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Cardiac output measurement by pulse dye densitometry using three wavelengths
Abstract
Pulse dye densitometry (PDD), based on the principles of pulse oximetry and dye-dilution technique, is a less invasive method of measuring cardiac output (CO). We have developed prototype equipment to measure CO in pediatric patients using this technique. The purpose of our study was to evaluate the accuracy of this new PDD system using three wavelengths for pediatric application by comparing measurement with an ultrasound flowmeter.
Laboratory investigation.
Hospital physiology research laboratory.
A total of 15 young piglets weighing approximately 10 kg each.
Measurement of CO by PDD was performed using general anesthesia. Indocyanine green, 0.2 mg/kg, was administered intravenously, and CO was calculated from the dye dilution curve obtained by the PDD system. The ultrasound flowmeter probe was placed on the ascending aorta in the animal, and CO was simultaneously calculated.
The two CO values, simultaneously obtained by the ultrasound flowmeter and PDD, were compared during various hemodynamic states. The bias between the CO measured by the ultrasound flowmeter and the CO measured by the PDD system using the reflection-type probe at the central site was 33.8 mL/min and the precision was 293.4 mL/min, indicating that CO measured by PDD had a good correlation with measurements obtained with the ultrasonic method.
We measured CO in young piglets at an acceptable level of bias and precision using a prototype PDD device. CO measurement by this new PDD system using three wavelengths can be useful and beneficial for critically ill infants and children. It is simple to perform, requiring an injection of dye into a peripheral intravenous catheter, and it will provide a less invasive bedside measurement of CO.
... The use of PDD to obtain reliable pulse waveforms in small children and neonates can be difficult [18]. In the early period of this study when using a nostril probe attached to the wing of the nose or the corner of the mouth, the signal quality was very poor and thus reliable data could not be obtained [15]. ...
Initial distribution volume of glucose (IDVG), which is not associated with significant modification of glucose metabolism, has been proposed as an indicator of the central extracellular fluid volume status in adults. However, data on IDVG in children are lacking. This study examined pharmacokinetic data on IDVG in children and compared IDVG with other clinical variables.
In total, 128 daily data sets from 60 consecutive pediatric intensive care patients (body weight ≥8.0 kg), consisting mostly of children undergoing cardiovascular surgery, were studied. Either 1 or 2 g of glucose based on body weight (approximately 0.1 g/kg) was administered. IDVG could not be determined from ten data sets from eight children because of body movement-associated glucose fluctuation during measurement. In the remaining 113 data sets from 55 children, IDVG was determined by applying the one-compartment model. Approximated IDVG based on the incremental plasma glucose level at 3 min postinjection (1-point IDVG), and approximated IDVG based on incremental plasma glucose levels at 3 and 5 min postinjection (2-point IDVG), were also calculated. Postoperative daily IDVG and the relationship between IDVG and cardiac output or circulating blood volume (CBV) were evaluated when data were available.
Convergence was assumed in each glucose clearance curve. Mean indexed IDVG (IDVGI) of the first measurement in 55 children was 144 ± 22 (SD) mL/kg, which was associated with a plasma glucose disappearance rate (Ke-glucose) of 0.094 ± 0.033/min. Bias and precision were smaller between 2-point IDVG and standard IDVG than between 1-point IDVG and standard IDVG (-0.02 ± 0.13 L versus 0.07 ± 0.20 L, p <0.001). Postoperative IDVGI in 37 children after cardiovascular surgery increased daily on postoperative days 1-2 (p ≤0.011). Linear correlations were observed between IDVGI and indexed cardiac output (r = 0.588, n = 28, p <0.001) and between IDVGI and indexed CBV (r = 0.547, n = 25, p = 0.0047).
IDVG is a potential marker of fluid volume status in children, even though body movement-associated glucose fluctuation is a major limitation. Two-point IDVG is preferable to 1-point IDVG for approximated IDVG.
... The technique exploits the spectral changes in the circulating blood after injection of a dye to monitor its concentration. Three wavelength systems using ICG 12 and indigo carmine 13 have been reported. We have employed similar techniques to those used in PDD to develop a prototype optical pulse photometer (PP) system to track the concentration and circulation half life of gold nanoshells. ...
Researchers employ increasingly complex sub-micron particles for oncological applications to deliver bioactive therapeutic or imaging compounds to known and unknown in vivo tumor targets. In practice, experimental homogeneity using nanoparticles can be difficult to achieve. While several imaging techniques have been previously shown to follow the accumulation of nanoparticles into tumor targets, a more rapid sensor that provides a quantifiable estimate of dose delivery and short-term systemic response could increase the clinical efficacy and greatly reduce the variability of these treatments. We have developed a pulse photometer that when placed on an optically accessible location will estimate the concentration of near-infrared absorbing nanoparticles. The goal is to monitor the accuracy of the delivered dose and the effective circulation time of nanoparticles immediately after intravenous delivery but prior to therapeutic intervention. We present initial tests of our prototype using murine models to assess its ability to quantify circulation half-life and nanoparticle concentration. Four mice were injected with nanoparticles and circulation half-life estimates ranged from 3- 43 minutes. UV-Vis spectrophotometry was used to independently verify these measurements using 5muL blood samples. Linear models relating the two methods produced R2 values of 0.91, 0.99, 0.88, and 0.24.
... Recently, optical CBV clinical measurements are implemented as in vivo pulse dye densitometry (PDD) (35,78,79). This method is based on the principles of pulse oximetry and a dye-dilution technique with ICG (78,(80)(81)(82)(83)(84)(85)(86)(87). ICG is safely cleared by kidneys (37), and new measurements are possible every 20-30 min (after the ICG concentration from the previous injection becomes negligible). ...
Recently, photoacoustic (PA) flow cytometry (PAFC) has been developed for in vivo detection of circulating tumor cells and bacteria targeted by nanoparticles. Here, we propose multispectral PAFC with multiple dyes having distinctive absorption spectra as multicolor PA contrast agents. As a first step of our proof-of-concept, we characterized high-speed PAFC capability to monitor the clearance of three dyes (Indocyanine Green [ICG], Methylene Blue [MB], and Trypan Blue [TB]) in an animal model in vivo and in real time. We observed strong dynamic PA signal fluctuations, which can be associated with interactions of dyes with circulating blood cells and plasma proteins. PAFC demonstrated enumeration of circulating red and white blood cells labeled with ICG and MB, respectively, and detection of rare dead cells uptaking TB directly in bloodstream. The possibility for accurate measurements of various dye concentrations including Crystal Violet and Brilliant Green were verified in vitro using complementary to PAFC photothermal (PT) technique and spectrophotometry under batch and flow conditions. We further analyze the potential of integrated PAFC/PT spectroscopy with multiple dyes for rapid and accurate measurements of circulating blood volume without a priori information on hemoglobin content, which is impossible with existing optical techniques. This is important in many medical conditions including surgery and trauma with extensive blood loss, rapid fluid administration, and transfusion of red blood cells. The potential for developing a robust clinical PAFC prototype that is safe for human, and its applications for studying the liver function are further highlighted.
... The spectral analysis of arterial blood has been employed in applications like oximetry [19,20], glucosimetry [21], and pulse dye densitometry [22][23][24]. These methods isolate the time-varying attenuation of light resulting from the arterial pulsation of each heartbeat. ...
Nanoparticle-assisted photo-thermal (NAPT) ablation has become a new and attractive modality for the treatment of cancerous tumors. This therapy exploits the passive accumulation of intravenously delivered optically resonant metal nanoparticles into tumors, however, the circulating bioavailability of these particles is often unknown. We present a non-invasive optical device capable of monitoring the circulation of optically resonant gold nanorods. The device, referred to as a pulse photometer, uses the technique of multi-wavelength photoplethysmography. We simultaneously report the circulation of gold nanorods and oximetry for six hours post-injection in mice with no anesthesia and remove the probe when not collecting data. The instrument shows good agreement (R(2) = 0.903, n = 30) with ex vivo spectrophotometric analysis of blood samples. The real-time feedback provided has a strong potential for reducing variability and thus improving the efficacy of similar clinical therapies.
... Studies in adults are limited, and recent data regarding the reproducibility and validity of the pulsed dye densitometry method are conflicting [51][52][53]. Although the first (experimental) studies in pediatric animals and patients applying blood volume and CO measurements are published, the technique has not been validated [54][55][56][57]. The applicability in clinical practice is, therefore, as yet unknown. ...
Cardiac output (CO) measurement is becoming increasingly important in the field of pediatric intensive care medicine and pediatric anesthesia. In the past few decades, various new technologies have been developed for the measurement of CO. Some of these methods are applicable to pediatric patients and some are already being used in children. The devices and methods have their advantages and limitations and, therefore, it is difficult for the clinician to decide which technique should be used. This article focuses on the currently available minimally invasive and noninvasive monitoring devices for CO measurement in children. A brief explanation of the technical aspects of each method and clinical use will be followed by the knowledge gained from infant animal and clinical pediatric studies. The goal of this article is to give an update of the various CO measurement technologies in children.
... However, with a new technique, called pulse dye densitometry (PDD), the injected ICG can also be detected noninvasively via a fingertip sensor. PDD has only been validated in adults and not in children because it appears to be very difficult to obtain reliable pulse waveforms from small children and neonates [18]. Advantages Non-invasive detection of ICG Major limitations Limited repeated measurements; inaccuracy due to poor peripheral perfusion, motion artefact or excess light; rarely severe side effects (ICG) ...
There is an increased interest in methods of objective cardiac output measurement in critically ill patients. Several techniques are available for measurement of cardiac output in children, although this remains very complex in newborns. Cardiac output monitoring could provide essential information to guide hemodynamic management. An overview is given of various methods of cardiac output monitoring with advantages and major limitations of each technology together with a short explanation of the basic principles.
Diese Studie hatte zum Ziel den PulseCOTM Hemodynamic Monitor (PulseCO) zur kontinuierlichen Herzauswurfmessung in der klinischen Anwendung bei Pferden in Allgemeinanästhesie zu evaluieren. Der PulseCO basiert auf dem Algorithmus der Analyse der Pulsstärke, einer neuen Variante der Pulskonturanalyse. Das untersuchte Patientenspektrum war sehr breit, da ausser erwachsenen Pferden auch Fohlen, Esel, ein Pony und ein Maultier mit einbezogen wurden. Die Evaluation des PulseCO erfolgte im Vergleich mit der Lithiumverdünnung, wobei die lineare Regressionsanalyse und die Bland-Altman-Analyse für die statistische Beurteilung herangezogen wurden. Insgesamt wurden 61 Messpaare von 28 Tieren untersucht. Der Vergleich mit der Lithiumverdünnung zeigte, dass der PulseCO absolut und über die erfasste Zeit eine für die klinische Anwendung genügende Genauigkeit aufwies. Ein Problem stellte der Umstand dar, dass der Algorithmus des PulseCO bei einer Herzfrequenz von unter 30 Schlägen pro Minute nicht funktionierte. Obwohl die Genauigkeit gut ist, eignet sich der PulseCO aufgrund dieses Umstandes nur bedingt für die klinische Anwendung, da bei trainierten Pferden eine Herzfrequenz von unter 30 Schlägen pro Minute in Allgemeinanästhesie durchaus vorkommt. Falls der Algorithmus entsprechend angepasst werden kann, ist der PulseCO eine genaue, wenig invasive Methode zur kontinuierlichen Herzauswurfbestimmung beim Pferd in Allgemeinanästhesie. The aim of this study was to evaluate the PulseCOTM Hemodynamic Monitor (PulseCO) for determination of continuous cardiac output for clinical application in anesthetized horses. This system uses a new pulse contour algorithm based on pulse power analysis. Additional to the adult horses there where included foals, donkeys, a pony and a mule, which expanded the regarded spectrum of patients. The PulseCO was evaluated in comparison with lithium dilution, using linear regression analysis and Bland-Altman analysis as statistical methods. In total 61 pairs of readings were obtained from 28 animals. Compared with lithium dilution, the PulseCO showed adequate accuracy for clinical use, both for absolute measurements and over the considered period of time. A problem was the fact that the PulseCO doesn't work, if the heart rate is below 30 beats per minute (bpm). Even tough accuracy of the PulseCO is good, it can be considered suitable only conditional, because heart rates below 30 bpm are common encountered in trained anesthetized horses. If the algorithm can be adjusted that it allows heart rates below 30 bpm, the PulseCO is an accurate, minimal invasive method to estimate continuous cardiac output in anesthetized horses.
Purpose of Review
The purpose of this review was to provide an overview of the recent concepts regarding cardiac output measurement devices that utilize non-pulse contour methods, especially in an intraoperative setting. The techniques include inert gas rebreathing method, partial CO2 rebreathing method, impedance cardiography, and its derivative technologies such as electrical velocimetry and bioreactance, transesophageal echocardiography/Doppler, and transthoracic echocardiography/Doppler. We focused on the invasiveness of the devices and their underlying technology.
Recent Findings
Although various types of cardiac output monitoring devices are available, none of them may be considered as an ideal device in terms of accuracy, trending ability of cardiac output changes, and reproducibility of measurements. There are increasing types of devices applicable for intraoperative use, yet only few data are available regarding the trending ability of cardiac output changes and reproducibility of the measurements. Therefore, the empirical application of these devices for various surgical patients may be done under the consideration of their invasiveness and their underlying technology, and it may provide us with more data over time.
Summary
The non-pulse contour-derived cardiac output measurement devices are classified according to their underlying principles, which closely reflect their advantages and disadvantages in the perioperative setting.
The fundamental goal of critical care medicine is to optimize cardiac output to maintain adequate organ perfusion and meet the body’s metabolic demands. Historically, monitoring cardiac output was limited to indirect measures of the physical exam and biochemistry. The pulmonary artery catheter was the first widely adapted instrument to quantify cardiac output at the bedside, but its use has been curtailed, especially in pediatrics, due to its invasiveness and associated complications. Newer cardiac output monitoring technologies have recently emerged and are being slowly integrated into routine clinical practice.
Cardiac output devices have evolved to become less invasive in hopes of minimizing side-effect profiles. In general, these devices fall into three broad categories: intermittent measurements based on transpulmonary dilution, continuous monitoring based on analysis and integration of the invasive arterial waveform, and continuous measurements based on changes to electrical impulses across the thoracic cavity. Lastly, commercial devices that determine the adequacy of distal perfusion through tissue-based assessment have also been recently introduced. Volume assessment of physiologic compartments (e.g., intravascular, intrapulmonary) is also possible by several companies. Adult data showing acceptable accuracy and precision exists for many of the newer devices, but validation in pediatric patients, particularly infants and neonates, is scant.
This chapter will provide readers a detailed review of the underlying physiology for the emerging cardiac output devices and present their validation studies in the field of pediatrics. It will also provide a framework for assessing their utility in a pediatric intensive care unit.
After liver surgery, the most common cause of death is hepatic failure; therefore, the preoperative evaluation of hepatic functional reserves is of great significance. Thus, a method has been applied to an optical measurement from the artery in a patient's finger. The indicator indocyanine green (ICG) was intravenously injected. Afterwards, the optical signals which were picked up from the sensor were measured with the signal conditioning module, and then collected to the PC by Lab-VIEW acquisition system. The ICG spectral signal is analyzed by the methods of delta absorption model, so the dilution and excretion curve of ICG concentration can be attained. The parameters reflecting the hepatic functional reserves can be calculated, including the mean transit time, the ICG 15 min retention rate, the EHBF (effective hepatic blood flow). Compared with the clinical "gold standard" methods of blood sampling to measure these two parameters by clinical controlled trials, 30 sets of data were obtained. About the 15 min retention rate of ICG, the two groups of data have fine linear relationship (coefficient of determination R2 = 0.9738, P < 0.001); and the EHBF, the coefficient of determination R2, P < 0.001. Through the analysis of the test data by Bland-Altman method, the two group results are consistent. Therefore, a simple and minimal invasive method for liver functional reserves was realized more practicability in clinic and relatively precision.
The measurement of circulating blood volume (CBV) is crucial in various medical conditions including surgery, iatrogenic problems, rapid fluid administration, transfusion of red blood cells, or trauma with extensive blood loss including battlefield injuries and other emergencies. Currently, available commercial techniques are invasive and time-consuming for trauma situations. Recently, we have proposed high-speed multi-wavelength photoacoustic/photothermal (PA/PT) flow cytometry for in vivo CBV assessment with multiple dyes as PA contrast agents (labels). As the first step, we have characterized the capability of this technique to monitor the clearance of three dyes (indocyanine green, methylene blue, and trypan blue) in an animal model. However, there are strong demands on improvements in PA/PT flow cytometry. As additional verification of our proof-of-concept of this technique, we performed optical photometric CBV measurements in vitro. Three label dyes—methylene blue, crystal violet and, partially, brilliant green—were selected for simultaneous photometric determination of the components of their two-dye mixtures in the circulating blood in vitro without any extra data (like hemoglobin absorption) known a priori. The tests of single dyes and their mixtures in a flow system simulating a blood transfusion system showed a negligible difference between the sensitivities of the determination of these dyes under batch and flow conditions. For individual dyes, the limits of detection of 3×10–6 M‒3×10–6 M in blood were achieved, which provided their continuous determination at a level of 10–5 M for the CBV assessment without a priori data on the matrix. The CBV assessment with errors no higher than 4% were obtained, and the possibility to apply the developed procedure for optical photometric (flow cytometry) with laser sources was shown.
This review article summarizes new trends in systemic haemodynamic monitoring in 2005. This part is aimed at the less invasive cardiac output measurement methods, particularly transoesophageal Doppler and venous oximetry, and the application of protocols for optimization of the haemodynamics and oxygen delivery.
Evaluation of the estimated continuous cardiac output (esCCO) allows non-invasive and continuous assessment of cardiac output. However, the applicability of this approach in children has not been assessed thus far. We compared the correlation coefficient, bias, standard deviation (SD), and the lower and upper 95 % limits of agreement for esCCO and dye densitography-cardiac output (DDG-CO) measurements by pulse dye densitometry (PDD) in adults and children. On the basis of these assessments, we aimed to examine whether esCCO can be used in pediatric patients. DDG-CO was measured by pulse dye densitometry (PDD) using indocyanine green. Modified-pulse wave transit time, obtained using pulse oximetry and electrocardiography, was used to measure esCCO. Correlations between DDG-CO and esCCO in adults and children were analyzed using regression analysis with the least squares method. Differences between the two correlation coefficients were statistically analyzed using a correlation coefficient test. Bland–Altman plots were used to evaluate bias and SD for DDG-CO and esCCO in both adults and children, and 95 % limits of agreement (bias ± 1.96 SD) and percentage error (1.96 SD/mean DDG-CO) were calculated and compared. The average age of the adult patients (n = 10) was 39.3 ± 12.1 years, while the average age of the pediatric patients (n = 7) was 9.4 ± 3.1 years (p
Researchers employ increasingly complex sub-micron particles for oncological applications to deliver bioactive therapeutic or imaging compounds to known and unknown in vivo tumor targets. These particles are often manufactured using a vast array of compounds and techniques resulting in a complex architecture, which can be quantified ex vivo by conventional metrology and chemical assays. In practice however, experimental homogeneity using nanoparticles can be difficult to achieve. While several imaging techniques have been previously shown to follow the accumulation of nanoparticles into tumor targets, a more rapid sensor that provides a quantifiable estimate of dose delivery and short-term systemic response could increase the clinical efficacy and greatly reduce the variability of these treatments. We have developed an optical device, the pulse photometer, that when placed on an accessible location will estimate the vascular concentration of near-infrared extinguishing nanoparticles in murine subjects. Using a technique called multi-wavelength photoplethysmography, the same technique used in pulse oximetry, our pulse photometer requires no baseline for each estimate allowing it to be taken on and off of the subject several times during experiments employing long circulating nanoparticles. We present a formal study of our prototype instrument in which circulation half-life and nanoparticle concentration of gold nanorods is determined in murine subjects with the aid of light anesthesia. In this study, we show good agreement between vascular nanorod concentrations (given in optical density) as determined by our device and with UV-VIS spectrophotometry using low volume blood samples.
Monitoring of cardiovascular function is critical to both clinical care and research as the use of sophisticated monitoring systems enable us to obtain accurate, reliable and real-time information on developmental hemodynamics in health and disease. Novel approaches to comprehensive hemodynamic monitoring and data acquisition will undoubtedly aid in developing a better understanding of developmental cardiovascular physiology in neonates. In addition, development and use of state-of-the-art, comprehensive hemodynamic monitoring systems enable the recognition of signs of cardiovascular compromise in its early stages, and provide information on the hemodynamic response to treatment in critically ill patients.
The indocyanine green (ICG) retention test is the most popular liver function test for selecting patients for major hepatectomy. Traditionally, it is done using spectrophotometry with serial blood sampling. The newly-developed pulse spectrophotometry is a faster alternative, but its accuracy on Child-Pugh A cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma has not been well documented. This study aimed to assess the accuracy of the LiMON(®), one of the pulse spectrophotometry systems, in measuring preoperative ICG retention in these patients and to devise an easy formula for conversion of the results so that they can be compared with classical literature records where ICG retention was measured by the traditional method.
We measured the liver function of 70 Child-Pugh A cirrhotic patients before hepatectomy for hepatocellular carcinoma from September 2008 to January 2009. ICG retention at 15 minutes measured by traditional spectrophotometry (ICGR15) was compared with ICG retention at 15 minutes measured by the LiMON (ICGR15(L)).
The median ICGR15 was 14.7% (5.6%-32%) and the median ICGR15(L) was 10.4% (1.2%-28%). The mean difference between them was -4.3606. There was a strong correlation between ICGR15 and ICGR15(L) (correlation coefficient, 0.844; 95% confidence interval, 0.762-0.899). The following formula was devised: ICGR15=1.16XICGR15(L)+2.73.
The LiMON provides a fast and repeatable way to measure ICG retention at 15 minutes, but with constant underestimation of the real value. Therefore, when comparing results obtained by traditional spectrophotometry and the LiMON, adjustment of results from the latter is necessary, and this can be done with a simple mathematical calculation using the above formula.
The aim of the present study was to explain why extravascular lung water index (EVLWI) is higher and why global end-diastolic blood volume index (GEDVI) is lower in young children when measured with the PiCCO system (Pulsion, Munich, Germany).
We pooled available data from literature from children concerning organ weight derived from autopsy studies and computed tomographic lung measurements. These data include age, height, body weight, body surface area (BSA), and lung and heart weights. For standard, age-dependent weight and height, we used published data from the World Health Organization. From the available data, we calculated the lung weight-to-body weight ratio, the heart weight-to-BSA ratio, and the end-diastolic volume-to-BSA ratio. We compared these ratios to body growth and development.
Lung weight develops more slowly and with less magnitude than does body weight. In addition, the (relatively) greater lung weight in younger children results in a higher amount of pulmonary blood volume. This explains the higher EVLWI in young children. End-diastolic blood volume and heart weight increase faster and are more pronounced compared with BSA. This explains the lower GEDVI in young children. We propose correction factors for comparing EVLWI and GEDVI with adult reference values.
Extravascular lung water index is higher and GEDVI is lower in young children because of changing organ-to-body weight relationships during growth.
There is an urgent clinical need to monitor the intravenous delivery and bioavailability of circulating nanoparticles used in cancer therapy. This work presents the use of photoplethysmography for the noninvasive real-time estimation of vascular gold nanoshell concentration in a murine subject. We develop a pulse photometer capable of accurately measuring the photoplethysmogram in mice and determining the ratio of pulsatile changes in optical extinction between 805 and 940 nm, commonly referred to as R. These wavelengths are selected to correspond to the extinction properties of gold nanoshells. Six 30-s measurements (5 min, 2, 4, 6, 8, 10 h) are taken under light anesthesia to observe the change in R as the nanoparticles clear from the circulation. Our model describes the linear fit (R(2)=0.85) between R and the concentration of nanoparticles measured via ex vivo spectrophotometric and instrumental neutron activation analysis. This demonstrates the utility of this technique in support of clinical nanoparticle therapies.
We demonstrate a photometer based on pulse oximeter technology designed to test the feasibility of using non-invasive optics to quantify in vivo circulation parameters of optically-active particles by measuring changes in optical extinction introduced by the particles in a murine animal model. A real-time estimate of relative concentration was produced by collecting log-scaled bandpass pulsatile and non-pulsatile intensity (760 nm or 940 nm) near the extinction peak of the employed gold nanoshells and mathematically subtracting the pre-injection intensity through the murine subject. The circulation half-lives in four mice were estimated between 3 and 43 minutes compared to direct optical measurement of 5 microL blood draws with UV/Vis spectrophotometry which demonstrated nanoparticle extinctions ranging from 0.246 to 7.408 optical density (OD). A linear model fit relating the two methods produced an R2 value of 0.75. The 1.795 OD negative bias (-4.98 x 10(9) nanoparticles/ml) between the two methods describes the 35.5% (or 12.0 minutes) average error of prediction of the half-life. This report demonstrates that the circulation parameters of optically-active particles employed at therapeutically-relevant concentrations can be monitored in real-time using non-invasive optical techniques and advises further refinement.
Transpulmonary thermodilution (TPTD) using the injection of ice-cold saline is a reliable technique for measuring cardiac output in adults and children. We describe two cases in which these measurements were erroneously influenced by diffusion of the temperature indicator. If the thermistor-tipped arterial catheter is in close proximity to the central venous catheter, the injection of an icecold indicator might lead to an early temperature drop in the arterial catheter thus producing a biphasic dilution curve. This is called the "cross-talk phenomenon". In the first case, concerning a child undergoing congenital cardiac surgery, we show that this phenomenon is dependent on blood flow. In the second case we demonstrate an animal experiment in which the cross-talk phenomenon occurred during a very low flow state. However in this case the venous catheter was positioned in the inferior caval vein and not in close proximity to the arterial catheter. The cross-talk phenomenon can also occur when the arterial catheter is not in close position to the central venous catheter. We conclude that when using TPTD measurements with arterial and venous catheters both positioned in the lower body, the cross-talk phenomenon may occur. Therefore the thermodilution curve should always be closely monitored for a biphasic shape, especially when the cardiac output is low. Copyright © 2009, Nederlandse Vereniging voor Intensive Care. All Rights Reserved.
Pressures in the right side of the heart and pulmonary capillary wedge can be obtained by cardiac catheterization without the aid of fluoroscopy. A No. 5 Fr double-lumen catheter with a balloon just proximal to the tip is inserted into the right atrium under pressure monitoring. The balloon is then inflated with 0.8 ml of air. The balloon is carried by blood flow through the right side of the heart into the smaller radicles of the pulmonary artery. In this position when the balloon is inflated wedge pressure is obtained. The average time for passage of the catheter from the right atrium to the pulmonary artery was 35 seconds in the first 100 passages. The frequency of premature beats was minimal, and no other arrhythmias occurred.
In the anesthetized pig, we studied the kinetics after intravenous bolus injection of two fractions of indocyanine green (ICG): the genuine ICGg (95-99% of total) and a degradation product, ICGdp (1-5%). Plasma concentrations were followed in the carotid artery and a hepatic vein. ICGg disappearance curves (n = 7) were biexponential with rate constants alpha = 0.189 +/- 0.021 min-1 and beta = 0.0356 +/- 0.0061 min-1. The hepatic extraction fraction was constant with time. A detailed mathematical analysis showed this to be in disagreement with the conventional assumption that the biexponential plasma disappearance curve is a result of backflux from the liver storage to plasma. In contrast, our observations were predicted by an alternative model assuming temporary extrahepatic, extravasal redistribution during first-order, one-way hepatic uptake. Nevertheless, when a large bolus of sulfobromophthalein (BSP) was injected 20 min after ICG, a net backflux of ICG could be demonstrated, presumably due to countertransport. Thus a sufficient description of ICGg kinetics must include the complex kinetic behavior of the hepatic membrane carrier involved. Mass spectrometry suggested that ICGdp is formed by two ICGg molecules. Plasma elimination of ICGdp was slower (alpha = 0.0094 +/- 0.0007 min-1). Analysis of the bile after bolus injection (n = 2) of ICGdp revealed two possible metabolites of ICGdp that were not found in urine. Since BSP injection did not alter the ICGdp disappearance curve, ICGdp is probably not taken up by the same hepatic membrane carrier as ICGg.
The cardiopulmonary effects of eucapnia (arterial CO2 tension [PaCO2] 40.4 +/- 2.9 mm Hg, mean +/- SD), mild hypercapnia (PaCO2, 59.1 +/- 3.5 mm Hg), moderate hypercapnia (PaCO2, 82.6 +/- 4.9 mm Hg), and severe hypercapnia (PaCO2, 110.3 +/- 12.2 mm Hg) were studied in 8 horses during isoflurane anesthesia with volume controlled intermittent positive pressure ventilation (IPPV) and neuromuscular blockade. The sequence of changes in PaCO2 was randomized. Mild hypercapnia produced bradycardia resulting in a significant (P < 0.05) decrease in cardiac index (CI) and oxygen delivery (DO2), while hemoglobin concentration (Hb), the hematocrit (Hct), systolic blood pressure (SBP), mean blood pressure (MBP), systemic vascular resistance (SVR), and venous admixture (QS/QT) increased significantly. Moderate hypercapnia resulted in a significant rise in CI, stroke index (SI), SBP, MBP, mean pulmonary artery pressure (PAP), Hct, Hb, arterial oxygen content (CaO2), mixed venous oxygen content (CvO2), and DO2, with heart rate (HR) staying below eucapnic levels. Severe hypercapnia resulted in a marked rise in HR, CI, SI, SBP, PAP, Hct, Hb, CaO2, CvO2, and DO2. Systemic vascular resistance was significantly decreased, while MBP levels were not different from those during moderate hypercapnia. No cardiac arrhythmias were recorded with any of the ranges of PaCO2. Norepinephrine levels increased progressively with each increase in PaCO2, whereas plasma cortisol levels remained unchanged. It was concluded that hypercapnia in isoflurane-anesthetized horses elicits a biphasic cardiopulmonary response, with mild hypercapnia producing a fall in CI and DO2 despite an increase in MBP, while moderate and severe hypercapnia produce an augmentation of the cardiopulmonary performance and DO2.
We continuously measured hepatic absorbance of in docyanine green (ICG) using near-infrared (NIR) spectroscopy after intravenous bolus injection in rabbits. Hepatic ICG concentration was obtained by subtracting out the absorbance of hemoglobin and other pigments within the liver. Two exponential rate constants, the first reflecting the dye uptake from plasma to the hepatocytes, and the second representing the dye removal from the liver by cytoplasmic transport and biliary excretion, were determined by fitting the time-course curve of hepatic ICG concentration to a two-compartment model with irreversible transfer between the two-compartments, as defined by the double-exponential equation: [ICG]liver(t) = -A exp(-αt) + B exp(-βt). The results showed that treatment with bilirubin, a competitive inhibitor of ICG uptake, caused a decrease in α-Treatment with either colchicine, which is toxic to microtubules, or with ouabain, an inhibitor of Na⁺ K⁺-ATPase, caused a decrease in β. These results were compatible with the kinetic model. This new method was then used in liver-injured rabbits inflicted with hemorrhagic shock and ischemia-reperfusion, to show that the first rate constant is primarily affected by hepatic microcirculatory condition, and the second refers closely to parenchymal liver damage. In another series of partial liver ischemia-reperfusions, it was possible to simultaneously and separately monitor the ICG profiles of post-ischemic and nonischemic areas. Thus, the kinetic analysis of hepatic ICG concentration curves, as directly measured by NIR spectroscopy, led to the separate evaluation of different clearance process of ICG in the liver, suggesting the advanced utility as a comprehensive liver function test. Copyright © 1996 by the American Association for the Study of Liver Diseases.
Schuster's scattering theory was applied to a blood model and a theoretical formula of the blood optical attenuation change for unit blood thickness change was obtained. Several factors affecting the optical attenuation of blood were investigated in vitro and the blood optical attenuation change for unit blood thickness change was measured in vitro for 600-1, 300nm. With an increase of the size of the transmittance window, and with an increase of the thickness of the blood, the blood optical attenuation for unit blood thickness change decreased to a certain limit. In the condition of this limit, it was able to select a suitable value for the scattering constant for each hematocrit so that the theoretical blood optical attenuance agreed with the measured value. As hematocrit increased, in low hematocrit range, the scattering constant increased almost proportionally to hematocrit, and after certain hematocrit value, the scattering constant decreased. These theory and experimental observations can be used to refine and improve the technology of pulse oximetry.
• In 12 patients with heart disease, hypercarbia was induced for carotid endarterectomy. Anesthesia was maintained with nitrous oxide in oxygen and methoxyflurane. In addition to intra-arterial measurements of blood pressure, cardiac output, systolic time intervals (STI), and pressure time indices (PTI) were determined in order to assess cardiovascular responses in these patients. Internal carotid stump blood pressure was measured in five patients before and after induction of hypercarbia. Mild elevation of the Paco2 level affected systolic time intervals but not heart rate and blood pressure. When Paco2 levels reached 56 to 65 torr, systolic but not diastolic blood pressure rose significantly, heart rate and cardiac output increased, while the shortening in the preejection period (PEP), left ventricular ejection lime (LVET), and the decrease in the PEP/LVET ratio signified increased mechanical cardiac activity. Hypercarbia caused intense sympathetic stimulation as demonstrated by twofold to threefold increases in plasma catecholamine levels. Stump blood pressure was elevated. Cardiac oxygen demand was significantly increased, while coronary filling time was shortened, as indicated by the increase in the tension time index and shortening in the diastolic time. This signified a relative myocardial underperfusion. Thus, while hypercarbia to levels of 66 to 70 torr increased internal carotid artery stump pressure, it also caused increased cardiac mechanical activity and concomitant unfavorable balance between myocardial oxygen consumption and supply. The measurement of STI and the computation of PTI provided early detection of alterations in cardiac function.
(Arch Surg 113:1196-1200, 1978)
Background
In the treatment of critically ill patients, blood volume (BV) measurement requires injection of some tracer substance and subsequent blood sampling to analyze the tracer concentration. To obviate both the sampling and laboratory analysis, techniques of pulse oximetry have been adapted to the noninvasive optical measurement in the patient's nose or finger of the arterial concentration of an injectable dye.
Methods
The authors report the clinical accuracy of a new noninvasive bedside BV measurement test that uses pulse spectrophotometry (the pulse method). The device detects pulsatile changes of tissue optical density of a nostril or a finger spanned by a probe emitting two infrared wavelengths (805 and 890 nm). After a peripheral or central intravenous injection of indocyanine green, the arterial dye concentration is continuously computed by reference to the previously measured blood hemoglobin concentration. Three types of tests of its accuracy are described here.
Results
In 10 healthy volunteers, the authors compared BV determined by the pulse method with an (131)I-labeled human serum albumin method. Three subject data sets were excluded because of motion artifact, a low signal:noise ratio, or both. For the other seven volunteers, the bias+/-SD of pulse spectrophotometric BV values were 0.20+/-0.24 l (or 4.2+/-4.9%) for the nose probe and 0.34+/-0.31 l (or 7.3+/-6.9%) for the finger probe, with a mean BV of 5 l. In 30 patients who underwent cardiac surgery, the pulse method was compared with a standard indocyanine green method using intermittent blood sampling. In three patients, the BV could not be determined by the pulse method because of motion artifact, low signal:noise ratio, or both. In 27 patients, the bias+/-SD of the BV by the pulse method was -0.23+/-0.37 l (-5.3+/-8.7%) for the nose and -0.25+/-0.5 l (-4.2+/-8.4%) for the finger. Patient BV ranged from 2.51 to 7.13 l (mean, 4.48 l). In 10 additional patients before cardiac surgery, BV was measured by the pulse method before and shortly after removal of 400 ml blood. The pulse method recorded a decrease of BV of 480+/-114 mL Three days after venesection, the mean BV was 117+/-159 ml less than the predonation control.
Conclusions
In most patients, the pulse method provides bedside measurement of BV without blood sampling (except for hemoglobin determination), with an estimated error less than 10%. In 10-30% of tests the method failed because of motion distortion of the record during the 10-min data collection period or because of insufficient pulse amplitude in the test tissue.
Pulse dye-densitometry (PDD) is a newly developed technique for monitoring the arterial concentration of indocyanine green. Using this method, circulating blood volume (CBV) can be calculated without using radioisotopes. In this study, the CBV value obtained by PDD was validated by comparison using the human serum albumin ((131)I-HSA) dilution method.
Eleven healthy volunteers underwent placement of cannulae into the radial artery and antecubital vein for withdrawal of blood samples and injection of indicator. Probes for PDD were attached to the right nostril and the right index finger. Indocyanine green (20 mg), dissolved in 4 ml water, and 25 microCi (131)I-HSA in 1 ml distilled water were injected simultaneously into the left antecubital vein. Blood samples were withdrawn 3, 6, 10, 20, 30, and 45 min after injection, then processed for spectrophotometric measurement of indocyanine green and scintillation counting.
The blood dye concentration correlated well with the values obtained by PDD (r=0.986, imprecision 0.04+/-0.11 mg/l, 10.0+/-31%. The imprecision of the CBV value obtained by PDD (nose probe) and by the (131)I-HSA dilution method was 3.99+/-10.54%, 0.259+/-0.593 l. The imprecision of the CBV obtained by in vitro spectrophotometry compared with PDD was 2.47+/-9.00%, 0.100+/-0.446 l.
This newly developed, less invasive method can measure CBV with an imprecision of 3.99+/-10.54%, 0.259+/-0.593 l (nose probe), and thus is also as accurate as the conventional radioisotope method.
Objectives: To determine whether changes in cardiac output, regional blood flow, and intracranial pressure during permissive hypercapnia are blood pH-dependent and can be attenuated by correction of intravascular acidemia.
Design: Prospective, controlled study.
Setting: Research laboratory.
Subjects: Female Marino ewes.
Interventions: Animals were instrumented with a pulmonary artery catheter, femoral arterial and venous catheters, a catheter in the third cerebral ventricle, and ultrasonic flow probes on the left carotid, superior mesenteric, and left renal arteries 1 wk before experimentation. At initiation of the protocol, ewes underwent endotracheal intubation and mechanical ventilation under general anesthesia. Minute ventilation was reduced to induce hypercapnia with a target PaCO2 of 80 torr (10.7 kPa). In the pH-uncorrected group (n equals 6), arterial blood pH was allowed to decreased without treatment. In the pH-corrected group (n equals 5), 14.4 mEq/kg of sodium bicarbonate was given intravenously as a bolus to correct arterial blood pH toward a target arterial pH of 7.40 (dose calculated by the Henderson-Hasselbalch equation).
Measurements and Main Results: Arterial blood pH, PCO2, cardiac output, intracranial pressure, and carotid, superior mesenteric, and renal artery blood flow rates were measured at normocapnic baseline and at every hour during hypercapnia for 6 hrs. In the pH-uncorrected group, arterial blood pH decreased from 7.41 plus minus 0.03 at normocapnia to 7.14 plus minus 0.01 (p less than .01 vs. normocapnia) as blood PCO2 increased to 81.2 plus minus 1.8 torr (10.8 plus minus 0.2 kPa). In the pH-corrected group, arterial blood pH was 7.42 plus minus 0.02 at normocapnia and was maintained at 7.37 plus minus 0.01 while PaCO2 was increased to 80.3 plus minus 0.9 torr (10.7 plus minus 0.1 kPa). Significant increases in cardiac output occurred with the initiation of hypercapnia for both groups (pH-uncorrected group: 4.3 plus minus 0.6 L/min at normocapnia vs. 6.8 plus minus 1.0 L/min at 1 hr [p less than .05]; pH-corrected group: 4.1 plus minus 0.4 at normocapnia vs. 5.7 plus minus 0.4 L/min at 1 hr [p less than .05]). However, this increase was sustained only in the uncorrected group. Changes in carotid and mesenteric artery blood flow rates, as a percent of baseline values, showed sustained significant increases in the pH-uncorrected groups (p less than .05) and only transient (carotid at 1 hr) or no (superior mesenteric) significant change in the pH-corrected groups. Conversely, significant increases in renal artery blood flow were seen only in the pH-uncorrected group during the last 2 hrs of the experiment (p less than .05). Organ blood flow, as a percent of cardiac output, did not change significantly in either group. Intracranial pressure increased significantly in the pH-uncorrected group (9.0 plus minus 1.5 mm Hg at normocapnia vs. 26.8 plus minus 5.1 at 1 hr, p less than .05), and remained increased, while showing no significant change in the pH-corrected group (8.5 plus minus 1.6 mm Hg at normocapnia to 7.7 plus minus 4.2 at 1 hr).
Conclusions: Acute hypercapnia, induced within 1 hr, is associated with significant increases in cardiac output, organ blood flow, and intracranial pressure. These changes can be significantly attenuated by correction of blood pH with the administration of sodium bicarbonate, without adverse effects on hemodynamics.
(Crit Care Med 1996; 24:827-834)
Objective. Pulse dye-densitometry (PDD) is a newly developed methodfor monitoring the indocyanine green (ICG) concentration
in an artery withwhich cardiac output (CO) and circulating blood volume (CBV) can bedetermined. We evaluated its accuracy
for clinical use. Methods. In 7patients under general anesthesia, ICG-sensitive optical probes (805 and 890nm) were attached
to a finger. Following injection of ICG, the arterialconcentration of dye was recorded optically by the non-invasive testinstrument
and sampled arterial blood ICG concentration was also measuredphotometrically for comparison. In order to validate the PDD
analysis, CO wasalso measured by both the dye dilution cuvette method and by thermodilutionin 8 patients scheduled for coronary
artery bypass grafting. In 30 otherpatients, CBV assessed by PDD was compared with its value estimated from bodysize. Results.
The blood dye concentration correlated well with thevalues obtained by PDD (r = 0.953, p < 0.01). Meanbias for the test PDD
CO was +0.15 ± 0.72 minl−1 (not significant (n.s.)) compared with the cuvette methodwhile the mean bias of the thermodilution method vs thecuvette method
was +0.79 ± 0.84 min l−1 (p < 0.0001.). The average value of CBV obtained by PDD was 3.81± 1.39 L compared with that estimated value, 3.72 ± 0.77
L (n.s.).Conclusions. CO determined by PDD agrees wellwith cuvette densitometry, and somewhat less well with CO by thermodilution.The
new method, by not requiring a pulmonary arterial catheter, is lessinvasivethan either older method, and yields in addition
a value of CBV.
Cardiac output–circulating blood volume–dye dilution method–indocyanine green–thermodilution method–pulse dye-densitometry–pulse oximetry
The responses to hypocapnia and to hypercapnia of both the systemic and the coronary circulations have been studied in the dog during intermittent positive pressure ventilation under halothane anaesthesia. In the absence of significant variations of myocardial contractility, the reduction of cardiac output, because of hypocapnia, was determined by the increase of systemic vascular resistance, while the increase of cardiac output because of hypercapnia was determined by an increase of heart rate without change of stroke volume. The alterations of coronary blood flow (reduction following hypocapnia, augmentation following hypercapnia) were considerably larger than the changes of cardiac output and of myocardial oxygen consumption. Such disparity between oxygen supply and demand, together with the effect of pH and PCO2 on the oxyhaemoglobin dissociation curve led to a marked reduction of coronary sinus PO2 in response to hypocapnia and a marked increase of coronary sinus PO2 in response to hypercapnia. The data suggests that PCO2 (or respiratory alterations of pH) may have a direct effect on the regulation of coronary blood flow. The low coronary sinus PO2 observed at hypocapnia may suggest the risk of myocardial ischaemia.
In 12 patients with heart disease, hypercarbia was induced for carotid endarterectomy. Anesthesia was maintained with nitrous oxide in oxygen and methoxyflurane. In addition to intra-arterial measurements of blood pressure, cardiac output, systolic time intervals (STI), and pressure time indices (PTI) were determined in order to assess cardiovascular responses in these patients. Internal carotid stump blood pressure was measured in five patients before and after induction of hypercarbia. Mild elevation of the Paco2 level affected systolic time intervals but not heart rate and blood pressure. When Paco2 levels reached 56 to 65 torr, systolic but not diastolic blood pressure rose significantly, heart rate and cardiac output increased, while the shortening in the preejection period (PEP), left ventricular ejection time (LVET), and the decrease in the PEP/LVET ratio signified increased mechanical cardiac activity. Hypercarbia caused intense sympathetic stimulation as demonstrated by twofold to threefold increases in plasma catecholamine levels. Stump blood pressure was elevated. Cardiac oxygen demand was significantly increased, while coronary filling time was shortened, as indicated by the increase in the tension time index and shortening in the diastolic time. This signified a relative myocardial underperfusion. Thus, while hypercarbia to levels of 66 to 70 torr increased internal carotid artery stump pressure, it also caused increased cardiac mechanical activity and concomitant unfavorable balance between myocardial oxygen consumption and supply. The measurement of STI and the computation of PTI provided early detection of alterations in cardiac function.
Our findings confirm that acute pulmonary edema, when caused by left ventricular failure, represents a form of acute perfusion failure (shock) with metabolic acidemia, lactacidemia, and a reduction in forward blood flow. It is associated with a marked increase in peripheral resistance and an increase in venous capacitance. Most importantly, acute pulmonary edema is associated with a reduction in the intravascular blood volume. Acute pulmonary edema is not fundamentally different from other types of shock in which the shock state is initiated by one primary defect, and during the course of its progression, other primary mechanisms are called into action. In the instance of acute cardiogenic edema, the primary defect is cardiac pump failure and the secondary defects include hypovolemia and distributive defects associated with arterial vasoconstriction and expanded venous capacitance. Furosemide reverses acute pulmonary edema by increasing rather than decreasing intravascular blood volume with consequent improvement in the distributive and hypovolemic defects. Under extreme conditions, the volume defect in acute pulmonary edema may be so great that the patient presents with primary hypovolemia. The utilization of volume repletion is warranted under these circumstances.
The effects of acute changes in arterial carbon dioxide and oxygen tension, produced by altering the inspired gas mixtures while maintaining constant-volume intermittent positive pressure ventilation, on global function, regional left ventricular function, and coronary hemodynamics were studied in eight sheep during halothane anesthesia. Hypercapnia (Paco2, 73.5 +/- 2.3 mm Hg, mean +/- SD) increased heart rate, stroke volume, and cardiac output but decreased systolic shortening in the base of the left ventricle. Hypocapnia (PaO2, 24 +/- 1.5 mm Hg) decreased cardiac output and coronary flow below levels seen with hypercapnia but not below levels seen with normocapnia. Systolic shortening decreased in both apical and basal regions, and left ventricular relaxation was impaired as evidenced by a reduction of the nadir of LV dP/dt. Hypoxemia (PaO2, 39 +/- 1.5 mm Hg) elicited a hyperdynamic response of the circulation, increased coronary blood flow, and exhausted the coronary flow reserve. Neither changes in PaCO2 nor changes in PaO2 caused postsystolic shortening, although hypercapnia caused nonuniformity of contraction in the left ventricle. Thus, marked alterations in oxygen and carbon dioxide tensions do not cause left ventricular dysfunction, even though moderate hypoxia reduces the coronary flow reserve.
We studied the effect of graded acute hypercapnic acidosis (HA) on sympathetic neural activation in 15 juvenile farm swine in vivo. In seven animals with acute HA, plasma norepinephrine (NE) concentration increased progressively from 189 +/- 34 to 483 +/- 80 pg/ml (P less than 0.04) as arterial CO2 partial pressure (PaCO2) increased in steps from 40 to 80 Torr (pH 7.17 +/- 0.01). Plasma epinephrine (EPI) concentration increased from 30 +/- 15 to 125 +/- 66 pg/ml (P = NS) over the same change in PaCO2. At PaCO2 of 110 Torr, plasma NE increased 3.4-fold above maximal basal concentrations; plasma EPI was 1.8-fold greater than basal under the same conditions. With HA, systemic vascular resistance (SVR) decreased from 1,748 +/- 110 to 1,392 +/- 145 dyn.s.cm-5 (P less than 0.0002), cardiac output (CO) increased from 3.4 +/- 0.3 to 4.3 +/- 0.3 l/min (P less than 0.01), and heart rate (HR) increased from 117 +/- 11 to 154 +/- 17 beats/min (P less than 0.03). To demonstrate that catecholamine secretion was related directly to acidosis caused by an increase in PaCO2, HCO3- was infused in eight other swine to buffer extracellular acute HA (pH 7.37 +/- 0.01 at PaCO2 of 80 Torr). Buffering attenuated the increase in plasma NE, which remained within the normal range at PaCO2 of 80 Torr. The decrease in SVR and increases in CO and HR also were also attenuated by HCO3- buffering of HA. We demonstrate the effects of graded acute HA on endogenous secretion of catecholamine and on the associated hemodynamic responses in swine.(ABSTRACT TRUNCATED AT 250 WORDS)
The hemodynamic effects of high arterial carbon dioxide pressure (PaCO2) during anesthesia in horses were studied. Eight horses were anesthetized with xylazine, guaifenesin, and thiamylal, and were maintained with halothane in oxygen (end-tidal halothane concentration = 1.15%). Baseline data were collected while the horses were breathing spontaneously; then the horses were subjected to intermittent positive-pressure ventilation, and data were collected during normocapnia (PaCO2, 35 to 45 mm of Hg), moderate hypercapnia (PaCO2, 60 to 70 mm of Hg), and severe hypercapnia (PaCO2, 75 to 85 mm of Hg). Hypercapnia was induced by adding carbon dioxide to the inspired gas mixture. Moderate and severe hypercapnia were associated with significant (P less than 0.05) increases in aortic blood pressure, left ventricular systolic pressure, cardiac output, stroke volume, maximal rate of increase and decrease in left ventricular pressure (positive and negative dP/dtmax, respectively), and median arterial blood flow, and decreased time constant for ventricular relaxation. These hemodynamic changes were accompanied by increased plasma epinephrine and norepinephrine concentrations. Administration of the beta-blocking drug, propranolol hydrochloride, markedly depressed the response to hypercapnia. This study confirmed that in horses, hypercapnia is associated with augmentation of cardiovascular function.
Systemic hemodynamic adjustments involved in the control of cardiac output (CO) were examined in chronically instrumented unanesthetized sheep inhaling gas mixtures resulting in hypocapnic hypoxia (H) [arterial pH (pHa) = 7.53, arterial partial pressure of O2 (Pao2) = 30 Torr, arterial partial pressure of CO2 (Paco2) = 29 Torr] or hypercapnic hypoxia (HCH) (pHa = 7.14, Pao2 = 34 Torr, Paco2 = 72 Torr) for 1 h. H (n = 7) and HCH (n = 6) resulted in 26% and 61% increases in CO, respectively, and mean systemic arterial pressure rose to a greater extent during HCH. Both H and HCH resulted in increased blood flow (microsphere method) to the peripheral systemic circulation including the brain, heart, diaphragm, and nonrespiratory skeletal muscle (the latter blood flow increased 120% during H and 380% during HCH). Gastrointestinal and renal blood flow remained unchanged during H and HCH. Transit time of green dye from the pulmonary artery to regional veins in the hindlimb and intestine was 5.0 and 8.2 s, respectively, during base-line conditions and remained unchanged with HCH. During HCH, regional O2 consumption increased 274% for the hindlimb and decreased 39% for the intestine. Total catecholamines rose 250% during H and 3,700% during HCH. During hypocapnic and hypercapnic hypoxia, CO is augmented in part by systemic hemodynamic adjustments that include a redistribution of blood flow and a translocation of blood volume to the fast transit time peripheral systemic circuit. The sympathetic nervous system may play an important role in mediating these systemic hemodynamic adjustments.
Perforation of the pulmonary artery due to insertion of a balloon-tipped, flow-directed (Swan-Ganz) catheter is described in four cases. These cases were found in a consecutive series of 270 autopsies done over a 1.5-year period and suggest that the incidence of this complication may be greater than the number of clinically reported cases implies. In three instances, a focal parenchymal hematoma or thrombotic nodule identified the site of rupture. Other pathologic features and the pathogenesis of the perforation are discussed. Difficulties in postmortem diagnosis include distinguishing perforation from hemorrhage due to trauma, thromboembolism, and coagulation abnormalities.
In thermodilution a known change in heat content of the blood is induced at one point of the circulation and the resultant change in temperature detected at a point downstream. When cardiac output is measured, a bolus of cool liquid is injected into the upper right atrium and the temperature change detected in the pulmonary artery. When flow in single blood vessels is measured, the distance between the site of injection and the site of detection is small; therefore, mixing must be attained by the kinetic energy of the injectate. The continuous constant rate injection technique is most suitable for measurement of venous flow. Since the blood flow in arteries can be markedly and unpredictably altered by the injection or the injectate, this technique is not suitable to measure flow in arteries. Measurement of venous flow by the bolus injection technique is tedious and time-consuming because of the complex formula. Minimal recirculation, simple and accurate calibration, intravascular detection of temperature and simple equipment are the advantages of the thermodilution technique.
A technique for measurement of cardiac output by thermodilution (COTD) in man has been described. Comparison with cardiac outputs determined simultaneously by the dye-dilution technique (CODYE) in 63 measurements in 20 patients showed close agreement of the 2 methods in a range of values from 2.9 to 8.0 liters/min (COTD = 0.96 CODYE + 0.2, r = 0.96). The reproducibility of measurements was 4.1 percent with the thermodilution and 5.4 percent with the dye-dilution technique. The thermodilution technique does not require withdrawal of blood during measurements and removal of blood for calibration. The calibration is simple and accurate. There is virtually no recirculation, so that a simple integrator can be used for determination of the area beneath the thermodilution curve.
To systemically evaluate the effects of acute hypoxemia and hypercapnic acidosis on the sympathetic nervous system, five unanesthetized mongrel dogs were studied during acute hypoxemia [arterial O2 tension (PaO2) 33 +/- 2 Torr], acute hypercapnic acidosis [arterial CO2 tension (PaCO2) 53 +/- 1 Torr; pH, 7.19 +/- 0.02], and combined acute hypoxemia and hypercapnic acidosis (PaO2, 36 +/- 1 Torr; PaCO2, 52 +/- 1 Torr; pH, 7.18 +/- 0.02). Combined acute hypoxemia and hypercapnic acidosis resulted in increased mean arterial pressure, cardiac output, and heart rate. Moreover, combining acute hypoxemia and hypercapnic acidosis acted synergistically to increase circulating norepinephrine and epinephrine. Acute hypoxemia alone and acute hypercapnic acidosis alone resulted in reversible increases in mean arterial pressure, cardiac output, heart rate, and circulating norepinephrine. Although plasma epinephrine concentrations increased during acute hypoxemia, circulating epinephrine was unchanged during acute hypercapnic acidosis. These data indicate that acute hypoxemia and hypercapnic acidosis result in synergistic increase in circulating catecholamines.
Hemodynamic measurement is now an important and feasible adjunct to clinical practice. Its successful application to alleviate illness in human beings is evident in its contribution to an understanding of the pathophysiology of disease and the efficacy of various interventions to alter the course of a variety of diseases. Its application is widespread in the high risk patient undergoing surgery and the critically ill medically treated patient. Hemodynamic measurement permits accurate determination of the state and, if necessary, of the continuously changing function of the heart as related to disease process and guides treatment and interventions on a rational physiologic basis.
This study validates the accuracy of miniature ultrasonic transit-time flow probes for measuring renal blood flow (RBF) in the rat. Probes for 1-mm and 2-mm vessels were calibrated ex vivo using excised arteries at varying flow rates and hematocrit (Hct). Correlation between measured and true flow rates for the 2-mm probe were identical (r = 1.0) at both normal and subnormal Hct values. Correlation for the 1-mm probe was high (r = 0.994) at normal Hct, but varied at both high flow rates and subnormal Hct values. In vivo correlation of RBF measurements using the 1-mm probe with the clearance and extraction of p-aminohippuric acid showed a high correlation (r = 0.84; n = 72, P < 0.0001) over a wide range of flow rates (0.5-21 ml/min) and Hct (36-74%). Zero flow levels remained steady, averaging -0.2 +/- 0.2 ml/min during occlusion in the living animal and -0.1 +/- 0.3 ml/min after exsanguination. This study shows that the ultrasonic transit-time flowmeter (1-mm and 2-mm probes) is a reasonably accurate and reliable method with which to measure RBF in the anesthetized, acute-instrumented rat.
The aim of this investigation was to validate and calibrate the 1- and 2-mm transit-time ultrasound, perivascular flow probes on the superior mesenteric artery and aorta of the rat by using an in vivo and in situ calibration system. The baseline blood flows measured by the flowmeter zero-flow function and the true-zero flow measurement, after complete occlusion of the vessels, were not different. The probes were then calibrated, in situ, by timed-volume measurements with a blood/saline pump-perfused circuit. The relationship between measured flow and true flow was linear for both probes. The slope of the 1-mm probe data was not significantly different from the line of identity, whereas the 2-mm probe data slightly overestimated the true flow (slope = 1.2, y-intercept = -3.2 ml/min). The slope of the middle region of the 2-mm probe data, however, was not significantly different from the line of identity, suggesting that the 2-mm probe has a window of accuracy over this range of flows. Progressive elimination of the low and high data points varying the most from the line of identity and reanalysis of the data revealed that the window of accuracy for the 2-mm probe, under our experimental conditions, was between 10.4 and 45.1 ml/min.
A transit time flowmeter, Transonic TC101 (Transonic Inc., USA) has been evaluated to study volume flow. Two flow probes, 4 and 6 mm, were used. The experiments were carried out in vivo on the carotid arteries (n= 16) in sheep and in vitro against a pre calibrated rotational pump. Exsanguination measurements, n= 32, were used for the calculation of the error of measurement in vivo. The error of measurement in vitro was calculated on 11 different flow rates from 0 to 150 ml min-1.
The variability in vivo was evaluated using data from 10, 30 s measurement periods with a 30 s pause between measurements. The variability in vitro was evaluated at three flow rates (46, 78, and 113 ml min-1). Five 1-min measurements with a 1-min pause between measurements were made.
The error of measurement in vivo was 12.05% and in vitro 5.50% (4 mm probe) and 14.90% (6 mm probe). In vivo the variability was between 1.1 and 4.4% and in vitro between 1.5 and 11.2%. The correlation coefficients between the flowmeter on the one hand and exsanguination and the rotational pump on the other were 0.99, 0.99 (4 mm probe) and 0.98 (6 mm probe).
It is concluded that the flowmeter has a small variability and error of measurement both in vivo and in vitro.
We continuously measured hepatic absorbance of indocyanine green (ICG) using near-infrared (NIR) spectroscopy after intravenous bolus injection in rabbits. Hepatic ICG concentration was obtained by subtracting out the absorbance of hemoglobin and other pigments within the liver. Two exponential rate constants, the first reflecting the dye uptake from plasma to the hepatocytes, and the second representing the dye removal from the liver by cytoplasmic transport and biliary excretion, were determined by fitting the time-course curve of hepatic ICG concentration to a two-compartment model with irreversible transfer between the two compartments, as defined by the double-exponential equation: [ICG]liver(t) = -A exp(-alpha t) + B exp(-beta t). The results showed that treatment with bilirubin, a competitive inhibitor of ICG uptake, caused a decrease in alpha. Treatment with either colchicine, which is toxic to microtubules, or with ouabain, an inhibitor of Na+,K(+)-ATPase, caused a decrease in beta. These results were compatible with the kinetic model. This new method was then used in liver-injured rabbits inflicted with hemorrhagic shock and ischemia-reperfusion, to show that the first rate constant is primarily affected by hepatic microcirculatory condition, and the second refers closely to parenchymal liver damage. In another series of partial liver ischemia-reperfusions, it was possible to simultaneously and separately monitor the ICG profiles of post-ischemic and nonischemic areas. Thus, the kinetic analysis of hepatic ICG concentration curves, as directly measured by NIR spectroscopy, led to the separate evaluation of different clearance process of ICG in the liver, suggesting the advanced utility as a comprehensive liver function test.
To validate the new CardioMed CM 4000 transit time ultrasound apparatus for intraoperative measurement of volume blood flow in vivo in man.
Open, prospective series.
Thirteen patients undergoing in situ saphenous vein grafting for chronic critical leg ischaemia and 12 patients subjected to myocardial revascularisation with the internal thoracic artery as coronary bypass.
During operations, volume blood flows were measured simultaneously by exsanguination from the cut distal end of the in situ saphenous vein graft or the internal thoracic artery and by the transit time flowmeter equipment. In addition, the feasibility to detect arteriovenous fistula during in situ saphenous vein grafting was examined.
Within the examined blood flow range, the volume blood flow determined by the transit time method corresponded to the directly measured blood flow. For in situ saphenous vein grafts: y = -2.4 + 0.95.x (r = 0.99; 35 measurements in 13 patients), and for internal thoracic artery grafts: y = -9.6 + 1.1.x (r = 0.99; 21 measurements in 12 patients), where y is blood flow determined by transit time, and x is directly measured blood flow by exsanguination (r = correlation coefficient) as calculated by the least squares regression method. Fistula detection was easy and swift.
The transit time apparatus was simple to use during intraoperative settings and gave fast, precise measurements of volume blood flow.
Two case reports describing patients having cardiac operations under extra corporeal circulation are presented. At the completion of the operation, a massive hemoptysis occurred in both patients after a Swan-Ganz catheter had perforated the pulmonary artery. A hemostasis lobectomy was then immediately required. The immediate and long term prognosis seems satisfactory. This is an unusual but serious complication. The incidence of this complication varies between 0.06 and 0.2%. The more frequently related risk factors include people over the age of 60, pulmonary artery hypertension, anticoagulant therapy, hypothermia and manipulation of the heart by the surgeon. When this accident occurs, many authors suspect the balloon. An early diagnosis is essential in the case of a major or even a minor hemoptysis, because this complication may be a lethal one as the mortality rate may reach 50%. According to us, the appropriate therapy which would reduce this mortality is a surgical one (hemostasis lobectomy).
The objective of the present study was to validate a transonic flowmeter system with two probes (model 3SS for cardiac output (CO) and 1RB for organ flows) in Sprague-Dawley (SD) rats first by measuring blood flow through pump-infused isolated renal artery and ascending aorta, and then through measurements of CO and renal, mesenteric, and hindquarter blood flow (RBF, MBF, HBF) in vivo. We measured in vivo baseline flow and changes in flow induced by dopamine and propranolol for CO, prostaglandin E2 (PGE2), and angiotensin II (AII) for RBF and pentobarbital sodium for MBF and HBF. Correlations between meter and pump flow were linear (r = 0.999, p < 0.001) with close agreement both in ascending aorta and renal artery flow measurements. The baseline values were 15 +/- 0.7 ml/100 g/min for CO, 4 +/- 0.1 ml/100 g/min for RBF, 7 +/- 0.3 ml/100 g/min for MBF, and 6 +/- 0.3 ml/100 g/min for HBF, respectively. The system reliably detected increase and/or decrease in CO and regional blood flows. The transonic flowmeter system is accurate, highly reproducible, and compatible with other established techniques for measuring CO and regional blood flows in the rat.
Pulse dye-densitometry (PDD) is a newly developed method for monitoring the indocyanine green (ICG) concentration in an artery with which cardiac output (CO) and circulating blood volume (CBV) can be determined. We evaluated its accuracy for clinical use.
In 7 patients under general anesthesia, ICG-sensitive optical probes (805 and 890 nm) were attached to a finger. Following injection of ICG, the arterial concentration of dye was recorded optically by the non-invasive test instrument and sampled arterial blood ICG concentration was also measured photometrically for comparison. In order to validate the PDD analysis, CO was also measured by both the dye dilution cuvette method and by thermodilution in 8 patients scheduled for coronary artery bypass grafting. In 30 other patients, CBV assessed by PDD was compared with its value estimated from body size.
The blood dye concentration correlated well with the values obtained by PDD (r = 0.953, p < 0.01). Mean bias for the test PDD CO was +0.15 +/- 0.72 min l-1 (not significant (n.s.)) compared with the cuvette method while the mean bias of the thermodilution method vs the cuvette method was +0.79 +/- 0.84 min l-1 (p < 0.0001.). The average value of CBV obtained by PDD was 3.81 +/- 1.39 L compared with that estimated value, 3.72 +/- 0.77 L (n.s.).
CO determined by PDD agrees well with cuvette densitometry, and somewhat less well with CO by thermodilution. The new method, by not requiring a pulmonary arterial catheter, is less invasive than either older method, and yields in addition a value of CBV.
Determination of blood flow is essential for monitoring rotary blood pumps. However, accurate measurement directly adjacent to the pump housing is difficult because of the highly irregular flow profiles near the fast spinning rotor. Therefore, a specially adapted flow probe based on the ultrasound transit time (USTT) principle was designed to evaluate the flow in centrifugal blood pumps. The probe can be directly mounted at the housing and creates 2 crossed measuring ultrasound beams. The mean value, Qm, of the 2 output signals corresponds to the blood flow and the difference, Qd, correlates to the vorticity of the flow profile in the pump outflow tract. In vitro measurements obtained an accuracy for mean flow values of better than +/-0.6 L/min in extreme working points and for vorticity values even as high as Qd = 3.5 L/min. Because of vorticity, however, the output signal contained considerable noise, and that required the application of a 10 Hz filter. Positioning of the ultrasound (US) beams parallel to the axial direction of the pump was superior to radial positioning. Additional measurement of the flow profile demonstrated that a large vorticity occurred (up to Qd equal to 3.5 L/min), and this vorticity was highly dependent upon the afterload of the pump. In vivo experiments demonstrated the reliability of the method. We concluded that USTT flow measurement can determine blood flow immediately adjacent to the pump housing with sufficient accuracy, and these measurements are superior to those from US-Doppler systems (which cannot handle the vorticity accurately enough) and electromagnetic devices (which lack zero stability).
To determine whether changes mixed-venous PCO2 or PO2 affect cardiac output independent of changes in arterial blood gases, we used extracorporeal gas exchange to increase mixed-venous PCO2 or decrease mixed-venous PO2 in adult sheep. Sheep were anesthetized, mechanically ventilated, and connected to a veno-venous extracorporeal circuit. The circuit included a gas exchanger which was used to increase mixed-venous PCO2 or decrease mixed-venous PO2; the native lungs were ventilated to maintain arterial PCO2 and PO2 at control levels. When mixed-venous PCO2 was increased by 32% above control levels for a period of 60 min, cardiac output increased significantly to 28% above control levels. Cervical vagotomy abolished this response. In contrast, decreasing mixed-venous PO2 by 29% did not increase cardiac output. These results demonstrate that increasing mixed-venous PCO2 can increase cardiac output independent of changes in arterial blood gases and that intact vagus nerves are necessary for this response to occur.
A new method for determining cardiac output (CO, l/min) using dye dilution combined with pulse dye densitometry (PDD), based on the principle of pulse oximetry, has been developed. The aim of the study was to determine the accuracy and precision of PDD by comparing it with the thermodilution method.
A prospective study was performed in 22 patients having surgery who were monitored using a pulmonary arterial catheter. In addition to the catheter, a specially designed photodetector was placed on the nasal wing. Ten milliliters of ice-cold indocyanine green dissolved in a 5% glucose solution (0.5 mg/ml) was injected. The dye and thermal dilution curves were simultaneously measured to calculate CO. Three to six injections were performed before and after surgery. Paired data were assessed in absolute terms, and the percentage errors were calculated by the degree of agreement and compared at three levels of CO (low < or = 3.5 < medium < or = 6 < high) by analysis of variance.
The mean and SDs of the differences between dye and thermodilution CO were 0.16 +/- 0.80 l/min or 4.5 +/- 19.6% for 191 paired data. Measurement after surgery failed in one patient. The percentage error with low CO (9.3 +/- 19.3%) was greater (P < 0.05) than those obtained with other CO.
Pulse dye densitometry could measure CO repeatedly in patients having major surgery with the same degree of accuracy as the thermodilution method; however, a considerable degree of error was observed in some patients.
We describe a patient who had clinical and radiologic presentation consistent with contained pulmonary artery rupture during difficult placement of a pulmonary artery catheter. We presented a rarely described case of contained pulmonary artery rupture with no adverse outcome. The presence of blood in the endotracheal tube may indicate a pulmonary artery rupture, a potentially life-threatening complication.
To investigate the precision and accuracy of continuous pulse contour cardiac output (PCCO) compared with intermittent transcardiopulmonary (TCPCO) and pulmonary artery thermodilution (TDCO) measurements in patients undergoing minimally invasive coronary bypass surgery (MIDCAB).
Prospective, controlled, clinical study.
University hospital.
Twelve patients undergoing MIDCAB.
Thirty-six measurements of PCCO and thermodilution cardiac output (CO) were simultaneously performed after the start of surgery, during bypass grafting, and at the end of surgery. TCPCO and TDCO were simultaneously assessed by three injections of ice-cold saline randomly spread over the respiratory cycle. The pulse contour device was initially calibrated with an additional set of aortic thermodilution measurements.
Absolute values of CO ranged between 1.6 and 9.2 L/min. A close agreement among the three techniques was observed at all measurements. Mean bias between PCCO and TDCO and TCPCO was 0.003 L/min (2 SD of differences between methods = 1.26 L/min) and 0.27 L/min (2 SD of differences between methods = 1.16 L/min), respectively. The correlation coefficients were r2 = 0.90 for TCPCO versus PCCO and r2 = 0.88 for TDCO versus PCCO.
The results of the present study show that compared with thermodilution CO, pulse contour analysis enables accurate measurement of continuous CO in patients undergoing MIDCAB.
To describe global hemodynamics and splanchnic perfusion changes in response to acute modifications in Paco2 in hemodynamically stable patients.
Prospective, randomized crossover study.
Medical-surgical intensive care unit at a community hospital (400,000 inhabitants).
Ten critically ill patients who were sedated, paralyzed, and mechanically ventilated.
Hypercapnia and hypocapnia were obtained by increasing and reducing instrumental deadspace in random order. After each intervention, patients returned to the basal condition. Each period lasted 80 min: 20 min to achieve stable Paco2 and 60 min for tonometer equilibration. In each period, global hemodynamic variables and tonometric data were collected. The periods were compared using analysis of variance.
Acute hypercapnia (Paco2 from 40+/-3 to 52+/-3 torr, p<.05) increased cardiac index (3.43+/-0.37 vs. 3.97+/-0.43 mL/min/m2, p<.05), heart rate (95+/-6 vs. 105+/-3 beats/min, p<.05), and mean pulmonary artery pressure (21+/-1 vs. 24+/-1 mm Hg, p<.05) and reduced systemic vascular resistance (992+/-98 vs. 813+/-93 dyne x sec/ cm5, p<.05) and oxygen extraction ratio (27+/-3% vs. 22+/-2%, p<.05). Standardized intramucosal Pco2 increased from 49+/-2 to 61+/-3 torr (p<.05) with an associated decrease in calculated intramucosal pH ([pHi] 7.35+/-0.03 vs. 7.25+/-0.02, p<.05), but the gastro-arterial Pco2 gradient (deltaPco2) did not change. Acute hypocapnia (Paco2 from 41+/-3 to 34+/-3 torr, p<.05; pH 7.41+/-0.01 to 7.47+/-0.02, p<.05) induced slight increments in systemic vascular resistance (995+/-117 vs. 1088 +/- 160 dyne x sec/cm5, p<.05) and oxygen extraction ratio (28+/-2% vs. 30+/-2%, p<.05). Standardized intramucosal Pco2 decreased (50+/-4 vs. 44+/-3 torr, p<.05), pHi increased (7.33+/-0.03 vs. 7.36+/-0.02; p<.05), but deltaPco2 did not change.
In this small group of stable patients, moderate acute variations in Paco2 had a significant effect on global hemodynamics, but splanchnic perfusion, assessed by deltaPco2, did not change. In these conditions, the use of pHi to evaluate gastric perfusion appears unreliable.
We prospectively studied the agreement between transpulmonary aortic fiberoptic-based and pulse dye densitometry (PDD) measurements of cardiac output and circulatory blood volumes.
Prospective clinical study.
Operative ICU of a university hospital.
Sixteen critically ill, deeply sedated patients receiving mechanical ventilation with ARDS (n = 8), sepsis/septic shock (n = 6), subarachnoid hemorrhage (n = 1), and severe head injury (n = 1). Measurements and results: Each patient received a 4F aortic catheter with an integrated fiberoptic and thermistor that was connected to a computer system for automatic calculation of the transpulmonary indicator dilution (TPID) technique for the measurement of cardiac output (COTPID), intrathoracic blood volume (ITBV), and total blood volume measured by TPID technique (TBVTPID). In each patient, an indocyanine green sensor was attached to one nasal wing and connected to an analyzer for the PDD measurement of cardiac output (COPDD), central blood volume (CBV), and TBV measured by PDD (TBVPDD). For all first measurements, linear regression analysis between COTPID and COPDD revealed that COPDD = 0.63 x COTPID + 3.69 (L/min) [r = 0.64, p = 0.008]. Mean bias between both techniques was - 0.8 L/min (SD, 1.7 L/min). Correlations between ITBV/CBV (r = 0.52) and TBVTPID/TBVPDD were only moderate: TBVPDD = 0.74 x TBVTPID + 2,362 (mL) [r = 0.60, p = 0.015; mean bias, - 999 mL; SD, 1,353 mL]. Over all 55 measurements, TPID measurements were on average 11.5% (cardiac output) and 17.6% (TBV) higher than PDD measurements. The differences between both measurements ranged from - 58 to 81% (cardiac output) and from - 47 to 82% (TBV; 95% reference ranges). The main source of variation were the intraindividual differences, resulting in different peaks and trends in the patients time courses depending on which measurement method was used.
PDD measurement of cardiac output and circulatory blood volumes agrees moderately with transpulmonary thermo-dye dilution technique in critically ill patients.
To evaluate the agreement between cardiac output (CO) measurements obtained by a new dye dilution technique using pulse dye densitometry (PDD) and thermodilution (TD) and the direct Fick method (F).
Prospective clinical study in a university hospital, cardiac surgery intensive care unit.
Fifty-eight cardiac surgery patients after admission to the intensive care unit (six were excluded due to a low pulse signal quality using the PDD method).
Mean CO was 5.3+/-1.8 l/min for PDD, 5.7+/-1.68 l/min for TD, and 6.16+/-1.66 l/min for F. There was a good correlation between PDD and TD ( r(2)=0.93) and between PDD and F ( r(2)=0.77). Bias and precision between PDD and TD were -0.39+/-0.5 l/min and -0.69+/-0.85 l/min between PDD and F. In general, PDD determined lower CO values than TD and F. Especially in patients with CO below 5 l/min PDD underestimated CO in comparison to TD and F (bias and precision: -0.51+/-0.40 l/min and -0.83+/-1.0 l/min).
Comparison between PDD and TD showed good agreement for the normal to high CO range. However, agreement was poor in patients with low CO. In the latter patient group PDD showed relevant underestimation of CO compared to TD and F. Due to these limitations PDD cannot entirely replace the pulmonary artery catheter for CO determination.
To establish a mouse model for the study of venoocclusive erectile dysfunction, we investigated erectile function in wild-type (WT), castrated (CAST), and castrated mice receiving immediate testosterone replacement (TEST). Adult C57BL6 mice ( approximately 30 g) underwent electrical stimulation of the cavernous nerve in vivo (parameters: 16 Hz frequency, 5 ms duration, 4V stimulatory voltage) with intracavernosal pressure (ICP) monitoring. A total of 55 mice (5 WT, 25 CAST, and 25 TEST) were evaluated. CAST and TEST (5.0 mg/pellet, 60-day release) mice were divided into groups of 5 and evaluated at 24 hours, 72 hours, 1 week, 2 weeks, and 4 weeks. Penile tissue was immunohistochemically stained for alpha-actin (marker for smooth muscle cells) and CD-31 (marker for endothelial cells). Stained slides were analyzed using Image Pro-plus software. In secondary studies, a Doppler flow meter was employed to evaluate penile blood flow. ICP measurements (mm Hg) were significantly decreased in CAST mice at 24 hour-, 72 hour-, 1 week-, 2 week-, and 4-week time points compared with WT mice (41.9 +/- 14.9, 19.1 +/- 4.2, 17.5 +/- 8.2, 14.2 +/- 4.4, and 10.0 +/- 3.8, respectively, vs 50.2 +/- 2.8), but TEST animals maintained or had an increase in ICP in comparison with WT mice (48.0 +/- 1.4, 52.3 +/- 1.3, 60.8 +/- 7.6, 80.5 +/- 2.1, and 81.5 +/- 1.2, respectively). Mean systemic arterial pressure remained approximately 80 mm Hg irrespective of treatment. CAST mouse penis specimens revealed decreased alpha-actin and CD-31 immunoreactivity only at the 4-week interval, compared with WT and TEST specimens. Doppler ultrasound flow rates (centimeter per second), taken before, during, and immediately after cavernous nerve stimulation, were WT 45.4 +/- 7.3, 30.6 +/- 5.2, 55.3 +/- 8.2 vs CAST (2 weeks) 22.2 +/- 2.5, 25.0 +/- 1.5, 23.1 +/- 2.0 vs TEST (2 weeks) 30.5 +/- 6.5, 25.7 +/- 2.0, 45.2 +/- 4.5. This prominently showed that intrapenile flow was not reduced normally during erectile stimulation in CAST mice. This is the first described mouse model of castration-induced veno-occlusive erectile dysfunction. Erectile response abnormalities as measured by ICP and Doppler ultrasound studies in CAST mice may be attributed to hypogonadal effects on erectile tissue function. Morphologic changes in the cavernosal tissue of CAST mice coincide with these abnormalities to some extent. This study defines an androgen-dependent mechanism of veno-occlusive erectile function in the mouse. The castrated mouse model can be applied in future studies of veno-occlusive erectile dysfunction.
The aim of this study was to validate the quantification of absolute renal perfusion (RP) determined by dynamic magnetic resonance imaging (MRI) and contrast media using an experimental model in the rabbit and a transit-timed ultrasound flow probe around the left renal artery as comparison.
An MR-compatible ultrasonic time-of-flight flow-probe was placed around the left renal artery in 9 New Zealand white rabbits. Absolute RP in basal state, after mechanical renal artery stenosis, intravenous dopamine, angiotensin II, or colloid infusion was measured using dynamic MRI and intravenous injection of gadoteridol. The results were correlated to the renal artery flow measured inside the magnet with the transit-timed flow-probe. For the signal intensity concentration conversion, we applied different calibrations according to various velocities measured in the aorta by a phase contrast sequence to correct for inflow effect. MRI-derived RP (in mL/min) was calculated by the maximum upslope method, where RP/volume was defined as the ratio of the cortex contrast enhancement slope over the maximum of the arterial input function determined in the aorta.
Reproducible arterial and renal transit curve with excellent contrast to noise ratio were obtained. The MRI derived perfusion was systematically underestimated by comparison to the ultrasonic transit-timed flow-probe but was linearly correlated with these measures (r = 0.80, P < 0.001).
Using a flow-sensitive calibration, an accurate arterial input function can be measured from the blood MR signal and used in a realistic model to assess the RP. There was a good correlation between the MR-derived RP and the renal artery blood flow measured by the flow-meter. This experimental study validates absolute RP quantification by MRI and contrast media injection and justifies further clinical studies.
1. A new graphical method for calculating flow, downslope and mean circulation time from semilogarithmic plots of indicator-dilution concentration-time curves is described. 2. The advantages of employing this method of calculation include speed and accuracy.
1. Indocyanine green given intravenously to dogs is distributed in the plasma compartment and rapidly removed by the liver. 2. Biliary excretion of the dye is delayed, but an average of 97.3% of the administered dose is eventually recovered from the bile in apparently unaltered form. Indocyanine green does not appear in the urine. 3. Indocyanine green interferes with hepatic uptake of BSP from the plasma. 4. Absorption of indocyanine green from the bowel is minimal.