The gastrointestinal tract is supplied by three main arteries: the celiac trunk and the superior and inferior mesenteric arteries. These arteries split into the plexuses: serosal, submucosal and mucosal. The splanchnic vascular bed receives 25% of the cardiac output and is responsible for most blood delivery to the mucosa and submucosa. Sixty-five to seventy-five percent of the total intestinal blood flow is distributed to the intestinal mucosa at rest [19], primarily because of high metabolic demands. Approximately 90% of total intestinal blood flow is distributed to the mucosa during maximal vasodilatation [20]. A specific arrangement of arteries and veins exists in the intestinal villi. They flow parallel in the opposite direction, and they are connected through a tight capillary network. This structure causes a decline in oxygen saturation from the villi’s base up to its top, and it could be the leading cause of the intestine’s susceptibility to hypoxic injury.

In order to maintain blood flow to the brain and heart during acute hypotension, systemic autoregulation can overwhelm the protective mechanisms of bowel local autoregulation [21]. The mucosa of the intestinal wall is the layer most susceptible to the effects of ischemia. The splanchnic region participates in the regulation of circulating blood volume and systemic blood pressure. Blood flow to vital organs is maintained by shifting the flow away from the splanchnic vessels. As a consequence, any significant reduction of splanchnic blood flow can be vital in acute hypoperfusion of the heart or brain. Blood flow through the mesenteric artery is proportional to blood pressure. Despite this, previous atherosclerotic involvement of the splanchnic circulation may exacerbate the severity of ischemic involvement [22]. In addition, during the shock condition, the blood supply to the intestinal mucosa is significantly reduced due to sympathetic stimulation. Ischemia damage starts from the mucosa and continues towards the serosa. Subsequent reperfusion of the intestine results in further damage to the mucosa [23]. In case of shock, the renin-angiotensin system promotes a relative increase in mesenteric vascular tone compared to other regional vessels [24]. Mesenteric vasoconstriction is usually observed as early as 10 minutes after the onset of hypotension [25]. Furthermore, lactate production increases due to anaerobic glycolysis in response to decreased oxygen uptake below demands. In case of the vasopressor use, the microcirculatory changes result from the alpha-adrenoreceptor stimulation [26, 27] and can persist even after intestinal blood flow returns to normal [28]. Another drug that can affect the microcirculatory flow is furosemide. After furosemide administration, the increased renal blood flow leads to diminished mesenteric perfusion. This may well happen probably due to the furosemide-related activation of the renin-angiotensin system with increased levels of angiotensin II [25, 29]. However, persistent intestinal hypoperfusion leads to hypoxic bowel injury, which likely contributes to the development of organ failure and an increase in intensive care unit (ICU) patient mortality. Increased permeability of damaged mucosa and capillary endothelium can cause water and macromolecular leak into the intestinal wall, resulting in intestinal wall thickening [30]. After 6 hours from 30 minutes of ischemia, it is possible to observe a statistically significant decline in crypt-villus heights compared to the corresponding non-ischemic reference specimens, and even more after 60 minutes of ischemia. In addition, mucosal alterations associated with ischemia-reperfusion injury are apparent and more expressed in differentiated enterocytes [31]. In the early phase, the ischemic mucosal injury might be reversible. The transmural injury was described after four to six hours of ischemia [32, 33], which induced a secondary systemic inflammatory response syndrome (SIRS).

The functional intestine barrier is crucial to prevent systemic microbes and toxins contamination. The reliability of the intestinal barrier depends on the proper function of epithelial components. Failure of the barrier function could allow bacteria or microbial products, such as endotoxin or flagellin, to enter the systemic circulation, thereby amplifying the inflammatory response [34, 35]. Ischemia-reperfusion injury predominantly affects the intestinal mucosa and submucosa due to oxidative stress and inflammation, and impairs the mechanisms that prevent the translocation of bacteria from the intestinal lumen [24, 36, 37]. During recovery, the bowel may not be functional, and attempts at enteral feeding may result in intestinal distension, osmotic diarrhea, and additional intestinal damage [33]. Therefore, enteral nutrition should be cautiously administered or delayed in patients with severe heart failure being treated with dobutamine or in cases of multi-organ failure [38]. Similarly, in extracorporeal cardiopulmonary resuscitation (ECPR), delayed enteral nutrition has been associated with improved neurologically favorable survival [39].

The risk of developing NOMI increases with age, the length of CPR and its quality. Surprisingly, atherosclerosis of the mesenteric arteries is not one of the risk factors for the severity of IR intestine injury [40]. The clinical signs of NOMI are not specific enough, as early symptoms are frequently absent. In addition, patients post-CPR are, in most cases, sedated for days after the event [9, 41]. As a result, NOMI is frequently diagnosed in advanced stages. Thus, the first symptom may be profuse diarrhoea or increased waste from the nasogastric tube, which are non-specific signs of intestinal dysfunction. NOMI could be further suspected in patients with the following symptoms mainly gastrointestinal bleeding, abdominal distension and abdominal mottling [5]. In the early stages of the disease, neither the visceral nor the parietal peritoneum is affected [42]. The early onset of profuse diarrhea (12 h) as a manifestation of ischemia-reperfusion injury has been described in patients with CA and return of spontaneous circulation (ROSC) and was associated with poor neurological outcomes [18, 43]. Similar results were observed in patients with prolonged CA [6, 44]. Although higher lactate and base excess values with lactic acidosis in patients post-CPR are non-specific signs, these values are considered alarming in terms of possible NOMI development [9].

Unfortunately, imaging methods are only of limited value for early diagnosis of NOMI.

Ultrasound is a readily available, non-invasive technique whose application in the case of NOMI is highly limited. For instance, distended intestinal bowel loops and hypoechogenic bowel wall thickening due to edema or fluid collections may be observed, but none of these findings is specific to NOMI [2].

Computed tomography (CT) can be used to detect intestinal ischemia, but several factors may also limit the value of this radiological examination. CT is helpful in the recognition of transmural intestinal necrosis and in excluding arterial occlusion [45, 46]. Unfortunately, the signs of non-occlusive intestinal ischemia are scarce in the early phase [47, 48]. Non-occlusive ischaemia of the large intestine typically manifests as ischaemic colitis. CT scan may show mural thickening, pericolic fat stranding, and mucosal hyperenhancement [46, 49]. Small bowel ischemia usually presents as a lack of wall enhancement and dilation. Identifying intestinal necrosis is crucial for further treatment, whether a surgical or conservative approach is chosen [46]. On the other hand, several further factors may limit the value of radiological examinations of CA patients. First, some patients are hemodynamically unstable initially, therefore, transportation for a CT scan can be rather complicated or even impossible. More than 40% of CA patients suffer from acute kidney injury due to IR damage [50, 51]. Furthermore, the majority of them undergo early coronary angiography because cardiac causes of CA are among the most frequent [44, 52]. Consequently, the concurrent administration of contrast media could precipitate acute kidney injury. The same problem can be observed with mesenteric angiography, the method of choice in diagnosis of acute mesenteric ischemia. Endoscopic methods for the upper or lower gastrointestinal tract may reveal mucosal lesions caused by IR injury [52]. Therefore, we can expect these lesions, especially in patients with prolonged CA, with higher doses of epinephrine or asystole. Despite its accessibility, the endoscopic examination also has several limitations. One of these is the unavailability of the small intestine. Moreover, mucosal necrosis and transmural necrosis do not always correspond. Inadequate preparation of the bowels can also complicate the examination, and the risk of perforation cannot be excluded [53].

This group of proteins is being investigated as a potential biomarker in various medical disciplines. The specific intestinal isoform (intestinal fatty acid-binding protein (I-FABP)) is a cytosolic protein expressed in mature enterocytes located at the tips of the intestinal villi, the areas most vulnerable to ischemia. The normal serum I-FABP levels span 8.33 $\pm$ 6.25 ng/mL [57]. In ischemic damage, this protein is quickly released into circulation. As a result, its serum levels increase from shallow standard to easily measurable levels. These may then reflect the severity of ischemia-reperfusion injury [54]. Several studies indicate that the sensitivity and specificity for mesenteric ischemia diagnosis are approximately (80–90% and 85–89%), respectively [15, 57]. In CA patients, FABP may also be used as a prognostic indicator. Some studies show that a higher baseline I-FABP value is associated with adverse neurological outcomes and prognosis [18, 58, 59]. A single-centre study of 69 patients admitted for CA showed that I-FABP levels were very high at admission but nearly undetectable the following day [18]. In one of the recent studies, the association between I-FABP, multiple organ dysfunction, and 30-day mortality was observed. In a cohort of 50 patients, elevated admission I-FABP levels (38 ng/L) were associated with a higher incidence of multiple organ dysfunction and mortality. Conversely, the mean I-FABP values at admission in patients with a better prognosis were 18.3 ng/L [56]. I-FABP can be detected by ELISA in serum or urine. However, these tests are not usually available in routine practice. FABP isoforms, different from intestinal FABP, are released from the brain tissue in cases of cerebral ischemia. The extent to which the values of these markers correspond to those of the intestine and the extent to which these values may support the prognostic significance of FABP are the subjects of ongoing research [60, 61, 62].

Plasma citrulline is a non-protein amino acid. It is predominantly produced by enterocytes of the small intestinal mucosa. It is known as a functional enterocyte mass marker. The average plasma concentration is about 40 umol/L [63, 64]. Most CA patients suffer from ischemia-reperfusion injury of the small intestine. Therefore, during the first 24 hours after CA, it is possible to observe decreased citrulline levels in these patients. Low plasma citrulline is mainly associated with elevated I-FABP concentrations and bacterial translocation [59]. This effect is likely to be more pronounced in patients with prolonged CA due to the severity of ischaemia and subsequent reperfusion injury. However, further research is also needed.

D-lactate may be an indicator of splanchnic hypoperfusion [65]. It is an isomeric form of lactate produced by colic bacteria as a typical result of bacterial metabolism. The normal level of D-lactate is around 5.47 $\pm$ 1.64 ug/mL. However, during ischemia, as the usual mucosal barrier is injured and permeability rises, D-lactate is released into the circulation. Since the liver cannot metabolize D-lactate due to a lack of D-lactate dehydrogenase, a higher blood concentration can be detected [57, 66]. It may also reflect the intensity of bacterial translocation [67].

Endotoxin (lipopolysaccharide or LPS) is a major component of Gram-negative bacterial membranes and is common in the human intestine [59, 67]. The average plasma concentration is approximately 3 pg/mL. If released into the circulation, it causes multiple toxic effects, primarily by activating toll-like receptor 4 (TLR4). The most significant reactions are leukocyte and immune system activation to produce pro-inflammatory cytokines and activation of the complement and coagulation systems. Endotoxemia, sepsis, or the exacerbation of the systemic inflammatory response result from the release of a large amount of endotoxin [68]. In the case of intestinal barrier injury, increased motility of the gastrointestinal tract as a consequence of nutritional administration may increase endotoxin translocation.

In association with endotoxemia, higher levels of biomarkers, such as I-FABP or citrulline, have been observed in patients after CA [59].