TY - JOUR T1 - Luminal polyethylene glycol alleviates intestinal preservation injury irrespective of molecular size JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.117.247023 SP - jpet.117.247023 AU - Anna Casselbrant AU - John Mackay Softeland AU - Mats Hellstrom AU - Mantas Malinauskas AU - Mihai Oltean Y1 - 2018/01/01 UR - http://jpet.aspetjournals.org/content/early/2018/05/08/jpet.117.247023.abstract N2 - Intestinal preservation injury (IPI) and the resulting mucosal injury raise several serious challenges early after intestinal transplantation (ITx). The current clinical approach using only vascular perfusion allows the shortest preservation period among the abdominal organs. The experimental addition of luminal polyethylene glycol (PEG) solutions has been repeatedly suggested to alleviate preservation injury, improve graft quality and prolong the preservation time. We investigated if the size of PEG in the solution influences the development of intestinal preservation injury. Small intestines of Sprague Dawley rats were perfused with University of Wisconsin solution. Group 1 underwent vascular perfusion only (clinical control), group 2 received additional luminal PEG3350 Da, group 3 received luminal PEG10000 Da whereas group 4 received luminal PEG20000 Da (n=8/group). Tissue samples were obtained after 4h, 8h and 14h. We studied the tissue damage (Chiu/Park score, Goblet cells, apoptosis, tight junctions), activation of c-Jun NH2-terminal kinase (JNK) and p38-mitogen-activated protein kinase (MAPK) and performed Ussing chamber assessments. Mucosal morphological and electrophysiological parameters were significantly improved in the groups receiving luminal PEG. There was significantly less apoptotic activity in group 2, 3 and 4. Both MAPKs revealed an activation peak after 4h with group 3 showing lesser p38-MAPK activation. PEG 20kDa interfered with protein immunodetection. The results indicate that luminal solutions of PEG of medium and large molecular weight significantly delay the onset and development of IPI. Hence, the present study provides further evidence that luminal interventions may allow for longer cold storage intervals of the intestinal grafts ER -