Microcirculatory perfusion deficits are not essential for remote parenchymal injury within the liver.
A normotensive model of hindlimb ischemia-reperfusion in Wistar rats was used to test the hypothesis that microvascular perfusion deficits contribute to the initiation of remote hepatic injury during a systemic inflammatory response. Animals were randomly assigned to one of three groups: 4 h of ischemia with 6 h of reperfusion (I/R-6; n = 4), 4 h of ischemia with 3 h of reperfusion (I/R-3; n = 5), or no ischemia (naive; n = 5). With intravital fluorescence microscopy, propidium iodide (PI; 0.05 mg/100 g body wt) was injected for the in vivo labeling of lethally injured hepatocytes (number/10(-1) mm(3)). PI-positive hepatocytes increased progressively over the 6-h period (naive 32.9 +/- 7.8 vs. I/R-3 92.8 +/- 11.5 vs. I/R-6 232 +/- 39.2), with no difference between periportal and pericentral regions of the lobule. Additionally, a significant decrease in continuously perfused sinusoids (naive 70.0 +/- 1.5 vs. I/R-3 65.0 +/- 1.0 vs. I/R-6 48.8 +/- 0.9%) was measured. Regional sinusoidal perfusion differences were only observed after 3 h of limb reperfusion. Indirect measures of hepatocellular injury using alanine transaminase levels support the progressive nature of hepatic parenchymal injury (0 h 57.8 +/- 6.5 vs. 3 h 115.3 +/- 20.7 vs. 6 h 125.6 +/- 19.5 U/l). Evidence from this study suggests that remote hepatic parenchymal injury occurs early and progresses after the induction of a systemic inflammatory response and that microvascular perfusion deficits are not essential for the initiation of such injury.
London Health Sciences Centre Research Incorporated and the Departments of Medical Biophysics and Surgery, University of Western Ontario, London, Ontario, Canada N6A 4G5.
R W
RW
Brock
M W
MW
Carson
K A
KA
Harris
R F
RF
Potter
D000818:Animals; D016923:Cell Death / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007511:Ischemia / Q000150:complications / Q000473:pathology*; D008099:Liver / Q000473:pathology*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology