Complement membrane attack complex and hemodynamic changes during human orthotopic liver transplantation.
Hemodynamic changes and elevation of intracellular calcium following reperfusion in human liver transplantation occur rapidly and do not match the time course of cytokine expression, therefore, we postulate involvement of other, pre-formed substances, such as complement. We studied 40 adult patients undergoing liver transplantation. Blood was drawn for estimation of C3, C4, C3 degradation product, membrane attack complex, and CH100 levels and elastase (a marker of neutrophil activation) at induction of anesthesia, 5 minutes before reperfusion, 5 minutes and 60 minutes after reperfusion. Cardiac output was measured by thermodilution and systemic vascular resistance was calculated at these same time points. There was a significant rise in C5b-9 membrane attack complex (P =.0012) with a corresponding fall in C3 (P =.0013) and C4 (P =.0002) levels and a rise in C3 degradation product levels (P =.0006). There was no significant change in CH100. These changes very closely followed the hemodynamic changes of a significant fall in systemic vascular resistance index (P =.0024) and increase in cardiac index (P =.0005). Elastase rose from 356 +/- 53 to 557 +/- 40 microg/L (P <.0001). There is complement activation and neutrophil activation at reperfusion in liver transplantation. Dilution alone cannot explain the fall in C3 and C4 levels as there is a corresponding increase in membrane attack complex and C3 degradation product levels with time. As both C3 and C4 are consumed, the classical pathway must be active, though alternative and lectin activated pathways may also be involved. These findings may, at least in part, explain the hemodynamic changes typically seen at reperfusion in liver transplantation.
Bellamy
Mark C
MC
Department of Anaesthesia, St James's University Hospital, Leeds, UK. m.c.bellamy@leeds.ac.uk
Gedney
Jacqui A
JA
Buglass
Helen
H
Gooi
Jimmy H C
JH
D000328:Adult; D001675:Bioethics; D002302:Cardiac Output; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D016031:Liver Transplantation; D018375:Neutrophil Activation; D010196:Pancreatic Elastase / Q000097:blood; D011788:Quality of Life; D015427:Reperfusion Injury / Q000503:physiopathology; D014655:Vascular Resistance
D003176:Complement C3; D003181:Complement C4; D015938:Complement Membrane Attack Complex; D010196:Pancreatic Elastase