Study of Vascular Endothelium Damage Due to Freezing

Microvascular injury is recognized as a major tissue damage mechanism of ablative cryosurgery. Details of this injury mechanism are not completely understood. But it is known that extracellular ice propagating through the vascular region leads to endothelial cell dehydration, which may cause their detachment from each other and eventually from the vessel wall. Soon after post-thaw reperfusion vessel leakage is evident and thrombi form in the vessels leading to vascular stasis and consequently tissue ischemia. To better understand the mechanical principles underlying this tissue injury mechanism, we have modeled water transport phenomena that arise during the freezing of the vasculature. Endothelial cells were modeled as an independent but connected array of ellipsoidal balloons whose size varies according to the osmotic pressure experienced during the freezing process. An assumption of minimum surface area permeable to water was made as the mechanism governing the cell shape change. Variations in intercellular gap dimensions under different freezing protocols were obtained numerically. The results were then compared to the observed behavior of cultured endothelial cells undergoing the same freezing protocol on a cryostage. The simulation and experimental results are in good agreement.