Arterial Compartment Research Articles

Genetic regulation of the flow‐induced carotid compartment remodeling in mice

Subclinical atherosclerosis is measured by intima‐media thickening (IMT) in human carotid arteries and strongly predicts cardiovascular risks. Human studies showed that carotid IMT is determined by genetic factors. Recently we identified several quantitative trait loci (QTL) that influence intima formation in response to low blood flow in a mouse genetic cross (C3HeB/FeJxSJL/J, N2=134). We hypothesized that different genomic regions control artery compartments of the remodeled carotid. In particular, we investigated 4 carotid compartment traits: intima+media, media ratio of the left‐to‐right (L/R), external elastic lamina (EEL) ratio L/R, and adventitia ratio L/R. Using genome‐wide scan we identified three highly significant QTLs: Imm1 (intima+media modifier 1 locus) on chromosome 2 (chr2; LOD=6.8), Imm2 on Chr11 (LOD=5.1), and Eelm1 (EEL modifier 1 locus) on chr2 (LOD=5.6). There were five significant QTLs: Imm3 on Chr18 (LOD=3.0), Mrm1 (media ratio L/R modifier 1; LOD=3.9) and Arm1 (adventitia ratio L/R modifier 1; LOD=3.3) on chr2; Mrm2 (LOD=2.9) and Arm2 (LOD=3.9) on chr11. Interval mapping showed that significant intima loci co‐localized with carotid remodeling traits on chr2 and chr11. However, the most significant loci for intima+media, media and EEL traits were localized on chr2, while the most significant adventitia trait locus was on chr11. In summary, for the first time we mapped artery compartment QTLs that regulate carotid remodeling in response to changes in blood flow. These results are important for our understanding of the genetic mechanisms that contribute to carotid IMT and atherosclerosis in humans. This study was supported by NIH HL‐62826 (PI: B.C. Berk).

A mechanical model of the cardiovascular system – a pedagogical tool

We have developed a mechanical model of the cardiovascular system for instructional use. The water‐circulating system includes a cardiac chamber for which the strength, duration and frequency of contraction may be varied; arterial and venous elements that each have variable compliance; and an arteriolar element with variable resistance. A PowerLab system (ADInstruments) is used to control the system and to display measured parameters. The cardiac element consists of a balloon enclosed in a plexiglass chamber that is cyclically pressurized via a FairchildTM electronic pressure regulator. Windkessels are used to mimic the compliant arterial and venous compartments. Two windkessels arranged in series mimic the peripheral and central venous compartments. Each is outfitted with a FairchildTM regulator to allow mimicry of the skeletal and thoracic pumps. Small bore silastic tubing arrayed in a parallel configuration comprise the variable peripheral resistance. An in‐line flow transducer and multiple pressure transducers enable measurement and evaluation of critical cardiovascular parameters in real time as system elements are manipulated. The highly visual and hands‐on nature of the system maximizes its use as a pedagogical tool at many different levels of instruction. Supported by The University of Scranton.

The shy Angeli and his elusive creature: the HNO route to vasodilation

what we now call Angeli's salt (AS) was discovered more than a century ago by the Italian chemist Angelo Angeli (Fig. 1) . He found that “salts of nitroxylaminic acid are readily resolved into the corresponding nitrites and the unsaturated residue nitroxyl” (HNO), proposing their use as suppliers of HNO (3). However, by analogy with the genial but very reclusive personality of the discoverer (17), the physiological properties of HNO didn't draw too much attention until early 1990s. In their seminal work, Fukuto and colleagues (19) reported that HNO elicits vasorelaxation in both the rabbit aorta and bovine intrapulmonary artery by a soluble guanylate cyclase (sGC)- dependent pathway. Later, it was evident that the thiol-donating agent l-cysteine can discriminate the vasodilatative profile of HNO from that of nitric oxide (NO·) or nitrosothiols: AS/HNO action can be blocked by this agent, whereas the NO· effect is potentiated (36). In combination with the suggestion that NO· is the only species able to directly activate sGC (9), these data led to the conclusion that HNO-induced vasorelaxation is due to its intracellular conversion to NO· with subsequent activation of sGC. For several years, this idea has relegated HNO to a mere precursor of the presence and biological activity of NO·, de facto negating to HNO its own right to exist.

Analytic solution during an infusion test of the linear unsteady poroelastic equations in a spherically symmetric model of the brain

This work determines the spatial and temporal distribution of cerebrospinal fluid (CSF) pressure and brain displacement during an infusion test in a spherically symmetric model of the brain. The response of CSF pressure and parenchymal displacement to blood pressure pulsations is determined in the solution. We use a spherically symmetric, three-component poroelastic model of the brain, differentiating between the solid elastic matrix, the CSF and the arterial blood compartments. The governing equations are linearized with quasi-constant poroelastic parameters. The solution does reproduce the average intracranial pressure increase during the test as well as the rise in CSF pressure pulsation amplitude due to transmission of blood pressure oscillations. In addition, the CSF flux into and out of the parenchyma is shown over time.

Impact of Different Vein Catheter Sizes for Mechanical Power Injection in CT: In Vitro Evaluation with Use of a Circulation Phantom

The purpose of this study was to evaluate the influence of different peripheral vein catheter sizes on the injection pressure, flow rate, injection duration, and intravascular contrast enhancement. A flow phantom with a low-pressure venous compartment and a high-pressure arterial compartment simulating physiological circulation parameters was used. High-iodine-concentration contrast medium (370 mg iodine/ml; Ultravist 370) was administered in the venous compartment through peripheral vein catheters of different sizes (14, 16, 18, 20, 22, and 24 G) using a double-head power injector with a pressure limit of 325 psi. The flow rate was set to 5 ml/s, with a total iodine load of 36 g for all protocols. Serial CT scans at the level of the pulmonary artery and the ascending and the descending aorta replica were obtained. The true injection flow rate, injection pressure, injection duration, true contrast material volume, and pressure in the phantom during and after injection were continuously monitored. Time enhancement curves were computed and both pulmonary and aortic peak time and peak enhancement were determined. Using peripheral vein catheters with sizes of 14-20 G, flow rates of approximately 5 ml/s were obtained. During injection through a 22-G catheter the pressure limit was reached and the flow rate was decreased, with a consecutive decreased pulmonary and aortic contrast enhancement compared to the 14- to 20-G catheters. Injection through a 24-G peripheral vein catheter was not possible because of disconnection of the canula due to the high flow rate and pressure. In summary, intravenous catheters with sizes of 14-20 G are suitable for CT angiography using an injection protocol with a high flow rate and a high-iodine-concentration contrast medium.

Quantification of liver perfusion with [15O]H2O-PET and its relationship with glucose metabolism and substrate levels

Hepatic perfusion plays an important role in liver physiology and disease. This study was undertaken to (a) validate the use of Positron Emission Tomography (PET) and oxygen-15-labeled water ([(15)O]H(2)O) to quantify hepatic and portal perfusion, and (b) examine relationships between portal perfusion and liver glucose and lipid metabolism. Liver [(15)O]H(2)O-PET images were obtained in 14 pigs during fasting or hyperinsulinemia. Carotid arterial and portal venous blood were sampled for [(15)O]H(2)O activity; Doppler ultrasonography was used invasively as the reference method. A single arterial input compartment model was developed to estimate portal tracer kinetics and liver perfusion. Endogenous glucose production (EGP) and insulin-mediated whole body glucose uptake (wbGU) were determined by standard methods. Hepatic arterial and portal venous perfusions were 0.15+/-0.07 and 1.11+/-0.34 ml/min/ml of tissue, respectively. The agreement between ultrasonography and [(15)O]H(2)O-PET was good for total and portal liver perfusion, and poor for arterial perfusion. Portal perfusion was correlated with EGP (r=or+0.62, p=0.03), triglyceride (r=or+0.66, p=0.01), free fatty acid levels (r=or+0.76, p=0.003), and plasma lactate levels (r=or-0.81, p=0.0009). Estimates of liver perfusion by [(15)O]H(2)O-PET compared well with those by ultrasonography. The method allowed to predict portal tracer concentrations which is essential in human studies. Portal perfusion may affect liver nutrient handling.

Endovascular Treatment for Type A Carotid Cavernous Fistulas with Detachable Coils

Objective: Carotid cavernous fistulae (CCF) after head traumas are abnormal communications between the internal carotid artery and venous compartments of the cavernous sinus. Fistulae are uncommon but well-documented sequelae of craniofacial trauma. We report our experiences in placing detachable coils in the management of rare cases of direct CCF after head injuries. Methods: From January 2002 to December 2007, nine patients were admitted and treated for traumatic direct CCF at our hospital. The medical records and neuroimaging studies were retrospectively reviewed. Results: All 9 patients had previous head trauma histories and ocular symptoms including exophthalmos, conjunctiva injection, and chemosis. Angiography was performed to confirm the CCF and for treatment planning. According to the angiograph, three patients had pseudo-aneurysms. All of the patients were treated with detachable coils via the trans-arterial endovascular maneuver. Among them, two patients had recurrences, the first at postoperative day one and the other eleven days after the surgery. Both recurrences were retreated endovascularly. All nine patients were successfully treated anigographically by means of trans-arterial embolization and improved symptomatically within a week. Conclusion: The etiology of CCF, especially type A, is well known. Also, the advances in interventional neuroradiology and cranial base surgery are chiefly responsible for the evolution of treatment strategies for CCF. Although other techniques and approaches with other materials may be useful, embolization with detachable coiling, as used in our cases, can be a safe and effective method to occlude the fistula and to improve symptoms. (J Kor Neurotraumatol Soc 2008;4:77-83)

Changes in the resistance in brachiocephalic artery and thoracic aorta basins during depressor reactions of the circulatory system

Acute experiments on narcotized cats with depressor shifts in the circulatory system induced by acetylcholine and histamine revealed more pronounced decrease in vascular resistance in the brachiocephalic artery in comparison with the thoracic aorta basin. Cardiac output was redistributed between these vascular basins: the bloodflow increased in the brachiocephalic artery and decreased in the thoracic aorta. Hemodynamic shifts in the arterial compartment of the vascular system are presumably essential for changes in the bloodflow in venae cavae.

Model of arterial tree and peripheral control for the study of physiological and assisted circulation

Peripheral vasomotion, interstitial liquid exchange, and cardiovascular system behaviour are investigated by means of a lumped parameter model of the systemic and peripheral circulation, from the aortic valve to the venules. This modelling work aims at combining arterial tree hemodynamics description, active peripheral flow regulation, and fluid exchange. The arterial compartment is constructed with 63 RCL segments and 30 peripheral districts including myogenic control on arterioles, metabolic control on venules, and Starling filtration through capillary membrane. The arterial behaviour is characterised as to the long term stability of pressure/flow waves in the different segments. Peripheral districts show autoregulatory capabilities against pressure changes over a wide range and also self-sustained oscillations mimicking vasomotor activity. A preliminary study was carried out as to the model response to changes induced by cardiopulmonary bypass (CPB). Among the induced alterations, the system responds mainly to hemodilution, which increased peripheral fluid loss and oedema beyond the compensatory capabilities of local regulation mechanisms. This resulted in an overall increase total arterial resistance. Local transport deficits were assessed for each district according to the different metabolic demand. This study shows the requirement of a suitable description of both arteries and peripheral mechanisms in order to describe cardiovascular response non-physiological conditions, as well as assisted circulation or other pathological conditions.

EQUILIBRIUM MULTIPLICITY IN A CARDIOVASCULAR SYSTEM MODEL

The aim of this paper is to show that, for some parameters, a two-dimensional cardiovascular system model can exhibit intrinsic equilibrium multiplicity generated by a backward bifurcation, regardless of the baroreflex effect. The model considers the dynamics of arterial and venous compartments and a feedback effect in the stroke volume induced by venous pressure changes. The results of the mathematical analysis indicate that multiple non-trivial equilibrium points exist when the stroke volume function is convex around the origin. Interestingly, this equilibrium point structure would imply that under certain stroke volume functions, the baroreflex system would have to stabilize and regulate an unstable operating condition produced by certain values of the stroke volume. The paper ends with the discussion of some implications for the reliability and robustness of the baroreflex-feedback mechanism.

A model of the interaction between autoregulation and neural activation in the brain

In this paper a model is proposed that predicts the response of the cerebral vasculature to changes in arterial blood pressure, arterial CO 2 concentration and neural stimulation. Cerebral blood flow (CBF) is assumed to be controlled through changes in arterial compliance, and hence arterial resistance and volume, through three feedback mechanisms, which act in a linear additive manner, based on CBF, arterial CO 2 and neural stimulus. Together with arterial, capillary and venous compartments, a tissue compartment is included, which contributes partly to the initial rise found in the deoxyhaemoglobin response to neural activation. Dynamic simulations of the model under different conditions show that there is significant interaction between the autoregulation and activation processes, and that the level of autoregulation has a strong influence on the CBF and deoxyhaemoglobin responses to neural activation. Overshoot in the deoxyhaemoglobin response is eliminated completely in the absence of this regulation. The feedback mechanism time constants significantly affect the CBF and deoxyhaemoglobin responses. Changes in arterial blood pressure (ABP) are found to have a strong influence on the neural activation response, with the amplitude of the response decreasing significantly at high baseline ABP. Dynamic changes in ABP also have a significant and potentially confounding impact on the measured deoxyhaemoglobin response to neural activation.

(ii) Paediatric epiphyseal fractures around the knee

<h2>Summary</h2> Physeal fractures around the knee are most common in children aged 9–14. The majority of these fractures will have a good outcome if they are adequately treated initially. There is a fairly clear consensus on how these fractures should be managed. Undisplaced fractures are treated with cast immobilisation and almost universally have a good outcome. Displaced Salter Harris I and II fractures of the proximal tibia and distal femur can usually be treated with closed reduction and fixation. Intraarticular fractures often require open reduction prior to internal fixation. Displaced fractures of the tibial spine, tibial tuberosity and patella are more difficult to reduce closed and an open reduction is frequently required. Most osteochondral fractures are simply excised arthroscopically. There are well recognised complications associated with paediatric knee fractures. Early complications include popliteal artery damage, ligament damage and compartment syndrome. Late complications are usually related to damage to the physis with leg length discrepancies and angular deformity.

In Vivo Blood-Brain Barrier Transport of Oxycodone in the Rat: Indications for Active Influx and Implications for Pharmacokinetics/Pharmacodynamics

The blood-brain barrier (BBB) transport of oxycodone was studied in rats. Microdialysis probes were inserted into the striatum and vena jugularis. Ten animals were given a bolus dose followed by a 120-min constant rate infusion to study the steady-state concepts of oxycodone BBB equilibration. Another 10 animals were given a 60-min constant rate infusion to study the rate of equilibration across the BBB. Oxycodone-D3 was used as a calibrator for the microdialysis experiments. The samples were analyzed with a liquid chromatography-tandem mass spectrometry method and a population pharmacokinetic model was used to simultaneously fit all the data using NONMEM. A two-compartment model which allowed for a delay between the venous and arterial compartments best described the pharmacokinetics for oxycodone in blood and plasma, whereas a one-compartment model was sufficient to describe the pharmacokinetics in the brain. The BBB transport of oxycodone was parameterized as CL(in) and K(p,uu). CL(in) describes the clearance of oxycodone across the BBB into the brain, whereas K(p,uu) describes the extent of drug equilibration across the BBB. CL(in) across the BBB was estimated to 1910 microl/min x g brain. K(p,uu) was estimated to 3.0, meaning that the unbound concentration of oxycodone in brain was 3 times higher than in blood, which is an indication of active influx of oxycodone at the BBB. This is the first evidence of an opioid having an unbound steady-state concentration in brain that is higher than unity, which can explain potency discrepancies between oxycodone and other opioids.

A reduced model of pulsatile flow in an arterial compartment

In this article we propose a reduced model of the input–output behaviour of an arterial compartment, including the short systolic phase where wave phenomena are predominant. The objective is to provide basis for model-based signal processing methods for the estimation from non-invasive measurements and the interpretation of the characteristics of these waves. Due to phenomena such that peaking and steepening, the considered pressure pulse waves behave more like solitons generated by a Korteweg–de Vries (KdV) model than like linear waves. So we start with a quasi-1D Navier–Stokes equation taking into account radial acceleration of the wall: the radial acceleration term being supposed small, a 2scale singular perturbation technique is used to separate the fast wave propagation phenomena taking place in a boundary layer in time and space described by a KdV equation from the slow phenomena represented by a parabolic equation leading to two-elements windkessel models. Some particular solutions of the KdV equation, the 2 and 3-soliton solutions, seems to be good candidates to match the observed pressure pulse waves. Some very promising preliminary comparisons of numerical results obtained along this line with real pressure data are shown.

Endovascular treatment of a direct post-traumatic carotid-cavernous fistula with electrolytically detachable coils

Carotid-cavernous fistulae are abnormal communications between the internal carotid artery and venous compartments of the cavernous sinus. Fistulae are uncommon but well-documented sequelae of craniofacial trauma. The characteristic clinical presentation includes ocular pain, chemosis, exophthalmus and visual disturbances. We report on a 28-year-old man with a history of severe craniocerebral injury, including multiple craniofacial fractures resulting from a fall from a height of approximately 6 meters, who was surgically treated one year ago. Two months before presentation, the patient began to exhibit progressive chemosis, proptosis, eyelid swelling, diplopia and exophthalmus. Computerized tomography and computerized tomographic angiography revealed findings consistent with a carotid-cavernous fistula of the right side of the cavernous sinus with dilatation of the right ocular vein. Digital subtractional angiography of the right internal carotid artery revealed a fistula between the cavernous part of the artery and the right cavernous sinus. There was only minimal blood flow in the supraclinoid part of the internal carotid artery because of the high pressure within the fistula. Our decision was to try to occlude the fistula by means of endovascular embolization. The origin of the fistula in the internal carotid artery was successfully obliterated with seven electolytically detachable coils. Control digital subtractional angiography at the end of the procedure demonstrated minimal residual flow through the fistula. Two months after the treatment, angiographic control revealed complete obliteration of the fistula. Clinical examination showed total resolution of signs and symptoms of a carotid-cavernous fistula. Endovascular transarterial embolization of carotid cavernous fistulae is a widely accepted, safe and successful treatment option. In the case that we describe we occluded the fistula and right cavernous sinus with electrolytically detachable coils that we could place into the sinus. Other endovascular treatment options include the use of detachable balloons, stent placement, transvenous embolization or surgical ligation of the fistula.

Application of selective saturation to image the dynamics of arterial blood flow during brain activation using magnetic resonance imaging

A saturation-based approach is proposed to image the arterial blood flow signal with temporal resolution of 1 to 2 s and in-plane spatial resolution of a few millimeters. Using a saturation approach to suppress the undesired background stationary signal allows the blood water that enters the slice to be imaged at some specified later time. Since the blood protons that are being imaged are not restricted to the intravascular space, this technique is also sensitive to tissue perfusion signal contributions. The signal uptake characteristics of the saturation method proposed were used to study the different signal contributions as a function of the acquisition parameters. A typical perfusion acquisition (FAIR) was also used for comparison. The proposed method was demonstrated in a functional motor activation experiment and the observed signal changes were smaller than those obtained using the FAIR acquisition. The dynamics of the saturation method and FAIR temporal signal changes were investigated and time constants between 2 and 44 s were estimated. The tissue signal contribution to the saturation method's signal was small over the range of acquisition parameters that sensitized it to the arterial compartment.

A three-compartment model of the hemodynamic response and oxygen delivery to brain

We describe a mathematical model linking changes in cerebral blood flow, blood volume and the blood oxygenation state in response to stimulation. The model has three compartments to take into account the fact that the cerebral blood flow and volume as measured concurrently using laser Doppler flowmetry and optical imaging spectroscopy have contributions from the arterial, capillary as well as the venous compartments of the vasculature. It is an extension to previous one-compartment hemodynamic models which assume that the measured blood volume changes are from the venous compartment only. An important assumption of the model is that the tissue oxygen concentration is a time varying state variable of the system and is driven by the changes in metabolic demand resulting from changes in neural activity. The model takes into account the pre-capillary oxygen diffusion by flexibly allowing the saturation of the arterial compartment to be less than unity. Simulations are used to explore the sensitivity of the model and to optimise the parameters for experimental data. We conclude that the three-compartment model was better than the one-compartment model at capturing the hemodynamics of the response to changes in neural activation following stimulation.

Failure of pentobarbital to reduce cerebral oxygen consumption in rats after non-haemorrhagic closed head injury

Different studies have advocated the use of barbiturates 4,1 in neurotrauma while others have presented contradictive data 7,9. The recent meta-analysis published by 6 shows a dramatic lack of effect with 68% of unresponsive patients and a 25% chance of inducing a blood pressure drop. Via a currently not completely understood mechanism, barbiturates depress cerebral oxygen consumption and cause a secondary decrease in cerebral blood flow. This vasoconstrictive action results in a decreased cerebral blood volume in the arterial compartment which consequently decreases ICP 2,8,3,5. Since it is unknown whether barbiturates suppress cerebral oxygen metabolism early after cerebral trauma, we evaluated the influence of pentobarbital on cerebral oxygen handling of normal rats and rats subjected to non-haemorrhagic closed head injury (CHI). Our multi-wavelength near infrared spectroscopy (NIRS)-system, developed at the University College London, can be used for the assessment of concentrations of oxyhaemoglobin, deoxyhaemoglobin and oxidised cytochrome oxidase in the brain in toto. Oxygen delivery was assessed by measuring cerebral perfusion and oxygen extraction, enabling the calculation of cerebral metabolic rate of oxygen (CMRO2). Mitochondrial function was assessed by studying changes in the oxidised cytochrome oxidase concentration. CHI causes changes in both systemic and cerebral haemodynamics. Cerebral blood flow was reduced to 66% of the control value but the cerebral metabolic rate of oxygen remained unchanged. Pentobarbital administration induced a significant lowering of the cerebral oxygen consumption in normal rats associated with a secondary decrease in cerebral perfusion. In rats subjected to CHI, pentobarbital was unable to lower the cerebral metabolic demand and did not cause a decrease in perfusion. Pentobarbital was unable to significantly modulate mitochondrial function, as assessed by the change in oxydised cytochrome oxidase signal, in traumatised rats whereas it exerted this effect in all control animals. The oxidised cytochrome oxidase signal, although unaltered when considering the whole group, clearly shows that we have 4 irresponsive animals and 2 responsive animals. Only 2 of 6 animals show the hyperoxidation of cytochrome oxidase after administration of the pentobarbital, a feature found in every pentobarbital treated control. This proportion, although a crude estimate, is in accordance with the findings mentioned above. We therefore conclude that pentobarbital is unable to perform its beneficial effects on the cerebral metabolic in 2 out of 6 rats subjected to CHI.

Microsurgical anatomy of the arterial compartment of the cavernous sinus: analysis of 24 cavernous sinus

The cavernous sinus is a complex compartment situated in both sides of the sella turcica, being its microsurgical anatomy knowledge of fundamental importance when consider to approach surgically. We studied the arterial microanatomy of 24 cavernous sinus at the microsurgical laboratory, considering that in all the internal carotid artery were filled with colored latex. The meningohypophyseal trunk was present in 18 cases (75%) with its origin in intracavernous portion of the internal carotid artery. In relation to the 18 presented cases with meningohypophyseal trunk, 14 (77.7%) had a trifurcate and 4 (23.3%) had a bifurcate pattern. The tentorial artery was present in all. Its origin was observed, arising from the meningohypophyseal trunk in 17 (70.8%) and as an isolated artery in some extension of the intracavernous portion in 7 (29.1%). An accessory tentorial artery was found in one specimen. The dorsal meningeal artery was present in 22 cases (91.6%). Its origin was in the meningohypophyseal trunk in 17 cases (77.2%), arising from internal carotid artery in 4 cases (18.1%) and from inferior hypophyseal artery in one case (4.1%).The inferior hypophyseal artery was present in all cases, having its origin at the meningohypophyseal trunk in 16 cases (66.6%). In the remaining 8 cases (33.3%) the artery was found arising alone from the intracavernous portion also. The artery of the inferior cavernous sinus or inferolateral trunk was present in all cases and had its origin from internal carotid artery in its intracavernous segment. The McConnell's artery was not found in any cavernous sinus.

Glutamine kinetics and protein turnover in end-stage renal disease.

Alanine and glutamine constitute the two most important nitrogen carriers released from the muscle. We studied the intracellular amino acid transport kinetics and protein turnover in nine end-stage renal disease (ESRD) patients and eight controls by use of stable isotopes of phenylalanine, alanine, and glutamine. The amino acid transport kinetics and protein turnover were calculated with a three-pool model from the amino acid concentrations and enrichment in the artery, vein, and muscle compartments. Muscle protein breakdown was more than synthesis (nmol.min(-1).100 ml leg(-1)) during hemodialysis (HD) (169.8 +/- 20.0 vs. 125.9 +/- 21.8, P < 0.05) and in controls (126.9 +/- 6.9 vs. 98.4 +/- 7.5, P < 0.05), but synthesis and catabolism were comparable pre-HD (100.7 +/- 15.7 vs. 103.4 +/- 14.8). Whole body protein catabolism decreased by 15% during HD. The intracellular appearance of alanine (399.0 +/- 47.1 vs. 243.0 +/- 34.689) and glutamine (369.7 +/- 40.6 vs. 235.6 +/- 27.5) from muscle protein breakdown increased during dialysis (nmol.min(-1).100 ml leg(-1), P < 0.01). However, the de novo synthesis of alanine (3,468.9 +/- 572.2 vs. 3,140.5 +/- 467.7) and glutamine (1,751.4 +/- 82.6 vs. 1,782.2 +/- 86.4) did not change significantly intradialysis (nmol.min(-1).100 ml leg(-1)). Branched-chain amino acid catabolism (191.8 +/- 63.4 vs. -59.1 +/- 42.9) and nonprotein glutamate disposal (347.0 +/- 46.3 vs. 222.3 +/- 43.6) increased intradialysis compared with pre-HD (nmol.min(-1).100 ml leg(-1), P < 0.01). The mRNA levels of glutamine synthase (1.45 +/- 0.14 vs. 0.33 +/- 0.08, P < 0.001) and branched-chain keto acid dehydrogenase-E2 (3.86 +/- 0.48 vs. 2.14 +/- 0.27, P < 0.05) in the muscle increased during HD. Thus intracellular concentrations of alanine and glutamine are maintained during HD by augmented release of the amino acids from muscle protein catabolism. Although muscle protein breakdown increased intradialysis, the whole body protein catabolism decreased, suggesting central utilization of amino acids released from skeletal muscle.