title: I-FABP as biomarker for the early diagnosis of acute mesenteric ischemia and resultant lung injury.
abstract: Acute mesenteric ischemia (AMI) is a life-threatening condition that can result in multiple organ injury and death. A timely diagnosis and treatment would have a significant impact on the morbidity and mortality in high-risk patient population. The purpose of this study was to investigate if intestinal fatty acid binding protein (I-FABP) and α-defensins can be used as biomarkers for early AMI and resultant lung injury. C57BL/6 mice were subjected to intestinal ischemia by occlusion of the superior mesenteric artery. A time course of intestinal ischemia from 0.5 to 3 h was performed and followed by reperfusion for 2 h. Additional mice were treated with N-acetyl-cysteine (NAC) at 300 mg/kg given intraperitoneally prior to reperfusion. AMI resulted in severe intestinal injury characterized by neutrophil infiltrate, myeloperoxidase (MPO) levels, cytokine/chemokine levels, and tissue histopathology. Pathologic signs of ischemia were evident at 1 h, and by 3 h of ischemia, the full thickness of the intestine mucosa had areas of coagulative necrosis. It was noted that the levels of α-defensins in intestinal tissue peaked at 1 h and I-FABP in plasma peaked at 3 h after AMI. Intestinal ischemia also resulted in lung injury in a time-dependent manner. Pretreatment with NAC decreased the levels of intestinal α-defensins and plasma I-FABP, as well as lung MPO and cytokines. In summary, the concentrations of intestinal α-defensins and plasma I-FABP predicted intestinal ischemia prior to pathological evidence of ischemia and I-FABP directly correlated with resultant lung injury. The antioxidant NAC reduced intestinal and lung injury induced by AMI, suggesting a role for oxidants in the mechanism for distant organ injury. I-FABP and α-defensins are promising biomarkers, and may guide the treatment with antioxidant in early intestinal and distal organ injury.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada; Division of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Khadaroo
authors.affiliation: Departments of Anesthesia, Medicine and Physiology, Keenan Research Center for Biomedical Science of St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Fortis
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Saad Y
authors.initials: SY
authors.lastname: Salim
authors.affiliation: Department of Pathology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Streutker
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Churchill
authors.affiliation: Departments of Anesthesia, Medicine and Physiology, Keenan Research Center for Biomedical Science of St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada; Department of Pathology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D042241:Early Diagnosis; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D055370:Lung Injury / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D065666:Mesenteric Ischemia / Q000139:chemically induced / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023084:alpha-Defensins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D023084:alpha-Defensins; D000111:Acetylcysteine