Development of a multi-scale closed loop model for hemorrhagic shock: a platform to assess REBOA performance

Project Summary Hemorrhagic shock is the leading cause of preventable death after a traumatic injury, and accounts for 91% of military and 35% of civilian fatalities after trauma. Injuries to non-compressible intracavity regions, such as the torso and abdomen, are a major clinical challenge due to a lack of appropriate interventions, and represent 30- 40% of early fatalities. To address this problem, endovascular hemorrhage control (EHC) devices and minimally invasive techniques such as Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) have been increasingly adopted. REBOA involves full inflation of a balloon catheter in the aorta, which restricts blood flow distal to the occlusion and consequently minimizes bleeding. While REBOA is effective at restoring proximal perfusion, the reductions in blood flow can result in ischemia-reperfusion injuries that increase the risk of subsequent renal failure. As such, there is a pressing need to identify optimal occlusion size, timing, and duration of REBOA deployment. To date, these important knowledge gaps are hindered by expensive and time intensive large animal models that slow the pace of innovation. To address this major gap, we propose to develop and validate a novel multi-scale computational model that will allow us to simulate the in vivo physiologic response to hemorrhagic shock. Using a 3D-0D closed loop approach of the cardiovascular system, we will be able to simulate the critical feedback loops and biologic response functions to render a physiologically relevant model. These methods have been previously used to inform the design of cardiovascular stents and inferior vena cava filters, but none to our knowledge have been exploited for the evaluation of REBOA or any other EHC device. Our central hypothesis is that computational modeling of blood flow within the aorta and systemic vascular network will generate accurate and robust values for pressure, flow and shear rates within  5% error, closely mimicking in vivo behavior. The objective is to use this computational framework to: 1) quantify the local and systemic hemodynamics (i.e., pressure, flow rate, shear stress, oxygen transport, etc.) during phases of active hemorrhage, aortic occlusion with REBOA, and resuscitation, 2) identify vascular regions that are vulnerable to ischemic damage as a result of the altered hemodynamics, 3) predict key physiologic responses related to vascular compliance, oxygen delivery and renal autoregulation during hemorrhage and aortic occlusion, and 4) determine optimal aortic occlusion size and duration of partial vs. full occlusion strategies to prevent ischemia- reperfusion injuries and renal failure. Successful development and validation of this in silico model will greatly contribute to the preclinical testing and optimization of EHC devices, minimizing the need for large animal studies and also open doors for the study of other transient hemodynamic conditions within the cardiovascular system.