Pulmonary endothelial cell ATP depletion following intestinal ischemia.
Multiple organ failure (MOF) is known to follow systemic inflammatory mediator activation associated with intestinal ischemia-reperfusion injury. In particular, the pulmonary microvasculature appears to be susceptible to MOF-related injury. This study was designed to evaluate the hypothesis that non-cellular plasma factors associated with intestinal ischemia without reperfusion also mediate pulmonary endothelial cell injury. Male Sprague-Dawley rats had intestinal ischemia induced by microvascular clip occlusion of the superior mesenteric artery for 30, 60, 90, or 120 min. Following each period of ischemia, plasma samples were obtained from the protal vein. Time-matched sham-operated animals served as controls. Monolayers of cultured rat pulmonary artery endothelial cells were then incubated with the plasma samples and ATP levels determined using a luciferin-luciferase assay. A 51Cr-release assay using labeled endothelial cells was performed under identical conditions to assess cytotoxicity. Endothelial cell ATP levels were 1.99 +/- 0.23 x 10(-11) mole/micrograms DNA in sham preparations. After a 4-hr incubation in plasma from the 90 and 120 min ischemia groups, cellular ATP levels fell significantly to 1.07 +/- 0.23 x 10(-11) mole/micrograms DNA, respectively (P less than 0.005). No significant cytotoxic injury resulted from incubation with plasma from the 120 min group (1.0 +/- 0.4% versus 0.8 +/- 0.4% in sham group, P = NS). All animals survived 24 hr in the sham, 30, and 60 min groups. However, survival was 40 and 0% in the 90 and 120 min groups, respectively (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Gerkin
T M
TM
Department of Surgery, University of Michigan Medical School, Ann Arbor 48109.
Welling
T H
TH
Turnage
R H
RH
Ryan
U S
US
Guice
K S
KS
Oldham
K T
KT
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000255:Adenosine Triphosphate