Effects of phosphodiesterase-III inhibitors on sevoflurane-induced impairment of rat diaphragmatic function.
BACKGROUND
Volatile anesthetics are known to cause diaphragmatic dysfunction using a whole body model. The first aim of the current study was to compare the impairing effect of halothane and sevoflurane on diaphragmatic contractile functions under unfatigued and fatigued conditions. The second purpose was to determine whether phosphodiesterase-III inhibitors can attenuate sevoflurane-potentiated reduction of contractility after fatigue.


METHODS
Using rat-isolated muscle strips, diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to halothane (1-3 MAC) or sevoflurane (1-3 MAC). Diaphragmatic functions were further assessed with exposure to 3 MAC sevoflurane in the presence and absence of milrinone, or olprinone. Cyclic adenosine monophosphate (cAMP) concentrations in the fatigued diaphragm were also measured.


RESULTS
Halothane (1-3 MAC) or sevoflurane (1-2 MAC) did not induce a direct inotropic effect under unfatigued and fatigued conditions. Sevoflurane at 3 MAC enhanced fatigue-induced impairment of twitch and tetanic tensions. Clinically relevant concentrations of olprinone improved the sevoflurane-induced potentiation of diaphragmatic dysfunction following fatigue, accompanied by restoration of diaphragmatic cAMP levels, although milrinone failed to do so.


CONCLUSIONS
Our findings suggest that sevoflurane has a greater decreasing effect on diaphragmatic contractility after fatigue than halothane, and that the clinical dose of olprinone surmounts the disadvantage of sevoflurane in various conditions where diaphragmatic fatigue is predisposed.
Uesugi
T
T
Department of Anesthesia and Perioperative Medicine, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
Mikawa
K
K
Nishina
K
K
Kodama
S-I
SI
Obara
H
H
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D010726:Phosphodiesterase Inhibitors; D000077149:Sevoflurane; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3