Physical and theoretical models of vascular and anatomical systems are being used in our laboratory to study a variety of phenomena such as hemodynamic effects on intra-arterial drug delivery, distribution of anti-HIV drugs, hemodynamic effects in vascular disease, and transport of drugs in visceral tissue. Several projects have been emphasized this past year. (1) We are studying the streaming phenomena associated with intra- arterial delivery of drug solutions via catheters into vertebral arteries for treating brain tumors in children We have fabricated a flow model of the vertebral-basilar artery network and have developed an computer-based data acquisition system that monitors delivery of dye to various arterial branches in the model. We are also performing numerical simulations of the flow in the vertebral geometry to predict distribution patterns of infused drugs. Our experiments and theory are aimed at developing methods for obtaining uniform delivery of drug solution to the desired arterial branches. (2) We have constructed a physiologic pharmacokinetic model of the distribution of a pro-drug, F-ddA, for treating HIV infection in the central nervous system of AIDS patients. The model will guide the design of more effective drugs that will be better absorbed in the gastrointestinal tract after oral doses, and will also penetrate adequately into the brain and cerebral spinal fluid. (3) We are studying the interrelationship between blood flow patterns and the mass transport of macromolecules into the arterial wall as a possible explanation of lesion site preferences associated with atherosclerosis tissues We have fabricated a mechanical model of a branching flow system that is made of semi-permeable wall material to study convection/ diffusion through the wall. We are theoretically simulating flow and transport in model arteries to corroborate our experiments. (4) Selective delivery of therapeutic agents to targeted hepatobiliary and renal tissues would make possible safer, more effective treatments by optimizing doses and reducing systemic toxicity. We are developing an infusion system for delivering drugs and gene vectors to the liver, gall bladder and urinary bladder under well-controlled and monitored conditions of pressure and flow. Pharmacokinetic studies will be performed, and infusate distribution will be measured in blood, liver and bladder. (This is a continuation of Intramural Research Project Z01-RR- 10324-09 BEI.)
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