ACUTE AND CHRONIC EFFECTS OF ETHANOL ON SPLANCHNIC LYMPH-FLOW AND PROTEIN CLEARANCE IN RATS

The ''intact cell hypothesis'' of alcoholic liver disease (ALD) purpor ts that ingested ethanol (EtOH) primarily targets cell types other tha n the hepatic parenchyma, such as perisinusoidal accessory cells (fat- storing and myofibroblast), resident or migratory immune cells, and si nusoidal endothelium. Hepatocellular dysfunction then presumably ensue s from an altered intrahepatic microenvironment resulting from EtOH-me diated target cell damage. To assess the splanchnic microcirculatory e ffects of EtOH, the fluid and protein flux in rat hepatic and intestin al lymph was examined after intragastric bolus (acute) and continuous (chronic) EtOH administration. Acutely, in anesthetized rats, the aver age pre-EtOH hepatic and intestinal lymph flow rates were indistinguis hable from the average post-EtOH lymph flow rates measured over 2-4hrs . Chronically, in rats receiving a continuous infusion of a nutritiona lly complete liquid diet containing 25% total calories as fat and 30-4 5% as EtOH over 8-16 weeks (Tsukamoto-French model), hepatic lymph flo w rates were increased compared to similarly infused controls (EtOH is ocalorically substituted with glucose) and chow-fed controls. Intestin al lymph flow rates were unchanged. Plasma and lymph total protein con centrations, venous and arterial blood pressures were unaltered by eit her acute or chronic EtOH administration. These findings are consisten t with early EtOH-mediated non-parenchymal cell alterations in ALD pat hogenesis.