Recirculatory Fibrinolytic-Assisted External Ventricular Drainage (EVD) for Intraventricular Hemorrhage

Background Elevated intracranial pressure and acute obstructive hydrocephalus secondary to intraventricular hemorrhage (IVH) can be treated by external ventricular drainage (EVD). The treatment time and the risk of EVD-related complications can be reduced with fibrinolytic agents’ instillation via an EVD catheter, but previous clinical trial results did not reveal a significant improvement in terms of long-term functional outcomes. A recirculatory fibrinolytic-assisted EVD system was designed. The clot dissolution effectiveness of the system under different drug dosages and fluid flow rates was tested in an ex vivo model. Results The results showed that the mean clot mass was quickly reduced in an initial fibrinolytic agent dose-independent stage, followed by a dose-dependent stage. Elevating fibrinolytic agent dosages beyond a certain threshold did not contribute to shorter dissolution times. Optimal treatment parameters for such a system were determined. A recirculatory flow rate of 10–18 ml/min with a low-dose of 30 000–60 000 IU of uPA resulted in an 80% clot mass reduction within four hours. Conclusions This recirculating fibrinolytic system is a promising novel modification of conventional IVH treatment that could reduce clot dissolution times and procedure-related complications.

Simulation of Airflow in an Idealized Emphysematous Human Acinus

Emphysema is the permanent enlargement of air spaces in the respiratory regions of the lung due to destruction of the inter-alveolar septa. The progressive coalescence of alveoli and alveolar ducts into larger airspaces leads to the disruption of normal airway wall motion and airflow rates within the pulmonary acinus. To contribute to the understanding of the individual effects of emphysema during its earliest stages, computational fluid dynamics (CFD) simulations of airflow in mathematically derived models of the pulmonary acinus were performed. The here generated computational domain consists of two generations of alveolar ducts within the pulmonary acinus, with alveolar geometries approximated as closely packed, 14-sided polygons. Physiologically realistic airflow rates and wall motions were used to study airflow patterns within subsequent generations of alveolar ducts during the inspiratory and expiratory phases of the breathing cycle. The effects of progressive emphysema on the airway wall motion and flow rates were simulated by sequentially removing all alveolar septa within each alveolar duct. Parametric studies were presented to independently assess the relative influence of progressive septal destruction of airway motion and flow rates. The results illustrate that septal destruction lowers the flow resistance through the alveolar ducts but has little influence on the mass transport of oxygen into the alveoli. Septal destruction has a net effect on the flow field by favoring the development of recirculatory flow patterns in individual alveoli.

Abstract 154: Hemodynamic Regulation of Tie1 in Aortic Valve Endothelial Cells

During the cardiac cycle, the ventricular side of the aortic valve (ventricularis) is exposed to high shear pulsatile flow, while the aortic side (fibrosa) is exposed to low shear recirculatory flow. The two sides have different transcriptional profiles, likely due to their distinct flow patterns. Tie1 is a mechanically sensitive orphan tyrosine kinase receptor found in endothelial cells (ECs). Tie1 is often found associated with Tie2, a tyrosine kinase receptor involved in EC survival. Tie1 prevents ligand binding to Tie2 until Tie1 is cleaved, via shear stress or other signals. Although studies have shown shear stress cleaves Tie1, none have been done in the aortic valve. Mechanically induced changes in Tie1 expression in the valve may be crucial to understand the effects of the hemodynamics of each side. ECs were isolated from the fibrosa and ventricularis of excised porcine aortic valves. The Flexcell 4000 Tension System was used for strain, and an insert for the Flexcell plates ( A, B, C ) was designed to apply shear stress at the same time. Full length Tie1 protein expression in porcine aortic valvular endothelial cells (pAVECs) decreased ~40% after 15% strain for 24 hours, while cleaved Tie1 endodomain levels increased ( D ). Additionally, qPCR results showed that Tie1 mRNA levels did not decrease as dramatically, also supporting Tie1 cleavage. Full length Tie1 protein expression in pAVECs also decreased ~60% after 7 hours of 10 dynes/cm 2 pulsatile bidirectional shear stress and decreased ~90% after 24 hours of 15% strain combined with 2 dynes/cm 2 pulsatile bidirectional shear stress ( E, F ). Akt, a protein kinase phosphorylated by activated Tie2, showed increased phosphorylation after 15 minutes of strain ( G ), providing evidence that cleaved Tie1 may be activating Tie2. These results show the varying responses in Tie1 expression to different shear stresses and strains and demonstrate that mechanical regulation plays an important role in its signaling in the aortic valve.

FSI Analysis of a Human Trachea Before and After Prosthesis Implantation

In this work we analyzed the response of a stenotic trachea after a stent implantation. An endotracheal stent is the common treatment for tracheal diseases such as stenosis, chronic cough, or dispnoea episodes. Medical treatment and surgical techniques are still challenging due to the difficulties in overcoming potential complications after prosthesis implantation. A finite element model of a diseased and stented trachea was developed starting from a patient specific computerized tomography (CT) scan. The tracheal wall was modeled as a fiber reinforced hyperelastic material in which we modeled the anisotropy due to the orientation of the collagen fibers. Deformations of the tracheal cartilage rings and of the muscular membrane, as well as the maximum principal stresses, are analyzed using a fluid solid interaction (FSI) approach. For this reason, as boundary conditions, impedance-based pressure waveforms were computed modeling the nonreconstructed vessels as a binary fractal network. The results showed that the presence of the stent prevents tracheal muscle deflections and indicated a local recirculatory flow on the stent top surface which may play a role in the process of mucous accumulation. The present work gives new insight into clinical procedures, predicting their mechanical consequences. This tool could be used in the future as preoperative planning software to help the thoracic surgeons in deciding the optimal prosthesis type as well as its size and positioning.