A histopathological study of anoxic-resuscitated liver allografts

Abstract

The possibility of resuscitating livers after warm ischaemia has been recently suggested. The aim of the present investigation was to analyse the effects of anoxia on the morphology of hepatic cells, to determine whether these effects are reversible after providing a resuscitation period between warm ischaemia (WI) and cooling, and to study the behaviour of the resuscitated liver in the recipient organism. Ten female, Large-White pigs acted as donors for 10 recipient animals of the same kind who received an orthotopic liver graft. Recipients were divided into two groups depending on whether the livers they received had undergone a resuscitation period (Group 1 (n=5) where animal livers were subjected to 5 min warm ischaemia (WI) without resuscitation, and Group 11 (n=5) where the livers were subjected to 5 min WI followed by 5 min resuscitation). Morphological and ultrastructural studies of liver cells were performed using light and electron microscopy. ATP, ADP and AMP levels were determined in liver biopsies by high performance liquid chromatography (HPLC). Plasma AST and bilirubin levels in the two groups were compared 24 h after transplantation. After 5 min of anoxia, hepatocytes showed two morphological pattems in response to WI. Some were appreciably condensed with dark mitochondria, peroxisomes and some cytoplasmic vacuoles. Others showed electronlucent organelles, inflamed mitochondria with broken cristae and disorganized endoplasmic reticulum. Hepatocytes showed globular microvilli and bleb formation with migration towards the sinusoids. One hour after the revascularisation of the resuscitated livers, the hepatocytes showed nearly normal morphological characteristics. However, the hepatocytes of nonresuscitated organs continued to show alterations. Kupffer cells were activated in the livers of both experimental groups. Ultrastructural changes and total tissue adenine nucleotide (TAN) levels recovered completely in resuscitated livers soon after transplant. These results suggest that when short WI periods are followed by equivalent periods of resuscitation, the hepatocytes of transplanted livers recover from the effects of anoxia.