 min. This method generates large amounts of data and requires the development of computer programs for automatic determination of break points and general data reduction.     

Continuous monitoring of lactate during exercise in humans using subcutaneous and transcutaneous microdialysis

We have evaluated the possibility of monitoring the plasma lactate concentration in human volunteers during cycle ergometer exercise using subcutaneous and transcutaneous microdialysis. In transcutaneous microdialysis, the relative increase in dialysate lactate concentration exceeded that of plasma lactate concentration by a factor of 6 during exercise due to exercise-induced lactate secretion in sweat. During exercise the subcutaneous microdialysis dialysate lactate concentration underestimated the plasma lactate concentration possibly due to diffusion limitation or adipose tissue lactate production. While it was demonstrated that microdialysis can be used for on-line lactate monitoring, neither subcutaneous nor transcutaneous dialysate lactate concentration were linearly related to the plasma lactate concentration during exercise, and it was found therefore that it was not possible to monitor directly plasma lactate concentration during exercise.     

Exercise-induced changes in blood zinc and related proteins in humans

Effects of cycle ergometer exercise (approximately 75% maximum ventilatory O2 consumption for 30 min) on the concentrations of zinc and related proteins in erythrocytes and/or plasma were studied on 11 sedentary male students. Lower concentrations of total zinc and of zinc derived from carbonic anhydrase I type (CA-I) in erythrocytes were observed immediately after exercise, but they disappeared after 30 min of rest. The change in total zinc concentration in erythrocytes correlated well with that in CA-I concentration immediately after exercise, as well as after rest. The concentration of carbonic anhydrase II type (CA-II)-derived zinc did not vary substantially at any time. On the other hand, there were significant increases in the plasma concentrations of total zinc and of alpha 2-macroglobulin (alpha 2-MG)-bound zinc immediately after exercise, whereas no such effect was noted in albumin-bound zinc. A positive correlation was found between total zinc and alpha 2-MG concentrations in plasma immediately after exercise. In addition, the change in the activity of alkaline phosphatase, a zinc metalloenzyme, correlated well with that in the total zinc concentration in plasma. These results suggest that a brief physical exercise induces the movement of zinc into plasma.     

Changes of blood volume distribution by postural changes in rats

During a space flight the human body responds to many different gravities. The launching of the rocket, the weightlessness, the re-entry of the spacecraft, and other factors influence the astronaut's body. The fluid shifts and the effect on the cardiovascular system arising from these gravitational changes have been frequently studied in space medicine by using body tilting, lower body negative pressure (LBNP) and centrifugal accelerators. There exist, however, few reports about the changes in whole body blood volume distribution caused by body tilting. These changes can be measured using radioisotopes: scintigraphy using 99mTechnetium-labeled human serum albumin (99mTc-HSA), etc. In humans, however, because the visual field of the scintillation camera is so small, the simultaneous measurement of whole body blood volume distribution cannot be done during body tilting. We therefore used rats, whose whole bodies can be encompassed within the visual field of the camera, and we discussed the changes in blood volume distribution induced by body tilting. We also measured the blood concentrations in each organ by using whole body autoradiography in mice, and discussed the effect of postural changes on some abdominal organs.     

Relationship of gastric emptying and volume changes after a solid meal in humans

Noninvasive imaging has been developed to measure gastric volumes. The relationship between gastric emptying and volume postprandially is unclear. The aims were to 1) develop a 3-dimensional (3D) single photon emission-computed tomography (SPECT) method to simultaneously measure gastric volume and emptying postprandially, 2) describe the course of gastric volume change during emptying of the meal, and 3) assess a 3D method measuring gastric emptying. In 30 healthy volunteers, we used (111)In-planar and (99m)Tc-SPECT imaging to estimate gastric emptying and volume after a radiolabeled meal. A customized analysis program of SPECT imaging assessed gastric emptying. A Bland-Altman plot assessed the performance of the new SPECT analysis compared with planar analysis. Gastric volume postprandially exceeds the fasting volume plus meal volume. The course of volume change and gastric emptying differ over time. Higher differences in volumes exist relative to fasting plus residual meal volumes at 15 min (median 763 vs. 568 ml, respectively, P < 0.001), 1 h (median 632 vs. 524 ml, P < 0.001), and 2 h (median 518 vs. 428 ml, P < 0.02), in contrast to similar volumes at 3 h (median 320 vs. 314 ml, P = 0.85). Analysis of SPECT imaging accurately measures gastric emptying compared with planar imaging with median differences of 1% (IQR -2.25 to 2.0) at 1 h, 1% (-3.25 to 2.25) at 2 h, and -2.5% (-4 to 0) at 3 h. Gastric volume exceeds meal volume during the first 2 postprandial hours, and simultaneous measurements of gastric volume and emptying can be achieved with a novel 3D SPECT method.     

Continuous non-invasive blood pressure monitoring in patients with sleep disorders.

Sleep related breathing disorders are of high prevalence and are often associated with essential hypertension. It is therefore necessary to study blood pressure continuously in all patients with sleep related breathing disorders and arterial hypertension as well as in all patients with essential hypertension and suspected sleep apnoea. To investigate the usefulness of a non-invasive continuous volume-clamp method during sleep we used this technique in parallel with 130 sleep recordings and performed a validation study of the Finapres instrument on a subgroup where continuous invasive blood pressure recordings were available. Absolute pressure values of Finapres are valid when the position and the movement of the sensor were carefully observed and only appropriate segments of the recordings were taken for further evaluation. The high beat to beat resolution of the systolic and diastolic pressure is the main advantage of this non-invasive technique because it reflects rapid blood pressure variations as they occur in sleep related breathing disorders. This could be investigated only invasively until now.     

A new method to study changes in microvascular blood volume in muscle and adipose tissue: real-time imaging in humans and rat

We employed and evaluated a new application of contrast-enhanced ultrasound for real-time imaging of changes in microvascular blood volume (MBV) in tissues in females, males, and rat. Continuous real-time imaging was performed using contrast-enhanced ultrasound to quantify infused gas-filled microbubbles in the microcirculation. It was necessary to infuse microbubbles for a minimum of 5-7 min to obtain steady-state bubble concentration, a prerequisite for making comparisons between different physiological states. Insulin clamped at a submaximal concentration (～75 μU/ml) increased MBV by 27 and 39% in females and males, respectively, and by 30% in female subcutaneous adipose tissue. There was no difference in the ability of insulin to increase muscle MBV in females and males, and microvascular perfusion rate was not increased significantly by insulin. However, perfusion rate of the microvascular space was higher in females compared with males. In rats, insulin clamped at a maximal concentration increased muscle MBV by 60%. Large increases in microvascular volume and perfusion rate were detected during electrical stimulation of muscle in rats and immediately after exercise in humans. We have demonstrated that real-time imaging of changes in MBV is possible in human and rat muscle and in subcutaneous adipose tissue and that the method is sensitive enough to pick up relatively small changes in MBV when performed with due consideration of steady-state microbubble concentration. Because of real-time imaging, the method has wide applications for determining MBV in different organs during various physiological or pathophysiological conditions.