RSA1-1 Toward elimination of sub-lethal blood trauma in mechanical circulatory support
Michael J Simmonds1,2
1Menzies Health Institute Queensland, 2Griffith University, Australia
Background: Despite being a lifesaving technology, it has long been known that mechanical circulatory support (MCS) leads to deterioration of blood quality. Given a precise definition of “blood quality” remains elusive, my team have systematically examined the functional and structural changes induce on blood cells and proteins in response to well-defined mechanical stresses, and indeed, clinically-utilised MCS. To address whether altered physical properties of blood results in physiologically-relevant outcomes, we have examined the sublingual microcirculation before, during, and after surgery requiring MCS.
Methods: In this session, a series of studies will be integrated that include: i. basic bench studies, for example, to examine changes in bulk blood properties (e.g., viscosity), mechanical properties of erythrocytes (e.g., cell deformability; shear modulus), and intracellular signalling pathways, and: ii. clinical studies that examine changes in blood quality during cardiac surgery requiring MCS.
Results: The work of my team has increasingly demonstrated that the supraphysiological shears typical of MCS leads to significantly impaired blood viscosity profiles, and in vitro works support that cell mechanical properties and aggregability of erythrocytes likely explains this response. Subcellular approaches indicate that both calcium handling and nitric oxide generation in erythrocytes are significantly impacted by supraphysiological shears, which coincide with impaired mechanical properties. In vivo studies during cardiac surgery present a different picture; often viscosity is highly impaired with much lower aggregability than would be expected based predictions from vitro studies. Nevertheless, rheological impacts to blood during surgery appear to impact microcirculatory flux throughout the surgical period and also persist to discharge.
Conclusions: The finger-print of poor blood quality response to MCS is emerging; it is clear that current technologies require considerable revision before optimal surgical outcomes may be realised.
RSA1-2 Hemorheological changes caused by pituitary adenylate cyclase-activating polypeptide administration during vessel anastomosis regeneration in the rat
Balazs Szabo1, Laszlo Adam Fazekas1, Adam Varga1, Barbara Barath1, Vince Szegeczki2, Tamas Juhasz2, Dora Reglodi3, Norbert Nemeth1
1Department of Operative Techniques and Surgical Research, University of Debrecen, Faculty of Medicine, Debrecen, Hungary, 2Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen Hungary, 3Department of Anatomy, Faculty of Medicine, University of Pecs, Pecs, Hungary
Introduction: The altered flow in an arterio-venous fistula (AVF) like elevated wall shear-stress (WSS) can damage the red blood cells and cause unfavorable histological changes. Changing the vessel geometry could alleviate the undesirable flow characteristics, which may help to avoid the aforementioned complications.
Objective: We aimed to investigate the hemorheological hematological and histological effect of a loop-shaped venous graft and the AVF, using 3D flow simulation.
Methods: Thirty male Wistar rats were divided into sham-operated, fistula, or loop groups (n = 10/each). The AFV and the loop-shaped graft were performed on the right femoral artery, using the superficial inferior epigastric vein. Blood samples were taken before/after the surgery, and at the 1st, 3rd and 5th postoperative weeks to measure the hemorheological, hematological parameters. Plastic castings were made from the lumen of the vessels, and these were scanned for 3D flow simulation. The vessels were removed for histological evaluation, and the result were compared with the flow pattern shown by the 3D flow simulation.
Results: There was a significant decrease of the hematocrit value in the loop group at the 1st postoperative week. In the fistula group the erythrocyte aggregation become significantly elevated by the end of the 5th week. Both hind limbs’ skin microcirculation notably decreased in the fistula group, this shows the AVFs remote effect. The 3D flow simulation showed an altered pattern of high WSS, this patter coincided with the location of the newly formed intima hyperplasia seen on the histological slides.
Conclusion: All measured hematological and hemorheological values normalized by the end of the 5th postoperative week, except in the fistula group where the values remained elevated. The 3D simulation proved to be accurate, because the flow patter changes matched the histological alterations. This suggest that this technique has high predictive capabilities.
RSA2-1 Blood flow thrombosis simulation to understand complex phenomenon of thrombosis under blood flow conditions
*Shinichi Goto1, Noriko Tamura3, Masamitsu Nakayama2, Shu Takagi4, Shinya Goto2
1Brigham and Women’s Hospital, Harvard Medical School, 2Tokai University School of Medicine, 3Niigata University of Health and Welfare, 4Graduate School of Engineering, The University of Tokyo
Background: Thrombus formation within the blood flow condition is a complex phenomenon involving multiple systems such as local activation of platelet, coagulation cascade, and fibrinolysis along with the mechanics of blood flow itself. Thus, systematic, and quantitative understanding is difficult.
Methods: We developed a computer simulation of arterial thrombi with a finite element discrete model by implementing the function of blood velocity, presence or absence of endothelial injury, platelet adhesion at an injured site, rate of platelet activation, rate of thrombin formation on activated platelet, rate of fibrin formation by thrombin, rate of plasmin generation, and the rate of fibrinolysis. The thrombus in this system was defined as the region where 60% or higher percentage of platelets were activated. The sizes of thrombi were measured continuously after starting endothelial injury in various conditions.
Results: Firstly, the contribution of various factors was compared. Of them, blood flow velocity had the largest effect on the rate of thrombus growth. The comparison of sized of thrombi formed 5 seconds after endothelial injury in various blood flow conditions revealed that the thrombus size was largest at the flow rate of 5 mm/s (thrombus size 0.009 mm3) and was smaller at lower (0.1 cm/sec: 0.001 mm3) and higher (1.0 cm/sec: 0.007 mm3) blood flow velocities. These results were validated with biological experiments using a flow chamber. Further analysis using the same simulation showed that higher thrombin activity but not higher Xa activity (compared to the baseline condition) increased the size of thrombi.
Conclusions: The computer simulation approach provides important insights into complex biological phenomenon.
RSA2-2 Suspension rheology of red blood cells under oscillatory shear flow
Naoki Takeishi1, Marco E Rosti2, Naoto Yokoyama3, Shigeo Wada1, Luca Brandt4
1Osaka University, 2OIST, 3Tokyo Denki University, 4KTH
Human red blood cells (RBCs) are constantly subjected to mechanical stimulation from both blood flow depending on heart bead (∼1 Hz), and from vessel walls in various organs including artificial blood pump. Rheological description of blood under oscillatory flow is thus of fundamental importance not only in physiological understanding about mechanical response of RBCs but also in novel artificial blood pump to minimize mechanical stimuli. We present a numerical analysis of dense suspnesion rheology of red blood cells (RBCs) with volume fraction 𝜑 = 0.41 in a wall-bounded oscillatory shear flow. The flow is assumed as almost inertialess. The RBCs, modeled as biconcave capsules whose membrane is assumed as an isotropic and hyperelastic material following Skalak constitutive law, is simulated for a wide range of input strain frequencies. The frequency-dependent viscoelastic character is quantified by complex moduli: storage mudulus G′ and loss modulus G′′, which is defined with the amplitude of particle stress tensor and the phase difference between the oscillatory strain and particle stress tensor. Our numerical results show that although there is almost no frequency-dependent deformation of individual RBCs, i.e., the cell deformation is consistent with that obtained under steady shear flow, the particle stress tensor starts to delay from oscillatory strain as the frequency increases, and the amplitude of particle stress tensor is constrained by higher frequency. Those numerical results will help to model a non-Newtonian fluid constitutive law based on dynamics of suspended components.
