Functional preservation of the mammalian kidney. VI. Viability assessment of rabbit kidneys perfused at 25°C with dimethyl sulfoxide in RPS-2

Hawkins, Helen E.; Clark, Peter E.; Lippert, Elizabeth C.; Karow, Armand M.

doi:10.1016/0022-4804(85)90039-3

Cited by 9 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We numerically evaluated 3 parameters under this pattern: ramp rate, ramp duration, and plateau duration. The empirical ramp rates were evaluated between 40 and 70 mM/min [ 6 , 15 ], which is justified as a reasonable range by the transport model, as shown in Figure S1. The empirical plateau concentration was set around 5 M, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Model-Guided Design and Optimization of CPA Perfusion Protocols for Whole Organ Cryopreservation

et al. 2023

View full text Add to dashboard Cite

Vitrification could enable long-term organ preservation, but only after loading high-concentration, potentially toxic cryoprotective agents (CPAs) by perfusion. In this paper, we combine a two-compartment Krogh cylinder model with a toxicity cost function to theoretically optimize the loading of CPA (VMP) in rat kidneys as a model system. First, based on kidney perfusion experiments, we systematically derived the parameters for a CPA transport loading model, including the following: Vb = 86.0% (ra = 3.86 μm), Lp = 1.5 × 10–14 m3/(N·s), ω = 7.0 × 10–13 mol/(N·s), σ = 0.10. Next, we measured the toxicity cost function model parameters as α = 3.12 and β = 9.39 × 10–6. Combining these models, we developed an improved kidney-loading protocol predicted to achieve vitrification while minimizing toxicity. The optimized protocol resulted in shorter exposure (25 min or 18.5% less) than the gold standard kidney-loading protocol for VMP, which had been developed based on decades of empirical practice. After testing both protocols on rat kidneys, we found comparable physical and biological outcomes. While we did not dramatically reduce toxicity, we did reduce the time. As our approach is now validated, it can be used on other organs lacking defined toxicity data to reduce CPA exposure time and provide a rapid path toward developing CPA perfusion protocols for other organs and CPAs.

show abstract

Section: Resultsmentioning

confidence: 99%