Effects of nucleoside transport inhibition on hepatosplanchnic perfusion, oxygen extraction capabilities, and TNF release during acute endotoxic shock

We explored the effects of the nucleoside transport inhibitor draflazine on regional blood flow. O-2 extraction capabilities, and tumor necrosis facto r (TNF) release in acute endotoxic shock. Fourteen anesthetized and mechani cally ventilated dogs received 2 mg/kg of Escherichia coil endotoxin and we re divided into two groups. Seven dogs received 0.1 mg/kg of draflazine 30 min before endotoxin, and 7 dogs served as a control group. Draflazine decr eased arterial pressure without influencing cardiac index. Mesenteric and p ortal blood flow and ileum mucosal perfusion increased, but renal blood flo w dramatically decreased. After endotoxemia, the draflazine-treated dogs ha d a lesser fall in cardiac index, filling pressures, and left ventricular s troke work index, and a lesser increase in pulmonary vascular resistance. A fter fluid resuscitation, they had a consistently lower renal blood flow an d ileum mucosal perfusion, but a higher mixed venous and hepatic oxygen sat uration and arterial pH than the control group. When cardiac index was redu ced by tamponade to study the O-2 extraction capabilities, renal blood flow and ileum mucosal perfusion remained lower in the draflazine group. Drafla zine did not influence whole-body O-2 extraction capabilities, but it delay ed the occurrence of liver O-2 supply dependency as indicated by a signific antly lower liver DO(2)crit (27.7 +/- 3.9 vs. 43.3 +/- 10.8 mL/min) and a h igher O(2)ERcrit (62.7 +/- 9.5 vs. 42.5 +/- 7.1%) than controls (both P < 0 .05). On the other hand, draflazine increased intestinal DO(2)crit (42.4 +/ - 15.4 vs. 27.7 +/- 6.5 mL/min, P < 0.05) compared to the control group. TN F levels remained higher in the draflazine group than in the control group, particularly 3 and 4 h after endotoxin administration. We conclude that nu cleoside transport inhibition with draflazine does not alter global and hep atosplanchnic hemodynamics but may decrease gut mucosal perfusion and renal blood flow. However, this intervention can improve liver O-2 extraction ca pabilities in acute endotoxic shock.