Background:
Non-occlusive mesenteric ischemia is a relatively common and possibly fatal complication associated with surgical interventions in elderly patients. The exact pathophysiology is still unknown but circumstantial evidence suggests that complement activation plays decisive role in this process. Our objective was to investigate the long−term consequences of complement C5a antagonist (AcPepA) treatment on the circulatory changes in a clinically relevant small animal model of transient mesenteric hypoperfusion.

Material and Methods:
In two groups of anesthetized rats (n=6, each) the mean arterial pressure of the splanchnic area was kept between 40-50 mmHg for 60min by partial aortic occlusion (PAO), a third group (n=6) served as control. The first group was treated with AcPepA (4 mg/kg iv) 15 min before the end of ischemia, while the vehicle for AcPepA was administered to the other groups. After 24 hrs the animals were re−anesthetized and systemic macrocirculation, mesenteric artery flow and ileal microcirculation were monitored for 2 hrs. Plasma HMGB−1, ET−1 and TNF−α levels were determined.

Result:
24 hrs after PAO the circulatory parameters were significantly deteriorated as compared to the control group, intramural red blood cell velocity was significantly decreased, while plasma HMGB−1, ET−1 and TNF−α levels were elevated. The AcPepA treatment normalized the macrocirculatory parameters, improved the intramural microcirculation and the changes in inflammatory parameters as compared to the PAO group.

Conclusion:
The C5a antagonist AcPepA treatment can effectively influence the potentially harmful, local and global long-term circulatory and inflammatory consequences of transient, acute mesenteric hypoperfusion.

Grant support: OTKA−K104656; TAMOP−4.2.2A−11/1/KONV−2012−0035; TAMOP−4.2.2A−11/1/KONV−2012−0073