RETRACTED ARTICLE: Different effects of olprinone on contractility in nonfatigued and fatigued diaphragm in dogs

Laboratory Investigation


Purpose: To evaluate the effects of low-dose olprinone, a phosphodiesterase Ill inhibitor, on contractility and its mechanism in nonfatigued and fatigued diaphragm in dogs.

Methods: Thirty six pentobarbitone-anesthetized dogs were studied. In Group la (n=6), animals without fatigue, received no study drug. In Group lb (n=6), dogs were given a bolus injection (10 μg·kg−1) followed by continuous infusion (0.1 μg·kg−1·min−1) of olprinone. In Groups lla, llb, and llc (n=8 each), diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz applied for 30 min. After producing fatigue, Group lla received no study drug; Group llb was infused with olprinone (10 μg·kg−1 loading dose plus 0.1 μg·kg−1·min−1 maintenance dose); Group llc was infused with nicardipine (5 μg·kg−1·min−1) during olprinone administration. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi).

Results: No difference in Pdi was observed between Groups la and lb. After fatigue, in Groups lla, llb, and llc, Pdi at low-frequency (20-Hz) stimulation decreased from prefatigued (baseline) values (P<0.05), whereas there was no change in Pdi at high-frequency stimulation (100-Hz). In Group llb, during olprinone administration, Pdi at both stimuli increased from fatigued values (P<0.05). In Group llc, the augmentation of Pdi to each stimulus in fatigued diaphragm by olprinone was abolished with an infusion of nicardipine.

Conclusion: Low-dose olprinone does not affect contractility in nonfatigued diaphragm, but increases contractility in fatigued diaphragm via its effect on transmembrane calcium movement in dogs.


Mean Arterial Pressure Nicardipine Milrinone Amrinone Right Atrial Pressure 


Objectif: Évaluer les effets d’une faible dose d’olprinone, un inhibiteur de la phosphodiestérase Ill, sur la contractilité et sur son mécanisme sur le diaphragme fatigué ou non, chez des chiens.

Méthode: Trente-six chiens anesthésiés au pentobarbital ont été étudiés. Dans le groupe la (n=6), les animaux non fatigués n’ont pas reçu de médicament à l’étude. Dans le groupe lb (n=6), les chiens ont reçu l’injection d’un bolus (10 μg·kg−1) d’olprinone, suivie d’une perfusion continue (0,1 μg·kg−1·min−1). Dans les groupes lla, llb, et llc (n=8 chacun), on a induit la fatigue diaphragmatique par une stimulation électrophrénique intermittente supramaximale bilatérale à une fréquence de 20 Hz appliquée pendant 30 min. Après l’induction de cette fatigue, les chiens du groupe lla n’ont pas reçu de médicament; ceux du groupe llb ont reçu une perfusion d’olprinone (10 μg·kg−1 en dose de charge plus 0,1μg·kg·min−1 comme dose de maintien); ceux du groupe llc ont reçu de la nicardipine (5 μg·kg−1·min−1) pendant l’administration d’olprinone. La contractilité diaphragmatique a été évaluée par pression transdiaphragmatique (Pdi).

Résultats: Aucune différence de Pdi n’a été observée entre les groupes la et lb. Après la production de fatigue chez les animaux des groupes lla, llb, et llc, la Pdi sous stimulation à basses fréquences (20 Hz) a diminué par rapport aux valeurs précédant la fatigue (valeurs de base),P<0,05, tandis qu’il n’y a pas eu de changement de Pdi sous stimulation à hautes fréquences (100 Hz). Dans le groupe llb, pendant l’administration d’olprinone, la Pdi a augmenté par rapport aux valeurs du muscle fatigué et ce, sous stimulation à toutes les fréquences utilisées (P<0,05). Dans le groupe llc, l’augmentation de Pdi par l’olprinone pour chaque stimulus du diaphragme fatigué a été abolie avec une perfusion de nicardipine.

Conclusion: Une faible dose d’olprinone n’a pas d’effet sur la contractilité d’un diaphragme non fatigué, mais accroît celle d’un muscle fatigué par ses effets sur le déplacement du calcium transmembranaire chez les chiens.


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© Canadian Anesthesiologists 2000

Authors and Affiliations

  1. 1.From the Department of AnesthesiologyUniversity of Tsukuba Institute of Clinical MedicineTsukuba City, IbarakiJapan

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