Pentoxifylline improves survival and reduces tumor necrosis factor, interleukin-6, and endothelin-1 in fulminant intra-abdominal sepsis in rats.
The influence of pentoxifylline (PTX) on mortality and some important mediators was studied in a model of cecal perforation with fulminant intra-abdominal sepsis in rats. Cumulative mortality was registered in three groups of animals: untreated sepsis (n = 36), sepsis + PTX 20 mg/kg/24 h (n = 24), and sepsis + PTX 80 mg/kg/24 h (n = 24). PTX therapy was started at sepsis induction or after 4 h, and mortality was reduced from 89% in untreated sepsis to 60-66% in the PTX groups. Levels of sepsis mediators were studied in two groups: untreated sepsis and sepsis + PTX 40 mg/kg started 1 h after sepsis induction. In both groups 6-10 animals were sacrificed at 4 and 8 h to measure blood levels of bacteria, endotoxin, tumor necrosis factor (TNF), interleukin-6 (IL-6), endothelin-1, lactate, neutrophils, and packed cell volume. Cecal perforation gave high levels of bacteria, endotoxin, TNF, IL-6, and endothelin-1, leading to dehydration, lactacidosis, neutropenia, and death. Treatment with PTX did not modify dehydration, neutropenia, or concentrations of bacteria and endotoxin. Release of endothelin-1 was delayed, TNF burst was nearly abolished, and levels of IL-6 and lactate were substantially suppressed. In summary, PTX improves survival and reduces blood concentrations of TNF, IL-6, lactate, and endothelin-1 in fulminant intra-abdominal sepsis in rats. The primary effect of PTX in this sequence is probably reduction of TNF.
Lundblad
R
R
Department of Surgery, Norwegian Radium Hospital, Oslo.
Ekstrøm
P
P
Giercksky
K E
KE
D000005:Abdomen / Q000382:microbiology*; D000818:Animals; D002429:Cecal Diseases; D004195:Disease Models, Animal; D016232:Endothelins / Q000097:blood / Q000187:drug effects*; D004731:Endotoxins / Q000097:blood; D015850:Interleukin-6 / Q000097:blood* / Q000493:pharmacokinetics; D007416:Intestinal Perforation; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D051379:Mice; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000517:prevention & control*; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects*
D016232:Endothelins; D004731:Endotoxins; D015850:Interleukin-6; D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D010431:Pentoxifylline