[Effects of olprynone hydrochloride and milrinone on the Ca(2+)-related functions of skinned skeletal muscle fibers from the guinea pigs].
It was reported that phosphodiesterase (PDE) inhibitors such as caffeine, theophylline and amrinone accelerate Ca(2+)-induced Ca2+ release (CICR) rate from sarcoplasmic reticulum (SR) in skeletal muscle. In this study, the effects of PDE III inhibitors, olprynone hydrochloride and milrinone, on the Ca(2+)-related functions (CICR rate from SR, Ca2+ uptake into SR and Ca2+ sensitivity of the contractile system) of the skeletal muscle were examined using the chemically skinned fiber technique (Endo's method) in the extensor digitorum longus of gunia pigs. Olprynone hydrochloride and milrinone accelerated CICR rate in a dose-dependent manner (at higher concentrations than their clinical concentrations). Initial rate of Ca2+ uptake into SR and Ca2+ sensitivity of the contractile system were not affected at 1 mM of olprynone hydrochloride and 0.3 mM of milrinone. These results suggest that olprynone hydrochloride and milrinone may be safe to use within the limits of the clinically recommended concentrations in a MH susceptable patient, especially in a case in which CICR rate is accelerated compared with that in a normal patient using the skinned fiber test.
Nakajima
E
E
First Department of Anesthesiology, Toho University School of Medicine, Tokyo.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003285:Contractile Proteins / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D020105:Milrinone / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D003285:Contractile Proteins; D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D020105:Milrinone; D002118:Calcium