Mitchell J. George

Verification of a computational cardiovascular system model comparing the hemodynamics of a continuous flow to a synchronous valveless pulsatile flow left ventricular assist device.

The purpose of this investigation is to use a computational model to compare a synchronized valveless pulsatile left ventricular assist device with continuous flow left ventricular assist devices at the same level of device flow, and to verify the model with in vivo porcine data. A dynamic system model of the human cardiovascular system was developed to simulate the support of a healthy or failing native heart from a continuous flow left ventricular assist device or a synchronous pulsatile valveless dual-piston positive displacement pump. These results were compared with measurements made during in vivo porcine experiments. Results from the simulation model and from the in vivo counterpart show that the pulsatile pump provides higher cardiac output, left ventricular unloading, cardiac pulsatility, and aortic valve flow as compared with the continuous flow model at the same level of support. The dynamic system model developed for this investigation can effectively simulate human cardiovascular support by a synchronous pulsatile or continuous flow ventricular assist device.

Preservation of native aortic valve flow and full hemodynamic support with the TORVAD using a computational model of the cardiovascular system

This article describes the stroke volume selection and operational design for the toroidal ventricular assist device (TORVAD), a synchronous, positive-displacement ventricular assist device (VAD). A lumped parameter model was used to simulate hemodynamics with the TORVAD compared with those under continuous-flow VAD support. Results from the simulation demonstrated that a TORVAD with a 30 ml stroke volume ejecting with an early diastolic counterpulse provides comparable systemic support to the HeartMate II (HMII) (cardiac output 5.7 L/min up from 3.1 L/min in simulated heart failure). By taking the advantage of synchronous pulsatility, the TORVAD delivers full hemodynamic support with nearly half the VAD flow rate (2.7 L/min compared with 5.3 L/min for the HMII) by allowing the left ventricle to eject during systole and thus preserving native aortic valve flow (3.0 L/min compared with 0.4 L/min for the HMII, down from 3.1 L/min at baseline). The TORVAD also preserves pulse pressure (26.7 mm Hg compared with 12.8 mm Hg for the HMII, down from 29.1 mm Hg at baseline). Preservation of aortic valve flow with synchronous pulsatile support could reduce the high incidence of aortic insufficiency and valve cusp fusion reported in patients supported with continuous-flow VADs.

Multiplate and TEG platelet mapping in a population of severely injured trauma patients

The objectives of this study were to compare thromboelastography platelet mapping (TEG PM) with impedance aggregometry (Multiplate, MP) in a single trauma population and relate their results clinically.

Clinical Cellular Therapeutics Accelerate Clot Formation: Cellular Therapeutics Accelerate Clot Formation

Clinical cellular therapeutics (CCTs) have shown preliminary efficacy in reducing inflammation after trauma, preserving cardiac function after myocardial infarction, and improving functional recovery after stroke. However, most clinically available cell lines express tissue factor (TF) which stimulates coagulation. We sought to define the degree of procoagulant activity of CCTs as related to TF expression. CCT samples from bone marrow, adipose, amniotic fluid, umbilical cord, multi‐potent adult progenitor cell donors, and bone marrow mononuclear cells were tested. TF expression and phenotype were quantified using flow cytometry. Procoagulant activity of the CCTs was measured in vitro with thromboelastography and calibrated thrombogram. Fluorescence‐activated cell sorting (FACS) separated samples into high‐ and low‐TF expressing populations to isolate the contribution of TF to coagulation. A TF neutralizing antibody was incubated with samples to demonstrate loss of procoagulant function. All CCTs tested expressed procoagulant activity that correlated with expression of tissue factor. Time to clot and thrombin formation decreased with increasing TF expression. High‐TF expressing cells decreased clotting time more than low‐TF expressing cells when isolated from a single donor using FACS. A TF neutralizing antibody restored clotting time to control values in some, but not all, CCT samples. CCTs demonstrate wide variability in procoagulant activity related to TF expression. Time to clot and thrombin formation decreases as TF load increases and this procoagulant effect is neutralized by a TF blocking antibody. Clinical trials using CCTs are in progress and TF expression may emerge as a safety release criterion. Stem Cells Translational Medicine 2018;7:731–739

Platelet biomechanics, platelet bioenergetics, and applications to clinical practice and translational research

Abstract The purpose of this review is to explore the relationship between platelet bioenergetics and biomechanics and how this relationship affects the clinical interpretation of platelet function devices. Recent experimental and technological advances highlight platelet bioenergetics and biomechanics as alternative avenues for collecting clinically relevant data. Platelet bioenergetics drive energy production for key biomechanical processes like adhesion, spreading, aggregation, and contraction. Platelet function devices like thromboelastography, thromboelastometry, and aggregometry measure these biomechanical processes. Platelet storage, stroke, sepsis, trauma, or the activity of antiplatelet drugs alters measures of platelet function. However, the specific mechanisms governing these alterations in platelet function and how they relate to platelet bioenergetics are still under investigation.

Inguinal Hernia Repair Using 3D Printed Surgical Instruments in the Cadaveric Model: A Feasibility Study

Background: 3D printing is an additive manufacturing process allowing the creation of solid objects directly from computer aided design (CAD). Design and fabrication of 3D printed surgical instruments has previously been performed with results indicating relevance to real surgical procedures. This study expands on previous work and investigates the feasibility of performing a cadaveric inguinal hernia repair using 3D printed surgical instruments. Methods: A CAD software package was used to design a general surgical set including hemostats, needle driver, scalpel handle, retractors and forceps. The digital models were manufactured on a 3D printer and used to perform a standard inguinal hernia repair on a human cadaver. Results: An acceptable inguinal hernia repair including mesh placement was successfully performed on a human cadaver using standard surgical techniques. Conclusions: General surgical procedures such as an inguinal hernia repair are feasible using 3D printed surgical instruments.