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


CONCLUSIONS
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.
Fujii
Y
Y
Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City, Ibaraki, Japan. yfujii@igaku.md.tsukuba.ac.jp
Toyooka
H
H
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D003964:Diaphragm / Q000187:drug effects; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D011728:Pyridones / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C059498:olprinone; D009529:Nicardipine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3