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

Purpose: To evaluate the effects of low-dose olprinone, a phosphodiesterase III inhibitor, on contractility and its mechanism in nonfatigued and fatig ued diaphragm in dogs. Methods: Thirty six pentobarbitone-anesthetized dogs were studied, In Group Ia (n=6), animals without fatigue, received no study drug. In Group Ib (n= 6), dogs were given a bolus injection (10 mug.k(-1)) followed by continuous infusion (0.1 mug.kg(-1).min(-1)) of olprinone. In Groups IIa, IIb, and II c (n=8 each), diaphragmatic fatigue was induced by intermittent supramaxima l bilateral electrophrenic stimulation at a frequency of 20-Hz applied for 30 min. After producing fatigue, Group IIa received no study drug; Group II b was infused with olprinone (10 mug kg loading dose plus 0.1 mug.kg(-1).mi n(-1) maintenance dose); Group IIc was infused with nicardipine (5 mug.k(-1 ).min(-1)) during olprinone administration. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). Results: No difference in Pdi was observed between Groups Ia and Ib. After fatigue, in Groups IIa, IIb, and IIc, Pdi at low-frequency (20-Hz) stimulat ion decreased from prefatigued (baseline) values (P < 0.05), whereas there was no change-in Pdi at high-frequency stimulation (100-Hz). In Group IIb, during olprinone administration, Pdi at both stimuli increased from fatigue d values (P < 0.05). In Group IIc, the augmentation of Pdi to each stimulus in fatigued diaphragm by olprinone was abolished with an infusion of nicar dipine. Conclusion: Low-dose olprinone does not affect contractility in nonfatigued diaphragm, but increases contractility in fatigued diaphragm via its effec t on transmembrane calcium movement in dogs.