A Network Thermodynamic Model of Kidney Perfusion With a Cryoprotective Agent

Abstract

A network thermodynamic model has been devised to describe the coupled movement of water and a permeable additive within a kidney during perfusion under the combined action of diffusive, hydrodynamic, and mechanical processes. The model has been validated by simulating perfusions with Me2SO, glycerol, and sucrose and comparing predicted weight and vascular resistance with experimental results obtained by Pegg (1993). The flows of CPA, water, colloid, and cellular impermeants are governed by a combination of the individual osmotic potential and pressure differences between compartments of the kidney, the viscoelastic behavior of the tissue, and the momentum transferred between the flows. The model developed in this study presents an analytical tool for understanding the dynamics of the perfused kidney system and for modifying perfusion protocols to minimize the changes in cell volume, internal pressure build-up, and increases in vascular resistance that currently present barriers to the successful perfusion of organs.

Model-guided design and optimization of CPA perfusion protocols for whole organ cryopreservation

“…Krogh cylinder model [35,37] A representative repeating functional unit of the organ containing vascular and tissue compartments Multi-dimensional model [28] A porous media model applied to a multi-dimensional microvascular unit (e.g., hepatic acinus) Network thermodynamic model [25] A multi-compartmental model using a network thermodynamic model transport between interstitial and intracellular compartments Toxicity models Solution effects model [30,31]/qv* model [5,9] Toxicity caused by dehydration/concentrated salt in the solution CPA toxicity models [1, 16-18, 23, 40, 41] Different mechanisms of CPA toxicity include: ion channels blockage [17], cell and mitochondrial membrane alteration [41], cellular apoptosis [23], telomerase activity inhibition [40], affecting ATP production [18], protein glycosylation [16], cytoskeleton and mitotic spindle architecture disruption, and DNA denaturation [1] CPA interaction models [21] Beneficial component interactions in the CPA cocktail Toxicity cost function model [2,3] The cumulative toxicity incurred during CPA exposure in cells and 3D tissues and f refer to the concentration in the tissue and the concentration of the fluid flowing in the capillary, respectively; and cpa and is refer to the total CPA concentration and then the concentration of just the impermeable solutes (e.g., sugars, sugar alcohols, and polymers), respectively. Exposure to high CPA concentrations causes injury to tissues by two mechanisms: (1) mechanical (osmotic) damage and (2) chemical (toxicity) damage.…”