Effects of in vivo pentoxifylline treatment on survival and ex vivo vascular contractility in a rat lipopolysaccharide shock model.
Depending on the dose and dosing, pentoxifylline (PTX) treatment can improve or worsen survival from lipopolysaccharide (LPS) shock in rats. Intraperitoneal (i.p.) PTX, 20 mg/kg, administered once 15 min after intravenous (i.v.) LPS (17 mg/kg), significantly improved survival in unanesthetized LPS-shocked rats. Multiple 20 mg/kg PTX injections (five total, spaced at 45 min intervals starting 15 min after LPS) significantly worsened survival. A lower dose, 12 mg/kg, given as a single or multiple injections, did not alter survival. We tested the ex vivo contractile response to norepinephrine (NE) of aortic rings isolated 3.75 hr after i.v. injection of PBS or LPS. Both untreated LPS-shocked and multiple 12 mg/kg PTX treated normal rats (i.v. PBS) had significantly diminished maximum contractility. The ex vivo vascular hypocontractility found in untreated LPS-shocked rats was not aggravated nor ameliorated by multiple 12 mg/kg PTX injections. The ex vivo effects on contractility of multiple 20 mg/kg PTX treatment of LPS shock could not be studied because survival times were shorter than 3.5 hr. In using PTX to treat LPS shock, potentially harmful vasodilation must be considered.
Fletcher
M A
MA
Septic Shock Research Program, Naval Medical Research Institute, Bethesda, MD 20889-5055.
McKenna
T M
TM
Owens
E H
EH
Nadkarni
V M
VM
D000818:Animals; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000401:mortality / Q000503:physiopathology*; D015996:Survival Rate; D014661:Vasoconstriction / Q000187:drug effects*
D008070:Lipopolysaccharides; D010431:Pentoxifylline