Microcirculatory perfusion deficits are not essential for remote parenchymal injury within the liver

A normotensive model of hindlimb ischemia-reperfusion in Wistar rats was us ed to test the hypothesis that microvascular perfusion deficits contribute to the initiation of remote hepatic injury during a systemic inflammatory r esponse. Animals were randomly assigned to one of three groups: 4 h of isch emia with 6 h of reperfusion (I/R-6; n = 4), 4 h of ischemia with 3 h of re perfusion (I/R-3; n = 5), or no ischemia (naive; n = 5). With intravital fl uorescence microscopy, propidium iodide (PI; 0.05 mg/100 g body wt) was inj ected for the in vivo labeling of lethally injured hepatocytes (number/10(- 1) mm(3)). PI-positive hepatocytes increased progressively over the 6-h per iod (naive 32.9 +/- 7.8 vs. I/R-3 92.8 +/- 11.5 vs. I/R-6 232 +/- 39.2), wi th no difference between periportal and pericentral regions of the lobule. Additionally, a significant decrease in continuously perfused sinusoids (na ive 70.0 +/- 1.5 vs. I/R-3 65.0 +/- 1.0 vs. I/R-6 48.8 +/- 0.9%) was measur ed. Regional sinusoidal perfusion differences were only observed after 3 h of limb reperfusion. Indirect measures of hepatocellular injury using alani ne transaminase levels support the progressive nature of hepatic parenchyma l injury (0 h 57.8 +/- 6.5 vs. El h 115.3 +/- 20.7 vs. 6 h 125.6 +/- 19.5 U /l). Evidence from this study suggests that remote hepatic parenchymal inju ry occurs early and progresses after the induction of a systemic inflammato ry response and that microvascular perfusion deficits are not essential for the initiation of such injury.