The goal of this proposal is to bring the development of the adjustable systemic-to-pulmonary artery (SPA) shunt to a Phase-I clinical trial. SPA shunts provide pulmonary blood flow in patients with single ventricle physiology. Mortality rates remain high after corrective surgery for neonatal single ventricle birth defect, particularly after the Norwood procedure for hypoplastic left heart syndrome. Contributing to the high mortality rates is the inability to precisely control pulmonary blood flow through SPA shunts. Currently utilized vascular polytetrafluoroethylene (ePTFE) grafts do not have a mechanism for precisely controlling blood flow through the shunts. This can create an imbalance in the proportion of blood flow to the lungs vs. the body. Our previous in vitro and in vivo studies have demonstrated the accuracy of a resistor mechanism in controlling flow through a PTFE shunt. Previous experiments, however, have not tested its physiological impacts in an animal model. The purpose of this proposal is to test the device in our "Good Laboratory Practice (GLP)" facility accoring to the recoomendations from the Food and Drug Administraton (see FDA recommendation letter). The testing will determine the adjustable SPA shunt's ability to control pulmonary blood flow to obtain target physiological parameters (e.g., arterial oxygen saturation and ratio between blood flow to the lungs and the body) within physiological limits. The applicants will utilize the excellent resources available at the Michael E. DeBakey Institute for Comparative Cardiovascular Sciences and Biomedical Devices at Texas A&M University. The institute was the site for testing the original DeBakey LVAD. The lead P.I. is the Head of the Dept of Physiology and Pharmacology and Director of the institute. This dual role enhances flexibility to ensure necessary resources are available and the necessary time can be devoted to the project. Its joint venture with the College of Veterinary Medicine offers "Good Laboratory Practice (GLP)" standard surgical facilities for both chronic and acute animal experiments, sterile surgical suites, veterinary care and other necessary supports. Dr. Mohiuddin has unique training in mechanical device design (BS, MS in Mechanical Eng) and cardiovascular physiology (PhD in Biomedical Sciences) which is necessary for the project. This project will also have access to Children's Memorial Hermann Hospital with 7 full-time pediatric cardiologists and a 20 bed pediatric intensive care unit. (See Dr. William I. Douglas support letter).
Every year approximately 1000 babies are born with a single working venrticle. In these patients, blood is supplied to the lungs by an implanted vascular shunt. Currently used shunts have no mechanism for flow control, contributing to high infant mortality rates. The applicants completed a novel device to regulate blood flow for this purpose. This study will follow the recommendations from the FDA for a GLP preclinical evaluation and bring the development of this device to clinical trials.