We are interested in liver regeneration as an example of normal controlled growth. Why does a liver regenerate when part of it is removed? Why does regeneration stop when a normal mass of liver is restored?

Technique of repeated partial hepatectomy (79, 101).-A technique of repeated partial hepatectomy has been developed and described. Up to 80 per cent of the liver can be excised and aspirated at the first stage. Any one of the three principal lobes (right or left lateral or median) will support life if all other parts of the liver are removed at the first stage. The caudate lobe will not support life if all other parts of the liver are removed at the first stage. Additional partial removal can be done by excision at the second and third stages. At later stages the method is that of aspiration or excision plus aspiration. The use of antibiotics and careful attention to the prevention of hypoglycemia, hemorrhage, and infection permitted the repeated partial hepatectomy of twenty-four rats through eight operations without mortality. Thereafter the accruement of scarring, the decreased effectiveness of antibiotics, and increasing debility of some of the animals led to some deaths. Six rats were carried successfully through twelve repeated partial hepatectomies. Although the liver regenerated rapidly following each new surgical insult, its functional capacity recovered less and less rapidly.

Groivth Of Liver In Parabions (Unpublished)

Two experiments upon regeneration of liver in pairs of male sibling rats in parabiotic union have been completed. It is known from the experiments of Aub and others that partial hepatectomy in one partner is followed by increased mitotic activity and liver size in the intact parabion. We have tested the possibility of producing hepatomegaly in the intact parabion by two procedures: (i) repeated partial hepatectomy in one partner; (2) removal of all the liver but the median lobe, which is then inclosed in a nylon bag to prevent regeneration. Both procedures have failed to cause a sustained enlargement of the intact liver. Regeneration of the liver is not suppressed in rats in parabiotic union with an intact partner.

Toxicity of ammonium acetate in normal and partially hepatectomized rats (108a).-Since the liver is the site of conversion of ammonia to urea, it was thought possible that the ammonia load is a stimulus for liver regeneration to normal size. The toxicity of ammonium acetate administered by a single intraperitoneal injection to rats was considerably increased if given 24 hours after 70 per cent partial hepatectomy. The prior intraperitoneal injection of L-arginine afforded protection against the lethal effects of ammonium acetate in both normal and partially hepatectomized animals. A procedure was devised for continuously infusing aqueous solutions into the stomachs of rats. Near-lethal doses of ammonium acetate infused continuously by this route to normal and partially hepatectomized rats for 24 hours did not affect the changes in liver weight or the increase in the incorporation of P32-labeled inorganic phosphate into liver deoxyribose nucleic acid, which accompanied liver regeneration.

Disease

The purpose of these studies was to test the hypothesis of Selye: that exposure of animals to nonspecific stress causes diseases due in major part to "derailment" of adrenal cortical functions.