SUSCEPTIBILITY OF HEPATIC MICROCIRCULATION TO REPERFUSION INJURY - A COMPARISON OF ADULT AND SUCKLING RATS

Primary graft failure and vascular thromboses are frequent complications of liver transplantation, yet the mechanisms responsible remain unclear. Previous work from our laboratory has shown that hepatic reperfusion injury results in damage at the microvessel level. The present study was performed to determine whether an increased susceptibility of immature animals to microvascular injury during reperfusion might be a contributing factor in these complications. Suckling (35 to 50 g) or adult (250 to 400 g) rats were subjected to 30 or 60 minutes of hepatic ischemia to the left and median lobes followed by 90 minutes of reperfusion. Control animals were sham-operated, time-matched rats. At the end of reperfusion, fluorescein-labeled albumin was injected systemically to mark perfused sinusoids. Frozen sections of liver biopsies were viewed under fluorescence microscopy. The perfused sinusoid density was determined by point count analysis and expressed as the number of intersections of perfused sinusoids with 25 randomly oriented points superimposed on the sinusoid field. In sham-operated rats, at both 30 and 60 minutes, there were no differences between sucklings and adults. After 30 minutes of ischemia and 90 minutes of reperfusion, adults showed a significantly decreased density of perfused sinusoids (4.5 ± 0.1 intersections per field) when compared with suckling rats (6.0 ± 0.3 intersections per field, P < .001). However, in rats subjected to 60 minutes of ischemia followed by 90 minutes of reperfusion, the microvascular injury was more severe in suckling rats (2.7 ± 0.2 intersections per field) than in adults (4.7 ± 0.2 intersections per field, P < .001). These results indicate that sinusoid density is equal in both adult and suckling rats, and that it remains constant throughout development. Although both groups showed significant microvascular damage during reperfusion following ischemia, the time course was different. While suckling rats were more tolerant of brief ischemia, the microvascular injury was more severe than that seen in adults when ischemia was prolonged. These data suggest that the duration of ischemia is a critical factor in the genesis of microvascular injury in younger rats. The more severe injury in suckling rats at 60 minutes further suggests that direct microvascular damage may contribute to graft failure and vascular thrombosis in pediatric transplant patients. © 1990.