BACKGROUND AND PURPOSE: The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH: Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (I(f) ), T-type and L-type Ca²⁺ currents (I(Ca,T) and I(Ca,L) , respectively), and slowly activating delayed rectifier K⁺ current (I(Ks) ), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS: In isolated SA node cells, sevoflurane (0.12-0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased I(f) , I(Ca,T) , I(Ca,L) and I(Ks) by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS: Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on I(f) , I(Ca,T) and I(Ca,L) . These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings.
BACKGROUND AND PURPOSE: The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH: Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (I(f) ), T-type and L-type Ca²⁺ currents (I(Ca,T) and I(Ca,L) , respectively), and slowly activating delayed rectifier K⁺ current (I(Ks) ), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS: In isolated SA node cells, sevoflurane (0.12-0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased I(f) , I(Ca,T) , I(Ca,L) and I(Ks) by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS: Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on I(f) , I(Ca,T) and I(Ca,L) . These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings.
Authors: Matteo E Mangoni; Brigitte Couette; Emmanuel Bourinet; Josef Platzer; Daniel Reimer; Jörg Striessnig; Joël Nargeot Journal: Proc Natl Acad Sci U S A Date: 2003-04-16 Impact factor: 11.205
Authors: James O Tellez; Halina Dobrzynski; Ian D Greener; Gillian M Graham; Emma Laing; Haruo Honjo; Simon J Hubbard; Mark R Boyett; Rudi Billeter Journal: Circ Res Date: 2006-11-02 Impact factor: 17.367