Loss of hepatic venous responsiveness after endotoxin in anesthetized cats

Endotoxin (from Salmonella enteriditis ) was administered either as an intravenous bolus injection after administration of indomethacin to prevent the acute anaphylactoid response or as a slow intravenous infusion to cats anesthetized with pentobarbital. Within 30 min, hepatic blood volume measured by plethysmography increased by 30%. However, unlike the outflow block seen in dogs after endotoxin, this increase in blood volume was associated with a fall in portal and hepatic lobar venous pressures. Responses to hepatic nerve stimulation (1-8 Hz), to intravenous infusions of norepinephrine (0.2-1.0 microgram X kg-1 X min-1), and to infusions into the hepatic artery of norepinephrine (0.1-0.5 microgram X kg-1 X min-1) and angiotensin II (0.1-0.5 microgram X kg-1 X min-1) were compared before and 150 min after endotoxin administration. Both portal pressure and hepatic blood volume responses to these stimuli were markedly depressed by 150 min after endotoxin. We conclude that in cats endotoxin causes a markedly depressed responsiveness of hepatic venous smooth muscle to agonists and a modest pooling of blood in the liver probably due to impairment of preexisting sympathetic tone. Although these hepatic venous effects were observed at a time when cardiac output was not markedly depressed, it is suggested that they may play a significant role in the later development of reduced cardiac output and shock.