Predicted oxygenation efficacy of a thoracic artificial lung.

A thoracic artificial lung (TAL) provides respiratory support for lung disease. How well a TAL improves blood oxygenation for a specific pathology depends on how the TAL is attached to the pulmonary circulation: in series with the natural lungs (NLs), in parallel, or in a hybrid series/parallel combination. A computational model, including hemodynamic and O(2) and CO(2) exchange components, predicts TAL effects on blood flow rates and gas transport in pulmonary disease states modeled by elevated pulmonary vascular resistance (PVR) or reduced oxygen diffusivity in the NLs.

Microchannel technologies for artificial lungs: (3) open rectangular channels.

Lithographic techniques were used to develop patterned silicone rubber membranes that provide 15 microm high microchannels for artificial lungs. Two types of devices were fabricated as a proof-of-concept: one has a series of parallel, straight, open rectangular channels that are each 300 microm wide, separated by 200-microm walls, and 3-mm long and the other is a wide rectangular channel with support posts, also 3- mm long. Experiments with 30% hematocrit, venous, bovine blood showed average oxygen fluxes ranging from 11 x 10(-7) moles/(min x cm(2)) at a residence time of 0.

Microchannel technologies for artificial lungs: (2) screen-filled wide rectangular channels.

Artificial lungs with blood-side channels on a 10-40 microm scale would be characterized, similar to the natural lungs, by tens of thousands to hundreds of millions parallel blood channels, short blood paths, low pressure drops, and low blood primes. A major challenge for developing such devices is the requirement that the multitude of channels must be uniform from channel to channel and along each channel. One possible strategy for developing microchannel artificial lungs is to fill broad rectangular channels with micro scale screens that can provide uniform support and stability.

Microchannel technologies for artificial lungs: (1) theory.

The feasibility of developing micro channel artificial lungs is calculated for eight possible strategies: 12 and 25 microm circular channels imbedded in gas-permeable sheets, 12 and 25 microm high open rectangular channels with gas-permeable walls, 12 and 25 microm high broad open channels with support posts and gas-permeable walls, and two 40 microm high screen-filled rectangular channels with gas-permeable walls. Each strategy is considered by imposing a pressure drop maximum of 10 mm Hg and limiting the possibility of shear-induced blood trauma. The pressure drop limit determines the acceptable channel length and required size to oxygenate 4 L/min of venous blood.

Pulmonic valve function during thoracic artificial lung attachment.

Pulmonic valve incompetence has been observed during implantation of total artificial lungs (TAL) and may contribute to right ventricular dysfunction in certain attachment modes. The roles of pulmonary system resistance and inertia on valve function were examined retrospectively using data from attachments of a prototype TAL in six pigs. The TAL was attached in parallel and in series with the natural lungs and a hybrid of parallel and series.

Hemodynamic consequences of thoracic artificial lung attachment configuration: a computational model.

A thoracic artificial lung (TAL) is being developed to assist treatment of acute and chronic pulmonary dysfunction. The TAL is attached directly to the pulmonary circulation. Depending on pathophysiology, the TAL may be attached in series with the natural lungs (NLs), in parallel with the NLs, or in an intermediate, hybrid configuration.

In vivo hemodynamic responses to thoracic artificial lung attachment.

A thoracic artificial lung (TAL) was attached to the pulmonary circulation in a porcine model. Proximal main pulmonary artery (PA) blood flow, in part or whole, was diverted to the TAL, and TAL outlet blood flow was split between the distal main PA and left atrium (LA). The right ventricle (RV) drove blood flow through the combined TAL/natural lung (NL) pulmonary system.

Blood flow pulsatility effects upon oxygen transfer in artificial lungs.

This report discusses theoretical effects of blood flow pulsatility upon the rate of oxygen transfer in artificial lungs, demonstrates the effects with in vitro tests upon commercial oxygenators, and applies the theory to these oxygenators and to a thoracic artificial lung. Steady flow gas transfer theory is applied to pulsatile flow by using the instantaneous value of flow rate at each instant of time, that is, quasi-steady gas transfer. The theory suggests that the local rate of oxygen transfer for a given device and blood composition is proportional to the flow rate to a power less than unity and to the hemoglobin saturation level.

Platelet and leukocyte activation and design consequences for thoracic artificial lungs.

Blood contact with the prosthetic surfaces of artificial lungs causes extensive activation of molecular and cellular mediators of coagulation and inflammation that can lead to patient morbidity and mortality. To determine the effects of artificial lung fiber bundle shear stress and surface area on blood activation, porcine blood was recirculated for 4 hours through circuits containing mock artificial lungs with bundle shear stresses of 11.6, 7.

Development of an implantable artificial lung: challenges and progress.

Unlike dialysis, which functions as a bridge to renal transplantation, or a ventricular assist device, which serves as a bridge to cardiac transplantation, no suitable bridge to lung transplantation exists. Our goal is to design and build an ambulatory artificial lung that can be perfused entirely by the right ventricle and completely support the metabolic O2 and CO2 requirements of an adult. Such a device could realize a substantial clinical impact as a bridge to lung transplantation, as a support device immediately post-lung transplant, and as a rescue and/or supplement to mechanical ventilation during the treatment of severe respiratory failure.

Hemodynamic effects of attachment modes and device design of a thoracic artificial lung.

A thoracic artificial lung (TAL) was designed to treat respiratory insufficiency, acting as a temporary assist device in acute cases or as a bridge to transplant in chronic cases. We developed a computational model of the pulmonary circulatory system with the TAL inserted. The model was employed to investigate the effects of parameter values and flow distributions on power generated by the right ventricle, pulsatility in the pulmonary system, inlet flow to the left atrium, and input impedance.

Partial prevention of monocyte and granulocyte activation in experimental vein grafts by using a biomechanical engineering approach.

Leukocytes interact with endothelial cells and contribute to the development of vascular diseases such as thrombosis and atherosclerosis. These processes are possibly influenced by mechanical factors. This study focused on the role of mechanical stretch in the activation of monocytes and granulocytes in experimental vein grafts.

Influence of a natural and a synthetic inhibitor of factor XIIIa on fibrin clot rheology.

We investigated the origins of greater clot rigidity associated with FXIIIa-dependent cross-linking. Fibrin clots were examined in which cross-linking was controlled through the use of two inhibitors: a highly specific active-center-directed synthetic inhibitor of FXIIIa, 1,3-dimethyl-4,5-diphenyl-2[2(oxopropyl)thio]imidazolium trifluoromethylsulfonate, and a patient-derived immunoglobulin directed mainly against the thrombin-activated catalytic A subunits of thrombin-activated FXIII. Cross-linked fibrin chains were identified and quantified by one- and two-dimensional gel electrophoresis and immunostaining with antibodies specific for the alpha- and gamma-chains of fibrin.

Structural origins of fibrin clot rheology.

The origins of clot rheological behavior associated with network morphology and factor XIIIa-induced cross-linking were studied in fibrin clots. Network morphology was manipulated by varying the concentrations of fibrinogen, thrombin, and calcium ion, and cross-linking was controlled by a synthetic, active-center inhibitor of FXIIIa. Quantitative measurements of network features (fiber lengths, fiber diameters, and fiber and branching densities) were made by analyzing computerized three-dimensional models constructed from stereo pairs of scanning electron micrographs.

A hypothesis regarding vascular acoustic emission accompanying arterial injury induced by balloon angioplasty.

Stress-induced structural damage is often accompanied by sound release. This behavior is known as acoustic emission (AE). We hypothesize that vascular injury such as that produced by balloon angioplasty is associated with AE.

In vitro identification of angioplasty-induced injury by use of vascular acoustic emissions.

Background: We have developed a novel method of diagnosing stress-induced vascular injury. This approach uses the sound energy released from atherosclerotic arterial tissue during in vitro balloon angioplasty to characterize type and severity of induced trauma.

Methods And Results: Thirty-two postmortem human peripheral arterial specimens 1.

New design for a pumping artificial lung.

A new prototype of a pumping artificial lung (PAL) has been designed and tested. The device performs the functions of both the pump and oxygenator components of an extracorporeal perfusion circuit. Previous prototypes that the authors developed (Type A) had gas exchanging microporous fibers formed into propeller-like vanes that, upon rotation, pump the blood.

Testing of an intrathoracic artificial lung in a pig model.

A low input impedance, intrathoracic artificial lung is being developed for use in acute respiratory failure or as a bridge to transplantation. The device uses microporous, hollow fibers in a 0.74 void fraction, 1.

Mixing of two solutions combined by gravity drainage.

A variety of medical therapies require the mixing of solutions from two separate bags before use. One scenario for the mixing is to drain the solution from one bag into the other by gravity through a short connecting tube. The degree of mixing in the lower bag depends on the relative densities of the two solutions, the geometry of the two bags and the connecting tube, and the placement of the connecting tube.

Computer-assisted design of an implantable, intrathoracic artificial lung.

A semiempirical mathematical model of convective oxygen transport is used to design a new, low pressure loss, implantable artificial lung that could be used as a bridge to lung transplantation in patients with advanced respiratory failure. The mass transfer and flow friction relations pertinent to the design of a cross-flow hollow fiber membrane lung are described. The artificial lung is designed to transfer over 200 ml/min of oxygen at blood flow rates up to 5 L/min.

Use of a mathematical model to predict oxygen transfer rates in hollow fiber membrane oxygenators.

A semi-empirical theoretical model of oxygen transfer is used to predict the rates of oxygen transfer to blood in hollow fiber membrane oxygenators over a wide range of inlet conditions. The predicted oxygen transfer rates are based on performance of the devices with water, which is more cost effective and easier to handle than blood for in vitro evaluations. Water experiments were conducted at three different flow rates to evaluate oxygen transfer performance in three commercially available membrane oxygenators.

A dynamic intravascular artificial lung.

Intravascular lung assist devices (ILADs) must transfer sufficient amounts of oxygen and carbon dioxide to and from limited surface areas. It has become apparent that passive devices, i.e.

Design and evaluation of a new, low pressure loss, implantable artificial lung.

The authors designed and tested an artificial lung intended for intrathoracic implantation as a bridge to lung transplantation in chronic pulmonary insufficiency or as an alternative in the treatment of advanced acute respiratory failure. The prototype devices are comprised of 380 microns outer diameter polypropylene matted fibers with a blood path length of 3.5 cm, frontal area of 128 cm2, void fraction (porosity) of 0.

A pumping artificial lung.

The authors have developed a single device that performs the functions of a centrifugal pump and a membrane artificial lung. Unlike other systems that combine pre-existing components, our device is constructed so that the vanes of an impeller pump are made up of gas exchanging microporous fibers. The device has a variety of applications: in an easily primed emergency cardiopulmonary bypass circuit, as a low surface area component of extracorporeal life support (ECLS) circuits, and as a low volume, high perfusion rate bridge to transplant.

A pumping intravascular artificial lung with active mixing.

Intravascular, as well as extracorporeal, artificial lungs need to be effective and efficient in transferring both oxygen and carbon dioxide. This paper describes the preliminary development of a device that not only is efficient in gas transfer, but also can reduce any pressure loss by providing its own pumping action. The exchange surfaces of the device consist of many short, microporous, hollow fibers arranged in layers like the threads of a screw and placed in a cross-flow configuration.