Alleviating ischemia-reperfusion injury in small bowel.
An amino acid-based solution has been recently developed and has demonstrated significant protective effects during cold storage of small bowel (SB). This study was designed to examine the role of this novel solution in ameliorating intestinal injury in an in vivo model of ischemia-reperfusion (IR). The impact of luminal treatment with an amino acid-based (AA) solution was assessed throughout reperfusion after 60-min warm ischemia (WI) in rodent SB. Energetics (ATP and total adenylates) remained significantly elevated throughout 60-min reperfusion in AA-treated tissue compared with untreated controls. Increases in end-products (ammonia and alanine) and increases in alanine aminotransferase and glutaminase activity implicated greater amino acid metabolism in AA-treated tissues. After reperfusion, malondialdehyde levels were similar between all groups. Glutathione levels were consistently elevated in AA-treated tissues and by 60 min reperfusion values were sixfold greater than control. AA-mediated protection during IR resulted in reduced neutrophil infiltration suggesting a weaker inflammatory response. Barrier function and electrophysiology parameters exhibited a clear pattern of mucosal preservation in AA-treated tissues; histology supported these findings. This study raises the possibility of a role for a luminal nutrient-rich solution during ischemic storage of small bowel in the clinic.
Salehi
Payam
P
Surgical-Medical Research Institute, 1074 Dentistry-Pharmacy Building, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
Madsen
Karen
K
Zhu
Jay
J
Castillo
Erika
E
Avila
Jose
J
Lakey
Jonathan R T
JR
Churchill
Thomas A
TA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology*; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D004594:Electrophysiology; D005978:Glutathione / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000596:Amino Acids; D019188:Organ Preservation Solutions; D000641:Ammonia; D000255:Adenosine Triphosphate; D005978:Glutathione; D010634:Phenobarbital