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Background Nonocclusive mesenteric ischemia can cause intestinal infarction but the diagnosis is challenging. This prospective study evaluated three plasma biomarkers of intestinal infarction after cardiac surgery. Materials and methods Patients were recruited after cardiac surgery if they required laparotomy (with or without intestinal resection) for suspected nonocclusive mesenteric ischemia. Plasma levels of D-lactate, intestinal fatty acid–binding protein (i-FABP), and smooth muscle actin (SMA) before laparotomy were measured. Results Twenty patients were recruited (68 ± 9 y, EuroSCORE: 8.7 ± 2.8, mortality 70%). A positive laparotomy ( n = 13) was associated with no change in D-lactate ( P = 0.95), decreased i-FABP ( P = 0.007), and increased SMA ( P = 0.01). All patients with high SMA had a positive laparotomy. A subgroup analysis was undertaken in the eight patients who required multiple laparotomies. D-lactate increased between the two laparotomies in nonsurvivors ( n = 4). Plasma i-FABP ( P = 0.008) and SMA ( P = 0.036) significantly decreased after the bowel resection, regardless of survival outcome. Conclusions None of the biomarkers were accurate enough to reliably diagnose intestinal infarction. However, all patients with high values of SMA developed intestinal infarction, thus warranting further investigation. An increasing D-lactate after intestinal resection suggests impending death. [ABSTRACT FROM AUTHOR]