Leucocyte and platelet adhesion in different layers of the small bowel during experimental total warm ischaemia and reperfusion

Abstract

Small bowel IR initiated an inflammatory and thrombotic response in the submucosal layer only. Attenuation of leucocyte adhesion improved submucosal capillary perfusion, preventing shedding of mucosal villi.

Intestinal ischemia/reperfusion: microcirculatory pathology and functional consequences

“…For example, disruption of P-selectin signaling either via blockade of the molecule or the genetic deficiency of P-selectin modulates cell trafficking and results in improved outcomes after mouse warm intestinal I/R [115]. In addition, blockade of ICAM-1 [42,113,114], PECAM-1 [114], and LFA-1 [56] has been demonstrated to effectively attenuate I/R-induced inflammatory cell response and thus intestinal injury.…”

“…As antiplatelet and antithrombotic therapies, phosphodiesterase inhibitors and acetylsalicylic acid were successfully studied and have been shown to induce organ protection upon intestinal I/R [111,112]. In addition, a myriad number of approaches implemented the application of antibodies directed against the adhesion molecules which are involved in the distinct cellular crosstalk between leukocytes, platelets, T cells, and endothelial cells [42,113,114]. For example, disruption of P-selectin signaling either via blockade of the molecule or the genetic deficiency of P-selectin modulates cell trafficking and results in improved outcomes after mouse warm intestinal I/R [115].…”

“…Besides the nature and duration of ischemia time [29,39,41], the severity of ischemia (partial or total) employed is crucial for the extent of gut injury. Total warm ischemia of 45-60 min (SMA occlusion and ligation of the inferior mesenteric artery) initiates more intense inflammatory and thrombotic reactions and yields 90-100% mortality in rats [41][42][43], while partial ischemia induced by SMA clamping only is better tolerated [43].…”

“…In the sham group no injury was found, whereas in the ischemia group grade 5 injury was observed (complete loss of villi). Bars =100 μm [with permission of Ann Surg, 40] eightfold improvement in flow through the submucosal capillaries upon complete attenuation of leukocyte interaction by anti-PAF or anti-ICAM[42]. However, inflammatory cell response is reported to be restricted to the submucosal layer, while all intestinal layers present with reduced perfusion [40], making it likely that apart from leukocytes other factors also affect capillary perfusion during I/R [37].…”

Diagnosis and management of splanchnic ischemia

“…This so-called ischemia-reperfusion cascade initiates an inflammatory and thrombotic response in the submucosal layer of the villus. In the future, antagonists of leukocyte vessel wall adhesions, an early event in the ischemia-reperfusion cascade, could attenuate these inflammatory and thrombotic responses [31] . Successful restoration of splanchnic blood flow, containing toxic products, from the ischemic area into the systemic circulation might trigger multiple organ failure.…”