[Effects of complement C5a inhibitor therapy in animal models of non-occlusive mesenteric ischemia]

Non-occlusive mesenteric ischemia (NOMI) develops without anatomical causes. Early diagnosis is challenging and treatments are of questionable effectiveness. We investigated the role of complement activation in the pathophysiology of NOMI in animal models through the inhibition of complement C5a.

60-min partial aortic occlusion (PAO; abdominal aorta, proximal to celiac trunk; mean arterial pressure: 30-40 mmHg) was established in Sprague-Dawley rats (n = 28) and 60-min cardiac tamponade in minipigs (n = 19; mean arterial pressure: 40-50 mmHg) to observe short- and long-term circulatory and inflammatory consequences of NOMI. Macro- and microhemodynamics, leukocyte infiltration, plasma levels of inflammatory mediators (endothelin, HMGB-1) were measured. C5a inhibitor (Acetyl-Peptid-A; 4 mg/kg iv) was administered at the 45th min of PAO or tamponade, respectively.

Twenty-four hours after PAO systemic inflammatory response increased cardiac output and superior mesenteric artery flow (SMAF). C5a inhibition reduced the elevated cardiac output (203.1 ± 5 vs 269.6 ± 8.1 ml/min/kg) and SMAF and increased ileal microcirculation (833.5 ± 33.8 vs 441.9 ± 22.4 μm/s). In pigs, after the tamponade, C5a inhibition reduced the immediate hemodynamic disturbances, temporarily increased SMAF and permanently the ileal microcirculation. The Acetyl-Peptid-A treatment reduced leukocyte infiltration and plasma levels of inflammatory mediators in both NOMI models.

Complement activation plays central role in the macro- and microcirculatory disturbance during NOMI. C5a inhibition reduces the inflammatory activation and influences the hemodynamic consequences of experimental NOMI.