Biology subjects

Eden, M. J.

Publications and source records attributed to Eden, M. J..

4 recordsLinked to original sources

bioRxiv2026

A translational porcine model to assess the graded impact of hemorrhage and aortic occlusion on cardiovascular hemodynamics and renal perfusion

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a lifesaving intervention used to manage non-compressible torso hemorrhage by temporarily occluding the aorta to minimize blood loss and preserve perfusion to vital organs. Partial REBOA (p-REBOA) has been proposed to mitigate ischemic injury associated with full-REBOA (f-REBOA). However, implementation of p-REBOA clinically has been challenging due to our limited understanding of the acute hemodynamics with p-REBOA particularly in relation to cardiac, carotid, and renal perfusion. In this study we developed and utilized a novel porcine model to continuously measure cardiac, carotid, renal and systemic hemodynamic responses to varying degrees of hemorrhagic shock and aortic occlusion. Yorkshire pigs (N=54) underwent instrumentation for continuous hemodynamic monitoring and hemorrhage was induced for 30 minutes to achieve 10%, 20%, or 30% blood volume loss (n=18/group), followed by randomized treatments of either no occlusion, p-REBOA, or f-REBOA occlusion strategies (n=6/group) for 30 minutes. After occlusion, shed blood was re-transfused over 15 minutes, and REBOA balloons were deflated and removed. This was followed by a 3-hour automated resuscitation and critical care period. Renal and carotid perfusion decreased progressively with hemorrhage severity. Interestingly, 30 minutes of f-REBOA resulted in significant ischemia-reperfusion injury where renal perfusion was profoundly suppressed to 40% of baseline renal flow. On the other hand, p-REBOA yielded superior renal perfusion, while maintaining cardiac function and carotid perfusion. p-REBOA also required less fluid and vasopressors. This translational pig model offers new opportunities to assess acute cardiovascular hemodynamics during interventions for the management of hemorrhagic shock.

physiology↗

bioRxiv2026

Calibration of a Closed-loop Model of Porcine Aortic Hemodynamics during Hemorrhage

Uncontrolled hemorrhage remains a leading cause of traumatic death, driven by rapid physiological deterioration that is often difficult to detect during the compensated phase. While large-animal models provide critical insights into these dynamics, they are resource-intensive, motivating the need for efficient computational frameworks that can mechanistically interpret cardiovascular responses. We developed and calibrated a closed-loop zero-dimensional (0D) lumped-parameter model (LPM) using hemodynamic data from 43 anesthetized swine subjected to controlled hemorrhage (10%, 20%, or 30% of total blood volume). The computational framework, incorporates a dynamic heart model with a custom time-varying elastance function, a multi-compartment aorta, and distal Windkessel models representing vascular beds. The model was calibrated at discrete time snapshots throughout the 30-minute hemorrhage protocol to reproduce group-averaged experimental waveforms for aortic flow, regional organ flows, and systemic pressures. The calibrated model successfully reproduced experimental hemodynamic targets and waveform morphology across all hemorrhage severities. Analysis of the calibrated parameters revealed distinct physiological mechanisms driving hemodynamic adaptation during hemorrhage: a preferential increase in renal resistance compared to carotid resistance, indicating flow redistribution to vital organs, and a progressive mobilization of venous unstressed volume to sustain cardiac filling. Furthermore, the model captured the distinct shift toward preload limitation state for 30% hemorrhage group. This study establishes a physiologically interpretable in-silico framework capable of predicting both global and regional hemodynamic responses to acute blood loss, providing a validated foundation for future applications in trauma care and resuscitation modeling.

physiology↗

bioRxiv2025

A Microstructurally-Motivated Framework to Study Autoregulation in the Coronary Circulation

Coronary autoregulation maintains relatively constant myocardial flow over a wide range of perfusion pressures through myogenic, shear-dependent, and metabolic control mechanisms. Understanding this phenomenon is challenging due to the coupled nature of these mechanisms and their heterogeneous effects throughout the coronary tree. In this study we developed a novel microstructurally-motivated model of coronary autoregulation based on constrained mixture theory, with anatomical and structural parameters calibrated through a homeostatic optimization framework. Autoregulation was simulated at three myocardial depths (subepicardium, midwall, and subendocardium), with the calibrated model accurately reproducing baseline hemodynamics and autoregulatory responses. For changes in epicardial pressure, our model reproduced experimentally measured subendocardium-to-subepicardium flow ratios (ENDO/EPI) and changes in vessel diameter, demonstrating its predictive capability. Furthermore, we extended Womersleys theory to simulate phasic coronary hemodynamics with a time-varying intramyocardial pressure. This microstructurally-motivated framework provides a mechanistic foundation for investigating coronary autoregulation and long-term vascular growth and remodeling in pathphysiological conditions. SummaryO_LICoronary autoregulation is defined as the capability of the coronary circulation to maintain the blood supply to the heart over a range of perfusion pressures. This phenomenon is facilitated through intrinsic mechanisms that control the vascular resistance by regulating the mechanical function of smooth muscle cells. Understanding the mechanisms involved in coronary autoregulation is one of the most fundamental questions in coronary physiology. C_LIO_LIThis paper presents a structurally-motivated coronary autoregulation model that uses a nonlinear continuum mechanics approach to account for the morphometry and vessel wall composition in two coronary trees in the subepicardial and subendocardial layers. C_LIO_LIThe model is calibrated against diverse experimental data from literature and is used to study heterogeneous autoregulatory response in the coronary trees. This model drastically differs from previous models, which relied on lumped parameter model formulations, and is suited to the study of long-term pathophysiological growth and remodeling phenomena in coronary vessels. C_LI

physiology↗

bioRxiv2024

Co-Therapy with S1P and Heparan Sulfate Derivatives to Restore Endothelial Glycocalyx and Combat Pro-Atherosclerotic Endothelial Dysfunction

Endothelial cell (EC) glycocalyx (GCX) shedding due to disturbed blood flow and chemical factors leads to low-density lipoprotein infiltration and reduced nitric oxide synthesis, causing vascular dysfunction and atherosclerosis. This study evaluates a novel therapy combining sphingosine-1-phosphate (S1P) and heparin (heparan sulfate derivative). We hypothesized that heparin/S1P would repair mechanically damaged EC GCX in disturbed flow (DF) regions and restore anti-atherosclerotic mechanotransduction function, addressing cardiovascular disease. We used a parallel-plate flow chamber to simulate flow conditions in vitro and a partial carotid ligation mouse model to mimic DF in vivo. Heparin and albumin-bound S1P were administered to assess their reparative effects on the endothelial GCX. Immunocytochemistry, fluorescent staining, confocal microscopy, cellular alignment studies, and ultrasound were performed to evaluate EC function and endothelial-dependent vascular function. Barrier functionality was assessed via macrophage uptake. Heparin/S1P mechanism-of-action insights were gained through fluid dynamics simulations and staining of GCX synthesis enzyme as well as S1P receptor. Statistical analyses validated results. In vitro data showed that heparin/S1P therapy improves the function of DF-conditioned ECs by restoring EC GCX and promoting EC alignment and elevated vasodilator eNOS (endothelial-type nitric oxide synthase) expression. The in vivo studies confirmed GCX degradation, increased vessel inflammation and hyperpermeability, and vessel wall thickening in the partially ligated left carotid artery. Heparin/S1P treatment restored GCX in the left carotid artery, enhancing GCX thickness and coverage of the blood vessel wall. This work advances a new approach to regenerating the EC GCX and restoring its function in ECs under DF conditions.

bioengineering↗