“Investigation of an Injection-Jet Self-Powered Fontan Circulation: A Novel Bridge and Destination Therapy for the Failing Fontan”

Eduardo Divo, PhD, MS, BS

Embry-Riddle Aeronautical University, Daytona Beach, FL

FL

2021

Funding for this project was generously provided by the Cortney Barnett Research Fund, which is intended to support research that seeks to prolong longevity and improve quality of life in patients who have undergone the Fontan procedure.

Project Title

"Investigation of an Injection-Jet Self-Powered Fontan Circulation: A Novel Bridge and Destination Therapy for the Failing Fontan"

Lay Summary

The Fontan circulation results from the third stage surgical procedure to palliate patients born with only one functioning ventricle. Despite successful implementation for over five decades, this altered circulation is prone to failure with overall survival rates of 50-80% to adulthood. Failure of this circulatory pattern is complex. Indeed, the general designation of “Fontan failure” refers to the unique features of the circulation characterized by (1) elevated systemic venous pressure and (2) limited preloading of the systemic (single) ventricle. The former may lead to problems with gastrointestinal absorption and to liver failure.

In this proposal we focus on the problem of elevated venous pressure (typically measured in the main vein from the lower body - the “inferior vena cava” or “IVC”). We have

previously proposed to reduce IVC pressure by means of an engineering phenomenon called the “injection jet” by constructing an injection jet “shunt” (IJS). The IJS is an artificial vessel, or graft, with a converging nozzle, connected from the aorta to the Fontan circulation, and with its blood flow powered by the single ventricle itself rather than requiring an external source of power typical of other “pump” proposals. The high speed flow exiting the nozzle transfers energy to the venous flow, lowering upstream IVC pressure and enhancing downstream flow. Under a grant from the American Heart Association, we performed initial computer-based (or “in-silico”) simulations showing that, in a failing Fontan, we can significantly lower IVC pressure while maintaining acceptable oxygen levels in the body.

In the present proposal, we aim to reproduce and cross-validate these encouraging in-silico results by developing an in-vitro benchtop replica of the Fontan circulation and

measuring the effects of the IJS. The in-vitro approach is very useful in developing this particular therapeutic palliation to the failing Fontan for several reasons: first, it provides a completely independent means to validate the computational results; second, because it is a physical simulation (rather than computational), it allows detailed investigation of the physics (or fundamental behavior) of the injection jet mechanism in this circulation independent of the approximations inherent in computational models of fluids by dealing with the fluid itself; and third, the settings of the model can be readily changed and further simulations rapidly carried out to find the optimal settings for maximizing the therapeutic effect in a patient-specific manner accounting for age and exercise conditions. Concomitantly, we will carry out “matched”

computational simulations to cross-validate the in-vitro results.

By achieving optimal, validated models in the proposed work, we will have set the stage for advancing to animal experiments and, ultimately, a clinical trial under appropriate future funding. Successful lowering of venous pressure in some Fontan patients may minimize or even prevent the serious, even fatal complications associated with excess elevation of this pressure.