Organ Blood Flow Research Articles

Acute neurological conditions during pregnancy and their management: a review.

Less vascular resistance, higher vascular permeability and improved cardiac output include anatomical and physiological changes related to pregnancy. These are needed to accommodate an increase in plasma volume and ensure significant organ infusion. Nevertheless, increases in oestrogen levels may lead to an increase in the risk of coagulation and thrombosis. Increased levels of progesterone increase the risk of thrombosis due to vasodilation, vascular stasis and edoema in these situations. The increased resistance in preeclampsia maternal systemic blood arteries can create high blood pressure that can interfere with blood flow in numerous organs (including liver, kidneys, brain and placenta). The risk of issues such as pulmonary edoema, placental abruption, pneumonia of aspiration, renal failure, hepatic failure and stroke in pregnant women is increased by Preeclampsia and eclampsia. Some peripheral neuropathies (carpal tunnel syndrome, peripheral facial palsy) and central neurological conditions (seizure, migraine, stroke, epilepsy) may become more common during pregnancy because of the exacerbation of the pre-existing neurologic condition or the onset of neurological disturbance caused by pregnancy physiological changes (such as headache or vascular disorders). During the three trimesters of pregnancy, neurological disorders are both peripheral and central. Therefore, an early and correct diagnosis is required to improve pregnancy care, treatment and perinatal outcomes. The aims of this paper areto identify, define and manage the most prevalent peripheral and centrally occurring neurological disorders in the pregnancy.

A population physiologically-based pharmacokinetic model to characterize antibody disposition in pediatrics and evaluation of the model using infliximab.

In order to better predict the pharmacokinetics (PK) of antibodies in children, and to facilitate dose optimization of antibodies in paediatric patients, there is a need to develop systems PK models that integrate ontogeny-related changes in human physiological parameters. A population-based physiological-based PK (PBPK) model to characterize antibody PK in paediatrics has been developed, by incorporating age-related changes in body weight, organ weight, organ blood flow rate and interstitial volumes in a previously published platform model. The model was further used to perform Monte Carlo simulations to investigate clearance vs. age and dose-exposure relationships for infliximab. By estimating only one parameter and associated interindividual variability, the model was able to characterize clinical PK of infliximab from two paediatric cohorts (n = 141, 4-19 years) reasonably well. Model simulations demonstrated that only 50% of children reached desired trough concentrations when receiving FDA-labelled dosing regimen for infliximab, suggesting that higher doses and/or more frequent dosing are needed to achieve target trough concentrations of this antibody. The paediatric PBPK model presented here can serve as a framework to characterize the PK of antibodies in paediatric patients. The model can also be applied to other protein therapeutics to advance precision medicine paradigm and optimize antibody dosing regimens in children.

Cardiopulmonary values and organ blood flows before and during heat stress: data in nine subjects at rest in the upright position.

Physiological changes associated with thermoregulation can influence the kinetics of chemicals in the human body such as alveolar ventilation (VA) and redistribution of blood flow to organs. In this study, the influence of heat stress on various physiological parameters was evaluated in nine male volunteers during sessions of exposure to wet-bulb globe temperatures (WBGT) of 21, 25, and 30°C for 4 h. Skin and core temperatures and more than 20 cardiopulmonary parameters were measured. Liver, kidneys, brain, skin, and muscles blood flows were also determined based on published measurements. Results show that most subjects (eight out of nine) have been affected by the inhalation of hot and dry air at the WBGT of 30°C. High respiratory rates, superficial tidal volumes, and low VA values were notably observed. The skin blood flow increased by 2.16-fold, whereas the renal blood flow and liver blood flow decreased by about by 11% and 18%, respectively. A complete set of key cardiopulmonary parameters in healthy male adults before and during heat stress was generated for use in physiologically based pharmacokinetic modeling. A toxicokinetic studies are ongoing to evaluate the impact of heat stress on the absorption, biotransformation and excretion rates of volatile xenobiotics.

VExUS Nexus: Bedside Assessment of Venous Congestion.

Organ dysfunction in the setting of heart failure is mainly determined by backward transmission of increased right atrial pressure. Although traditional point-of-care ultrasound applications such as inferior vena cava and lung ultrasound have been increasingly incorporated in the clinical care of congestive heart failure, they do not directly evaluate the hemodynamic consequences of high right atrial pressure on organ blood flow. Congestion induces alterations in the venous flow patterns of abdominal organs that can be readily assessed using Doppler imaging. These alterations have been consistently associated with congestive organ dysfunction and adverse clinical outcomes. In this article, we provide a comprehensive overview of the bedside assessment of venous congestion using Doppler imaging. The review focuses mainly on the normal and abnormal Doppler patterns of the hepatic, portal, and intrarenal veins along with clinical examples of how to incorporate this tool in the management of patients with venous congestion.

Age-Related Changes in Pediatric Physiology: Quantitative Analysis of Organ Weights and Blood Flows : Age-Related Changes in Pediatric Physiology.

Development of comprehensive and updated quantitative relationships between physiological parameters and age for pediatrics remains to be accomplished. Towards this goal, we have performed a thorough literature search and collected published data on organ weights and organ blood flow rates for 0-20-year-old male and female human subjects. The data were used to develop continuous relationships between physiological parameters and age, using a single form of mathematical equation. Four sets of equations (0-2years male, 0-2years female, 2-20years male, 2-20years female) for the body weight vs. age, height vs. age, and organ weight vs. age relationships and 2 sets of equations (0-20years male, 0-20years female) for organ flow rate vs. age relationship were developed. The variability of each physiological parameter was also estimated, and the equations allow simulation of a virtual population for a specific age, weight, and sex. We further compared the physiological parameters vs. age curves simulated using our equations to the existing databases (Simcyp Simulator and PK-Sim). The predicted physiological parameters were comparable between our study and the existing databases, validating our equation's utility. Additionally, we described body weight-normalized organ weights and organ blood flow rates as a function of age, to provide an insight into how the contribution of each organ towards total body weight and total blood flow changes throughout ontogenesis. The physiological parameter database and equations presented here can serve as an open source to facilitate the development of pediatric physiologically based pharmacokinetic models.

Variation in Methylmercury Metabolism and Elimination in Humans: Physiological Pharmacokinetic Modeling Highlights the Role of Gut Biotransformation, Skeletal Muscle, and Hair.

The biological half-life (t1/2) of methylmercury (MeHg) shows considerable individual variability (t1/2 < 30 to > 120 days), highlighting the importance of mechanisms controlling MeHg metabolism and elimination. Building on a prior physiologically based pharmacokinetic (PBPK) model, we elucidate parameters that have the greatest influence on variability of MeHg t1/2 in the human body. Employing a dataset of parameters for mean organ volumes and blood flow rates appropriate for man and woman (25-35 years) and child (4 - 6 years), we demonstrate model fitness by simulating data from our prior controlled study of MeHg elimination in people. Model predictions give MeHg t1/2 of 46.9, 38.9, and 31.5 days and steady-state blood MeHg of 2.6, 2.6, and 2.3 µg/l in man, woman, and child, respectively, subsequent to a weekly dose of 0.7 µg/kg body weight. The major routes of elimination are biotransformation to inorganic Hg in the gut lumen (73% in adults, 61% in child) and loss of MeHg via excretion within growing hair (13% in adults, 24% in child). Local and global sensitivity analyses of model parameters reveal that variation in biotransformation rate in the gut lumen, and rates of transport between gut lumen and gut tissue, have the greatest influence on MeHg t1/2. Volume and partition coefficients for skeletal muscle (SM) and gut tissue also show significant sensitivity affecting model output of MeHg t1/2. Our results emphasize the role of gut microbiota in MeHg biotransformation, transport kinetics at the level of the gut, and SM mass as moderators of MeHg kinetics in the human body.

Least Squares Finite Element Method for Hepatic Sinusoidal Blood Flow

AbstractThe simulation of complex biological systems such as the description of blood flow in organs requires a lot of computational power as well as a detailed description of the organ physiology. We present a novel Least‐Squares discretization method for the simulation of sinusoidal blood flow in liver lobules using a porous medium approach for the liver tissue. The scaling of the different Least‐Squares terms leads to a robust algorithm and the inherent error estimator provides an efficient refinement strategy.

Современные представления об особенностях эпидемиологии окклюзии ретинальных вен

Impaired blood flow in various organs and tissues is a common cause of disabling disorders that even result in a lethal outcome. Despite an extremely rapid development of modern medicine, the rate of these disorders is still high thus emphasizing the importance of further detailed studies on this issue. In addition to systemic vascular diseases, local blood flow disturbances are also prevalent among population. These disturbances result from more significant blood flow disorders. Retinal vein occlusion is not an exclusion. Acute retinal vein occlusions account for more than half of ocular vascular diseases and may lead to extremely severe ophthalmic complications that result in poor vision, blindness, and reduced quality of life in both young and elderly patients. The diversity of clinical presentations, their severity, and clinical course make the diagnosis challenging thus altering the assessment of the prevalence of these diseases. Keywords: retinal vein occlusion, epidemiology, systemic vascular disorders, risk factors, retinal vessels. For citation: Moshetova L.К., Usharova S.А., Simonova S.V.,Turkina К.I. Epidemiology of retinal vein occlusions: state-of-the-art. Russian Journal of Clinical Ophthalmology. 2021;21(2):86–89. DOI: 10.32364/2311-7729-2021-21-2-86-89.

The unfavorable role of titanium particles released from dental implants.

Titanium is considered to be a metal material with the best biological safety. Studies have proved that the titanium implanted in the bone continuously releases titanium particles (Ti particles), significantly increasing the total titanium content in human body. Generally, Ti particles are released slowly without causing a systemic immune response. However, the continuous increased local concentration may result in damage to the intraepithelial homeostasis, aggravation of inflammatory reaction in the surrounding tissues, bone resorption and implant detachment. They also migrate with blood flow and aggregate in the distal organ. The release of Ti particles is affected by the score of the implant surface structure, microenvironment wear and corrosion, medical operation wear, and so on, but the specific mechanism is not clear. Thus, it difficult to prevent the release completely. This paper reviews the causes of the Ti particles formation, the damage to the surrounding tissue, and its mechanism, in particular, methods for reducing the release and toxicity of the Ti particles.

Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part III: Sheep and goat.

This report is the third in a series of studies that aimed to compile physiological parameters related to develop physiologically based pharmacokinetic (PBPK) models for drugs and environmental chemicals in food‐producing animals including swine and cattle (Part I), chickens and turkeys (Part II), and finally sheep and goats (the focus of this manuscript). Literature searches were conducted in multiple databases (PubMed, Google Scholar, ScienceDirect, and ProQuest), with data on relevant parameters including body weight, relative organ weight (% of body weight), cardiac output, relative organ blood flow (% of cardiac output), residual blood volume (% of organ weight), and hematocrit reviewed and statistically summarized. The mean and standard deviation of each parameter are presented in tables. Equations describing the growth curves of sheep and goats are presented in figures. When data are sufficient, parameter values are reported for different ages or production classes of sheep, including fetal sheep, lambs, and market‐age sheep (mature sheep). These data provide a reference database for developing standardized PBPK models to predict drug withdrawal intervals in sheep and goats, and also provide a basis for extrapolating PBPK models from major species such as cattle to minor species such as sheep and goats.

Important pharmacokinetic parameters for individualization of 177 Lu-PSMA therapy: A global sensitivity analysis for a physiologically-based pharmacokinetic model.

The knowledge of the contribution of anatomical and physiological parameters to interindividual pharmacokinetic differences could potentially be used to improve individualized treatment planning for radionuclide therapy. The aim of this study was therefore to identify the physiologically based pharmacokinetic (PBPK) model parameters that determine the interindividual variability of absorbed doses (ADs) to kidneys and tumor lesions in therapy with 177 Lu-labeled PSMA-targeting radioligands. A global sensitivity analysis (GSA) with the extended Fourier Amplitude Sensitivity Test (eFAST) algorithm was performed. The whole-body PBPK model for PSMA-targeting radioligand therapy from our previous studies was used in this study. The model parameters of interest (input of the GSA) were the organ receptor densities [R0 ], the organ blood flows f, and the organ release rates λ. These parameters were systematically sampled NE times according to their distribution in the patient population. The corresponding pharmacokinetics were simulated and the ADs (model output) to kidneys and tumor lesions were collected. The main effect and total effect were calculated using the eFAST algorithm based on the variability of the model output: The main effect of input parameter represents the reduction in variance of the output if the "true" value of parameter would be known. The total effect of an input parameter represents the proportion of variance remaining if the "true" values of all other input parameters except for are known. The numbers of samples NE were increased up to 8193 to check the stability (i.e., convergence) of the calculated main effects and total effects . From the simulations, the relative interindividual variability of ADs in the kidneys (coefficient of variation CV=31%) was lower than that of ADs in the tumors (CV up to 59%). Based on the GSA, the most important parameters that determine the ADs to the kidneys were kidneys flow ( =0.36, =0.43) and kidneys receptor density ( =0.25, =0.30). Tumor receptor density was identified as the most important parameter determining the ADs to tumors ( and up to 0.72). The results suggest that an accurate measurement of receptor density and flow before therapy could be a promising approach for developing an individualized treatment with 177 Lu-labeled PSMA-targeting radioligands.

Features of the course of nephropathies in combination with CAKUT-syndrome in young children

Background . Children with CAKUT-syndrome (congenital malformations of the urinary tract) quickly develop an inflammatory process, which, in combination with dysplasia and/or urodynamic disorders, creates a high risk of developing early chronic renal failure. Purpose of the study : to identify the main factors of the formation, features of the clinical course of nephropathies, morphometric parameters and features of the organ blood flow of the kidneys in young children against the background of CAKUT syndrome. Methods . Study design: It carried out a cohort prospective study. The main group included 26 children with pyelonephritis against the background of CAKUT syndrome at the age from zero to 36 months of life, the comparison group consisted of 29 children with non-obstructive pyelonephritis of the same age. It carried out a comparative analysis of antenatal and postnatal anamnesis, clinical, laboratory and instrumental data in the considered groups of children with nephro-urological pathology. Additionally, it researches the morphometric parameters of the kidneys and the Doppler indices of the renal vessels. The research conducted during 2016–2018. Results . In children with a chronic course of nephropathy in combination with CAKUT-syndrome, possible predictors of an early onset of the disease are: anemia, damage to the urinary tract with pathological urinary syndrome during pregnancy and a combination with defects of this system in the woman herself, and the development of placental insufficiency. In the group with CAKUT syndrome, a decrease in renal filtration function (in 88.5% of children) and persistent trace proteinuria (in 65.4% of children) are recorded by the end of the first year of life. According to ultrasound, in addition to signs of obstructive nephropathy, it recorded decreases in the thickness of the parenchyma and a violation of organ hemodynamics with an increase in the resistance index. In the observed group of children, CAKUT syndrome combined in 100% of cases with connective tissue dysplasia syndrome also. Conclusion . Thus, CAKUT syndrome leads to early realization of nephropathies in children with a rapid decline in renal function.

Disclosure of suboptimal health status through traditional Chinese medicine-based body constitution and pulse patterns

ObjectivesSuboptimal health status (SHS) is a dynamic state wherein people have not been diagnosed with a disease but tend to develop diseases. People with SHS often experience fatigue and other nonspecific symptoms, which are related to a deviated body constitution in traditional Chinese medicine (TCM). However, the correlation between TCM constitution and SHS has not been adequately investigated. Furthermore, no study has explored the radial pulse analysis—an assistive objective indicator of TCM constitution—in healthy people and people with SHS. DesignA cross-sectional study. Settings/LocationCenter for Traditional Medicine, Taipei Veterans General Hospital, Taiwan. SubjectsSixty-six adults (27 healthy participants and 39 participants with SHS) who were aged 20–39 years. Outcome MeasuresThe body constitution questionnaire (BCQ) scores, suboptimal health status questionnaire-25 (SHSQ-25) scores, and radial pulse waves detected using sphygmography were recorded. Pulse wave analyses are presented as the ratio of frequency below 10 Hz to that above 10 Hz (SER10), which represent energy changes in organ blood flow. ResultsParticipants with SHS had significantly higher Yang-Xu, Yin-Xu, and stasis scores of BCQ compared with healthy participants. The SHSQ-25 scores of the participants with SHS were moderately correlated with their Yang-Xu, Yin-Xu, and stasis scores (r = 0.65, 0.66, and 0.72, respectively; all p < 0.001), but weak correlations were discovered for healthy participants. The participants with SHS had significantly higher SER10 at the left guan (the “liver” system in TCM) than did the healthy participants. ConclusionsSHS is moderately correlated with TCM-based constitution and those with SHS had increased SER10 at the leftguan of the radial pulse.

Comparison Between Two Pharmacologic Strategies to Alleviate Rewarming Shock: Vasodilation vs. Inodilation.

Rewarming from hypothermia is often challenged by coexisting cardiac dysfunction, depressed organ blood flow (OBF), and increased systemic vascular resistance. Previous research shows cardiovascular inotropic support and vasodilation during rewarming to elevate cardiac output (CO). The present study aims to compare the effects of inodilatation by levosimendan (LS) and vasodilation by nitroprusside (SNP) on OBF and global oxygen transport during rewarming from hypothermia. We used an in vivo experimental rat model of 4 h 15°C hypothermia and rewarming. A stable isotope-labeled microsphere technique was used to determine OBF. Cardiac and arterial pressures were monitored with fluid-filled pressure catheters, and CO was measured by thermodilution. Two groups were treated with either LS (n = 7) or SNP (n = 7) during the last hour of hypothermia and throughout rewarming. Two groups served as hypothermic (n = 7) and normothermic (n = 6) controls. All hypothermia groups had significantly reduced CO, oxygen delivery, and OBF after rewarming compared to their baseline values. After rewarming, LS had elevated CO significantly more than SNP (66.57 ± 5.6/+30% vs. 54.48 ± 5.2/+14%) compared to the control group (47.22 ± 3.9), but their ability to cause elevation of brain blood flow (BBF) was the same (0.554 ± 0.180/+81 vs. 0.535 ± 0.208/+75%) compared to the control group (0.305 ± 0.101). We interpret the vasodilator properties of LS and SNP to be the primary source to increase organ blood flow, superior to the increase in CO.

Association between indocyanine green fluorescence blood flow speed in the gastric conduit wall and superior mesenteric artery calcification: predictive significance for anastomotic leakage after esophagectomy.

Near-infrared fluorescence using indocyanine green (ICG) has been applied as a real-time navigation tool to observe blood flow in gastric conduit wall after esophagectomy. Atherosclerosis might impair the blood flow of the systemic organs. The aim of the study was to investigate the significances of ICG blood flow speed in the gastric conduit wall and atherosclerotic calcification for the prediction of anastomotic leakage after esophagectomy. The 109 esophageal cancer patients were prospectively enrolled. ICG fluorescence blood flow speed in the gastric conduit wall and abdominal aortic calcification index (ACI), celiac artery (CA) calcification, and superior mesenteric artery (SMA) calcification were determined. Then, the correlation between ICG fluorescence blood flow speed and anastomotic leakage as well as ACI, CA, and SMA calcification were evaluated. Anastomotic leakage occurred in 15 patients. ACI ranged from 0 to 65. CA calcification and SMA calcification were present in 25 and 12 patients. Multivariate analysis demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall of 2.07cm/s or less (P < 0.001) and SMA calcification (P = 0.026) were the significant independent predictors of anastomotic leakage. Only SMA calcification was significantly associated with ICG fluorescence blood flow speed in the gastric conduit wall (P = 0.026). This study demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall can predict anastomotic leakage after esophagectomy and microvascular perfusion of capillary vessels of the gastric conduit might be impaired by systemic atherosclerosis.

Synchronous Changes in Microcirculation Parameters of the Upper Limbs in Asymmetric Physical Loads

This is the first study on synchronous changes in microcirculation in the symmetrical organs of humans during asymmetric physical loads of the upper limbs. The study was conducted in healthy volunteers by the method of laser Doppler flowmetry (LDF). LDF signal transducers were fixed symmetrically on the lower parts of the right and left shoulders (3 cm above the elbow bend). Physical loads included the left or right arm swings in standing position for 1 min. Measurements were made in three states: (1) initial state, (2) immediately after physical activity, and (3) 5 min after loads. The changes in the mean perfusion value and the components of amplitude-frequency spectrum of blood flow fluctuations (myogenic, neurogenic, respiratory, and cardiac) were evaluated in both sides of the body. We observed the asymmetry of changes in microcirculation parameters after physical loads. It is shown that both left and right swings change the microcirculation parameters of both the left and right sides, and the changes on the left are more pronounced than on the right. A nonlinear relationship was observed between the changes in microcirculation parameters of symmetrical areas of paired organs and heart rate. Our data illustrate the specific regulation patterns of microcirculation blood flow in paired organs, which is associated with functional asymmetry. The physiological mechanisms of this asymmetry require further experimental and clinical research.

MATHEMATICAL MODELLING OF IMMUNE PROCESSES AND ITS APPLICATION

The aim of the study was to develop a mathematical model to research hypoxic states in case of simulation of an organism infectious lesions. The model is based on the methods of mathematical modeling and the theory of optimal control of moving objects. The processes of organism damage are simulated with the mathematical model of immune response developed by G.I. Marchuk and the members of his scientific school, adapted to current conditions. This model is based on Burnet’s clone selection theory of the determining role of antigen. Simulation results using the model are presented. The dependencies of infectious courses on the volumetric velocity of systemic blood flow is analyzed on the complex mathematical model of immune response, respiratory and blood circulation systems. The immune system is shown to be rather sensitive to the changes in blood flow via capillaries. Thus, the organ blood flows can be used as parameters for the model by which the respiratory, immune response, and blood circulation systems interact and interplay.

A comparative study of bolus phenylephrine and mephentermine for treatment of hypotension during spinal anaesthesia for caesarean section

Background: Spinal anesthesia for caesarean section has several advantages over general anaesthesia like decreased risk of failed intubation, decreased risk of pulmonary aspiration of gastric contents, avoidance of the depressant effects of general anesthetics on neonate etc.Aim and Objectives: This comparative study was designed to evaluate the efficacy of Mephentermine and Phenylephrine in treating hypotension during spinal anaesthesia for cesarean section. The incidence of undesirable side effects like maternal bradycardia, nausea and vomiting also noted.Methodology: The study was conducted in the Department of OBG the Maternity Hospital, Osmania Medical College during the year August 2018- November 2019.The study includes 60 patients grouped into two groups.Results: Both Phenylephrine and Mephentermine maintained the arterial pressure effectively within 20% of baseline values. The mean value of heart rate was high in Mephentermine group compared with Phenylephrine group. The mean values of Systolic BP, Diastolic BP and MAP were higher in Phenylephrine group compared with Mephentermine group throughout the study period. Phenylephrine group required fewer number of bolus doses when compared with Mephentermine. The heart rate generally remained low throughout the study period in Phenylephrine group and the incidence of bradycardia was more in Phenylephrine group when compared with Mephentermine group. The occurrence of nausea and vomiting were similar in both groups.Conclusion: Thus, it can probably enhance organ blood flow more than mephentermine. Mephentermine increases heart rate and thus may be avoided in population where the effect may be detrimental.

Investigating the Theoretical Basis for In Vitro-In Vivo Extrapolation (IVIVE) in Predicting Drug Metabolic Clearance and Proposing Future Experimental Pathways.

Extensive studies have been conducted to predict in vivo metabolic clearance from in vitro human liver metabolism parameters (i.e., in vitro-in vivo extrapolation (IVIVE)) with little success. Here, deriving IVIVE from first principles, we show that the product of fraction unbound in the blood and the predicted in vivo intrinsic clearance determined from hepatocyte or microsomal incubations is the lower boundary condition for in vivo hepatic clearance and the prerequisite for IVIVE predictions to be valid, regardless of extraction ratio. For 60-80% of drugs evaluated here, this product is markedly less than the in vivo measured clearance, a result that violates the lower boundary of the predictive relationship. This can only be explained by (a) suboptimal in vitro metabolic stability assay conditions, (b) significant error in the assumption that in vitro intrinsic clearance determinations will predict in vivo intrinsic clearance simply by scaling-up the amount of enzyme (in vitro incubation to in vivo liver), and/or (c) the methods of determining fraction unbound are incorrect. We further suggest that widely employed organ blood flow values underpredict the effective blood flow within the organ by approximately 2.5-fold, thus impacting IVIVE of high clearance compounds. We propose future pathways that should be investigated in terms of the relationship to experimentally measured clearance values, rather than model-dependent intrinsic clearance. IVIVE outcome can be improved by estimating the ratio of unbound drug concentration in the liver tissue to the liver plasma, examining the assumption of the free drug theory (i.e., there are no transporter effects at the blood cell membrane) and the finding that the upper limit of organ clearance may be greater than blood flow entering the organ.

Contrast-enhanced ultrasound imaging for assessing organ perfusion in rainbow trout (Oncorhynchus mykiss)

Contrast-enhanced ultrasound (CEUS) imaging has great potential as a non-lethal, inexpensive monitoring tool in aquatic toxicology. It is a well-established clinical imaging approach that combines real-time, quantitative assessment of organ blood flow, with morphological data. In humans, it has been extensively used to measure changes in blood flow that can be attributed to cancer, inflammation, and other biological abnormalities. However, it has yet to be explored as a tool for fish physiology or environmental toxicology. In this study, our goal was to determine if CEUS could be used to visualize and measure blood flow in the liver of a rainbow trout. All rainbow trout received two injections of an ultrasound contrast agent, microbubbles. A subset received a third injection after administration of propranolol, a non-specific beta1 & 2-blocker, to determine if changes in blood flow could be detected. Ultrasound contrast time-intensity curves (TIC) were obtained, fit to a lognormal model, and different perfusion parameters were calculated. Contrast enhancement was observed in all rainbow trout livers, with high percentage between repeated measurements, including blood flow (80.6 ± 27.3%), area under the curve (73.2 ± 14%), blood volume (84 ± 14.2%) and peak enhancement (86.7 ± 7.5%). After administration of propranolol, we detected a non-significant (p > 0.05) increase in area under the curve (102.6 ± 44.2%), peak enhancement (77.3 ± 106.4), blood volume (48.2 ± 74.5%), and decrease in hepatic blood flow (−17.3 ± 37.1%). These data suggest that CEUS imaging is suitable to measure organ blood flow in fish, and demonstrates tremendous potential for exploring different organs, fish species, and effects of chemical contaminants in future studies.