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THE AIM: (1) To develop a mathematical model of the passage of a diffusible indicator through microcirculation based on a stochastic description of diffusion and flow; (2) To use Goresky transform of the dilution curves of the diffusible indicators for the estimation of the permeability of a tissue-capillary barrier. THE METHOD: We assume that there are two causes for flow to be stochastic: (a) All microvessels are divided between open and closed microvessels. There exists random exchange between the two groups. (b) The flow through open microvessels is also random. We assume that each diffusing tracer has a probability to leave the intravascular space, and has a probability to return. We also assume that all considered processes are stationary (stability of microcirculation). CONCLUSION: (a) The distribution of the time to pass microcirculation by diffusing indicator is given by a compound Poisson distribution; (b) The permeability of tissue-capillary barrier can be obtained from the means, delay, and dispersions of the dilutions of intravascular and diffusing traces.

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Death after severe hemorrhage remains an important cause of mortality in people under 50 years of age. Keratin resuscitation fluid (KRF) is a novel resuscitation solution made from keratin protein that may restore cardiovascular stability. This postulate was tested in rats that were exsanguinated to 40% of their blood volume. Test groups received either low or high volume resuscitation with either KRF or lactated Ringer's solution. KRF low volume was more effective than LR in recovering cardiac function, blood pressure and blood chemistry. Furthermore, in contrast to LR-treated rats, KRF-treated rats exhibited vital signs that resembled normal controls at 1-week.

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OBJECTIVES: No simple method exists for repeatedly measuring cardiac output in intensive care pediatric and neonatal patients. The purpose of this study is to present the theory and examine the in vitro accuracy of a new ultrasound dilution cardiac output measurement technology in which an extracorporeal arteriovenous tubing loop is inserted between existing arterial and venous catheters. DESIGN: Laboratory experiments. SETTING: Research laboratory. SUBJECTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In vitro validations of cardiac output, central blood volume, total end-diastolic volume, and active circulation volume were performed in a model mimicking pediatric (children 2-10 kg) and neonatal (0.5-3 kg) flows and volumes against flows and volumes measured volumetrically. Reusable sensors were clamped onto the arterial and venous limbs of the arteriovenous loop. A peristaltic pump was used to circulate liquid at 6-12 mL/min from the artery to the vein through the arteriovenous loop. Body temperature injections of isotonic saline (0.3-10 mL) were performed. In the pediatric setting, the absolute difference between cardiac output measured by dilution and cardiac output measured volumetrically was 3.97% +/- 2.97% (range 212-1200 mL/min); for central blood volume the difference was 4.59% +/- 3.14% (range 59-315 mL); for total end-diastolic volume the difference was 4.10% +/- 3.08% (range 24-211 mL); and for active circulation volume the difference was 3.30% +/- 3.07% (range 247-645 mL). In the neonatal setting the difference for cardiac output was 4.40% +/- 4.09% (range 106-370 mL/min); for central blood volume the difference was 4.90% +/- 3.69% (range 50-62 mL); and for active circulation volume the difference was 5.39% +/- 4.42% (range 104-247 mL). CONCLUSIONS: In vitro validation confirmed the ability of the ultrasound dilution technology to accurately measure small flows and volumes required for hemodynamic assessments in small pediatric and neonatal patients. Clinical studies are in progress to assess the reliability of this technology under different clinical situations.

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Lung water (LW) reflects the water content of the lung interstitium. Because hemodialysis patients have expanded total body water (TBW) they may also have increased LW. Hypertonic saline promotes a flux of water from lung to blood, which is measured by ultrasound flow probes on hemodialysis tubing. The volume of flux is an indirect measure of LW. Our purpose was to determine the feasibility and reproducibility of LW derived with ultrasound velocity dilution, to determine the effect of ultrafiltration on LW in stable hemodialysis patients, and to compare changes in LW with fluid compartment shifts using bioimpedance. Lung water, cardiac output, total body water, and extracellular and intracellular fluid volumes were measured in 24 stable hemodialysis patients at the beginning of hemodialysis and after ultrafiltration. The LW values at the beginning of hemodialysis (298.8 +/- 90.2 ml or 3.67 +/- 1.47 ml/kg) fell during hemodialysis (250.8 +/- 55.8 ml or 3.12 +/- 0.96 ml/kg; p < 0.05), as did TBW and extracellular fluid volumes (p < 0.001). Cardiac output, cardiac index, and central blood volume also decreased significantly with ultrafiltration (p < 0.005, p < 0.005, and p < 0.01, respectively). Results showed that stable hemodialysis patients have higher specific LW values (3.67 ml/kg) than the normal population (2 ml/kg) and ultrafiltration produces a significant decline in LW values.

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OBJECTIVE: To describe a stochastic model of the variability and heterogeneity of blood flow through the microcirculation, and to show the ability of vasomotion to vary oxygen consumption at a steady blood flow. METHODS: The description of vasomotion is based on whether each microvessel is open for blood flow or closed. Over a unit time period, let alpha be the probability that a given vessel is open and will remain open, beta be the probability that an open vessel will close, nu be the probability that a closed vessel will remain closed, and mu be the probability that a closed vessel will become open. Two main parameters that characterize such a scheme are: the fraction of open microvessels [n o= mu/(beta+mu)], and the rate of vasomotion defined as the rate of switching between open and closed microvessels (R=beta+mu). A model of O2 transport to tissues is based on the following assumptions: (a) the flux of O2 is due to passive diffusion, (b) the amount of O2 dissolved in tissue is negligible as compared with that contained in arterial blood, and (c) aerobic metabolism is proportional to the delivery of O2. RESULTS: The stochastic model substantiates the possibility that vasomotion can control O2 consumption. The rate of vasomotion activity can change O2 consumption by 2-8-fold, depending on the fraction of open microvessels. CONCLUSION: A stochastic description of blood flow through the microcirculation system demonstrates that vasomotion rate could be a factor influencing O2 consumption.

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Urea rebound after hemodialysis is generally attributed to urea entering the circulation from poorly perfused tissue and/or entering from regions with low membrane permeability for urea. Another explanation for rebound is based on disorders in the microcirculation, connected with the phenomenon of vasomotion, i.e., cyclic opening and closing of microvessels. The purpose of the following mathematical model is to explain observed urea rebound by the vasomotion phenomenon. The significance of vasomotion is related to the fact that a significant fraction, up to 80-95%, of all microvessels are closed while others are being perfused. The rate with which open microvessels "migrate" through the tissue determines quality of perfusion. A stochastic scheme for describing vasomotion is developed. Probabilities to change the state of microvessels are defined as follows: alpha = probability to be open and remain open; beta = to be open and become closed; v = to be closed and remain closed; mu = to be closed and become open. The activity of vasomotion is defined by the rate of vasomotion, R, R = beta + mu, and can be measured using a curve of urea concentration.

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PURPOSE: The goals of this investigation were to evaluate the accuracy and reliability of the Angioflow meter system with use of in vitro and in vivo methods and to compare it to the standard Transonics HD01 system in a clinical setting. MATERIALS AND METHODS: The Angioflow meter system consists of a 6-F endovascular catheter and a laptop computer containing proprietary software for this application. Bench-top testing with use of a flow model was performed to determine the accuracy of the Angioflow meter system. Initial in vivo studies were performed with use of an animal model to assess the endovascular performance of the Angioflow meter system. Subsequently, a human clinical trial was performed to compare the Angioflow meter to the standard Transonics HD01 system. Twenty-five patients with dysfunctional (<600 mL/min) hemodialysis grafts were referred for fistulography and angioplasty. Intragraft blood flow measurements were obtained before and after angioplasty with use of both the Angioflow meter system and the Transonics HD01 system. A comparison of the two systems was performed. RESULTS: Bench-top testing and animal studies demonstrated an excellent (r =.98) correlation between the measurements of the Angioflow meter and volumetric flow measurements. In the clinical trial, there was reasonable correlation (r =.72) between the blood flow measurements obtained with use of the Angioflow meter and Transonics HD01 system. The reproducibility of consecutive measurements with the Angioflow meter was excellent (r =.98). The mean increase in intragraft blood flow after angioplasty was 320 mL/min. CONCLUSION: The Angioflow meter is an accurate and reliable endovascular device for measuring intragraft blood flow during interventional procedures. Use of this catheter-based system should prove beneficial for quantifying the success of endovascular interventions, the assessment of arterial inflow, and identification of inconspicuous lesions.

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