Abstract P154: A Computational Model of the Effect of Cardiac Arrest on the Coagulation System
Objective: The PULSE initiative identified prevention of diffuse coagulopathies to be a priority in resuscitation science. Coagulopathy is a potential significant complication of cardiac arrest that involves the complex nonlinear interplay of the coagulation and inflammation system (CIS). This complexity has made it difficult to study it in an integrative fashion at the microvessel level in cardiac arrest. We developed a 2-D Agent Based Model (ABM) to begin to better understand the CIS in cardiac arrest.
Methods: The ABM utilizes a 2-D particle system. Particles move and interact on a discrete spatial grid. The particles of the system are the cells, reactants, enzymes, and reaction products. The system is designed to model a blood vessel in vivo. The grid is in the shape of a rectangle. The sides of the rectangle represent endothelial cells; particles are capable of interacting with the endothelial cells. In a steady state, blood flow was suddenly discontinued for 20 minutes followed by return of spontaneous circulation (ROSC) for another 20 minutes. The levels of circulating coagulation factors and their products and function were continually monitored.
Results: After 20 minutes of no flow, we observed a state of hypercoagulability, impaired fibrinolysis, and systemic microthrombi formation consistent with post-arrest clinical studies in the literature. Endothelial cell response to hypoxia results in elevated levels of TAT and fibrin monomers consistent with activation of the coagulation system. Concomitant lack of D-dimer and FSPs demonstrated the decreased expression of TM, TFPI, and tPA. Following ROSC, the activation of the anticoagulation system and proinflammatory mediators resulted in a disruption of the equilibrium between the coagulation, anti-coagulation, fibrinolytic and inflammatory systems consistent with a clinical state of low grade DIC. This was also consistent with the literature.
Conclusions: The ABM model simulates the effects of cardiac arrest on the CIS and may be useful for studying arrest induced CIS changes as well as what effects various interventions such as hypothermia may have. Data obtained will be used to target mediator levels for verification as well as to design studies that may modulate the CIS to improve outcomes.