Influence of Fructose-1,6-Diphosphate on Endotoxin-Induced Lung Injuries in Sheep

Abstract

Fructose-1,6-diphosphate (FDP) is reported to have a salutary effect in endotoxin shock and sepsis. This investigation describes the effect of FDP on pulmonary and systemic hemodynamics, lung lymph protein clearance, and leukocyte count in sheep infused with Escherichia coli endotoxin. Anesthetized sheep (n = 18), some of which underwent thoracotomy to cannulate lymphatic nodes, were used in this study. After stabilization, all sheep received E. coli endotoxin, 5 microg/kg i.v. infusion over 30 min. Concomitant with the endotoxin infusion, half of the animals were randomly selected to receive an i.v. bolus of FDP (10%), 50 mg/kg, followed by a continuous infusion of 5 mg.kg(-1).min(-1) for 4 h; the rest were treated in the same manner with glucose (10%) in 0.9% NaCl. Pulmonary artery pressure (PAP) and resistance in the glucose group increased from 20.8 +/- 1.6 to 36.7 +/- 3.2 mmHg (P < 0.007) and from 531 +/- 114 to 1137 +/- 80 dyn.s(-1).cm(-5), respectively (P < 0.005). Despite an increase during endotoxin infusion, these parameters in the FDP group returned to control values. There were no differences in left ventricular pressures, cardiac output, heart rate, and arterial oxygen tension between the groups. In the glucose group, lymph protein clearance was higher (P < 0.01) and blood leukocyte count was lower (P < 0.02). The wet/dry lung weight ratio (g/g) for the glucose group was 5.57 +/- 0.04 and for the FDP-treated group 4.76 +/- 0.06 (P < 0.0005). FDP treatment attenuated significantly the characteristic pulmonary hypertension, lung lymph protein clearance, and pulmonary vascular leakage seen in sheep infused with endotoxin.