Propofol attenuates diaphragmatic dysfunction induced by septic peritonitis in hamsters

Background: Sepsis or peritonitis impairs diaphragmatic contractility and e ndurance capacity. Peroxynitrite, a powerful oxidant formed by superoxide a nd nitric oxide, has been implicated in the pathogenesis. Propofol scavenge s this reactive molecule. The authors conducted the current study to evalua te whether propofol prevents diaphragmatic dysfunction induced by septic pe ritonitis. Methods: Forty male Golden-Syrian hamsters (120-140 g) were randomly classi fied into five groups. Groups sham and sham-propofol 50 underwent sham lapa rotomy alone, whereas groups sepsis, sepsis-propofol 25, and sepsis-propofo l 50 underwent cecal Ligation with puncture. Groups sham and sepsis receive d infusion of intralipid, whereas groups sham-propofol 50, sepsis-propofol 25, and sepsis-propofol 50 received propofol at rates of 50, 25, and 50 mg . kg(-1) . h(-1), respectively. Intralipid or propofol was subcutaneously i nfused from 3 h before surgery until 24 h after operation, when all hamster s were killed. Diaphragmatic contractility and fatigability were assessed i n vitro using diaphragm muscle strips. Peroxynitrite formation in the diaph ragm was assessed by nitrotyrosine immunostaining. Plasma nitrite-nitrate c oncentrations and diaphragmatic concentrations of malonidaldehyde were dete rmined. Using another set of animals, diaphragmatic inducible nitric oxide synthase activity was also measured. Results: Twitch, tetanic tensions, and tensions during fatigue trials were reduced in group sepsis compared with group sham. In group SEPSIS, diaphrag m malondialdehyde and inducible nitric oxide synthase activity, and plasma nitrite-nitrate concentrations increased and positive immunostaining for ni trotyrosine residues was found. Propofol attenuated these changes. Conclusions: Pretreatment with propofol attenuated diaphragmatic dysfunctio n induced by septic peritonitis in hamsters assessed by contractile profile s and endurance capacity. This beneficial effect of propofol may be caused, in paa, by inhibition of Lipid peroxidation in the diaphragm caused by the powerful oxidant.