Red blood cells (RBCs) demonstrate procoagulant properties in vitro, and elevated hematocrit is associated with reduced bleeding and increased thrombosis risk in humans. These observations suggest RBCs contribute to thrombus formation. However, effects of RBCs on thrombosis are difficult to assess because humans and mice with elevated hematocrit typically have coexisting pathologies. Using an experimental model of elevated hematocrit in healthy mice, we measured effects of hematocrit in 2 in vivo clot formation models. We also assessed thrombin generation, platelet-thrombus interactions, and platelet accumulation in thrombi ex vivo, in vitro and in silico. Compared with controls, mice with elevated hematocrit (RBC) formed thrombi at a faster rate and had a shortened vessel occlusion time. Thrombi in control and RBC mice did not differ in size or fibrin content, and there was no difference in levels of circulating thrombin-antithrombin complexes. In vitro, increasing the hematocrit increased thrombin generation in the absence of platelets; however, this effect was reduced in the presence of platelets. In silico, direct numerical simulations of whole blood predicted elevated hematocrit increases the frequency and duration of interactions between platelets and a thrombus. When human whole blood was perfused over collagen at arterial shear rates, elevating the hematocrit increased the rate of platelet deposition and thrombus growth. These data suggest RBCs promote arterial thrombosis by enhancing platelet accumulation at the site of vessel injury. Maintaining a normal hematocrit may reduce arterial thrombosis risk in humans.

Computational simulations using a two-dimensional lattice-Boltzmann immersed boundary method were conducted to investigate the motion of platelets near a vessel wall and close to an intravascular thrombus. Physiological volume fractions of deformable red blood cells and rigid platelet-size elliptic particles were studied under arteriolar flow conditions. Tumbling of platelets in the red-blood-cell depleted zone near the vessel walls was strongly influenced by nearby red blood cells. The thickness of the red-blood-cell depleted zone was greatly reduced near a thrombus, and platelets in this zone were pushed close to the surface of the thrombus to distances that would facilitate their cohesion to it. The distance, nature, and duration of close platelet-thrombus encounters were influenced by the porosity of the thrombus. The strong influence on platelet-thrombus encounters of red-blood-cell motion and thrombus porosity must be taken into account to understand the dynamics of platelet attachment to a growing thrombus.

2Highlights 1  Neurocranial rotation dynamics of fish is described by an inverse dynamic model. 2  The inertial cost of accelerating the neurocranium is small in largemouth bass. 3  Kinetic energy of the neurocranium is probably converted into suction work. 4  Suction performance is not limited by cranial mass in generalized percomorph fish. 5 Abstract 6To expand the buccal cavity, many suction-feeding fishes rely on a considerable contribution 7 from dorsal rotation of the dorsal part of the head including the brains, eyes, and several 8 bones forming the braincase and skull roof (jointly referred to as the neurocranium). As the 9 neurocranium takes up a large part of the total mass of the head, this rotation may incur a 10 considerable inertial cost. If so, this would suggest a significant selective pressure on the 11 kinematics and mass distribution of the neurocranium of suction feeders. Here, an inverse 12 dynamic model is formulated to calculate the instantaneous power required to rotate the 13 neurocranium, approximated by a quarter ellipsoid volume of homogeneous density, as well 14 as to calculate the instantaneous suction power based on intra-oral pressure and head volume 15 quantifications. We applied this model to largemouth bass (Micropterus salmoides) and 16 found that the power required to rotate the neurocranium accounts for only about 4% of the 17 power required to suck water into the mouth. Furthermore, recovery of kinetic energy from 18 the rotating neurocranium converted into suction work may be possible during the phase of 19 neurocranial deceleration. Thus, we suggest that only a negligible proportion of the power 20 output of the feeding muscles is lost as inertial costs in the largemouth bass. Consequently, 21 the feeding performance of piscivorous suction feeders with generalised morphology, 22 comparable to our model species, is not limited by neurocranial motion during head 23 3 expansion. This suggests that it is thus not likely to be a factor of importance in the evolution 1 of cranial shape and size. 2

Suction feeding is the most common form of prey capture across aquatic feeding vertebrates and many adaptations that enhance efficiency and performance are expected. Many suction feeders have mechanisms that allow the mouth to form a planar and near-circular opening that is believed to have beneficial hydrodynamic effects. We explore the effects of the flattened and circular mouth opening through computational fluid dynamics simulations that allow comparisons with other mouth profiles. Compared to mouths with lateral notches, we find that the planar mouth opening results in higher flow rates into the mouth and a region of highest flow that is positioned at the centre of the mouth aperture. Planar mouths provide not only for better total fluid flow rates through the mouth but also through the centre of the mouth near where suction feeders position their prey. Circular mouths are shown to provide the quickest capture times for spherical and elliptical prey because they expose the prey item to a large region of high flow. Planar and circular mouths result in higher flow velocities with peak flow located at the centre of the mouth opening and they maximize the capacity of the suction feeders to exert hydrodynamic forces on the prey.