Blood and Lungs
This project has two components. One component is to study the adhesion of blood platelets to an injured vessel site. This is a critical initial stage for the formation of a platelet plug to stop bleeding. The second component is to study the deposition of aerosol particles in the lungs to help study the effects of airborne pollutants, and infective and toxic agents.
Blood Flow: The adhesion of platelets to an injured vessel site is a critical initial stage for the formation of a platelet plug to stop bleeding. The two important factors in this process are: (1) the spatial distribution of platelets in the blood vessel, where a near-wall concentration of the platelets should obviously accelerate the formation of the platelet plug; (2) the adhesion dynamics between a platelet and the vessel when the platelet migrates to the vicinity of the vessel. The fluid dynamics plays an important role here --- in our previous work, we demonstrated that the margination of the platelets is greatly enhanced and dominated by their shear-induced diffusivity from the velocity fluctuations of the motion of red cells. One therefore must resolve the hydrodynamic interactions between RBCs and platelets to accurately predict the distribution of platelets in vessels.
In battlefields, both hematocrit (the volume fraction of red cells in blood) and the blood flow rate can drop severely from blood loss during trauma. The reduction of hematocrit and flow rate can both slow down the margination of platelets toward the vessel wall and in turn hamper the formation of the platelet plug. The resulted coagulopathy can be life-threatening, and hemorrhage accounts for 30% to 40% of all combat fatalities . Resuscitation of moderate to severe hemorrhagic shock requires administration of various blood products and solutions to maintain perfusion. The addition of products and solutions often fails to fully recover adequate perfusion and perturbs hemostasis to both a pro- and/or anti-coagulated state. The biochemical research arm of the US Army Blood Research group is focused upon the Acute Coagulopathy of Trauma that has been characterized as an uncontrollable bleeding diathesis in approximately 1/3 of trauma patients presented to a site of primary care. A part of this phenomenon may be due to the lack of platelet concentration at the blood/vessel wall interface due to inadequate hematocrit as a result of loss of platelet margination via RBC physical effects in blood flow.
Simulations can provide design criteria for a blood transfusion protocol as a possible means of fighting coagulopathy . We will obtain a comprehensive computer simulation and understanding of the dependence of the platelet/particle distribution and their wall adhesion rates on factors including the RBC hematocrit, the flow rate, and the particle shape. The application of these simulations will be applied directly to resuscitation of hemorrhagic shock of soldiers.
Lung Flow: The lung and its extended network of airways provide in fact a portal of entry for airborne pollutants and infective and toxic agents, some of which affect almost every battlefield soldier. Deposition is the quantity of aerosol particles that once inhaled are not expelled by the breath because they get deposited on surfaces along the respiratory tract. Only a fraction of those retained particles are viable (infectious) and therefore can cause disease. Acquiring the ability to predict with accuracy aerosol deposition is, thus, of critical importance for understanding the pathways for pathogenesis and disease development, and for the assessment of risks posed to population subgroups from accidental exposure to fine particles and vapors.
We will develop a “virtual inhaler” with the power to simulate accurately the deposition of 100 micron to 1 nm particles through 8 generations of the lung bronchi in both humans and the animals. We will examine, with these computational simulations the sensitivity of deposition to particle size, shape and electrochemical properties, to inhalation conditions and breathing cycle, to airborne/mucus interaction at the walls, and to realistic patient-specific geometries features. Ultimately, these deposition patterns will be related to the viability and non-viability of disease creation through inhalation.