title: Olprinone for the treatment, but not prevention, of fatigue-induced changes in guinea-pig diaphragmatic contractility.
abstract: Olprinone, a phosphodiesterase III inhibitor, improves the contractility in fatigued diaphragm in vivo, but no data are available for the treatment and prevention of fatigue-induced changes in vitro. We therefore examined the efficacy of Olprinone for the treatment and prevention of fatigue-induced changes in guinea-pig diaphragmatic contractility. The guinea-pig diaphragm strips were randomly allocated according to dose of Olprinone (0, 10(-6), 10(-5), and 10(-4) M) (n = 7 each) and were stimulated directly in an organ bath. Diaphragmatic contractility was measured by assessing twitch tension and force at 20-Hz and 100-Hz stimulation. Diaphragmatic fatigue was induced by generating rhythmic, repetitive contractions produced by 20-Hz stimulation for 5 min. In the first experiment, after the fatigue-producing period, Olprinone was administered to the organ bath for 5 min. In the second experiment, Olprinone was pretreated for 5 min, and then diaphragmatic fatigue was produced. In Experiment 1, after a fatigue-producing period, tetanic force to each stimulus decreased from baseline values (P < 0.05). Olprinone 10(-5)-10(-4) M caused an increase in force at both stimuli from fatigued values (P < 0.05). In Experiment 2, no change in tetanic force was observed by pretreatment with Olprinone (0-10(-4) M). After producing fatigue, tetanic force to each stimulus decreased from baseline values (P < 0.05). These results suggest that Olprinone 10(-5)-10(-4) M improves the fatigue-induced changes in guinea-pig diaphragmatic contractility and that pretreatment with Olprinone does not prevent diaphragmatic fatigability.
  
  
  CONCLUSIONS
  Olprinone is effective for the treatment, but not prevention, of fatigue-induced changes in guinea-pig diaphragmatic contractility.
authors.affiliation: *Department of Anaesthesiology, University of Tsukuba Institute of Clinical Medicine; and †Tsukuba Research Laboratories, Eisai Co, Ltd, Tsukuba City, Ibaraki, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Uemura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyooka
authors.forename: Setsuko
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kohei
authors.initials: K
authors.lastname: Sawada
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Adachi
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003964:Diaphragm / Q000187:drug effects; D006168:Guinea Pigs; D007093:Imidazoles / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects*; D011728:Pyridones / Q000627:therapeutic use*
chemical_list: D002316:Cardiotonic Agents; D007093:Imidazoles; D011728:Pyridones; C059498:olprinone