Effects of alpha-trinositol on systemic inflammation and renal function in ovine bacterial sepsis.
Neuronally secreted peptides are important mediators of hemodynamic changes in the systemic inflammatory response. The inositol derivative D-myo-inositol[1,2,6]triphosphate (alpha-trinositol) has been demonstrated to be a specific nonpeptide antagonist of vasoconstriction induced by neuropeptide Y. We induced sepsis by a 48 h continuous infusion of Pseudomonas aeruginosa (10(6) colony-forming unit/min intravenously [i.v.]) in 12 chronically instrumented, conscious sheep. After 24 h, the animals were randomized to receive either alpha-trinositol (i.v. bolus of 2 mg/kg, followed by a continuous infusion of 3.5 mg/kg/h) or the saline carrier. alpha-Trinositol increased the heart rate (108 +/- 4 to 152 +/- 9 beats per minute) and reduced the stroke volume index (65 +/- 5 to 49 +/- 2 mL/beat/m2) but did not change cardiac index. Left ventricular stroke work decreased significantly (80 +/- 9 to 58 +/- 7 g.m/m2). All blood flows except the infrarenal aortic flow were increased after 24 h, but treatment decreased only the flow to the hind limb region. Urine output and fractional sodium excretion significantly increased without osmotic diuretic effects after alpha-trinositol. In treated animals, we found significantly lower leukocyte counts in all organ tissues. We conclude that alpha-trinositol modulates the cardiac performance and the local inflammatory response in tissues, and improves the fluid balance in septic sheep.
Lingnau
W
W
Department of Anesthesia and Intensive Care Medicine, Leopoid-Franzens-University of Innsbruck, Austria.
McGuire
R
R
Booke
M
M
Traber
L D
LD
Traber
D L
DL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy*; D002464:Cell Migration Inhibition; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D007295:Inositol Phosphates / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007295:Inositol Phosphates; C059368:atrinositol