The long-term objective of the proposed work is to develop implantable intrathoracic artificial lungs. (ITALs). These devices are to attached to the pulmonary circulation, utilize the right ventricle to drive blood flow, and perform the gas transfer function of the natural lungs. They can be used as a bridge-to-transplant for the tens of thousands who die each year from chronic obstructive pulmonary disease, cystic fibrosis, or idiopathic pulmonary fibrosis or a therapy for approximately 75,000 who die each year in America from acute respiratory failure. Several variations of the ITAL will be necessary to address the differing requirements of these disease processes. Designing and developing ITALS involve three primary issues: (a) oxygen and carbon dioxide gas exchange, (b) hemodynamic compatibility , and (c) physiologic compatibility. Issue (a) will be addressed by mathematical models, which have previously been successfully applied to commercial and experimental oxygenators for heart-lung machines. Our focus in the proposed work is, therefore, issues (b) and (c). The device must be designed such that diverting blood flow through the device causes neither excessive blood trauma nor right ventricular or end-organ dysfunction. These issues will be addressed with (i) theoretic modeling, (ii) in- vitro studies, and (iii) in-vivo studies. Previously developed models of gas transfer, hemodynamic effects of implantation in a combined artificial/natural lung system, and shear stress induced blood trauma will be utilized to redesign devices, if necessary, to satisfy issues (a) through (c). In-vitro studies will examine, in a controlled setting, effect of pulsatile flow on gas transfer and hemodynamic characteristics of the device and of shear stress and various fiber surface treatments on blood trauma. In-vivo studies will be used to examine effects of various implantation techniques on right ventricular function, hematologic disturbance, and end organ function. These implantation techniques include placing the ITAL inlet at the pulmonary artery (PA) and outlet at the left atrium (parallel implantation), with banding of the distal pulmonary artery or pulmonary veins to divert flow from the natural lungs to the artificial lungs or placing the ITAL inlet at the proximal PA and outlet at the distal PA (series implantation) with banding on the PA between inlet and outlet. Acute experiments using a porcine model will be used primarily to determine the effect of hemodynamic and hematologic effects of implantation with minimal pharmacological intervention in-vivo. Long-term, two to seven days experiments using an ovine model will be used to determine the hemodynamic, hematologic, and end-organ effects of implantation in a clinically relevant setting. The results of the in-vitro and in-vivo studies will be used to confirm the theoretical models and direct ITAL designs for various etiologies.
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