Olprinone improves diaphragmatic contractility and fatigability during abdominal sepsis in a rat model.
BACKGROUND
Respiratory failure with diaphragmatic fatigability is common in patients suffering sepsis or septic shock. However, the development and progress of diaphragmatic fatigability remains poorly understood, and no method has been established to treat fatigability. In this study, we hypothesize that neutrophil activation contributes to the development of diaphragmatic fatigability. We also sought to investigate whether a phosphodiesterase inhibitor, olprinone, improves diaphragmatic fatigability associated with abdominal sepsis and inhibits an increase in myeloperoxidase activity in diaphragmatic muscle.


METHODS
Male Wistar rats were randomly assigned to a sham group, coecal legation perforation group (CLP), and a phosphodiesterase inhibitor (PDE) pretreated group. At 16 h after surgical procedure, the left hemidiaphragm was removed for the measurement of diaphragmatic contractility and fatigability. In addition, for the measurement of serial changes in myeloperoxidase activity, the right hemidiaphragm was also removed at 4, 8 or 16 h after the surgical procedure in each group.


RESULTS
In a septic model involving rats, we observed that diaphragmatic muscles were fatigable and myeloperoxidase activity increased. We also demonstrated that intraperitoneal administration of olprinone improves diaphragmatic fatigability and inhibits an increase in myeloperoxidase activity induced by abdominal sepsis.


CONCLUSIONS
Olprinone represents a potential therapy for cases of respiratory failure with diaphragmatic fatigability resulting from inhibition of neutrophil activation.
Miyakawa
H
H
Department of Anesthesiology, Faculty of Medicine, Oita University, Oita, Japan. hiroshi@med.oita-u.ac.jp
Oishi
K
K
Hagiwara
S
S
Kira
S
S
Kitano
T
T
Iwasaka
H
H
Noguchi
T
T
D000005:Abdomen / Q000473:pathology*; D000704:Analysis of Variance; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D002432:Cecum / Q000601:surgery; D003964:Diaphragm / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018763:Muscle Fatigue / Q000187:drug effects*; D018375:Neutrophil Activation / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000503:physiopathology*
D002316:Cardiotonic Agents; D007093:Imidazoles; D011728:Pyridones; C059498:olprinone; D009195:Peroxidase