Effect of C1-INH on ischemia/reperfusion injury in a porcine limb ex vivo perfusion model

Effects of C1 inhibitor on endothelial cell activation in a rat hind limb ischemia-reperfusion injury model

“…22,23 Our study confirms this by demonstrating that deposition of IgM, C1r, and C4d was significantly increased in reperfused limbs of the nontreated I/R injury group. Pretreatment with 100 IU/kg C1 INH reduced deposition of IgM and C4d, consistent with earlier data obtained by in vitro, 24 ex vivo, 25,26 and in vivo experiments. 27 Deposition of the C1 complex, measured as C1r, was not affected by C1 INH administration.…”

“…This is in line with earlier data on C1q of our group 28 and suggests that the protective role of C1 INH may not depend on inhibition of C1q binding or the formation of the C1 complex. 29 However, in contrast to data from ex vivo porcine limb reperfusions published by our group, 26 quantification of C3b/c deposits was not significantly different between C1 INH treatment and controls (data not shown). This may be due to different animal models (amputation ex vivo and limb I/R injury in vivo) and species (pigs vs rats).…”

“…Pretreatment of the rats with 100 IU/kg C1 INH clearly reduced fibrin deposition, in line with an experimental porcine limb amputation study of our group. 26 This suggests either a direct effect of C1 INH treatment on the coagulation cascade or an indirect effect through prevention of EC activation.…”

“…32 In this study, loss of HS expression was observed in both contralateral and reperfused limbs after I/R, in line with previous data published by Rehm et al 33 Shedding of HS was prevented by pretreatment with both 50 IU/kg and 100 IU/kg of C1 INH, consistent with earlier reports in a xenograft rejection model 34 and our data. 26,28 5 0 PAI-1 is a member of the serine protease inhibitor (serpin) family and a key regulator of the fibrinolytic system. Increased PAI-1 expression is a marker of EC activation, indicating decreased fibrinolytic activity of the endothelium.…”

Leukoreduction in ex vivo perfusion circuits: comparison of leukocyte depletion efficiency with leukocyte filters

“…Perfusion solutions containing red blood cells (RBCs) as the oxygen carrier improve outcomes when compared to acellular perfusates. 4,5 Whole blood-based perfusates have been shown to be effective oxygen carriers, largely in part to the high concentration of RBCs. 6 In addition, whole blood-based perfusates contain protectants against free-radical injury as well as physiologically necessary ions and nutrients 6 and have been shown to minimize injury during EVP improving organ function.…”