? Since 1990, lung transplantation has become the preferred clinical procedure for patients with end-stage lung failure due to such conditions as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PHT). Availability of donor organs is far less than required, and unfortunately limits this clinical option to approximately 1,000 patients per year. It is clear that mechanical alternatives to transplantation are required. To achieve clinical success, an implantable artificial lung must satisfy a myriad of design challenges. Activities at a number of university medical centers are aimed at various aspects of artificial lung development, and the technology has progressed to the point where at least one group anticipates clinical trials within the next two years. This system, as with most others in development, is a paracorporeal device, and uses oxygen rather than ambient air as the exchange gas. We propose to develop a key technology that represents an advance beyond such devices. Our compact gas exchange array features ambient air gas exchange and a bloodside pressure drop low enough to use the natural heart as the blood pump. The device consists of 24 subarrays, each made of multiple hollow gas exchange tubes. It fits into the body with the top of the array near the top of the hemi-thorax, the bottom near the diaphragm, the concave medial side facing the heart, the convex lateral side facing the ribs, and the anterior and posterior sides facing the anterior and posterior surfaces of the hemi-thorax cavity. Results of a preliminary analysis using an existing performance prediction code are promising, but further proof of the feasibility of this innovation is needed. Phase I will analytically evaluate the blood-side diffusion coefficient required for confident design and sizing of the subarrays. We will then assess the performance of sample subarrays with a bench-top test fixture and use the resulting data to validate performance code predictions and update the code. Finally, we will use the updated code to conceptualize a design for an implantable artificial lung. This work will set the stage for animal tests in Phase II with a second-generation, properly sized prototype. Preliminary versions of associated ancillary devices will also be developed in Phase I1. ? ?
| Edelbauer, Monika; Datta, Dipak; Vos, Ingrid H C et al. (2010) Effect of vascular endothelial growth factor and its receptor KDR on the transendothelial migration and local trafficking of human T cells in vitro and in vivo. Blood 116:1980-9 |
