Effect of aprotinin on neutrophil function after major vascular surgery.
High-dose aprotinin reduces blood loss and blood transfusion requirements during liver transplantation and cardiac and vascular surgery. The mechanism of the haemostatic effect of aprotinin is unclear. A general effect on the anti-inflammatory response may be involved. Because leucocyte activation is part of this process, white cell function was measured in patients undergoing aortic surgery who received high-dose aprotinin therapy (n = 10) and was compared with the results from controls who did not (n = 10). The test group received an intravenous bolus (2 x 10(6) kallikrein inhibitor units) of aprotinin after induction of anaesthesia followed by continuous infusion (0.5 x 10(6) kallikrein inhibitor units/h) until the end of the operation. Blood samples were obtained before operation, immediately after surgery, and 1 and 7 days after operation. Aprotinin maintained significantly better postoperative white cell function as measured by bipolar shape formation (P less than 0.001), unstimulated nitroblue tetrazolium (NBT) reduction (P less than 0.001) and chemotaxis (P less than 0.001). Endotoxin-stimulated NBT reduction was similar in both groups, indicating that neutrophils from treated individuals retained the capacity to respond to oxidative stimuli. Aortic surgery activates neutrophils in vivo, as reflected by impaired chemotaxis and increased superoxide production. Aprotinin protects the cells against this potentially deleterious effect without affecting their ability to respond when provoked. Whether this affects leucocyte interaction with coagulation pathways and contributes to the reduction in blood loss remains to be determined.
Lord
R A
RA
University Department of Haematology, General Hospital, Southampton, UK.
Roath
O S
OS
Thompson
J F
JF
Chant
A D
AD
Francis
J L
JL
D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000601:surgery*; D001018:Aortic Diseases / Q000601:surgery*; D007611:Aprotinin / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011184:Postoperative Period
D007611:Aprotinin