Non-identifiability of parameters for a class of shear-thinning rheological models, with implications for haematological fluid dynamics.

Choosing a suitable model and determining its associated parameters from fitting to experimental data is fundamental for many problems in biomechanics. Models of shear-thinning complex fluids, dating from the work of Bird, Carreau, Cross and Yasuda, have been applied in highly-cited computational studies of hemodynamics for several decades. In this manuscript we revisit these models, first to highlight a degree of uncertainty in the naming conventions in the literature, but more importantly to address the problem of inferring model parameters by fitting to rheology experiments. By refitting published data, and also by simulation, we find large, flat regions in likelihood surfaces that yield families of parameter sets which fit the data equally well. Despite having almost indistinguishable fits to experimental data these varying parameter sets can predict very different flow profiles, and as such these parameters cannot be used to draw conclusions about physical properties of the fluids, such as zero-shear viscosity or relaxation time of the fluid, or indeed flow behaviours. We verify that these features are not a consequence of the experimental data sets through simulations; by sampling points from the rheological models and adding a small amount of noise we create a synthetic data set which reveals that the problem of parameter identifiability is intrinsic to these models.

Influence of microvascular sutures on shear strain rate in realistic pulsatile flow.

Arterial thrombus formation is directly related to the mechanical shear experienced by platelets within flow. High shear strain rates (SSRs) and large shear gradients cause platelet activation, aggregation and production of thrombus. This study, for the first time, investigates the influence of pulsatile flow on local haemodynamics within sutured microarterial anastomoses. We measured physiological arterial waveform velocities experimentally using Doppler ultrasound velocimetry, and a representative example was applied to a realistic sutured microarterial geometry. Computational geometries were created using measurements taken from sutured chicken femoral arteries. Arterial SSRs were predicted using computational fluid dynamics (CFD) software, to indicate the potential for platelet activation, deposition and thrombus formation. Predictions of steady and sinusoidal inputs were compared to analyse whether the addition of physiological pulse characteristics affects local intravascular flow characteristics. Simulations were designed to evaluate flow in pristine and hand-sutured microarterial anastomoses, each with a steady-state and sinusoidal pulse component. The presence of sutures increased SSRmax in the anastomotic region by factors of 2.1 and 2.3 in steady-state and pulsatile flows respectively, when compared to a pristine vessel. SSR values seen in these simulations are analogous to the presence of moderate arterial stenosis. Steady-state simulations, driven by a constant inflow velocity equal to the peak systolic velocity (PSV) of the measured pulsatile flow, underestimated SSRs by ∼ 9% in pristine, and ∼ 19% in sutured vessels compared with a realistic pulse. Sinusoidal flows, with equivalent frequency and amplitude to a measured arterial waveform, represent a slight improvement on steady-state simulations, but still SSRs are underestimated by 1-2%. We recommend using a measured arterial waveform, of the form presented here, for simulating pulsatile flows in vessels of this nature. Under realistic pulsatile flow, shear gradients across microvascular sutures are high, of the order ∼ 7.9 × 106 m-1 s-1, which may also be associated with activation of platelets and formation of aggregates.

Microarterial anastomoses: A parameterised computational study examining the effect of suture position on intravascular blood flow.

This study investigates the extent to which individual aspects of suture placement influence local haemodynamics within microarterial anastomoses. An attempt to physically quantify flow characteristics of blood past microvascular sutures is made using computational fluid dynamics (CFD) software. Particular focus has been placed on increased shear strain rate (SSR), a known precipitant of intravascular platelet activation and thrombosis. Measurements were taken from micrographs of sutured anastomoses in chicken femoral vessels, with each assessed for bite width, suture angle and suture spacing. Computational geometries were then created to represent the anastomosis. Each suture characteristic was parameterised to allow independent or simultaneous adjustment. Flow rates were obtained from anonymised Doppler ultrasound scans of analogous vessels during preoperative assessment for autologous breast reconstruction. Vessel simulations were performed in 2.5mm ducts with blood as the working fluid. Vessel walls were non-compliant and a continuous Newtonian flow was applied, in accordance with current literature. Suture bite angle and spacing had significant effects on local haemodynamics, causing notably higher local SSRs, when simulated at extremes of surgical practice. A combined simulation, encompassing subtle changes of each suture parameter simultaneously i.e. representing optimum technique, created a more favourable SSR profile. As such, haemodynamic changes associated with optimum suture placement are unlikely to influence thrombus formation significantly. These findings support adherence to the basic principles of good microsurgical practice.

The effects of dietary cabbage on xenobiotic-metabolizing enzymes and the binding of aflatoxin B1 to hepatic DNA in rats.

The effect of dietary cabbage (Brassica oleracea) on the binding of aflatoxin B1 (AFB1) to hepatic DNA and on the activities of liver and intestinal microsomal and cytosolic enzymes was studied in weanling male Fischer 344 rats. Freeze-dried cabbage was fed to rats at a level of 25% in the diet for 21 days, while others received a basal diet. In the cabbage-fed group there was an 87% (P less than 0.01) reduction in the binding of AFB1 to hepatic DNA 2 hr after the ip injection of [3H]AFB1 (3 micrograms/kg). There was also a 41% (P less than 0.05) increase in liver weight expressed relative to body weight. Hepatic and intestinal glutathione S-transferase activities were significantly increased (2.1- and 2.3-fold, respectively) over those in rats fed the basal diet. Hepatic and intestinal microsomal epoxide hydrolase activities were significantly increased (2.6- and 1.4-fold, respectively) over the basal group. Intestinal aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECD) activities were significantly increased (2.3- and 2.5-fold, respectively), over the basal group but dietary cabbage had no significant effect on hepatic AHH or ECD activities.