(G-269) Quantifying the Cardiovascular Response to Varying Degrees of Hemorrhage for the Establishment of a Computational Fluid Dynamic (CFD) Model

Saturday, October 14, 2023

9:30 AM – 10:30 AM PDT

Location: Exhibit Hall - Row G - Poster # 269

Presenting Author(s)

William Adu-Jamfi (he/him/his)

Undergraduate Student
University of Virginia
Lynchburg, Virginia, United States

Co-Author(s)

Fahim Mobin, MS

PhD Student
Wake Forest College of Medicine
Murphy, Texas, United States
AR

Antonio Renaldo

PhD Student
Wake Forest School of Medicine, United States
SJ

Sandra Januszko

Research Lab Technician II
Wake Forest, Department of Biomedical Engineering, United States
JJ

James Jordan

Associate Professor
Wake Forest School of Medicine, United States
SK

Samuel Kirse

MD Student
WFSM, United States
TW

Timothy Williams

Vascular Surgeon
Wake Forest School of Medicine, United States
CF

Carlos Figueroa

Senior Associate Chair
Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States

Primary Investigator(s)

Elaheh Rahbar

Associate Professor
Wake Forest School of Medicine, United States

Co-Author(s)

LN

Lucas Neff

Assistant Professor of Pediatric Surgery
Wake Forest School of Medicine, United States

Introduction:: Hemorrhage, characterized by the loss of blood, remains a significant concern in both civilian and military settings, contributing to approximately 30-40% of trauma mortality worldwide.¹ Understanding the cardiovascular response to varying degrees of hemorrhage is crucial for improving patient outcomes and developing effective lifesaving interventions. In this study, we aimed to quantify the cardiovascular response to different levels of hemorrhage in an established swine model of hemorrhagic shock. By analyzing changes in vessel diameter, cardiac output (CO), and pressure-volume (P-V) loops at 10%, 20%, and 30% hemorrhage levels, we sought to provide valuable insights into the underlying hemodynamic alterations associated with hemorrhage. Moreover, we aimed to utilize these findings to build and refine a computational fluid dynamic (CFD) model for hemorrhage. Using the Cardiovascular Integrated Modeling and Simulation (CRIMSON) platform, we report preliminary findings that shed light on the hemodynamic changes associated with varying degrees of hemorrhage.

Materials and Methods:: Yorkshire swine underwent controlled hemorrhage (10%, 20%, and 30% of total blood volume) over 30 minutes. Analysis focused on two key time points: T0 (baseline) and T30 (end of hemorrhage). Pigs (n=3) were instrumented with flow and pressure probes to acquire continuous hemodynamic data, and a P-V loop catheter was positioned in the left ventricle via apical stick to collect raw P-V data. Python algorithms were developed to process raw hemodynamic data to generate boundary conditions for the CFD model and quantify CO and stroke volumes (SV). To determine vascular diameter changes during hemorrhage, contrast-enhanced CT scans were performed on an additional 7 pigs. Using TeraRecon's AQi software (v.4.7, Durham, NC), vascular diameters at 34 specific locations were quantified, including the aorta, carotid, brachiocephalic, celiac, and renal arteries. These CT scans were then imported into CRIMSON® (v.1.4.5, Ann Arbor, MI) to create 3D geometric models of the aorta and its immediate branch vessels. The ascending aorta served as the inlet to the CFD model with the distal aorta and takeoff vessels serving as the outlets. The ascending aortic flow rate from the in vivo models served as the input boundary condition, while the outlet boundaries were connected to 0D three-element Windkessel models. The simulations assumed steady, incompressible flow with no-slip conditions at the arterial walls, and the arterial walls were assumed to be rigid. Models were calibrated to pressure and flow profiles obtained from the in vivo porcine hemorrhage models.

Results, Conclusions, and Discussions:: The ensemble-averaged P-V loops show that at baseline, the average SV and CO across all animals was 48.23 ± 31.15 mL and 5.65 ± 2.63 L/min, respectively. At T30, SV decreased to 45.8, 12.0, and 8.03 mL for 10%, 20%, and 30% hemorrhage, respectively (Figure 1A), which is at least half of the starting SV. Similarly, CO decreased to 5.18, 1.66, and 1.17 L/min for 10%, 20%, and 30% hemorrhage, respectively (Figure 1B). In our imaging cohort, we observed no significant changes (p ≤.05) in any of the vessel diameters between baseline (i.e., T0), 10%, 20%, and 30% hemorrhage, indicating a consistent maintenance of large arterial vascular diameters with minor variations (Figures 1C-D). Simulations of 10% hemorrhage showed mean blood pressures of 55 mmHg across most of the aorta, while 20% hemorrhage had mean pressure of approximately 32 mmHg (Figure 1E). Additionally, at T30, 20% hemorrhage exhibited substantial reductions in mean blood velocity (cm/s) across all vessels compared to 10% hemorrhage, indicating a more severe impact on blood circulation (Figure 1E). These CFD simulations match well with our experimental data.

In this study, the aorta and its greater vasculature displayed minimal diameter changes in response to varying degrees of hemorrhage up to 30% total blood volume, suggesting that most changes in vascular diameters during hemorrhage are likely to occur in smaller arterioles and/or the microvasculature. Furthermore, we observed substantial reductions in SV and CO, even at low levels of hemorrhage (e.g., 10%). The 40% decrease in SV and average CO at 10% hemorrhage indicates that there may be a nonlinear relationship between total blood volume lost and cardiac performance. These observations have important implications for our understanding of vascular response to hemorrhagic conditions and how to improve the fidelity of CFD models. Nevertheless, these results indicate a direct relationship between the severity of hemorrhage and its impact on the circulatory system. Further studies are needed to better understand the underlying mechanisms regulating vascular behavior during hemorrhagic events, and identifying the critical thresholds for cardiac parameters that can contribute to the advancement of diagnostic and therapeutic approaches for critically injured patients.

Acknowledgements (Optional): : This study is supported in part by the NSF REU Site: IMPACT (Award EEC#1950281) in the Department of Biomedical Engineering at Wake Forest School of Medicine, DOD (W81XWH-22-1-0309, Rahbar PI), and NIH R01 (HL162633-01 (PI: Rahbar)).

References (Optional): : [1] Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma. 2006 Jun;60(6 Suppl):S3-11. doi: 10.1097/01.ta.0000199961.02677.19. PMID: 16763478.