A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid.

AIMS/HYPOTHESIS: We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM. METHODS: We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup (n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM. RESULTS: pGDM was associated with increased IHCL (p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index (p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD-, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD-, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance (p = 0.05), increased rate of VLDL apoB synthesis. CONCLUSIONS/INTERPRETATION: pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.

Non-invasive assessment of ventriculo-arterial coupling using aortic wave intensity analysis combining central blood pressure and phase-contrast cardiovascular magnetic resonance.

BACKGROUND: Wave intensity analysis (WIA) in the aorta offers important clinical and mechanistic insight into ventriculo-arterial coupling, but is difficult to measure non-invasively. We performed WIA by combining standard cardiovascular magnetic resonance (CMR) flow-velocity and non-invasive central blood pressure (cBP) waveforms. METHODS AND RESULTS: Two hundred and six healthy volunteers (age range 21-73 years, 47% male) underwent sequential phase contrast CMR (Siemens Aera 1.5 T, 1.97 × 1.77 mm2, 9.2 ms temporal resolution) and supra-systolic oscillometric cBP measurement (200 Hz). Velocity (U) and central pressure (P) waveforms were aligned using the waveform foot, and local wave speed was calculated both from the PU-loop (c) and the sum of squares method (cSS). These were compared with CMR transit time derived aortic arch pulse wave velocity (PWVtt). Associations were examined using multivariable regression. The peak intensity of the initial compression wave, backward compression wave, and forward decompression wave were 69.5 ± 28, -6.6 ± 4.2, and 6.2 ± 2.5 × 104 W/m2/cycle2, respectively; reflection index was 0.10 ± 0.06. PWVtt correlated with c or cSS (r = 0.60 and 0.68, respectively, P < 0.01 for both). Increasing age decade and female sex were independently associated with decreased forward compression wave (-8.6 and -20.7 W/m2/cycle2, respectively, P < 0.01) and greater wave reflection index (0.02 and 0.03, respectively, P < 0.001). CONCLUSION: This novel non-invasive technique permits straightforward measurement of wave intensity at scale. Local wave speed showed good agreement with PWVtt, and correlation was stronger using the cSS than the PU-loop. Ageing and female sex were associated with poorer ventriculo-arterial coupling in healthy individuals.

Separation of the reservoir and wave pressure and velocity from measurements at an arbitrary location in arteries.

Previous studies based on measurements made in the ascending aorta have demonstrated that it can be useful to separate the arterial pressure P into a reservoir pressure P* generated by the windkessel effect and a wave pressure p generated by the arterial waves: P = P*+p. The separation in these studies was relatively straightforward since the flow into the arterial system was measured. In this study the idea is extended to measurements of pressure and velocity at sites distal to the aortic root where flow into the arterial system is not known. P* is calculated from P at an arbitrary location in a large artery by fitting the pressure fall-off in diastole to an exponential function and assuming that p is proportional to the flow into the arterial system. A local reservoir velocity U* that is proportional to P* is also defined. The separation algorithm is applied to in vivo human and canine data and to numerical data generated using a one-dimensional model of pulse wave propagation in the larger conduit arteries. The results show that the proposed algorithm is reasonably robust, allowing for the separation of the measured pressure and velocity into reservoir and wave pressures and velocities. Application to data measured simultaneously in the aorta of the dog shows that the reservoir pressure is fairly uniform along the aorta, a test of self-consistency of the assumptions leading to the algorithm. Application to data generated with a validated numerical model indicates that the parameters derived by fitting the pressure data are close to the known values which were used to generate the numerical data. Finally, application to data measured in the human thoracic aorta indicates the potential usefulness of the separation.

Wave intensity analysis in the internal carotid artery of hypertensive subjects using phase-contrast MR angiography and preliminary assessment of the effect of vessel morphology on wave dynamics.

OBJECTIVE: Hypertension is associated with reduced cerebral blood flow, but it is not known how this impacts on wave dynamics or potentially relates to arterial morphology. Given the location of the internal carotid artery (ICA) and risks associated with invasive measurements, wave dynamics in this artery have not been extensively assessed in vivo. This study explores the feasibility of studying wave dynamics in the internal carotid artery non-invasively. APPROACH: Normotensive, uncontrolled and controlled hypertensive participants were recruited (daytime ambulatory blood pressure <135/85 mmHg and >135/85 mmHg, respectively; n = 38). Wave intensity, reservoir pressure and statistical shape analyses were performed on the right ICA and ascending aorta high-resolution phase-contrast magnetic resonance angiography data. MAIN RESULTS: Wave speed in the aorta was significantly lower in normotensive compared to hypertensive participants (6.7 ± 1.8 versus 11.2 ± 6.2 m s-1 for uncontrolled and 11.8 ± 4.6 m s-1 for controlled hypertensives, p = 0.02), whilst there were no differences in wave speed in the ICA. There were no significant differences between the groups for the wave intensity or reservoir pressure. Interestingly, a significant association between the anatomy of the ICA and wave energy (FCW and size, r 2 = 0.12, p = 0.04) was found. SIGNIFICANCE: This study shows it is feasible to study wave dynamics in the ICA non-invasively. Whilst changes in aortic wave speed confirmed an expected increase in arterial stiffness, this was not observed in the ICA. This might suggest a protective mechanism in the cerebral circulation, in conjunction with the effect of vessel tortuosity. Furthermore, it was observed that ICA shape correlated with wave energy but not wave speed.

Modelling the circle of Willis to assess the effects of anatomical variations and occlusions on cerebral flows.

Blood flow in the circle of Willis (CoW) is modelled using the 1-D equations of pressure and flow wave propagation in compliant vessels. The model starts at the left ventricle and includes the largest arteries that supply the CoW. Based on published physiological data, it is able to capture the main features of pulse wave propagation along the aorta, at the brachiocephalic bifurcation and throughout the cerebral arteries. The collateral ability of the complete CoW and its most frequent anatomical variations is studied in normal conditions and after occlusion of a carotid or vertebral artery (VA). Our results suggest that the system does not require collateral pathways through the communicating arteries to adequately perfuse the brain of normal subjects. The communicating arteries become important in cases of missing or occluded vessels, the anterior communicating artery (ACoA) being a more critical collateral pathway than the posterior communicating arteries (PCoAs) if an internal carotid artery (ICA) is occluded. Occlusions of the VAs proved to be far less critical than occlusions of the ICAs. The worst scenario in terms of reduction in the mean cerebral outflows is a CoW without the first segment of an anterior cerebral artery combined with an occlusion of the contralateral ICA. Furthermore, in patients without any severe occlusion of a carotid or VA, the direction of flow measured at the communicating arteries corresponds to the side of the CoW with an absent or occluded artery. Finally, we study the effect of partial occlusions of the communicating arteries on the cerebral flows, which again confirms that the ACoA is a more important collateral pathway than the PCoAs if an ICA is occluded.

Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop.

In a previous paper we demonstrated that the linear portion of the pressure-velocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r (2) = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously.

Arterial waveform parameters in a large, population-based sample of adults: relationships with ethnicity and lifestyle factors.

This corrects the article DOI: 10.1038/jhh.2016.78.

Arterial waveform parameters in a large, population-based sample of adults: relationships with ethnicity and lifestyle factors.

Little is known about how aortic waveform parameters vary with ethnicity and lifestyle factors. We investigated these issues in a large, population-based sample. We carried out a cross-sectional analysis of 4798 men and women, aged 50-84 years from Auckland, New Zealand. Participants were 3961 European, 321 Pacific, 266 Maori and 250 South Asian people. We assessed modifiable lifestyle factors via questionnaires, and measured body mass index (BMI) and brachial blood pressure (BP). Suprasystolic oscillometry was used to derive aortic pressure, from which several haemodynamic parameters were calculated. Heavy alcohol consumption and BMI were positively related to most waveform parameters. Current smokers had higher levels of aortic augmentation index than non-smokers (difference=3.7%, P<0.0001). Aortic waveform parameters, controlling for demographics, antihypertensives, diabetes and cardiovascular disease (CVD), were higher in non-Europeans than in Europeans. Further adjustment for brachial BP or lifestyle factors (particularly BMI) reduced many differences but several remained. Despite even further adjustment for mean arterial pressure, pulse rate, height and total:high-density lipoprotein cholesterol, compared with Europeans, South Asians had higher levels of all measured aortic waveform parameters (for example, for backward pressure amplitude: ß=1.5 mm Hg; P<0.0001), whereas Pacific people had 9% higher loge (excess pressure integral) (P<0.0001). In conclusion, aortic waveform parameters varied with ethnicity in line with the greater prevalence of CVD among non-white populations. Generally, this was true even after accounting for brachial BP, suggesting that waveform parameters may have increased usefulness in capturing ethnic variations in cardiovascular risk. Heavy alcohol consumption, smoking and especially BMI may partially contribute to elevated levels of these parameters.

Can the modified Allen's test always detect sufficient collateral flow in the hand? A computational study.

Blood flow in the largest arteries of the arm up to the digital arteries is numerically modelled using the one-dimensional equations of pressure and flow wave propagation in compliant vessels. The model can be applied to different anatomies of arterial networks and can simulate compression of arteries, these allowing us to simulate the modified Allen's test (MAT) and to assess its suitability for the detection of sufficient collateral flow in the hand if radial blood supply is interrupted. The test measures blood flow in the superficial palmar arch before and during compression of the radial artery. The absence of reversal flow in the palmar arch with the compression indicates insufficient collateral flow and is referred to as a positive MAT. This study shows that small calibres of the superficial palmar arch and insufficient compression of the radial artery can lead to false-positive results. Measurement of the drop in digital systolic pressures with compression of the radial artery has proved to be a more sensitive test to predict the presence of sufficient ulnar collateral flow in networks with small calibres of the superficial palmar arch. However, this study also shows that digital pressure measurements can fail in detecting enough collateral flow if the radial artery is insufficiently compressed.

Reversible and irreversible interactions between elastin and plasma lipoproteins.

The interactions between radiolabeled, human plasma lipoproteins and elastin derived from bovine ligamentum nuchae were investigated using a washout technique. The interaction was characterised by Ki, a coefficient of irreversible binding, and Kr, the reversible partition coefficient. For both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) the Ki values decreased as total lipoprotein concentration increased, suggesting that the binding is saturable, and were similar in magnitude to those measured by other workers using elastin derived from the human aorta. For both LDL and HDL the Kr values were independent of lipoprotein concentration in the range 0.1 microgram/ml-1.5 micrograms/ml. At a total protein concentration of 1.5 mg/ml in the incubation medium, the reversible interactions were comparable in magnitude to the irreversible.

Wave intensity in the ascending aorta: effects of arterial occlusion.

We examine the effects of arterial occlusion on the pressure, velocity and the reflected waves in the ascending aorta using wave intensity analysis. In 11 anaesthetised, open-chested dogs, snares were used to produce total arterial occlusion at 4 sites: the upper descending aorta at the level of the aortic valve (thoracic); the lower thoracic aorta at the level of the diaphragm (diaphragm); the abdominal aorta between the renal arteries (abdominal) and the left iliac artery, 2 cm downstream from the aorta iliac bifurcation (iliac). Pressure and flow in the ascending aorta were measured, and data were collected before and during the occlusion. During thoracic and diaphragm occlusions a significant increase in mean aortic pressure (46% and 23%) and in wave speed (25% and 10%) was observed, while mean flow rate decreased significantly (23% and 17%). Also, the reflected compression wave arrived significantly earlier (45% and 15%) and its peak intensity was significantly greater (257% and 125%), all compared with control. Aortic occlusion distal to the renal arteries, however, caused an indiscernible change in the pressure and velocity waveforms, and in the intensities and timing of the waves in the forward and backward directions. The measured pressure and velocity waveforms are the result of the interaction between the heart and the arterial system. The separated pressure, velocity and wave intensity are required to provide information about arterial hemodynamic such as the timing and magnitude of the forward and backward waves. The net wave intensity is simpler to calculate but provides information only about the predominant direction of the waves and can be misleading when forward and backward waves of comparable magnitudes are present simultaneously.

Influence of heart rate and vasoactive drugs on blood flow patterns at the canine ilio-femoral bifurcation.

OBJECTIVE: The aim was to study the effects of altered heart rate and vasoactive drugs on the blood velocity patterns in the region of an arterial bifurcation. METHODS: Blood velocity profiles were measured in an exposed iliofemoral bifurcation of paced dogs using a pulsed Doppler ultrasound velocimeter with high temporal and spatial resolution. RESULTS: Decrease of the heart rate from 120 beats.min-1 (2 Hz) to 60 beats.min-1 (1 Hz) increased the peak forward velocity (30%), the peak reverse velocity (20%), and the duration of reverse flow (25%). Each drug caused qualitatively similar changes in velocity patterns at both heart rates. The systemic administration of angiotensin II reduced peak forward velocity (-26% at 2 Hz and -33% at 1 Hz) and forward flow duration (-15% at 1 Hz), the peak reverse velocity (-30% at 1 Hz), and reverse flow duration (-20% at 2 Hz and -28% at 1 Hz). Glyceryl trinitrate also reduced the peak forward velocity (-19% at both 2 and 1 Hz) but prolonged forward flow duration (28% at 2 Hz and 17% at 1 Hz) and that of reverse flow (45% at 2 Hz and 24% at 1 Hz), and also decreased the degree of oscillation (-16% at 2 Hz). Barnidipine hydrochloride (a calcium channel antagonist) also increased the duration of forward flow (48% at 1 Hz) and of reverse flow (31% at 2 Hz) but reduced the peak reverse velocity (-29% at 1 Hz) and flow oscillation (-22% at 2 Hz and 20% at 1 Hz). CONCLUSIONS: These dramatic changes in the pattern of blood flow, including alterations in the amplitudes and durations of the different phases of the flow cycle, are expected to have important consequences on the shear dependent responses of endothelial cells in the region of the bifurcation.

Net albumin transport across the wall of the rabbit common carotid artery perfused in situ.

We have studied the transport of radioactively labelled albumin in the rabbit common carotid artery perfused in situ at 100 cm H2O luminal pressure in the anaesthetized living animal, assessing the distribution of concentration across the wall by means of sequential frozen sectioning. We have compared the findings with those of experiments in which we have attempted to saturate the wall with label. Our findings support the belief that there is a net transport of macromolecules across the arterial wall. They show in addition that the wall is inhomogeneous. The distribution volume for label is greater in the adventitia than the media, which appears to offer a larger resistance. The transport process is seemingly dominantly diffusional.

Glucose production by the human placenta in vivo.

The human placenta transports glucose by facilitated diffusion down a concentration gradient from mother to fetus. It has previously been considered incapable of glucose synthesis. However, recent work has demonstrated the presence in placental tissue of glucose-6-phosphatase, which is required for the final step in the synthesis of glucose. Following continuous intravenous infusion into the maternal circulation of the stable isotope, 6,6-(2)H(2)glucose, during elective caesarean section, we have observed isotope dilution in the umbilical vein, without further dilution in the umbilical artery. Using a mathematical model containing maternal, placental and fetal compartments, the data were compatible with the release of glucose by the placenta. We conclude that the human placenta at term can produce glucose.

Abnormal carotid arterial wall dynamics in symptom-free hypopituitary adults.

OBJECTIVE: Although vascular mortality is increased in hypopituitary adults on routine replacement, there are limited data on the atherosclerotic process during life in these patients. Measurement of arterial stiffness may provide an index of early vascular changes that predispose to the development of major vascular accidents. DESIGN: Thirty-four hypopituitary adults on conventional replacement therapy and 39 age- and sex-matched controls were studied. They had no history or clinical evidence of macrovascular disease. The common carotid artery distensibility coefficient (DC), compliance coefficient (CC) and arterial stiffness index (beta index) were calculated from high-resolution ultrasonic imaging of the two common carotid arteries and from the brachial blood pressure. RESULTS: There was no difference between patients and controls in carotid diastolic diameter (mean +/- S.E.M) (5.55 +/- 0.16 vs 5.45 +/- 0.08 mm) and pulse pressure (6.66 +/- 0.30 vs 6.58 +/- 0.24 kPa). The increase in diameter during systole was significantly lower in the hypopituitary patients (0.39 +/- 0.02 vs 0.50 +/- 0.03 mm, P < 0.001). The DC was significantly lower in patients than in controls (24.2 +/- 2.29 vs 30.1 +/- 2.01 10(-3) kPa-1, P < 0.05). The carotid CC was also significantly lower in patients than in controls (5.7 +/- 0.49 vs 7.0 +/- 0.45 10(-7) m2 kPa-1, P < 0.05). The beta index was higher in the patient group (8.4 +/- 1.3 vs 5.9 +/- 0.37, P < 0.05). When men and women were considered separately, the differences between patients and controls were statistically significant in women but not in men and were more marked in the older women subgroup. CONCLUSIONS: Asymptomatic hypopituitary adults (especially women) on conventional replacement therapy have increased stiffness of the common carotid arteries. These findings provide additional evidence for a process leading to premature atherosclerosis in this group of patients.

Left ventricular wave speed.

Left ventricular (LV) wave speed (LVWS) was studied experimentally and confirmed in theory. Combining the definition of elastance (E) with the equations for the conservation of mass and momentum shows that LVWS is proportional to the square root of ELA, where L is long-axis length and A is the cross-sectional area, and the density of the blood. (We defined ELA = gamma, where gamma is compressibility.) We studied nine open chest, anesthetized dogs, three of which were studied during caval constriction when LV end-diastolic pressure was < or =0 mmHg. The hearts were paced at approximately 90 beats/min, and LV cross-sectional area was measured by using two pairs of ultrasonic crystals; E was calculated from the LV pressure-area loop. A pulse generator was connected to the LV apex, and LVWS was measured by using two pressure transducers: one near the apex and the other near the base. Their distance was measured roentgenographically and compared with the diameter of a reference ball. LVWS ranged from approximately 1 m/s during diastole to approximately 10 m/s during systole. The slope of the log c (where c is wave speed) vs. log gamma was 0.546, which is in agreement with theory (0.5). When gamma < or = 0, LVWS was approximately 1.5 m/s.

Wave-intensity analysis: a new approach to coronary hemodynamics.

In 10 anesthetized dogs, we measured high-fidelity left circumflex coronary (P(LCx)), aortic (P(Ao)), and left ventricular (P(LV)) pressures and left circumflex velocity (U(LCx); Doppler) and used wave-intensity analysis (WIA) to identify the determinants of P(LCx) and U(LCx). Dogs were paced from the right atrium (control 1) or right ventricle by use of single (control 2) and then paired pacing to evaluate the effects of left ventricular contraction on P(LCx) and U(LCx). During left ventricular isovolumic contraction, P(LCx) exceeded P(Ao), paired pacing increasing the difference. Paired pacing increased DeltaP(X) (the P(LCx)-P(Ao) difference at the P(Ao)-P(LV) crossover) and average dP(LCx)/dt (P < 0.0001 for both). During this time, WIA identified a backward-going compression wave (BCW) that increased P(LCx) and decreased U(LCx); the BCW increased during paired pacing (P < 0.0001). After the aortic valve opened, the increase in P(Ao) caused a forward-going compression wave that, when it exceeded the BCW, caused U(LCx) to increase, despite P(LV) and (presumably) elastance continuing to increase. Thus WIA identifies the contributions of upstream (aortic) and downstream (microcirculatory) effects on P(LCx) and U(LCx).

Measurement of the charge properties of articular cartilage by an electrokinetic method.

The charge structure of the surface of articular cartilage determines its interactions with the macromolecules and cells of synovial fluid. It may thereby be important to the physiological function and pathological degeneration of the tissue. To determine whether the electrokinetic properties of the surface differ from those of the bulk tissue, we measured the streaming potential generated by the flow of electrolyte over the surface of a cartilage plug mounted in a chamber built for that purpose. We then calculated the effective surface charge density. In nonfibrillated cartilage from the human femoral head, the surface charge density, 0.037+/-0.004 Cm(-2) (mean+/-SD), was approximately half that measured at the surface of slices cut from the middle and deep zones. In addition, the surface charge density fell relatively little at low pH; this is consistent with a higher proportion of strongly acidic groups. The variations in surface charge density were found to be similar to those in total fixed charge density in the slices by the tracer cation method. Therefore, no evidence exists that the actual surface differs in composition from the immediately underlying matrix. The addition of synovial fluid (0.0025 ml/ml) to the superfusing solution reduced the surface charge density by 25+/-9% (n=5), and we attributed this to the binding of synovial-fluid macromolecules.

The theoretical distributions and diffusivities of small ions in chondroitin sulphate and hyaluronate.

The electrostatic interactions between polyionic glycosaminoglycans and small mobile ions are investigated using the Poisson-Boltzmann equation and a rod-in-cell model of the polyelectrolyte. Calculations are made for the range of polyelectrolyte concentrations and buffer compositions for which measurements of ion distributions and diffusivities are reported in a companion paper (Maroudas et al., Biophys. Chem. 32 (1988) 257). We conclude that the distribution of mobile ions is largely determined by the 'far-field' potential and is adequately described by the Poisson-Boltzmann theory and also by more approximate theories such as ideal Donnan or 'condensation' theory. The measured variations in cation diffusivities, particularly the increase in diffusivity with increasing matrix concentration at low ionic strengths, are predicted qualitatively using an approximate diffusion theory together with the calculated potential fields. However, the same theory applied to anion diffusion gives qualitatively wrong results.

The distributions and diffusivities of small ions in chondroitin sulphate, hyaluronate and some proteoglycan solutions.

The distributions and diffusivities of Na+, Ca2+ and Cl- in chondroitin sulphate (CS), hyaluronate (HA) and proteoglycan solutions were measured using equilibrium dialysis and a capillary tube method. Measurements were made for a range of glycosaminoglycan (GAG) concentrations up to those normally found in dense connective tissue (10% CS, 2.5% HA), ionic strengths up to normal physiological concentrations (0.15 M) and for different combinations of monovalent and divalent cations. The partition coefficients, Ki, of the positive ions increased with increasing matrix concentration and with decreasing ionic strength but with one exception the selectivity coefficient KCaNa = square root of KCa/KNa was close to unity, indicating nearly ideal Donnan distributions. The ionic diffusivities decreased very much like those of small neutral solutes with increasing matrix concentration and with one exception were relatively independent of ionic strength, The exception in both cases was low matrix concentrations and low ionic strengths for which the diffusivity of Ca2+ was an order of magnitude lower and selectivity coefficients were approximately 2. We conclude that at physiological ionic strengths and GAG concentrations the distributions of small ions are determined by simple electrostatic interactions, without binding or condensation, and the diffusivities are not affected by the electrostatic field.