Effects of phosphodiesterase‐III inhibitors on sevoflurane‐induced impairment of rat diaphragmatic function

Abstract

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. 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. 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. 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.