Reperfusion plasma contains a neutrophil activator.
Aortic aneurysm repair produces inflammatory mediators, neutrophil activation, and remote organ injury. Reperfusion plasma from these patients produces microvascular injury in an ex vivo chemotactic model. This study investigates the mechanism of this injury. Vena caval blood was obtained before and 15 minutes after aortic clamp removal (n = 16) or at laparotomy (n = 10). Plasma or saline solution was introduced into unit dose chambers fixed atop dermabrasions on the back of depilated anesthetized rabbits. Animals were treated with intravenous saline solution (n = 4); made neutropenic with nitrogen mustard (n = 4); pretreated with the xanthine oxidase inhibitor allopurinol (n = 4); or cotreated intravenously with the free radical scavengers superoxide dismutase (SOD) and catalase (n = 4). Three hours later neutrophil counts (polymorphonuclear cells [PMN]/mm3) and activity (free radical production by flow cytometry), protein leakage, and inflammatory mediators (thromboxane [TX] and leukotriene B4 [LTB4]) were measured. In contrast to control plasma in untreated rabbits, reperfusion plasma produced TX and LTB4 generation (1090 +/- 105 and 794 +/- 91 pg/ml, respectively, p < 0.01), PMN accumulation (1636 +/- 210/mm3, p < 0.01) and activation (276 +/- 31 mean fluorescent units), and microvascular permeability (554 +/- 90 micrograms/ml, p < 0.01). Neutropenia (3 +/- 1 PMN/mm3) and cotreatment with SOD and catalase abolished these responses, whereas pretreatment with allopurinol did not. Human reperfusion plasma contains a soluble factor that stimulates free radical generation by rabbit neutrophils to produce a microvascular injury characterized by de novo TX production, neutrophil accumulation and activation, and increased microvascular permeability to protein.
Department of Vascular Surgery, Queen Elizabeth Hospital, Edgbaston, Birmingham, U.K.
I S
IS
Paterson
F C
FC
Smith
G M
GM
Tsang
J D
JD
Hamer
C P
CP
Shearman
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000601:surgery; D002374:Catalase / Q000494:pharmacology; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D003869:Dermabrasion; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000097:blood*; D012867:Skin / Q000098:blood supply / Q000473:pathology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis
D011506:Proteins; D007975:Leukotriene B4; D013929:Thromboxane B2; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase