PARENTERAL MONOACETOACETIN AND LIVER-REGENERATION INTERACTION AFTER PARTIAL-HEPATECTOMY IN THE RAT

Parenteral nutrients can be used to manipulate cell proliferation afte r partial hepatectomy. The relationship among macronutrients-glucose, monoacetoacetin, amino acids-and liver regeneration after partial hepa tectomy was investigated. Male rats were anesthetized, received a 70% hepatectomy, and received a low-dose infusion of (1) glucose or (2) mo noacetoacetin and a high-dose infusion of (3) glucose, (4) glycerol-gl ucose, or (5) monoacetoacetin-glucose beginning 6 hours after surgery. The five nonprotein nutrient combinations were infused with and witho ut amino acids. Rats were killed 48 hours after partial hepatectomy, a nd the label and mitotic indices were determined. Each of the five tre atments had a higher label index with ammo acids present than with ami no acids absent. Low-dose glucose and monoacetoacetin as well as high- dose glucose and glucose-glycerol had higher mitotic indices with amin o acids than without ammo acids. High-dose monoacetoacetin-glucose was associated with a greater mitotic index than was any other nonprotein substrate treatment, and this response was independent of amino acids being present or absent. In summary, (1) amino acids were needed for maximal cell proliferation rate; (2) the absence of amino acids and no t the presence of glucose resulted in reduction of the label and mitot ic indices for regenerating liver; (3) high-dose monoacetoacetin incre ased mitosis with or without amino acids; and (4) monoacetoacetin acti vity was dose dependent. The results indicate that the best nutrient f or treatment of patients with liver injury is acetoacetate. The second best nutrient would be the combination of high-dose glucose and ammo acids. The results further indicate that glucose should not be adminis tered to patients with liver injury unless accompanied by amino acids.