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Anesth Analg 2003;96:1679-1782
© 2003 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Olprinone for the Treatment, but Not Prevention, of Fatigue-Induced Changes in Guinea-Pig Diaphragmatic Contractility

Aki Uemura, MD*, Yoshitaka Fujii, MD*, Hidenori Toyooka, MD*, Setsuko Suzuki{dagger}, Kohei Sawada, PhD{dagger}, and Hideyuki Adachi, PhD{dagger}

*Department of Anaesthesiology, University of Tsukuba Institute of Clinical Medicine; and {dagger}Tsukuba Research Laboratories, Eisai Co, Ltd, Tsukuba City, Ibaraki, Japan

Address correspondence and reprint requests to Yoshitaka Fujii, Department of Anaesthesiology, University of Tsukuba Institute of Clinical Med, 2-1-1, Amakubo, Tsukuba City, Ibaraki 305-8576, Japan. Address e-mail to yfujii{at}md.tsukuba.ac.jp

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.

IMPLICATIONS: Olprinone is effective for the treatment, but not prevention, of fatigue-induced changes in guinea-pig diaphragmatic contractility.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2003 by the International Anesthesia Research Society.