Olprinone decreases elevated concentrations of cytokine-induced neutrophil chemoattractant-1 in septic rats.
OBJECTIVE
The diaphragm is one of the organs directly affected by abdominal sepsis. Evidence suggests that sepsis induces diaphragmatic fatigability and that activated neutrophils play a crucial role in the development of diaphragmatic fatigability. In the present study, we investigated whether olprinone, a phosphodiesterase inhibitor, influenced the kinetics of cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the diaphragm under abdominal septic conditions.


METHODS
Male Wistar rats were randomly assigned to a sham group, a cecal ligation and perforation group, and a phosphodiesterase inhibitor-pretreated group. To measure serial changes in CINC-1 concentrations, the right hemidiaphragm was removed at 4, 8, and 16 h after the surgical procedure in each group.


RESULTS
In the cecal ligation and perforation group, CINC-1 concentrations in the diaphragm were significantly elevated compared with those in the sham group at both 4 and 8 h after the cecal ligation and perforation procedure. In the phosphodiesterase inhibitor-pretreated group, olprinone significantly attenuated the elevated CINC-1 concentrations at both 4 and 8 h after the surgical procedure. However, we observed no statistically significant differences in CINC-1 concentrations between the cecal ligation and perforation group and the phosphodiesterase inhibitor-pretreated groups at 16 h after the surgical procedure.


CONCLUSIONS
Olprinone decreases elevated CINC-1 concentration in the diaphragm under septic conditions. This suggests that olprinone may inhibit neutrophil recruitment to the diaphragm.
Miyakawa
Hiroshi
H
Department of Anesthesiology, Faculty of Medicine, Oita University, Yufu, Oita, Japan.
Kira
Shinichiro
S
Okuda
Kentaro
K
Takeshima
Naozumi
N
Mori
Masakazu
M
Noguchi
Takayuki
T
D000818:Animals; D054360:Chemokine CXCL1 / Q000187:drug effects* / Q000378:metabolism; D003964:Diaphragm / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D016896:Treatment Outcome
D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C059498:olprinone