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Luminal Polyethylene Glycol Alleviates Intestinal Preservation Injury Irrespective of Molecular Size

Artikel i vetenskaplig tidskrift
Författare Anna Casselbrant
John M. Söfteland
Mats Hellström
Mantas Malinauskas
Mihai Oltean
Publicerad i Journal of Pharmacology and Experimental Therapeutics
Volym 366
Nummer/häfte 1
Sidor 29-36
ISSN 0022-3565
Publiceringsår 2018
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för kirurgi
Institutionen för kliniska vetenskaper, Avdelningen för gastrokirurgisk forskning och utbildning
Institutionen för kliniska vetenskaper
Sidor 29-36
Språk en
Länkar dx.doi.org/10.1124/jpet.117.247023
Ämnesord barrier function, reperfusion injury, esophageal mucosa, rat, transplantation, ischemia, disease, weight, complications, activation, Pharmacology & Pharmacy
Ämneskategorier Kirurgi

Sammanfattning

Intestinal preservation injury (IPI) and the resulting mucosa injury raise several serious challenges early after intestinal transplantation. 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 whether the molecular mass of PEG in 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, and group 4 received luminal PEG20000 Da (n = 8/group). Tissue samples were obtained after 4, 8, and 14 hours. 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 we performed Ussing chamber assessments. Mucosal morphologic and electrophysiologic parameters were significantly improved in the groups receiving luminal PEG. There was significantly less apoptotic activity in groups 2, 3, and 4. Both MAPKs revealed an activation peak after 4 hours with group 3 showing lesser p38-MAPK activation. PEG 20 kDa interfered with protein immunodetection. The results indicate that luminal solutions of PEG of medium and large molecular mass significantly delay the onset and development of IPI, providing further evidence that luminal interventions may allow for longer cold storage intervals of intestinal grafts.

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