Prostaglandin E-major urinary metabolites as a new biomarker for acute mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia (AMI) is an emergent vascular disease caused by cessation of the blood supply to the small intestine. Despite advances in the diagnosis, intervention, and surgical procedures, AMI remains a life-threatening condition. Prostaglandin E2 major urinary metabolite (PGE-MUM), the urinary metabolite of prostaglandin E2, is known to be stable in urine and has been suggested to be a valuable biomarker for intestinal mucosal inflammation, such as ulcerative colitis. We therefore investigated whether or not PGE-MUM levels reflect the degree of ischemia in an intestinal ischemia-reperfusion model. METHODS: Male rats were used to establish a superior mesenteric artery occlusion (SMAO) group, in which the superior mesenteric artery was clamped, and a sham group. The clamping times in the SMAO group were either 30 minutes or 60 minutes, and reperfusion times were either 3 hours or 6 hours, after which PGE-MUM values were measured. RESULTS: The histological injury score of the SMAO (30-minute ischemia and 6-hour reperfusion group, 1.8 ± 0.4; 60-minute ischemia and 6-hour reperfusion group, 4.7 ± 0.5) and were significantly greater than that of the sham group (0.4 ± 0.7, p < 0.05). The PGE-MUM levels in the SMAO group (30-minutes ischemia and 6-hour reperfusion group, 483 ± 256; 60-minutes ischemia and 6-hour reperfusion group, 889 ± 402 ng/mL) were significantly higher than in the sham group (30-minute and 6-hour observation group, 51 ± 20; 60-minute and 6-hour observation group, 73 ± 32 ng/mL; p < 0.05). Furthermore, the PGE-MUM value was corrected by the concentration of urinary creatinine (Cr). The PGE-MUM/urinary Cr levels in the SMAO group were also significantly higher than in the sham group ( p < 0.05). CONCLUSION: We found that intestinal ischemia-reperfusion increased urinary PGE-MUM levels depending on the ischemic time. This suggests the potential utility of PGE-MUM as a noninvasive marker of intestinal ischemia.

Urine intestinal fatty acid-binding protein predicts acute mesenteric ischemia in patients.

BACKGROUND: Acute mesenteric ischemia (AMI) has a high morbidity and mortality and often presents as a diagnostic challenge. Currently, there is no blood, urine, or radiologic tests that provide a definitive diagnosis of AMI. The aim of this study was to evaluate the clinical accuracy of urine intestinal fatty acid-binding protein (I-FABP) to diagnosis AMI. MATERIALS AND METHODS: Twenty patients referred to the Acute Care Surgery service at University of Alberta Hospital with suspected AMI taken to the operating room for definitive diagnosis were recruited. Pathologic findings from surgical specimens confirmed a gold standard diagnosis for intestinal ischemia. The patients found to be nonischemic became the internal controls. Conventional clinical markers were examined in blood including white blood cell count, lactate, and creatinine. Blood was also examined by enzyme-linked immunosorbent assays (ELISAs) for I-FABP and interleukin-6. Urine was examined preoperatively and 6 and 24 h postoperatively for I-FABP. RESULTS: Thirteen patients were pathologically diagnosed with AMI while five patients were nonischemic; two were excluded due to missing biologic specimens. There was no difference in age or gender between ischemic and nonischemic patients (56 ± 5 versus 66 ± 11 years old, respectively; six females with ischemic and three females in the nonischemic group). There was no difference in serum lactate and creatinine between the two groups. Serum interleukin-6 levels in patients with AMI were significantly higher than nonischemic controls (0.4 ± 0.2 ng/mL versus 0.2 ± 0.07 ng/mL, respectively, P = 0.03). There was a nonstatistically significant increase in serum I-FABP in AMI patients compared to internal controls (9 ± 3 ng/mL versus 2.4 ± 0.9 ng/mL, respectively, P = 0.2). Urine I-FABP was significantly higher in patients diagnosed with AMI than in controls (7 ± 1 ng/mL versus 2 ± 1 ng/mL, respectively, P = 0.007). The receiver operating characteristic curve illustrated that urine I-FABP discriminates significantly between patients with AMI and controls (area under receiver operating characteristic = 0.88, P = 0.03). CONCLUSIONS: The traditional clinical markers lactate and white blood cell count were not able to differentiate AMI from nonischemic bowel. However, we found that urine I-FABP was a noninvasive biomarker with high specificity and sensitivity for accurately diagnosing AMI in patients. A noninvasive accurate tool for AMI would facilitate for a rapid treatment, while preventing unnecessary surgical interventions in high-risk patient populations.