Physiology Of Microcirculation Research Articles

In Silico Design of Heterogeneous Microvascular Trees Using Generative Adversarial Networks and Constrained Constructive Optimization.

Designing physiologically adequate microvascular trees is of crucial relevance for bioengineering functional tissues and organs. Yet, currently available methods are poorly suited to replicate the morphological and topological heterogeneity of real microvascular trees because the parameters used to control tree generation are too simplistic to mimic results of the complex angiogenetic and structural adaptation processes invivo. We propose a method to overcome this limitation by integrating a conditional deep convolutional generative adversarial network (cDCGAN) with a local fractal dimension-oriented constrained constructive optimization (LFDO-CCO) strategy. The cDCGAN learns the patterns of real microvascular bifurcations allowing for their artificial replication. The LFDO-CCO strategy connects the generated bifurcations hierarchically to form microvascular trees with a vessel density corresponding to that observed in healthy tissues. The generated artificial microvascular trees are consistent with real microvascular trees regarding characteristics such as fractal dimension, vascular density, and coefficient of variation of diameter, length, and tortuosity. These results support the adoption of the proposed strategy for the generation of artificial microvascular trees in tissue engineering as well as for computational modeling and simulations of microcirculatory physiology.

Plasma resuscitation improves and restores intestinal microcirculatory physiology following haemorrhagic shock.

Intestinal ischaemia-reperfusion injury following resuscitated haemorrhagic shock (HS) leads to endothelial and microcirculatory dysfunction and intestinal barrier breakdown. Although vascular smooth muscle machinery remains intact, microvascular vasoconstriction occurs secondary to endothelial cell dysfunction, resulting in further ischaemia and organ injury. Resuscitation with fresh frozen plasma (FFP) improves blood flow, stabilizes the endothelial glycocalyx and alleviates organ injury. We postulate these improvements correlate with decreased tissue CO2 concentrations, improved microvascular oxygenation and attenuation of intestinal microvascular endothelial dysfunction. Male Sprague-Dawley rats were randomly assigned to groups (n = 8/group): (1) sham, (2) HS (40% mean arterial blood pressure [MAP], 60 min) + crystalloid resuscitation (CR) (shed blood saline) and (3) HS + FFP (shed blood + FFP). MAP, heart rate (HR), ileal perfusion, pO2 and pCO2 were measured at intervals until 4 h post-resuscitation (post-RES). At 4 h post-RES, the ileum was rinsed in situ with Krebs solution. Topical acetylcholine and then nitroprusside were applied for 10 min each. Serum was obtained, and after euthanasia, tissues were harvested and snap-frozen in liquid N2 and stored at -80°C. FFP resuscitation resulted in sustained ileal perfusion as well as rapid sustained return to baseline microvascular pO2 and pCO2 values when compared to CR (p < 0.05). Endothelial function was preserved relative to sham in the FFP group but not in the CR group (p < 0.05). FFP-based resuscitation improves intestinal perfusion immediately following resuscitation, which correlates with improved tissue oxygenation and decreased tissue CO2 levels. CR resulted in significant damage to endothelial vasodilation response to acetylcholine, while FFP preserved this function.

Lower Limb Dynamic Activity Significantly Reduces Foot Skin Perfusion: Exploring Data with Different Optical Sensors in Age-Grouped Healthy Adults

Introduction: The human lower limb is widely used as a model to study in vivo microcirculatory physiology and pathophysiology. It is a preferential target for critical comorbidities (overweight, diabetes, and peripheral vascular disease). Movement and activity are consistently regarded as beneficial, but the related adaptive physiology is still poorly understood. Our goal was to better identify the foot microcirculatory changes after a regular walking gait activity in healthy subjects of different ages. Methods: Twelve healthy participants of both sexes, with normal BMI and Ankle-Brachial Index, were selected and grouped according to age – group I (21.0 ± 1 y.o.) and group II (55.8 ± 3 y.o.). The protocol involved 2 phases of 5-min duration each – phase 1, a static standing position, and phase 2, 5-min walking with a comfortable pace on a pre-established circuit. Perfusion changes were assessed in the dorsal region of both feet before (baseline, phase 1) and after (phase 2) the gait period by noninvasive optical technologies – laser Doppler flowmetry (LDF), photoplethysmography, and polarized spectroscopy (PSp). Comparative statistics were performed with a 95% confidence level. Results: All instruments detected an asymmetric nonsignificant perfusion between right and left feet during rest in all participants with values in females consistently lower than men. Older participants exhibited lower baseline values than the younger group. Gait evoked a perfusion reduction in all participants relative to phase 1 detected with all technologies, with statistically significant changes recorded with LDF (group I, p = 0.033, and group II, p = 0.028) and PSp (group II, p = 0.041). Furthermore, LDF revealed that gait significantly reduced perfusion velocity in the older group (p = 0.003). Corresponding changes in the younger group were present but discrete. Recovery to baseline levels was also slower in the older group. Discussion/Conclusions: Our results confirm that perfusion is age dependent and demonstrate the clinical relevance of simple dynamic activities such as gait. This reduction of the dorsal foot perfusion occurs in depth, being more pronounced with the movement intensity, suggesting a wide application potential in early diagnostics as for rehabilitation.

COMPARAÇÃO ENTRE SOLUÇÃO SALINA 0,9% E CRISTALOIDES BALANCEADOS: REVISÃO BIBLIOGRÁFICA

Um marco importante na medicina foi o desenvolvimento dos fluidos intravenosos. Obteve-se impacto imediato nos desfechos de doenças, como a cólera, e nos pacientes politraumatizados. Sua importância desencadeou um interesse pelo estudo da fisiologia e anatomia da macro e microcirculação, criação de novos fluidos, bem como o impacto do tipo das soluções sobre os desfechos clínicos. &#x0D; A solução salina, popularizada como solução fisiológica ou normal, é uma das soluções mais antigas e mais utilizadas no mundo. As soluções balanceadas, como o Plasma-lyte®, Ringer Lactato, entre outros, que utilizam tampões e ânions fracos na composição, começaram a ser apresentadas e se mostraram mais fisiológicas e com desfechos clínicos melhores em uma variedade extensa de pacientes.&#x0D; As descobertas da anatomia e fisiologia da microcirculação, alterações hidroeletrolíticas e ácido-básicas específicas de cada doença, hipercloremia e seus malefícios trouxeram uma discussão ampla e importante na indicação de cada cristaloide. O tipo e a quantidade de fluido a ser administrada no perioperatório têm impacto direto no desfecho dos pacientes.&#x0D; As soluções balanceadas vêm se apresentando como alternativa superior à solução salina 0,9% no contexto perioperatório.

Lower limb massage in humans increases local perfusion and impacts systemic hemodynamics.

Massage is commonly used as a complementary therapy for many different conditions. Demonstration of its physiological impact and understanding of its therapeutic mechanisms is still insufficient and often inconclusive. This study aims to characterize the physiological effects of effleurage, one of the most popular techniques, on human in vivo microcirculation and its impact on cardiovascular function. Two differently oriented variations of the technique, referred to influence physiological outcomes, were applied to 32 young (mean 19.8 ± 1.6 yr old) healthy volunteers of both sexes in a single, randomly chosen limb after informed written consent. Each protocol included a 10-min baseline (Phase I), a 5-min massage (Phase II), and a 10-min recovery (Phase III) register. A 30-min washout period separated both protocols. Perfusion was assessed by laser Doppler flowmetry (LDF) and reflection photoplethysmography (PPG), with their sensors applied distally in both feet. Blood pressure and pulse were also obtained. LDF signals were further analyzed in their components by the (Morlet) wavelet transform to probe the mechanisms involved. Results showed that effleurage consistently evoked a significant (P < 0.001) perfusion increase in the massaged limb, also visible in the contralateral limb (not significant) independently from the orientation (variant) used. No matter the perfusion differences known between sexes, the adaptive response was equivalent in both sexes. The component analysis of the LDF curves also suggests that these procedures, although brief and superficial, do modify multiple components of cardiovascular integration, with cardiac, respiratory, and myogenic components appearing to play a major role in reestablishing distal microcirculatory homeostasis.NEW & NOTEWORTHY The impact of effleurage, a well-known massage procedure used in human rehabilitation, in the lower limb hemodynamics, is demonstrated. When applied in a sole limb, massage increases skin microcirculatory flowmotion not only locally but also beyond, affecting systemic hemodynamics. This observation is an interesting example of the efficacy of cardiovascular integration mechanisms involving distal microcirculatory homeostasis. The proposed methodology allows a mechanistic view over skin flowmotion regulation, being applicable to further explore massage and its impact on microcirculatory physiology.

Different lasers reveal different skin microcirculatory flowmotion - data from the wavelet transform analysis of human hindlimb perfusion

Laser Doppler flowmetry (LDF) and reflection photoplethysmography (PPG) are standard technologies to access microcirculatory function in vivo. However, different light frequencies mean different interaction with tissues, such that LDF and PPG flowmotion curves might have distinct meanings, particularly during adaptative (homeostatic) processes. Therefore, we analyzed LDF and PPG perfusion signals obtained in response to opposite challenges. Young healthy volunteers, both sexes, were assigned to Group 1 (n = 29), submitted to a normalized Swedish massage procedure in one lower limb, increasing perfusion, or Group 2 (n = 14), submitted to a hyperoxia challenge test, decreasing perfusion. LDF (Periflux 5000) and PPG (PLUX-Biosignals) green light sensors applied distally on both lower limbs recorded perfusion changes for each experimental protocol. Both techniques detected the perfusion increase with massage, and the perfusion decrease with hyperoxia, in both limbs. Further analysis with the wavelet transform (WT) revealed better depth-related discriminative ability for PPG (more superficial, less blood sampling) compared with LDF in both challenges. Spectral amplitude profiles consistently demonstrated better sensitivity for LDF, especially regarding the lowest frequency components. Strong correlations between components were not found. Therefore, LDF and PPG flowmotion curves are not equivalent, a relevant finding to better study microcirculatory physiology.

Evidence on microcirculatory dynamics that preserves the equivalent perfusion steady state in both inferior limbs

The microcirculatory physiology critically depends on a highly structured network of vessels arranged to deliver oxygen to the tissues in a optimized way. In turn, oxygen is also a critical regulatory element of these functions, not only acting locally, influencing resistance, but also controlled by other local and systemic (homeostatic) regulators. Using oxygen as a challenger we detected an interesting regional perfusion dynamics taking place in the mouse, after an hindlimb ischemia procedure, where the contralateral non operated limb contributed to recover the equivalent circulatory steady state in both limbs. A similar cooperation perfusion event, involving both limbs, has only been referred as a long‐term vascular adaptation to ischemia in patients with peripheral arterial occlusive disease, but never, to our knowledge, experimentally pursued.More recently the impact of postural vasoconstriction in the human foot perfusion, the veno‐arterial reflex (VAR), measured with photoplethysmography (PPG) revealed a pronounced reduction of perfusion in the dependent foot followed by a reduction in the contralateral foot. This effective impact of VAR in the contralateral limb was here demonstrated for the first time, suggesting a different perspective about a wider regional control in the lower limb perfusionHomeostasis, e.g. that the initial reflex in the depending limb, explained by a myogenic‐endothelial cooperation, seems now to be only a part of a wider mechanism. In the present study, we show evidence of this cooperation between limbs, using non‐invasive techniques such as PPG, Laser Doppler Flowmetry (LDF) and a new non‐contact polarization spectroscopy system. The study includes 49 volunteers, both sexes, divided into two groups ‐ a young (n=34, 19.86 ± 1.58 years old) and older, also healthy group (n=15, 55.22 ± 6.04 years old), submitted to two massage protocols (applied on the ascending and descending direction) in one randomly selected limb, using the contralateral as the control. Each protocol consisted in three phases ‐ resting (I), massage (II) and recovery (III). Signals were registered in both feet (toes) and decomposed by the wavelet transform (WT) (p&lt;0.05). PPG, LDF and spectroscopy all similarly revealed the same features – a significant increase of blood perfusion in both limbs (massaged and non‐massaged) during the maneuver, more pronounced in the younger group suggesting the existence of a similar homeostatic cooperation, evoked to reestablish the local circulation setpoint.The wavelet transform analysis of PPG and LDF curves have shown that in younger volunteers, the myogenic and sympathetic components seem to vary most with massage, when compared with the older group. This also confirms that age influences the efficiency of these regulatory mechanisms, and that this strategy helps to look deeper into the physiological processes here involved.Support or Funding InformationSupported by national funds from FCT ‐ IP within the project UID/DTP/04567/2016.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Observations on the perfusion recovery of regenerative angiogenesis in an ischemic limb model under hyperoxia.

This study combines two well‐known vascular research models, hyperoxia and hind limb ischemia, aiming to better characterize capacities of the hyperoxia challenge. We studied two groups of C57/BL6 male mice, a control (C) and a hind limb ischemia (HLI) group. Perfusion from both limbs was recorded in all animals by laser Doppler techniques under an oxygen (O2) saturated atmosphere, once for control and, during 35 days for the HLI group. We used a third set of normoxic animals for HLI morphometric control. The expected variability of responses was higher for the younger animals. In the HLI group, capillary density normalized at Day 21 as expected, but not microcirculatory physiology. In the operated limb, perfusion decreased dramatically following surgery (Day 4), as a slight reduction in the non‐operated limb was also noted. Consistently, the response to hyperoxia was an increased perfusion in the ischemic limb and decreased perfusion in the contralateral limb. Only at Day 35, both limbs exhibited similar flows, although noticeably lower than Day 0. These observations help to understand some of the functional variability attributed to the hyperoxia model, by showing (i) differences in the circulation of the limb pairs to readjust a new perfusion set‐point even after ischemia, an original finding implying that (ii) data from both limbs should be recorded when performing distal measurements in vivo. Our data demonstrate that the new vessels following HLI are not functionally normal, and this also affects the non‐operated limb. These findings confirm the discriminative capacities of the hyperoxia challenge and suggest its potential utility to study other pathologies with vascular impact.

Optimization of the parameters of microcirculatory structural adaptation model based on improved quantum-behaved particle swarm optimization algorithm

The vessels in the microcirculation keep adjusting their structure to meet the functional requirements of the different tissues. A previously developed theoretical model can reproduce the process of vascular structural adaptation to help the study of the microcirculatory physiology. However, until now, such model lacks the appropriate methods for its parameter settings with subsequent limitation of further applications. This study proposed an improved quantum-behaved particle swarm optimization (QPSO) algorithm for setting the parameter values in this model. The optimization was performed on a real mesenteric microvascular network of rat. The results showed that the improved QPSO was superior to the standard particle swarm optimization, the standard QPSO and the previously reported Downhill algorithm. We conclude that the improved QPSO leads to a better agreement between mathematical simulation and animal experiment, rendering the model more reliable in future physiological studies.

Infrared image monitoring of local anesthetic poisoning in rats

To evaluate the thermographic predictive value of local anesthetic poisoning in rats that indicates the early recognition of thermal signs of intoxication and enable the immediate start of advanced life support. Wistar rats underwent intraperitoneal injection of saline and ropivacaine; they were allocated into pairs, and experiments performed at baseline and experimental times. For thermography, central and peripheral compartment were analyzed, checking the maximum and average differences of temperatures between groups. Thermographic and clinical observations were performed for each experiment, and the times in which the signs of intoxication occurred were recorded. In the thermal analysis, the thermograms corresponding to the times of interest were sought and relevant data sheets extracted for statistical analysis. Basal and experimental: the display of the thermal images at times was possible. It was possible to calculate the heat transfer rate in all cases. At baseline it was possible to see the physiology of microcirculation, characterized by thermal distribution in the craniocaudal direction. It was possible to visualize the pathophysiological changes or thermal dysautonomias caused by intoxication before clinical signs occur, characterized by areas of hyper-radiation, translating Autonomic Nervous System pathophysiological disorders. In animals poisoned by ropivacaine, there was no statistically significant difference in heat transfer rate at the experimental time. The maximum temperature, medium temperature, and heat transfer rate were different from the statistical point of view between groups at the experimental time, thus confirming the systemic thermographic predictive value.

Infrared image monitoring of local anesthetic poisoning in rats

Background and objectivesTo evaluate the thermographic predictive value of local anesthetic poisoning in rats that indicates the early recognition of thermal signs of intoxication and enable the immediate start of advanced life support. MethodsWistar rats underwent intraperitoneal injection of saline and ropivacaine; they were allocated into pairs, and experiments performed at baseline and experimental times. For thermography, central and peripheral compartment were analyzed, checking the maximum and average differences of temperatures between groups. Thermographic and clinical observations were performed for each experiment, and the times in which the signs of intoxication occurred were recorded. In the thermal analysis, the thermograms corresponding to the times of interest were sought and relevant data sheets extracted for statistical analysis. ResultsBasal and experimental: the display of the thermal images at times was possible. It was possible to calculate the heat transfer rate in all cases. At baseline it was possible to see the physiology of microcirculation, characterized by thermal distribution in the craniocaudal direction. It was possible to visualize the pathophysiological changes or thermal dysautonomias caused by intoxication before clinical signs occur, characterized by areas of hyper-radiation, translating autonomic nervous system pathophysiological disorders. In animals poisoned by ropivacaine, there was no statistically significant difference in heat transfer rate at the experimental time. ConclusionsThe maximum temperature, medium temperature, and heat transfer rate were different from the statistical point of view between groups at the experimental time, thus confirming the systemic thermographic predictive value.

A Novel Assessment of Flexibility by Microcirculatory Signals

Flexibility testing is one of the most important fitness assessments. It is generally evaluated by measuring the range of motion (RoM) of body segments around a joint center. This study presents a novel assessment of flexibility in the microcirculatory aspect. Eighteen college students were recruited for the flexibility assessment. The flexibility of the leg was defined according to the angle of active ankle dorsiflexion measured by goniometry. Six legs were excluded, and the remaining thirty legs were categorized into two groups, group H (n = 15 with higher flexibility) and group L (n = 15 with lower flexibility), according to their RoM. The microcirculatory signals of the gastrocnemius muscle on the belly were monitored by using Laser-Doppler Flowmetry (LDF) with a noninvasive skin probe. Three indices of nonpulsatile component (DC), pulsatile component (AC) and perfusion pulsatility (PP) were defined from the LDF signals after signal processing. The results revealed that both the DC and AC values of the group H that demonstrated higher stability underwent muscle stretching. In contrast, these indices of group L had interferences and became unstable during muscle stretching. The PP value of group H was a little higher than that of group L. These primary findings help us to understand the microcirculatory physiology of flexibility, and warrant further investigations for use of non-invasive LDF techniques in the assessment of flexibility.

In vivo assessment of peripheral vascular function by tcpo2 and skin blood flow modelling

There are multiple techniques and methods to assess peripheral vascular function in vivo but not without limitations. More discriminative, sensitive and also practical evaluation strategies are needed to fully characterize the peripheral vascular function. In the present work, a new quantitative descriptor, the 'elimination half-life time' was developed from flow-related variables as a non-invasive microcirculatory rate parameter to describe vascular dynamics. Fifty-four healthy volunteers and six type 2 diabetic patients, both genders, were submitted to a dynamical procedure consisting in the inhalation of a 100% saturated atmosphere of oxygen for 10 min. The tcpO(2) and microcirculatory blood flow [Laser Doppler Flowmetry (LDF)] were measured in a randomly selected leg with a Periflux 5000 system before, during and after the procedure. A monocompartmental model was adjusted to tcpO(2) and LDF data. The tcpO(2) constant elimination rate, expressed as the Oxygen elimination half-life, was used as an indicator of the vulnerability of peripheral tissue and compared in healthy versus non-healthy individuals. Under normal conditions, the saturated ventilation increases the tissue's O(2) availability, as an expression of the natural capacity to adjust the tissue hemodynamics to new metabolical/perfusion conditions. Diabetic patients are expected to suffer vascular impairment and ischemia. Under O(2) overloading conditions, those hypoxic territories tend to uptake all the delivered oxygen, expressed as a significant increase in the O(2) elimination half-life. This approach allows to propose 'elimination half-life time' as the first quantitative descriptive parameter combining miogenic, hemodynamic and metabolic aspects of the microcirculatory physiology and to help to identify the individual's vascular vulnerability.

Nitric Oxide Protection Against Murine Cerebral Malaria Is Associated With Improved Cerebral Microcirculatory Physiology

Cerebral malaria (CM) is a leading cause of death in Plasmodium falciparum infections. In the Plasmodium berghei ANKA (PbA) murine model, CM pathogenesis is associated with low nitric oxide (NO) bioavailability and brain microcirculatory complications, with a marked decrease in cerebral blood flow, vasoconstriction, vascular plugging by adherent cells, and hemorrhages. Using intravital microscopy through a closed cranial window, here we show that NO supplementation in the form of a NO donor (dipropylenetriamine NONOate [DPTA-NO]) prevented vasoconstriction and improved blood flow in pial vessels of PbA-infected mice. Arterioles and venules of smaller diameters (20-35.5 μm) showed better response to treatment than vessels of larger diameters (36-63 μm). Exogenous NO provided protection against brain hemorrhages (mean, 1.4 vs 24.5 hemorrhagic foci per section) and inflammation (mean, 2.5 vs 10.9 adherent leukocytes per 100 μm vessel length) compared with saline treatment. In conclusion, NO protection against CM is associated with improved brain microcirculatory hemodynamics and decreased vascular pathology.

In vivo functional chronic imaging of a small animal model using optical‐resolution photoacoustic microscopy

Optical-resolution photoacoustic microscopy (OR-PAM) has been validated as a valuable tool for label-free volumetric microvascular imaging. More importantly, the advantages of noninvasiveness and measurement consistency suggest the use of OR-PAM for chronic imaging of intact microcirculation. Here, such chronic imaging is demonstrated for the first time by monitoring the healing process of laser-induced microvascular lesions in a small animal model in vivo. The central part of a 1 mm by 1 mm region in a nude mouse ear was treated under a continuous-wave laser to create a microvascular lesion for chronic study. The region of interest was imaged before the laser treatment, immediately after the treatment, and throughout the healing process using both the authors' OR-PAM system and a commercial transmission-mode optical microscope. Three-dimensional microvascular morphology and blood oxygenation information were imaged simultaneously at capillary-level resolution. Transmission-mode optical microscopic images were acquired for comparison. OR-PAM has potential important applications in microcirculatory physiology or pathophysiology, tumor angiogenesis, laser microsurgery, and neuroscience.

Microcirculatory characteristics of acupuncture points obtained by laser Doppler flowmetry

Acupuncture points (acupoints) form part of the meridian system that constitutes the most fundamental concept in oriental medicine, but their physiological basis has not been clarified. In this study we employed laser Doppler flowmetry (LDF) to extract the microcirculatory characteristics of acupoints and their surrounding tissues, and we interpreted the results from the viewpoint of microcirculatory physiology. Three groups of measurements were performed focusing on the following two important acupoints in oriental medicine in healthy volunteers (n = 13 for group A and n = 9 for groups B and C, respectively): Hoh-Ku (Li4, on the hand) and Ching-Ku (B64, on the foot). The two groups of measurements around Hoh-Ku (Groups A and B) were so designed as to examine the effect of the direction of the nonacupoint away from the acupoint, whereas comparison between the Hoh-Ku and the Ching-Ku measurements was to verify whether the phenomenon was consistent in the upper and the lower extremities. We found that the mean LDF signals were significantly larger at the acupoints than in their surrounding tissues (all p < 0.05), which indicates a larger blood supply into the microvascular beds of acupoints. The results indicate that the physical properties of the vascular structure of acupoints may affect the perfusion resistance, and thereby modulate the microcirculatory perfusion in accordance with tissue needs. This finding facilitates the localization of acupoints, helps in identifying the connection between microcirculatory physiology and responses to acupoint stimulation, and introduces an objective research method for understanding the mechanisms that underlie oriental medicine.

Characterization of circulatory disorders in β-thalassemic mice by noninvasive ultrasound biomicroscopy

Beta-thalassemia is an inherited hematological disease caused by a decrease or absence of production of beta-globin that requires chronic therapeutic interventions. This condition leads to important arterial and venous thromboembolic events, transitory ischemic attacks, and microcirculatory obstructions, indicative of circulatory disturbances. To investigate the presence of microcirculatory disorders without the confounding effect of treatments, we used beta-thalassemic mice with typical clinical characteristics of human beta-thalassemia major. One impediment to the understanding of microcirculatory physiology, in particular for beta-thalassemic mice, has been the lack of an appropriate noninvasive imaging approach. We thus developed a novel noninvasive high-frequency ultrasound imaging method to evaluate murine vascular hemodynamic properties. In our beta-thalassemic mice, total peripheral vascular resistance was significantly increased (P < 0.01) compared with wildtype littermates, whereas mean blood pressure, heart rate, and cardiac output were similar (P = nonsignificant). Importantly, the vascular hemodynamics in beta-thalassemic mice were significantly affected according to the Pourcelot indexes measured in the common carotid artery and abdominal aorta (P < 0.01 and P < 0.05, respectively). Hence, our beta-thalassemia characterization of vascular hemodynamics by noninvasive ultrasonic approaches proves the existence and provides unique quantitative assessment of microcirculatory flow disturbances in those mice.

Le syndrome hépatorénal chez le patient cirrhotique

Hepatorenal syndrome is a particular form of functional renal failure which may develop in patients with liver cirrhosis. On a clinical standpoint, precise diagnostic criteria have been established to clearly define this entity, whereas recent advances in the understanding of the biology of vasoactive mediators and the physiology of microcirculation have allowed to better anticipate its pathophysiological mechanisms. During the course of cirrhosis, sinusoidal portal hypertension leads to splanchnic and systemic vasodilation, responsible for a reduction of effective arterial blood volume. As a result, a state of intense renal vasoconstriction develops, leading to renal failure in the absence of any organic renal disease. At this stage, liver transplantation is the only definitive therapy able to reverse renal dysfunction. In recent years, innovative therapies have shown promise to prolong survival in patients with hepatorenal syndrome, including the administration of analogs of vasopressin (mainly terlipressin), the insertion of transjugular intrahepatic portosystemic shunts and the use of novel techniques of dialysis. On a preventive viewpoint, several simple measures have been shown to reduce the risk of hepatorenal syndrome in cirrhotic patients, including the appropriate use of diuretics, the avoidance of nephrotoxic drugs, the prophylaxis of spontaneaous bacterial peritonitis and optimal fluid management in patients undergoing large volume paracentesis.

Computational framework for generating transport models from databases of microvascular anatomy.

Quantitative descriptions of transport and exchange in physiological systems should make use of the emerging wealth of data on vascular anatomic structure. These descriptions may take the form of computational models which then must be incorporated into the comprehensive database of knowledge of microcirculatory physiology being developed under the title, The Microcirculation Physiome Project. Toward this end we present a simple and efficient computational method for simulating transport (advection, permeation, diffusion) in tissues containing microvascular structures of arbitrary complexity. The method is convenient because transport is simulated on a regular Cartesian lattice, and efficient because features of the anatomy are resolved within individual volume elements of the lattice. As a result, relatively low-resolution lattices yield accurate results. Therefore the method provides a feasible approach for studying a general class of transport problems in the context of realistic representations of vascular anatomy.

A Web‐Based Research Tool for Functional Genomics of the Microcirculation: The Leukocyte Adhesion Cascade

Currently, microvascular data are almost exclusively deposited in scholarly journals. With the increasing availability of molecular data and the construction of genomic databases, a need arises to organize physiological data in a more accessible format. The microcirculation is a functional system that spans all organ systems and shares certain characteristics of organization with metabolic pathways, which have successfully been organized around genomic information for several prokaryotes. Here, we present a web-based research and teaching tool (http:@hsc.Virginia.EDU/medicine/basic-sci/biomed/l ey/) that covers a small aspect of microcirculatory physiology, the leukocyte adhesion cascade. Currently, the site is organized in a flat-text mode with hypertext links to GenBank, Medline, and online journals where available. The web-based research and education tool is useful for graduate student education, and as a research resource for genetic researchers interested in gene function and for physiologists and biomedical engineers interested in the molecular basis of the leukocyte adhesion cascade. Our effort is intended to be a beginning toward a distributed database for the microcirculation (microcirculation physiome. see http://www.bme.jhu.edu/news/microphys). We invite all microvascular researchers to provide annotations and comments to make the research and teaching tool more useful to the scientific community.