Paclitaxel prevents loss of pulmonary endothelial barrier integrity during cold preservation

Cold preservation is the most practical method to maintain the viability of isolated lungs. However, rapid cooling may affect pulmonary endothelial function. We examined the effects of microtubule stabilization with paclitaxel on pulmonary endothelial barrier integrity under cold temperature.

Human pulmonary arterial endothelial cells were incubated at 4 degrees C for 2 hr in the presence or absence of paclitaxel (2.5 micromol/L). Microtubules was visualized using immunocytochemical techniques. Ultrasonic attenuation was measured with scanning acoustic microscopy. Endothelial barrier integrity was measured as transendothelial electric resistance. In addition, we examined graft function in a rat lung transplantation model, in which the donor lung had been preserved in the presence of paclitaxel (2.5 micromol/L) at 4 degrees C for 12 hr.

Low temperature caused a reversible microtubule disassembly, but the structure of microtubules was preserved by paclitaxel. Paclitaxel prevented the cooling-induced decrease in ultrasonic attenuation and transendothelial electric resistance. In a rat transplantation model, we found that preservation with paclitaxel successfully improved the oxygenation performance of the donor lung, which demonstrated only mild congestion and less significant interstitial edema without fluid accumulation in the alveolar spaces.

Our results indicate that microtubule stabilization with paclitaxel may be beneficial to prevent the loss of the endothelial barrier during cold preservation. We conclude that the use of paclitaxel in organ preservation solutions is useful in protecting pulmonary endothelial barrier integrity during cold preservation, thereby reducing the occurrence of early graft failure.