Net Fluid Movement Research Articles

Horizontal Chimney Effect

Abstract An analysis of natural convection in horizontal slots has been carried out. It is demonstrated that a proper combination of heating and groove patterns can create a net horizontal fluid movement, which we refer to as the horizontal chimney effect. Groove shapes that can be easily manufactured as well as heating patterns that can be easily created using heating wires were considered. It has been shown that both patterns must be properly tuned. The direction of the net horizontal flow can be changed by changing the relative positions of the patterns. Changes of groove geometry can change the flow rate by up to 100%. Simultaneous use of grooves and heating at both plates can nearly double the system effectiveness. The strength of the flow increases with reduction of the Prandtl number.

Genesis of Antibiotic Resistance (AR) LIV: “Confounder Effect”: Sepsis with Comorbidity ‐ An Indomitable Turbulence Modeling Consignment

To delineate the hemodynamic basis of exacerbated mortality rate in Early Resuscitation Protocol (ERP) for sepsis with comorbidity, here we present the results of a comparative simulation analysis of “Net Filtration Pressure” (NFP) at homeostasis (Laminar) vs Sepsis with comorbidity (Laminar‐transition‐turbulence‐collapse) in the contexture of Fahraeus – Lindqvist Effect (FLE), plasma skimming, swirling & sigma effect and its role in Critical Closing Pressure (CCP) (Transition to Turbulence consequent collapse). At homeostasis, Starling Forces: NFP= (BHP+IFOP) − (BCOP+IFHP)] at the arterial end, net pressure is outward at 10 mmHg (filtration) and at the venous end, net pressure is inward at −9 mmHg (reabsorption). [Starling equation: Jv = Kf ([Pc − Pi] − σ [πc − πi]), where Jv is the net fluid movement between compartments and [Pc − Pi] − σ [πc − πi] is the net driving force, Pc is the capillary hydrostatic pressure, Pi is the interstitial hydrostatic pressure, πc is the capillary oncotic pressure, πi is the interstitial oncotic pressure, Kf is the filtration coefficient – a proportionality constant, and σ is the reflection coefficient (Fig 3a ‐ Ind J Ana. 2019; 63(1):6). The ERP, NCT01663701 (JAMA.2017;318(13):1233) based sepsis cohort data are sepsis‐ suspected infection plus ≥2 (SIRS), MAP < 65mmHg, sepsis‐induced hypotension 89mmHg/55mmHg (~ 2 liters of bolus administered within 1 hr of enrollment, edema, hypoxemia, hypoperfusion, tachypnea, and respiratory failure due to a lack of ventilator support. For simulation of Starling forces, the impact of FLE, plasma skimming effect, sigma effect (blood flow is not continuum), loss and/or dysfunctional glycocalyx (Crit Care. 2019;23(1):259) (substituting πg = 0mmHg (null & void) instead of πi, revised starling equation: Jv = Kf ([Pc − Pi] − σ [πc − πg] (Br J Ana. 2012 Mar;108(3):384) induce sustained leakage & hemoconcentration cellular aggregates (RBC, WBC, thrombocytes) – large eddies, CCP derived based on Law of La Place, and swirling effect (variable Schmidt number) were considered. Based on the simulation analysis, the prediction of NFP at arterial and venous end would be ~ +10mmHg favoring fluid filtration into the interstitial space causing edema, intra vascular hypotension, hypoperfusion and rheological factors predicted to be PI <1.05%, SpO2≦95%, PaO2 of 55 mmHg, SaO2<90%, SvO2<90%, StO2 below normal, DO2I below normal range, FiO2 <0.21(21%), PaCO2< 38 – 42 mmHg and PaO2/FiO2 <200mmHg. If numerous thrombi are forming simultaneously (equivalent to large‐eddy: Laminar to turbulence transition, then coagulation factors and platelets can become depleted (plasma skimming) causing hemorrhage (septic embolism tend to break up but not in this instance since glycocalyx is null and void) analogous to large‐eddy cascading in to smaller eddies (Fully Turbulent flow). Absence of cascading would likely to obstruct the blood flow and induce ischemia‐induced infarcts in the capillary bed. Though the “Counter‐Inflammatory response syndrome” would likely to mitigate thrombosis, plasma skimming/sigma effect on the cellular aggregates, would lead to thrombosis (large eddies) and CCP.Support or Funding InformationSupported by professional development funds provided by SWTJC to Subburaj Kannan

Oscillating Flow of Viscous Incompressible Fluid Through Sinusoidal Periodic Tube at Low Reynolds Number

The flow in tubes with periodically varying cross-section has many interests due to its various practical applications such as it can be used as particle separation devices. In this paper, we have examined the oscillatory flow of a viscous incompressible fluid in a sinusoidal periodic tube at low Reynolds number. The numerical study is undertaken to examine fluid movement at different cross-sections for different time. The boundary element method (BEM) has been formulated for the infinite sinusoidal periodic tube to solve the governing equations for obtaining components of surface force on the tube wall. We have calculated the axial and radial velocities at different cross-sections for different time and compared them. We find that the behaviors of the velocity curves for different cross-sections remain the same for the same phase of time over the oscillation. On the contrary, the behavior of the velocity curves become different for different phase of time. For the tube geometry, the axial velocity at the converging and diverging regions are the same while the radial velocity at these regions are the same in magnitudes but in opposite direction. In addition, the radial velocity is maximum in the half way between the tube axis and the tube wall, and it is minimum on the tube axis and on the tube wall. The obtained velocity indicates that the net fluid movement after each complete oscillation is zero, which is an assumption to separate particles in such periodic tube.

Fluid and ion transfer across the blood-brain and blood-cerebrospinal fluid barriers; a comparative account of mechanisms and roles.

The two major interfaces separating brain and blood have different primary roles. The choroid plexuses secrete cerebrospinal fluid into the ventricles, accounting for most net fluid entry to the brain. Aquaporin, AQP1, allows water transfer across the apical surface of the choroid epithelium; another protein, perhaps GLUT1, is important on the basolateral surface. Fluid secretion is driven by apical Na+-pumps. K+ secretion occurs via net paracellular influx through relatively leaky tight junctions partially offset by transcellular efflux. The blood–brain barrier lining brain microvasculature, allows passage of O2, CO2, and glucose as required for brain cell metabolism. Because of high resistance tight junctions between microvascular endothelial cells transport of most polar solutes is greatly restricted. Because solute permeability is low, hydrostatic pressure differences cannot account for net fluid movement; however, water permeability is sufficient for fluid secretion with water following net solute transport. The endothelial cells have ion transporters that, if appropriately arranged, could support fluid secretion. Evidence favours a rate smaller than, but not much smaller than, that of the choroid plexuses. At the blood–brain barrier Na+ tracer influx into the brain substantially exceeds any possible net flux. The tracer flux may occur primarily by a paracellular route. The blood–brain barrier is the most important interface for maintaining interstitial fluid (ISF) K+ concentration within tight limits. This is most likely because Na+-pumps vary the rate at which K+ is transported out of ISF in response to small changes in K+ concentration. There is also evidence for functional regulation of K+ transporters with chronic changes in plasma concentration. The blood–brain barrier is also important in regulating HCO3 − and pH in ISF: the principles of this regulation are reviewed. Whether the rate of blood–brain barrier HCO3 − transport is slow or fast is discussed critically: a slow transport rate comparable to those of other ions is favoured. In metabolic acidosis and alkalosis variations in HCO3 − concentration and pH are much smaller in ISF than in plasma whereas in respiratory acidosis variations in pHISF and pHplasma are similar. The key similarities and differences of the two interfaces are summarized.

Physiology of the pleural space.

The pleural cavity is created between the 4(th) and 7(th) week of embryologic development. These embryonic components of visceral and parietal pleurae develop different anatomic characteristics with regard to vascular, lymphatic, and nervous supply. There are two layers: a superficial mesothelial cell layer facing the pleural space and an underlying connective tissue layer. The pleura might present inflammatory response and maintenance of the pleural fluid is observed. The latter function is especially important in the mechanical coupling of the lung and chest wall. Fluid is filtered into the pleural space according to the net hydrostatic oncotic pressure gradient. It flows downward along a vertical pressure gradient, presumably determined by hydrostatic pressure and resistance to viscous flow. There also may be a net movement of fluid from the costal pleura to the mediastinal and interlobar regions. In these areas, pleural fluid is resorbed primarily through lymphatic stomata on the parietal pleural surface. In the current review we will present the physiology of the pleural space in a step by step manner.

Extracellular hydration, cardiovascular risk, and the interstitium: a three-dimensional view

Volume expansion is a major contributor to poor cardiovascular outcomes in kidney disease. The relationship of extracellular volume (ECV) overload to cardiovascular changes in chronic kidney disease (CKD) remains speculative. Recent studies are challenging traditional concepts and providing new insight into mechanisms and the relationship of ECV to cardiovascular health. A dynamic role of the extracellular interstitium in inducing cardiovascular risk is emerging in CKD.

Epithelial Sodium Channels Play a Role in Air & Water Borne Diseases

+, Cl and water from the airway lumen into the vascular space. ENaC is considered the rate limiting step in the net movement of fluid out of the alveolar space. Thus, strategies to enhance ENaC activity at the apical membrane are of interest in order to improve outcomes associated with diseases such as pneumonia and acute lung injury. ENaC in the airways is regulated by a variety of agents including G-coupled protein receptors (e.g. adrenergic, purinergic and dopaminergic), chemokines (TGF-β, TNF-α), reactive oxygen/nitrogen species (H 2 O 2 , O 2 ., NO) and hormones (glucocorticoids). The multitude of regulatory pathways highlights the importance of ENaC in the lung [3-6]. Single channel electrophysiology measurements from lung tissue demonstrate that there are two types of ENaC—highly selective cation (HSC) and non-selective cation (NSC) channels. HSC ENaC channels preferentially transport Na + (Na + /K + selectivity >40) while NSC ENaC channels are less discriminant (Na + /K + selectivity 1.4) [7]. In addition to differences in cation selectivity, HSC channels and NSC channels differ in their unitary conductance and other biophysical properties. However, they both play an important role in epithelial Na + reabsorption.

Molecular regulation of tumor angiogenesis and perfusion via redox signaling.

Angiogenesis is one of several processes that form new blood vessels in higher animals, but it has received the most research attention and popular interest due to its important roles in cancer and wound repair. During early embryogenesis, the first capillary networks form by a process known as vasculogenesis. Cells in the mesoderm differentiate into vascular endothelial cells and spontaneously connect to form a network of tubes known as a vascular plexus15. In contrast to angiogenesis, embryonic vasculogenesis occurs in the absence of blood flow. This primitive vascular network connects to primitive arteries and veins in the embryo, which establishes blood flow in the developing tissue. The directional flow is one signal that can promote differentiation of the vascular plexus into a hierarchical network of arteries, arterioles, capillaries, venules, and veins16. This differentiation process is known as arteriogenesis. Arteriogenesis is also directed by growth factors released from growing nerves in the embryo, which results in the parallel organization of blood vessels and nerved noted by early anatomical studies17. During later development and in adult tissues, angiogenesis plays a major role in new blood vessel formation. Angiogenesis is defined as the formation of new blood vessels from an existing perfused vessel bed. This occurs by sprouting of endothelial cells in the vessel wall, either arterial or venous vessels depending on the soluble factors present18,19, which degrade and invade through the underlying basement membrane barrier and then further invade through the underlying extracellular matrix. As the leading cell moves forward, following endothelial cells proliferate and differentiate to form a luminal space. The leading cell eventually finds another vessel, with which it fuses to establish a patent perfused vessel. Further cycles of this process accompanied by arteriogenesis produces a mature vascular network. In addition to endothelial cells, mature blood vessels require supporting smooth muscle cells. During development, these can be recruited from mesenchymal stem cells or from bone-marrow-derived cells. Arterial vessels develop a thick layer of well organized vascular smooth muscle cells (VSMC) to accommodate the greater hydrostatic pressure in the arterial vasculature. These arterial smooth muscle cells, as will be discussed in greater detail below, also play an important role in adjusting blood flow to specific tissues in response to changing metabolic needs. Veins also have well organized smooth muscle layers, but thinner than those in arteries. The VSMC in capillaries are known as pericytes. In contrast to large vessels, capillary endothelial tubes are not completely covered by pericytes. Rather, the pericytes play important roles in capillary stability and function by secreting factors that regulate endothelial cell function and through direct contact with the adjacent capillary endothelium20. Due to the positive hydrostatic pressure in perfused vessels, a net flow of water, ions, and small solutes constantly occurs across the vessel wall. This is opposed by an osmotic gradient resulting from the lower macromolecular solute concentration in the interstitial space, but nonetheless, net fluid movement occurs from perfused vessels into the underlying tissue. To maintain a constant blood volume, higher animals have a second vascular network, the lymphatics, that return this fluid to the cardiovascular system21. Lymphatics are a blind ended tree of specialized vascular cells, which form by a process known as lymphangiogenesis. It has recently become clear that angiogenesis is not the only mechanism responsible for neovascularization of tumors and wounds in the adult22. In adult tissues, vasculogenesis is mediated by recruitment of circulating endothelial precursor cells that differentiate from hematopoietic stem cells in the bone marrow. These along with specialized monocytic stem cells cooperate to form new vessels at sites of injury and in some cancers. The relative contribution of angiogenesis versus vasculogenesis to tumor neovascularization is currently being actively debated, but it is clear that some tumors depend significantly on bone marrow precursor recruitment, whereas this plays a minimal role in others23,24. Likewise, the role of lymphangiogenesis in tumor growth appears to be quite variable, with a subset of tumors being highly dependent on this process25. This review focuses on the role of redox signaling in angiogenesis and angiogenesis inhibition, but the reader should remain aware that some proangiogenic factors can stimulate vasculogenesis, lymphangiogenesis, and arteriogenesis as well as angiogenesis. Correspondingly, angiogenesis inhibitors can often inhibit more than one of these processes. Therefore, the redox signaling pathways discussed here have been initially defined and are best understood in the context of angiogenesis, but their true function may be more general.

Position of the New Zealand Dietetic Association (Inc): Nutrition for exercise and sport in New Zealand

Position of the New Zealand Dietetic Association (Inc): Nutrition for exercise and sport in New Zealand

Enhanced optical coherence patterns of diabetic macular oedema and their correlation with the pathophysiology

To describe different patterns of diabetic macular oedema (DMO) using a computerized alignment and averaging of sequences in optical coherence tomography (OCT) B-scans and to show the correlation of these patterns with the pathophysiology of the condition. We carried out a prospective, uncontrolled study, including 46 human subjects with untreated DMO. Enhanced OCT images were produced. We correlated different OCT patterns of DMO with ETDRS visual acuity and with the thickness of the central 1-mm of the macula. We also correlated these patterns with theories of the pathophysiology of DMO. Enhanced OCT images enabled us to examine how different layers of the macula were affected. The external limiting membrane (ELM) was clearly seen in all stages, including advanced stages. The sequence of DMO events in different macular layers can be divided into five patterns. Morphologically, DMO starts at the outer nuclear layer/Henle's layer. As the oedema progresses, cysts are seen in the fovea and the DMO spreads further into the inner nuclear layer. The ELM seems to act as a barrier for proteins and plays an important role in the development of DMO. Enhanced OCT revealed new details of DMO pathophysiology. The different morphological patterns of DMO seen in enhanced OCT may represent different levels of severity of the disease.

Dentinal fluid flow and cuspal displacement in response to resin composite restorative procedures

Objectives The aim of this study was to correlate the rate and magnitude of dentinal fluid flow (DFF) with cuspal displacement in response to resin composite restorative procedures. Methods Ten extracted human maxillary premolar teeth with an extensive MOD cavity preparation were connected to an automated fluid flow measurement apparatus (Flodec), and a direct current differencial transformer (DCDT) was attached to each cusp. The rate, magnitude and direction of DFF and cuspal displacement were recorded simultaneously in response to each stage of resin composite restorative procedures. Results Cuspal displacement and DFF in outward and inward directions accompanied each stage of the procedures. Drying produced rapid cuspal contraction. Bonding caused slight cuspal expansion, whereas light curing of resin induced gradual but extensive cuspal contraction, which persisted following light curing. During baseline outward DFF was low and increased slightly during etching. In contrast, substantial outward DFF occurred during drying. Light curing of the bonding agent and the resin composite produced inward DFF. Following light curing, an outward DFF began and continued for atleast 15 min. Significance The large, rapid fluid movement and cuspal displacement during restoration, and the prolonged outward fluid flow post-curing have implications for post-operative sensitivity. While mechanical stresses within dentin associated with cuspal displacement appear capable of inducing DFF, the net fluid movement is the result of complex interactions either directly or indirectly of several stimuli (thermal, evaporation, osmotic, and possibly mechanical).

Fluid Transport across the Isolated Porcine Ciliary Epithelium

To quantify spontaneous fluid transport across the isolated porcine ciliary epithelium and determine its sensitivity to the electrolyte transport inhibitors ouabain and bumetanide, as well as bath Cl(-) and HCO(3)(-) levels. A complete annulus of ciliary body was mounted in a custom-designed chamber appropriate for quantifying net fluid movement, as well as the transepithelial potential difference (PD) across the in vitro ciliary epithelium. A spontaneous and stable fluid flow (FF) in the blood-to-aqueous direction was measured over a 4-hour period. This flux solely reflected the secretory activity of the isolated ciliary epithelium (CE), given the absence of externally applied osmotic or pressure gradients. In contrast to FF, the PD declined during the 4 hours in vitro, suggesting that the integrity of the tight junctions may have been compromised during this time so that an increased movement of counter ions via the paracellular pathway could have shunted the PD, while at the same time transcellular fluid transport remained unaffected. The FF in the blood-to-aqueous direction (2.3 +/- 0.2 muL/hr; n = 7) was eliminated by a unilateral reduction in the bath Cl(-) levels on the blood side of the preparation and restored on reintroducing the anion to the bathing medium. This linkage between FF and blood side [Cl(-)] is consistent with the existence of a net Cl(-) flux across the porcine CE in the same direction as the fluid transport. Addition of bumetanide to the blood-side bath inhibited FF by approximately 40%, whereas the removal of CO(2)/HCO(3)(-) from the blood-side bathing solution elicited a approximately 50% reduction in FF. Ouabain inhibited the FF from either side of the preparation, although the effects were more rapid when the glycoside was applied to the blood side of the tissue. Overall, these findings indicate the dependence of FF on active ionic transport by the isolated CE. Isolated porcine ciliary epithelial preparations transport fluid in the blood-to-aqueous direction, indicating that measurements of volumetric fluid flow across this preparation may serve as a suitable model for future studies directed toward the pharmacological control of secretion.

Ligand-Induced 5-HT3 Receptor Internalization in Enteric Neurons in Rat Ileum

Release of 5-hydroxytryptamine (5-HT) from mucosal enterochromaffin cells and activation of 5-HT(3) receptors (5-HT(3)Rs) on neurons in the gut wall is important in the response of the gut to the luminal environment. Intestinal inflammation is associated with increased levels of mucosal 5-HT. The aims of the study were to determine the following: (1) if 5-HT(3)R undergoes ligand-induced internalization in myenteric neurons, and (2) the effect of long-term increase of mucosal 5-HT on 5-HT(3)Rs. Acute effects of exogenous 5-HT or endogenous release of 5-HT by luminal glucose on cellular localization of 5-HT(3)Rs was determined by immunohistochemistry and confocal microscopy. Treatment with the serotonin re-uptake inhibitor, fluoxetine, for 6 days (20 mg/kg daily orally) was used to increase mucosal 5-HT chronically in rats. Net ileal fluid movement was measured in anesthetized rats by the weight change of a 2.5% agarose cylinder. Acute increases in 5-HT induced by exogenous or endogenous 5-HT decreased 5-HT(3)R immunoreactivity at the neuronal cell membrane by 70% and 60%, respectively. Chronic fluoxetine treatment increased mucosal levels of 5-HT and decreased membrane 5-HT(3)R immunoreactivity by 27%. Net fluid absorption was decreased by a 5-HT(3)R agonist or by luminal glucose; this was attenuated 88% and 99%, respectively, by fluoxetine treatment. Long-term increase in 5-HT in the intestinal mucosa results in increased 5-HT(3)R internalization in myenteric neurons. Chronic changes in mucosal 5-HT may alter gastrointestinal secretory and motor function via ongoing loss of receptor from neuronal membrane, causing a mismatch between luminal content and absorption.

Spontaneous Fluid Transport across Isolated Rabbit and Bovine Ciliary Body Preparations

To quantify spontaneous fluid transport across the isolated ciliary bodies of rabbit and bovine and to determine their osmotic permeabilities. A complete annulus of ciliary body was mounted in a custom-designed chamber appropriate for detecting net fluid movement across the in vitro preparation. A net fluid flow in the blood-to-aqueous direction was measured. It was generally observed that tissue freshness is a critical parameter for detection of such flow. The spontaneous, baseline fluid transport rate lasted, on average, approximately 4 hours. This flow solely reflects the secretory activity of the isolated ciliary epithelium, since the in vitro arrangement precludes contributions from ultrafiltration. Both the isolated rabbit and bovine ciliary body epithelia transported fluid in the absence of an external osmotic or pressure gradient. After corrections for area and possible collapse of the processes, a total flux rate of approximately 23 microL/hour or 13% of the in vivo flow in rabbit was estimated. This value agrees with predictions of ionic fluxes and short-circuit current measurements, which are also obtained in vitro. The fluid flow is bicarbonate dependent in rabbit and chloride dependent in bovine, consistent with ionic transport mechanisms described in these species. Ouabain inhibited the fluid flow across both species, indicating dependence on active ionic transport. Irrespective of the spontaneous fluid transport, a flow elicited by an osmotic gradient allowed for a calculation of the osmotic permeability coefficient (P(f); approximately 10(-3) cm/s) in line with reports in other epithelia. In addition, mannitol permeability (5.6 x 10(-6) cm/sec) was similar to that measured in "tight" epithelia, as determined by measurements of radiolabeled fluxes of the sugar across rabbit ciliary bodies mounted in the chambers used for the present fluid transport study. This work demonstrates that isolated ciliary epithelial preparations transport fluid in the blood-to-aqueous direction. The present observations suggest that mounting arrangements for measuring volumetric fluid flow across the ciliary epithelium is suitable for future studies directed toward the pharmacological control of secretion.

Expression of the aquaporin 8 water channel in a rat salivary epithelial cell.

Aquaporins are a family of water channels considered to play an important role in fluid transport across plasma membranes. Among the reported isoforms, relatively little is known about the functional role of aquaporin 8 (AQP8), and there are no cell lines known to express the AQP8 protein. We report here that the rat submandibular epithelial cell line, SMIE, expresses AQP8. Using RT-PCR, the presence of mRNA for AQP8 was demonstrated in these cells. Confocal immunofluorescence experiments revealed that the AQP8 protein is primarily present in the apical membranes of SMIE cells. When grown as a polarized monolayer on collagen coated polycarbonate filters, and exposed on their apical surface to different hyperosmotic (440, 540, or 640 mOsm) solutions, net fluid movement across SMIE cells was 8-25-fold that seen under isosmotic conditions. Similarly, when grown on coverslips and then exposed to a hypertonic solution, SMIE cells shrunk as a function of time. Together, these results suggest that SMIE cells endogenously express functional AQP8 water channels.

Distal air space epithelial fluid clearance in near-term rat fetuses is fast and requires endogenous catecholamines.

Knowledge about the conversion of the epithelium in the distal air spaces of the lung from secretion to absorption is imperative to the understanding of postnatal lung development; little such information is available in rats. Distal air space fluid clearance was therefore measured in 21- to 22-day gestation rat fetuses and newborn (40 h) rats. Distal air space fluid clearance was measured from the increase in (131)I-albumin concentration in an isosmolar, physiological solution instilled into the developing lungs. There was no net fluid movement across the distal air space epithelium in the lungs of 21-day gestation fetuses. Twenty-four hours later, distal air space fluid was cleared at a rapid rate in the 22-day gestation fetuses. Within the first 40 h after birth, the rate rapidly declined to adult levels. The high distal air space fluid clearance at 22 days gestation and at 40 h after birth was mediated by beta-adrenergic receptors as demonstrated by elevated plasma epinephrine levels and inhibition by propranolol. Interestingly, the elevated distal air space fluid clearance in the 22-day gestation fetuses was only minimally amiloride sensitive; however, amiloride sensitivity increased over the first 40 h after birth. In conclusion, these studies demonstrate that 1) rapid rates of net alveolar fluid clearance occur late in gestation in the rat and 2) this clearance is driven by elevations of endogenous epinephrine.

Volume Kinetic Analysis of the Distribution of 0.9% Saline in Conscious versus Isoflurane-anesthetized Sheep

The distribution and elimination of 0.9% saline given by intravenous infusion has not been compared between the conscious state and during inhalational anesthesia. Six adult sheep received an intravenous infusion of 25 ml/kg of 0.9% saline over 20 min in the conscious state and also during isoflurane anesthesia and mechanical ventilation. The distribution and elimination of infused fluid were studied by volume kinetics based on serial analysis of hemoglobin dilution in arterial blood and by mass balance that incorporated volume calculations derived from volume kinetic analysis and measurements of urinary volumes. The mass balance calculations indicated only minor differences in the time course of plasma volume expansion between the conscious and anesthetized states. However, isoflurane anesthesia markedly reduced urinary volume (median, 9 vs. 863 ml; P < 0.03). In conscious sheep, the central and peripheral volume expansion predicted by volume kinetics agreed well with the calculations based on mass balance. However, during isoflurane anesthesia and mechanical ventilation, calculation using volume kinetic analysis of the variable kr, an elimination factor that, in conscious humans and sheep, is closely related to urinary excretion, represented both urinary excretion and peripheral accumulation of fluid. This suggests that the previous assumption that kr approximates urinary excretion of infused fluid requires modification, i.e., kr simply reflects net fluid movement out of plasma. In both conscious and anesthetized, mechanically ventilated sheep, infusion of 0.9% saline resulted in minimal expansion of plasma volume over a 3-h interval. In conscious sheep, infused 0.9% saline was rapidly eliminated from the plasma volume by urinary excretion; in contrast, the combination of isoflurane anesthesia and mechanical ventilation reduced urinary excretion and promoted peripheral accumulation of fluid.

Modeling tracer transport in an osteon under cyclic loading.

A mathematical model is developed to explain the fundamental conundrum as to how during cyclic mechanical loading there can be net solute (e.g., nutrient, tracer) transport in bone via the lacunar-canalicular porosity when there is no net fluid movement in the canaliculi over a loading cycle. Our hypothesis is that the fluid space in an osteocytic lacuna facilitates a nearly instantaneous mixing process of bone fluid that creates a difference in tracer concentration between the inward and outward canalicular flow and thus ensures net tracer transport to the osteocytes during cyclic loading, as has been shown experimentally. The sequential spread of the tracer from the osteonal canal to the lacunae is investigated for an osteon experiencing sinusoidal loading. The fluid pressure in the canaliculi is calculated using poroelasticity theory and the mixing process in the lacunae is then simulated computationally. The tracer concentration in lacunae extending radially from the osteonal canal to the cement line is calculated as a function of the loading frequency, loading magnitude, and number of loading cycles as well as the permeability of the lacunar-canalicular porosity. Our results show that net tracer transport to the lacunae does occur for cyclic loading. Tracer transport is found to increase with higher loading magnitude and higher permeability and to decrease with increasing loading frequency. This work will be helpful in designing experimental studies of tracer movement and bone fluid flow, which will enhance our understanding of bone metabolism as well as bone adaptation.

The inhibition of cholera toxin-induced 5-HT release by the 5-HT(3) receptor antagonist, granisetron, in the rat.

1. The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera. 5-HT released from enterochromaffin cells after cholera toxin exposure is thought to activate non-neuronally (5-HT(2) dependent) and neuronally (5-HT(3) dependent) mediated water and electrolyte secretion. CT-secretion can be reduced by preventing the release of 5-HT. Enterochromaffin cells possess numerous receptors that, under basal conditions, modulate 5-HT release. 2. These include basolateral 5-HT(3) receptors, the activation of which is known to enhance 5-HT release. 3. Until now, 5-HT(3) receptor antagonists (e.g. granisetron) have been thought to inhibit cholera toxin-induced fluid secretion by blockading 5-HT(3) receptors on secretory enteric neurones. Instead we postulated that they act by inhibiting cholera toxin-induced enterochromaffin cell degranulation. 4. Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 microg kg(-1), lidoocaine 6 mg kg(-1) or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection. 5. Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity. 6. Both lidocaine and granisetron inhibited fluid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. 7. The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT(3) receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid secretion.

NGF administered by microdialysis into rabbit vitreous.

Microdialysis has been used in eye research for almost a decade. We have previously developed and used it mainly for chronic experiments and here it is used in acute experiments. It is highly suitable for both administration and withdrawal of substances from the eye, as it only permits molecules to cross the intraocular membrane without any net fluid movement in or out of the eye. We have here investigated the ability of 125I labeled NGF (nerve growth factor) to cross a previously implanted high permeability membrane of a new type (polyether sulphone, PES, cutoff at 100000 daltons) in the rabbit vitreous. It was perfused for different time periods with a solution containing NGF The radioactivity of the entire vitreous was then counted. The results show detectable levels (up to 10(-11)M) of the substance after the perfusions. We conclude that microdialysis with PES membranes is a possible method for the intraocular administration of NGF.