(H-316) Validating Various Viscosity Testing in a Versatile Oxygenation Perfusion System

Introduction:: As recently as the last ten years, there has been an increased focus on improving the efficiency of organ preservation processes for enhanced transplantation outcomes. The most common approach to organ preservation is static cold storage (SCS); however, studies have shown that this method is associated with time-dependent ischemic injury and limited preservation times. Contemporary methods involve machine perfusion (MP), which prevents ischemia by perfusing the organ with an oxygen-rich blood substitute. We have designed a versatile oxygenating perfusion system (VOPS) to reduce time-related ischemia injuries and improve the likelihood of organ viability for replantation. The VOPS device was designed to preserve tissues by maintaining a homeostatic environment and allowing oxygen circulation within the tissue. We hypothesized that this device is capable of reaching the required perfusion parameters for a human kidney with a range of different preservation solution viscosities.

Materials and Methods:: Pressurized oxygen was delivered to silicone tubing in a pulsatile fashion that caused a cyclical effect of inflation and deflation. As the pressurized oxygen entered the tubes, the pressure within the pump chamber increased above the hydrostatic pressure in the main organ chamber. This caused a pressure difference that forced a bolus of oxygenated fluid from the main chamber into the pump chamber through the perfusion port. During the pulsatile process, the silicone tubing experienced deflation, dropping the pressure in the pump chamber beyond the pressure in the main organ chamber thus a bolus of oxygenated fluid was then forced back into the pump chamber; this process allowed for a pulsatile flow of oxygen throughout the device. The vascular resistance element was silicone tubing cut to a length that intends to mimic the resistance a kidney would experience during normal blood flow (0.22 mmHg/mL/min). Circulation of the calcium chloride solution occurred at various viscosities (1, 3, 5, 6.5 cP). The oxygen pressure for this study ranged from 27.6 – 110.3 kPa. Perfusion pressure was monitored via pressure transducers (PX309-030G5V, Omega Engineering, Inc.); flow rates were measured with an ultrasonic flowmeter (2PXL-TS410, Transonic Systems Inc.), and all data were recorded using LabVIEW virtual interface (NI 9221 and NI USB-9162, LabVIEW 2019 SP1, National Instruments), then uploaded to MATLAB (MATLAB R2020a, The MathWorks, Inc.) for further computation of cited variables, giving insight of the oxygenation rates, perfusion parameters and mean flow rate in relation to varying viscosity levels.

Results, Conclusions, and Discussions:: The results of these tests required gathering data by using a baseline parameter set and a tuned set to collect peak perfusion and mean flow rates. Baseline data was amassed using constant variables of vascular resistance and silicone tube length; however, it incorporated varying oxygenation pressures (27.6 to 110.3 kPa). The table below displays the peak perfusion pressure and mean flow rate for all viscosities tested (1,3,5, 6.5 cP). The trend displayed for this testing showed an inverse relationship between viscosity and peak perfusion pressures. As the viscosity increased, the peak perfusion pressures decreased, no matter the oxygen pressure rate. However, this relationship did not translate to the mean flow rates. As viscosity increased (but only between 1 and 3 cP), so did the mean flow rates. When the viscosity was tested at 5 and 6.5 cP, there was a witnessed decrease in the mean flow rate. The figure below demonstrates these relationships.
The use of the vascular resistance validates the VOPS device’s capacity to deliver the appropriate peak perfusion pressures and mean flow rates within a targeted range gathered by data collected in porcine kidney preservation studies performed by Urbanellis et al. for each viscosity tested.

Conclusions
The team hypothesized the VOPS device would be capable of perfusing oxygen efficiently while using various viscosity levels. Our results indicated a non-intuitive ideal viscosity for the current design of the VOPS device in terms of balancing oxygen supply pressures to reach appropriate perfusion parameters for the preservation of a human kidney. While the VOPS device met the perfusion parameters at more oxygen supply pressures with one tested viscosity, all viscosity solutions tested reached the flow parameters essential for kidney preservation. This provides evidence that the VOPS is highly versatile as it can potentially be used with several preservation solutions that are currently used to preserve human kidneys for transplant.

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