Role of Portal Blood Supply in Liver Regeneration

Abstract

IT has been known for many years that in laboratory animals, such as the rat, partial hepatectomy is followed by liver regeneration. In recent years it has been generally accepted that this response is initiated by some sort of humoral mechanism¹. This view was, however, originally based on parabiotic and serum injection experiments, the validity of which has been contested. We have therefore been led to re-examine the alternative and much older ‘blood-flow’ theory³. This postulates that after partial hepatectomy the remaining liver fragment acquires a much more generous blood supply, since it has to accommodate portal vein blood previously destined for the excised lobes. It is this over-generous blood supply which is said to act as the stimulus to hyperplasia. The strongest evidence in favour of this theory was derived from experiments on domestic fowls, by taking advantage of the anastomosis between the post-caval and portal veins through the coccygeo-mesenteric vein. It is therefore possible to increase portal blood flow by simple ligation of the postcaval vein between the kidneys and the liver. According to the ‘blood-flow’ theory this should itself cause hyperplasia of the liver. Furthermore, the ‘blood-flow’ theory would predict that, in the fowl, partial hepatectomy would not be followed by liver regeneration, since the blood which would normally be accommodated by the missing lobes could instead return to the heart via the anastomosis. It was claimed that both these theoretical predictions were fulfilled experimentally⁴. Since the number of fowls used in these original experiments was small, and since the criteria of liver growth were very crude, it seemed worthwhile to repeat them in an improved form using mitotic frequency as an index of liver growth. For this purpose we have used 26-week-old pullets of the “Sussex Legbar” strain weighing about 1,200 g. For both operations the fowls were anaesthetized lightly with intravenous ‘Nembutal’, and anaesthesia completed with ether. In the partial hepatectomy the entire left lobe of the liver was removed through an incision in the left side parallel to the edge of the sternum and 1 cm above it. Ligation of the postcaval vein was performed through an incision in the right flank⁴.