Blood Glucose Control Using a Novel Continuous Blood Glucose Monitor and Repetitive Intravenous Insulin Boluses: Exploiting Natural Insulin Pulsatility as a Principle for a Future Artificial Pancreas

The aim of this study was to construct a glucose regulatory algorithm by employing the natural pulsatile pattern of insulin secretion and the oscillatory pattern of resting blood glucose levels and further to regulate the blood glucose level in diabetic pigs by this method. We developed a control algorithm based on repetitive intravenous bolus injections of insulin and combined this with an intravascular blood glucose monitor. Four anesthetized pigs were used in the study. The animals developed a mildly diabetic state from streptozotocin pretreatment. They were steadily brought within the blood glucose target range of 4.5–6.0 mmol/L in 21 to 121 min and kept within that range for 128 to 238 min (hypoglycemic values varied from 2.9 to 51.1 min). The study confirmed our hypotheses regarding the feasibility of this new principle for blood glucose control, and the algorithm was constantly improved during the study to produce the best results in the last animals. The main obstacles were the drift of the IvS-1 sensor and problems with the calibration procedure, which calls for an improvement in the sensor stability before this method can be applied fully in new studies in animals and humans

The coherence of macrocirculation, microcirculation, and tissue metabolic response during nontraumatic hemorrhagic shock in swine

Hemorrhagic shock is clinically observed as changes in macrocirculatory indices, while its main pathological constituent is cellular asphyxia due to microcirculatory alterations. The coherence between macro‐ and microcirculatory changes in different shock states has been questioned. This also applies to the hemorrhagic shock. Most studies, as well as clinical situations, of hemorrhagic shock include a “second hit” by tissue trauma. It is therefore unclear to what extent the hemorrhage itself contributes to this lack of circulatory coherence. Nine pigs in general anesthesia were exposed to a controlled withdrawal of 50% of their blood volume over 30 min, and then retransfusion over 20 min after 70 min of hypovolemia. We collected macrocirculatory variables, microcirculatory blood flow measurement by the fluorescent microspheres technique, as well as global microcirculatory patency by calculation of Pv‐aCO2, and tissue metabolism measurement by the use of microdialysis. The hemorrhage led to anticipated changes in macrocirculatory variables with a coherent change in microcirculatory and metabolic variables. In the late hemorrhagic phase, the animals' variables generally improved, probably through recruitment of venous blood reservoirs. After retransfusion, all variables were normalized and remained same throughout the study period. We find in our nontraumatic model consistent coherence between changes in macrocirculatory indices, microcirculatory blood flow, and tissue metabolic response during hemorrhagic shock and retransfusion. This indicates that severe, but brief, hemorrhage with minimal tissue injury is in itself not sufficient to cause lack of coherence between macro‐ and microcirculation

Blood Glucose Control Using a Novel Continuous Blood Glucose Monitor and Repetitive Intravenous Insulin Boluses: Exploiting Natural Insulin Pulsatility as a Principle for a Future Artificial Pancreas

The aim of this study was to construct a glucose regulatory algorithm by employing the natural pulsatile pattern of insulin secretion and the oscillatory pattern of resting blood glucose levels and further to regulate the blood glucose level in diabetic pigs by this method. We developed a control algorithm based on repetitive intravenous bolus injections of insulin and combined this with an intravascular blood glucose monitor. Four anesthetized pigs were used in the study. The animals developed a mildly diabetic state from streptozotocin pretreatment. They were steadily brought within the blood glucose target range of 4.5–6.0 mmol/L in 21 to 121 min and kept within that range for 128 to 238 min (hypoglycemic values varied from 2.9 to 51.1 min). The study confirmed our hypotheses regarding the feasibility of this new principle for blood glucose control, and the algorithm was constantly improved during the study to produce the best results in the last animals. The main obstacles were the drift of the IvS-1 sensor and problems with the calibration procedure, which calls for an improvement in the sensor stability before this method can be applied fully in new studies in animals and humans

Cardiac power integral: a new method for monitoring cardiovascular performance

Cardiac power (PWR) is the continuous product of flow and pressure in the proximal aorta. Our aim was to validate the PWR integral as a marker of left ventricular energy transfer to the aorta, by comparing it to stroke work (SW) under multiple different loading and contractility conditions in subjects without obstructions in the left ventricular outflow tract. Six pigs were under general anesthesia equipped with transit time flow probes on their proximal aortas and Millar micromanometer catheters in their descending aortas to measure PWR, and Leycom conductance catheters in their left ventricles to measure SW. The PWR integral was calculated as the time integral of PWR per cardiac cycle. SW was calculated as the area encompassed by the pressure– volume loop (PV loop). The relationship between the PWR integral and SW was tested during extensive mechanical and pharmacological interventions that affected the loading conditions and myocardial contractility. The PWR integral displayed a strong correlation with SW in all pigs (R2 > 0.95, P < 0.05) under all conditions, using a linear model. Regression analysis and Bland Altman plots also demonstrated a stable relationship. A mixed linear analysis indicated that the slope of the SW-to-PWR-integral relationship was similar among all six animals, whereas loading and contractility conditions tended to affect the slope. The PWR integral followed SW and appeared to be a promising parameter for monitoring the energy transferred from the left ventricle to the aorta. This conclusion motivates further studies to determine whether the PWR integral can be evaluated using less invasive methods, such as echocardiography combined with a radial artery catheter

Minimally invasive beat-by-beat monitoring of cardiac power in normal hearts and during acute ventricular dysfunction

Cardiac power, the product of aortic flow and blood pressure, appears to be a fundamental cardiovascular parameter. The simplified version named cardiac power output (CPO), calculated as the product of cardiac output (CO) in L/min and mean arterial pressure (MAP) in mmHg divided by 451, has shown great ability to predict outcome in a broad spectrum of cardiac disease. Beat-by-beat evaluation of cardiac power (PWR) therefore appears to be a possibly valuable addition when monitoring circulatory unstable patients, providing parameters of overall cardiovascular function. We have developed a minimally invasive system for cardiac power measurement, and aimed in this study to compare this system to an invasive method (ttPWR). Seven male anesthetized farm pigs were included. A laptop with in-house software gathered audio from Doppler signals of aortic flow and blood pressure from the patient monitor to continuously calculate and display a minimally invasive cardiac power trace (uPWR). The time integral per cardiac cycle (uPWR-integral) represents cardiac work, and was compared to the invasive counterpart (ttPWR-integral). Signals were obtained at baseline, during mechanically manipulated preload and afterload, before and after induced global ischemic left ventricular dysfunction. We found that the uPWR-integral overestimated compared to the ttPWR-integral by about 10% (P < 0.001) in both normal hearts and during ventricular dysfunction. Bland-Altman limits of agreement were at +0.060 and -0.054 J, without increasing spread over the range. In conclusion we find that the minimally invasive system follows its invasive counterpart, and is ready for clinical research of cardiac power parameters

Continuous monitoring of the bronchial epithelial lining fluid by microdialysis-3

<p><b>Copyright information:</b></p><p>Taken from "Continuous monitoring of the bronchial epithelial lining fluid by microdialysis"</p><p>http://respiratory-research.com/content/8/1/78</p><p>Respiratory Research 2007;8(1):78-78.</p><p>Published online 1 Nov 2007</p><p>PMCID:PMC2169243.</p><p></p>en circles and dotted line, number three closed triangles and medium dashed line, number four open triangles and dash-dot-dot line, and number five closed squares and long dashed line. Plot A and B show arterial lactate along the X-axis and bronchial (R0.82 ± 0.18) and ureacorrected bronchial lactate (R0.91 ± 0.11) along the Y-axis respectively. Paired t-test of Rfor the individual bronchial and ureacorrected bronchial lactate XY-plots showed significant difference (p < 0.05). Plot C and D show arterial fluorescein isothiocyanate dextran 4000 Da (FD-4) along the X-axis and bronchial (R0.53 ± 0.38) and ureacorrected bronchial FD-4 (R0.72 ± 0.34) along the Y-axis. Paired t-test of Rfor the individual bronchial and ureacorrected bronchial FD-4 XY-plots was not significant

Continuous monitoring of the bronchial epithelial lining fluid by microdialysis-0

<p><b>Copyright information:</b></p><p>Taken from "Continuous monitoring of the bronchial epithelial lining fluid by microdialysis"</p><p>http://respiratory-research.com/content/8/1/78</p><p>Respiratory Research 2007;8(1):78-78.</p><p>Published online 1 Nov 2007</p><p>PMCID:PMC2169243.</p><p></p>d bronchial microdialysis are corrected by the arteriobronchial urea gradient. * Paired T-test showed significant difference from arterial microdialysis at low steady state (arterial blood lactate ~5 mmol/L) (p < 0.05). † Paired t-test showed significant difference from arterial microdialysis at high steady state (arterial blood lactate ~10 mmol/L) (p < 0.05). ns Non significant from arterial microdialysis at high steady state (arterial blood lactate ~10 mmol/L)