Leukocyte activation does not mediate myocardial leukocyte retention during endotoxemia in rabbits.
Our goal was to determine whether coronary leukocyte retention after endotoxin infusion was due primarily to leukocyte activation. Leukocytes were activated by infusion of endotoxin into 12 blood donor rabbits. Separately, 12 isolated rabbit hearts were perfused with blood from an endotoxemic support rabbit to expose coronary endothelium to an inflammatory stimulus. During an infusion of 20 ml of donor blood into the isolated heart, the coronary transit time of leukocytes was determined by deconvolution of multiple measurements of injectate and collected leukocyte concentrations. With no leukocyte activation or inflammatory stimulation of endothelium, leukocyte transit time was 9.2 +/- 3.5 s, and 11.6 +/- 4.1 x 10(6) leukocytes were retained in the coronary circulation. Leukocyte activation alone did not alter transit time (9.8 +/- 3.2 s) or retention (9.3 +/- 4.6 x 10(6) leukocytes). Inflammatory stimulation of endothelium with and without leukocyte activation increased transit time (18.0 +/- 3.6 and 18.9 +/- 3.8 s, respectively; P < 0. 05) and retention (24.8 +/- 8.4 and 25.3 +/- 6.8 x 10(6) leukocytes, respectively; P < 0.05) to the same extent. Differential counts showed that neutrophils (but not lymphocytes) were slowed and retained. Inflammatory stimulation of endothelium caused coronary capillary endothelial swelling and pseudopod formation. Thus increased coronary neutrophil transit time and retention are due to structural changes of coronary endothelial cells or other effects of the inflammatory response occurring within coronary capillaries, not only due to activation of leukocytes.
Goddard
C M
CM
Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada V6Z 1Y6.
Poon
B Y
BY
Klut
M E
ME
Wiggs
B R
BR
vanEeden
S F
SF
Hogg
J C
JC
Walley
K R
KR
D000818:Animals; D003326:Coronary Circulation; D019446:Endotoxemia / Q000097:blood* / Q000503:physiopathology*; D004927:Escherichia coli Infections / Q000097:blood* / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D011817:Rabbits