Anesthesia and analgesia
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Anesthesia and analgesia · Aug 1999
The combined effects of sevoflurane and remifentanil on central respiratory activity and nociceptive cardiovascular responses in anesthetized rabbits.
We studied the effects of sevoflurane and remifentanil, alone and in combination, on phrenic nerve activity (PNA), resting heart rate (HR), arterial pressure (MAP), and changes in HR (delta HR) and MAP (delta MAP) evoked by electrical stimulation of tibial nerves in anesthetized rabbits. The 50% effective dose (95% confidence intervals) for the depressant effects of sevoflurane on delta HR, delta MAP, and PNA were 2.3 (1.8%-2.6%), 2.7 (2.3%-2.9%), and 3.4 (3.1%-3.7%), respectively, and for remifentanil were 0.100 (0.050-0.132), 0.850 (0.720-1.450), and 0.090 (0.080-0.145) microgram.kg-1.min-1, which were reduced to 0.046 (0.021-0.065), 0.110 (0.080-0.200), and 0.030 (0.020-0.040) microgram.kg-1.min-1, respectively, by 1% sevoflurane. Depression of evoked cardiovascular responses relative to PNA was greater for sevoflurane and less for remifentanil both alone and in combination with sevoflurane. Sevoflurane acted synergistically with remifentanil on PNA and delta MAP, but not delta HR, for which their combined effect was additive. Coadministration of 1% sevoflurane with the highest infusion rate of remifentanil (1.6 micrograms.kg-1.min-1) used during combined administration reduced resting HR and MAP by 25% (P < 0.05) and 41% (P < 0.05), respectively, which was greater than the predicted reductions of only 14% and 15% if their combined effects had been additive. We conclude that sevoflurane caused a relatively greater depression of nociceptive cardioaccelerator and pressor responses compared with PNA and vice versa for remifentanil. When coadministered, their combined effects on PNA, resting HR, MAP, and delta MAP were synergistic, whereas they were merely additive for delta HR. ⋯ Although sevoflurane caused relatively greater depression of nociceptive cardiovascular responses compared with phrenic nerve activity, remifentanil either alone or combined with sevoflurane caused a much greater depression of phrenic nerve activity than cardio-accelerator and pressor responses. This could imply that, during major surgery using anesthesia combining sevoflurane and remifentanil, spontaneous ventilation is not acceptable, and depression of the resting circulation may be much greater than anticipated.
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Anesthesia and analgesia · Aug 1999
Methylene blue, a soluble guanylyl cyclase inhibitor, reduces the sevoflurane minimum alveolar anesthetic concentration and decreases the brain cyclic guanosine monophosphate content in rats.
The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signal pathway plays an important role in anesthetic and analgesic effects. We sought to determine the involvement of inhibition of soluble guanylyl cyclase (sGC) in the anesthetic mechanism and site of action of volatile anesthetics. We examined the effect of intracerebroventricular (ICV) administration of methylene blue (MB), a sGC inhibitor, on the minimum alveolar anesthetic concentration (MAC) of sevoflurane and the brain cGMP content in rats in vivo. We also investigated the effect of sevoflurane on NO-stimulated sGC activity in vitro. The rats were divided into three groups. After the ICV administration of MB, sevoflurane MAC and brain cGMP contents were measured in the first group and the second group, respectively. In the third group, brain cGMP contents were determined after sevoflurane anesthesia without the ICV administration of MB to examine the direct effect of sevoflurane on brain cGMP contents. MB significantly decreased sevoflurane MAC and brain cGMP content in a dose-dependent manner. Sevoflurane itself also dose-dependently decreased cGMP contents in brain in vivo and inhibited the NO-stimulated sGC activity in vitro. These results suggest that the inhibition of the NO-cGMP signal pathway at the sGC level could be involved in anesthetic or analgesic effects, and the inhibitory effect of sevoflurane on sGC would be one of the sites of action of this anesthetic. ⋯ Because the nitric oxide-cyclic guanosine monophosphate signal pathway mediates nociception and the site of action of halogenated volatile anesthetics in uncertain, we examined the possible involvement of inhibition of soluble guanylyl cyclase in the anesthetic mechanism. The inhibitory effect of sevoflurane on soluble guanylyl cyclase could be one of sites of this anesthetic.