Influence of fructose-1,6-diphosphate on endotoxin-induced lung injuries in sheep.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
FDP treatment attenuated significantly the characteristic pulmonary hypertension, lung lymph protein clearance, and pulmonary vascular leakage seen in sheep infused with endotoxin.
Markov
Angel K
AK
Division of Cardiovascular Diseases, Department of Medicine, Jackson State University, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. amarkov@medicine.umsmed.edu <amarkov@medicine.umsmed.edu>
Warren
E Taliferio
ET
Cohly
Hari H P
HH
Sauls
David J
DJ
Skelton
Thomas N
TN
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004731:Endotoxins; D015633:Extravascular Lung Water / Q000378:metabolism; D005635:Fructosediphosphates / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D007958:Leukocyte Count; D008196:Lymph / Q000502:physiology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D002317:Cardiovascular Agents; D004731:Endotoxins; D005635:Fructosediphosphates; C044101:endotoxin, Escherichia coli; C029063:fructose-1,6-diphosphate