Complement Activation during Cardiopulmonary Bypass

Abstract

We observed complement activation in 15 adults undergoing total cardiopulmonary bypass. Plasma levels of C3a were significantly elevated (P < 0.0001) at the beginning of the procedure, and they continued to increase steadily thereafter. At the end of the procedure, C3a levels were more than five times higher than preoperative levels. Plasma levels of C5a (a factor that binds avidly to neutrophils) did not change significantly during cardiopulmonary bypass. Instead, there was significant neutrophilia (P = 0.03) during bypass, and significant transpulmonary neutropenia (P = 0.0002) occurred when cardiopulmonary circulation was reestablished at partial bypass. The neutropenia is consistent with pulmonary-vascular sequestration of C5a-activated granulocytes. We also found that incubation of blood with the nylon-mesh liner of bubble oxygenators, as well as vigorous oxygenation of whole blood, promotes conversion of complement. We conclude that the complement-derived inflammatory mediators C3a and C5a produced during extracorporeal circulation may contribute to the pathogenesis of "post-pump syndromes."

Complement activation during systemic lupus erythematosus: C3A and C5a anaphylatoxins circulate during exacerbations of disease

“…Our observation that plasma levels of C3a were higher than those of C5a confirms previous reports of these values in other diseases (10)(11)(12). This result may be due to at least 2 factors that relate to production and clearance of these cleavage products.…”

“…While C3a and C5a are rapidly converted by plasma carboxypeptidase N to desArg forms, which lack anaphylatoxin activity, it is important to note that C3a desArg and C5a desArg retain the capacity to activate platelets ( 5 ) and neutrophils (7,8), respectively. Indeed, the aggregation of these cells in small vessels upon exposure to C3a and C5a is believed to play a central role in the development of the tissue injury observed during endotoxic shock (14), adult respiratory distress syndrome (23), and LCrebral injury after cardiopulmonary bypass (12). It is therefore not unlikely that in some SLE patients, the exposure of neutrophils and platelets to these complement-derived mediators would be a cause of significant vascular injury.…”

Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation.

“…Previous studies have demonstrated that complement activation occurs during CPB ( 1-4). Additionally, the role of complement in the associated morbidity and mortality has been indirectly demonstrated in a number of studies (42)(43)(44), where indices of cardiac and pulmonary dysfunction in adults and multisystem organ failure in infants and children correlated significantly with complement activation. However, the exact role of the various activated complement products such as C3a, C3b, C5a, and CSb-9 in the induction of many of the specific cellular changes associated with CPB is ill-defined because of the paucity of effective complement inhibitors.…”

Up‐Regulation of Endothelial Cell Adhesion Molecules Characterizes Disease Activity in Systemic Lupus Erythematosus

“…It is important to note that, regardless of the mechanism which leads to their production, the complement-derived anaphylatoxins generated in the plasma of patients with active SLE are potential inflammatory mediators: C3a des Arg and C5a desArg activate platelets (29) and neutrophils (30), respectively. Aggregation of these cells in small vessels following exposure to C3a desArg and C5a desArg has been invoked as a cause of vascular injury in diverse clinical syndromes including the adult respiratory distress syndrome (3 l), cerebral injury following extracorporeal circulation (32,33), reperfusion injury of the myocardium (34,35), and endotoxic shock (36). We have recently provided serologic and histologic evidence which suggests that syndromes of reversible hypoxemia and cerebritis in SLE may have a similar pathogenic mechanism (37).…”