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

摘要

PURPOSE: To evaluate the effects of low-dose olprinone, a phosphodiesterase III inhibitor, on contractility and its mechanism in nonfatigued and fatigued 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 ug x kg(-1)) followed by continuous infusion (0.1 microg x kg(-1) x min(-1)) of olprinone. In Groups IIa, IIb, and IIc (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 IIa received no study drug; Group IIb was infused with olprinone (10 ug x kg(-1) loading dose plus 0.1 microg-kg(-1) min(-1) maintenance dose); Group IIc was infused with nicardipine (5 microg x kg(-1) x 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) stimulation 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 fatigued 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 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.