Rheological and clot microstructure evaluation of heparin neutralization by UHRA and protamine.

The current study reports the use of small amplitude oscillatory rheometry to investigate the dynamics of blood clot formation upon heparin neutralization under three different oscillatory frequencies, two of which were mimicking physiological heart rates. We utilized two different heparin antidotes, namely protamine and newly developed universal heparin reversal agent (UHRA-7), at different concentrations to determine the quality of blood clot formed upon heparin neutralization by analyzing several key rheological parameters. Scanning electron microscopy (SEM) was used to determine the morphology and microstructure of the blood clot after heparin neutralization to support the rheological observations. The current study revealed that the structure of blood clots formed had significant differences when an oscillatory frequency that mimicked the physiological heart rate was used in comparison to a lower frequency commonly used in current clinical measurements. The limited working dose range for protamine and its intrinsic anticoagulation behaviour was observed. The neutralization profile of UHRA-7 showed a large window of activity. The global assessment of rheological parameters and microstructure of the clot together revealed additional details describing anticoagulant reversal and blood coagulation dynamics by relating the blood clot's fiber thickness and the oscillatory measurements, including storage modulus and blood clot's contractile force. Additionally, a mechanical characterization was conducted to provide a further assessment of blood coagulation using the rheological data.

The influence of hematocrit on the hemodynamics of artificial heart valve using fluid-structure interaction analysis.

Patients with severe aortic stenosis could regain the proper hemodynamic performance and cardiovascular output by restoring the diseased aortic valve with an artificial heart valve replacement. However, given the uniqueness of each patient, the hemodynamic improvements after an aortic valve replacement could vary. The biomechanical and hemodynamical parameters can be influenced by some major factors including the patient's blood pressure and hematocrit. Therefore, the objective of this study is to analyze the hemodynamics and valve mechanics of a bileaflet mechanical heart valve and investigate the hemorheological characteristics under the change of hematocrit. The fully coupled fluid-structure interaction (FSI) approach was used to model the hemodynamics and valve dynamics. Particle image velocimetry (PIV) experiments were conducted with in vitro benchtop model using ViVitro Pulse Duplicator to verify and validate the FSI models. The current numerical analysis revealed the hematocrit influenced the shear stress distributions over a cardiac cycle. The structural stresses in the mechanical valve were also affected by the distributions of the shear stress in the blood flow. Parameter dependencies found in the current study indicate that the hematocrit is influential when conducting patient-specific modelling of prosthetic heart valves.

Influence of dynamic flow conditions on adsorbed plasma protein corona and surface-induced thrombus generation on antifouling brushes.

The information regarding the nature of protein corona (and its changes) and cell binding on biomaterial surface under dynamic conditions is critical to dissect the mechanism of surface-induced thrombosis. In this manuscript, we investigated the nature of protein corona and blood cell binding in heparinized recalcified human plasma, platelet rich plasma and whole blood on three highly hydrophilic antifouling polymer brushes, (poly(N, N-dimethylacrylamide) (PDMA), poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) using an in vitro blood loop model at comparable arterial and venous flow, and static conditions. A fluid dynamics model was used initially to better understand the resulting flow patterns in a vertical channel containing the substrates to arrive at the placement of the substrates within the blood loop. The protein binding on the brush modified substrates was determined using ellipsometry, fluorescence microscopy and the nature of the protein corona was investigated using mass spectrometry based proteomics. The flow elevated fouling on brush coated surface from blood. The extent of plasma protein adsorption and platelet adhesion onto PDMA brush was lower than other surfaces in both static and flow conditions. The profiles of adsorbed protein corona showed strong dependence on the test conditions (static vs. flow), and the chemistry of the polymer brushes. Specially, the PDMA brush under flow conditions was more enriched with coagulation proteins, complement proteins, vitronectin and fibronectin but was less enriched with serum albumin. Apolipoprotein B-100 and complement proteins were the most abundant proteins seen on PMPC and PHPMA surfaces under both flow and static conditions, respectively. Unlike PDMA brush, the flow conditions did not affect the composition of protein corona on PMPC and PHPMA brushes. The nature of the protein corona formed in flow conditions influenced the platelet and red blood cell binding. The dependence of shear stress on platelet adhesion from platelet rich plasma and whole blood highlights the contribution of red blood cells in enhancing platelet adhesion on the surface under high shear condition.

Hemodynamic assessments of the ascending thoracic aortic aneurysm using fluid-structure interaction approach.

Current assessment and management of ascending thoracic aortic aneurysm (ATAA) rely heavily on the diameter of the ATAA and blood pressure rather than biomechanical and hemodynamic parameters such as arterial wall deformation or wall shear stress. The objective of the current study was to develop an accurate computational method for modeling the mechanical responses of the ATAA to provide additional information in patient evaluations. Fully coupled fluid structure interaction simulations were conducted using data from cases with ATAA with measured geometrical parameters in order to evaluate and analyze the change in biomechanical responses under normotensive and hypertensive conditions. Anisotropic hyperelastic material property estimates were applied to the ATAA data which represented three different geometrical configurations of ATAAs. The resulting analysis showed significant variations in maximum wall shear stress despite minimal differences in flow velocity between two blood pressure conditions. Additionally, the three different ATAA conditions identified different aortic expansions that were not uniform under pulsatile pressure. The elevated wall stress with hypertension was also geometry-dependent. The developed models suggest that ATTA cases have unique characteristic in biomechanical and hemodynamic evaluations that can be useful in risk management.