Increasing isoflurane from 0.9 to 1.1 minimum alveolar concentration minimally affects dorsal horn cell responses to noxious stimulation

BACKGROUND: The spinal cord appears to be the site at which isoflurane suppresses movement that occurs in response to a noxious stimulus. In an attempt to localize its site of suppressant action, the authors determined the effect of isoflurane on dorsal horn neuronal responses to supramaximal noxious stimulation at end-tidal concentrations that just permitted and just prevented movement. METHODS: Rats (n = 14) were anesthetized with isoflurane, and after lumbar laminectomy, the minimum alveolar concentration (MAC) for each rat was determined using a supramaximal mechanical stimulus. In these same rats, after extracellular microelectrode placement in the lumbar spinal cord, dorsal horn neuronal responses to the supramaximal stimulus were determined at the concentrations of isoflurane that bracketed each rat's MAC (0.1% higher and lower than MAC). The MAC of isoflurane was then re-determined. RESULTS: Dorsal horn neuronal response was 1,757+/-892 impulses/min at 0.9 MAC and 1,508+/-988 impulses/min at 1.1 MAC, a 14% decrease (P < 0.05). Cell responses varied, with some cells increasing their response at the higher concentration of isoflurane. The MAC of isoflurane was 1.38+/-0.2% before and 1.34+/-0.2% after determination of dorsal horn neuronal responses. CONCLUSIONS: Isoflurane, at concentrations that bracket MAC, has a variable and minimal depressant effect on dorsal horn cell responses to noxious mechanical stimulation. These data suggest that the major action of isoflurane to suppress movement evoked by a noxious stimulus might occur primarily at a site other than the dorsal horn.     

Experimental muscle pain increases the human stretch reflex

In this study we investigated the effect of human experimental muscle pain on H- and stretch reflexes as indicators of changes in muscle spindle sensitivity. Fourteen healthy, male volunteers participated in the study. Muscle pain was produced by infusion of 5% hypertonic saline over a period of 10-15 min in m. soleus and in m. tibialis anterior. Reflexes were elicited in the relaxed and active soleus muscle (10-15 Nm ankle torque) before, during and after muscle pain. Control measurements were made with infusions of 0.9% isotonic saline. Surface electromyograms (EMG) were measured from the soleus muscle, and torque was measured from the ankle joint. With pain in the soleus muscle the mechanical stretch reflex response (ankle torque) increased significantly (P = 0.0007) as compared to before pain. With pain in the tibialis anterior muscle both the mechanical and EMG responses increased significantly (P = 0.001; P = 0.0003) as compared to before pain. The H-reflex showed no significant changes during the infusions in either muscles. This study has demonstrated a muscle pain-related increase in the amplitude of the stretch reflex without a corresponding increase in the H-reflex amplitude. One explanation could be an increased dynamic sensitivity of the muscle spindles during muscle pain caused by an increased firing rate in the dynamic gamma-motoneurones. However, the data could not support the vicious cycle model because the excitability of the alpha-motoneurone pool was unchanged.     

Molecular mechanism of cell membrane lipids

The effects of nembutal and ketamine anesthesia on motor evoked potentials (MEPs) and spinal segment reflex (H-response, F and M waves) were investigated in rats by magnetic stimulation. These potentials were generated by magnetic stimulation of the motor cortex and the spinal cord (L4-L5). After application of nembutal, MEP and H-response decreased in amplitude, eventually disappearing. The amplitudes of F and M waves increased and persisted at the increased levels during anesthesia. The latencies of F and M waves were constant before and after anesthesia. Following ketamine administration, the threshold, latency and amplitude of the magnetically induced MEPs, and M, F and H responses were not influenced systematically. The results suggested that MEPs and H-response depression and/or disappearance due to synaptic site suppression after nembutal anesthesia, and the increase and persistence of increased F and M waves amplitudes were all due to the increasing motoneuron excitability, whereas ketamine did not affect synaptic sites subjected to magnetic stimulation.     

The effects of vision and task complexity on Hoffmann reflex gain

Previous research demonstrates modulation of the Hoffmann reflex amplitude and gain during changes in environmental conditions. H-reflex gain (defined in this study as the ratio of H-reflex amplitude to average soleus background EMG) is considered a functional measure of reflex modulation. In this study the effects of manipulating visual input and surface stability were to investigated in 17 subjects under four experimental conditions: (1) vision-stable surface, (2) no vision-stable surface, (3) vision-unstable surface, and (4) no vision-unstable surface. In each condition, subjects performed fifteen trials of a single leg stance for 7 s. The H-reflex was electrically elicited at the end of each trial by delivering a 1 ms square wave stimulation to the tibial nerve in the popliteal online for each trial (sampling rate = 2 kHz). An analysis of variance revealed significant decreases in H-reflex gain for the visual (F1.16 = 4.71, P < 0.05) and, surface conditions (F1.16 = 7.67, P < 0.05), however there was no interaction (F1.16 = 0.48, P < 0.05), between these variables. These results suggest that supraspinal mechanisms, possibly presynaptic inhibition, modulate H-reflex gain across environmental conditions. We conclude that visual and possibly cutaneous inputs were responsible for driving presynaptic inhibition and thus decreasing H-reflex gain.     

Changes in the excitability of soleus muscle short latency stretch reflexes during human hopping after 4 weeks of hopping training

Changes in the excitability of the human triceps surae muscle short latency stretch reflexes were investigated in six male subjects before and after 4 weeks of progressive two-legged hopping training. During the measurements the subjects performed 2-Hz hopping with: preferred contact time (PCT) and short contact time. The following reflex parameters were examined before and after the training period: the soleus muscle (SOL) Hoffmann-reflex (H-reflex) at rest and during hopping, the short latency electromyogram (EMG) components of the movement induced stretch reflex (MSR) in SOL and medial gastrocnemius muscle (MG), and the EMG amplitude of the SOL and MG tendon reflexes (T-reflexes) elicited at rest. The main results can be summarized as follows: the SOL T-reflex had increased by about 28% (P < 0.05) after training while the MG T-reflex was unchanged; the SOL MSR (always evident) and the MG MSR (when observable) did not change in amplitude with training, and before training the SOL H-reflex in both hopping situations was significantly depressed to about 40% of the reference value at standing rest (P < 0.05). After training the H-reflex during PCT hopping was no longer depressed. As the value of the measured mechanical parameters (the total work rate, joint angular velocity and the ankle joint work rate) was unchanged after training in both hopping situations, the reflex changes observed could not be ascribed to changes in the movement pattern. To explain the observed changes, hypotheses of changes in the excitability of the stretch reflex caused by the training were taken into consideration and discussed.     

Sensitivity of H-reflexes and stretch reflexes to presynaptic inhibition in humans

The sensitivity of soleus H-reflexes, T-reflexes, and short-latency stretch reflexes (M1) to presynaptic inhibition evoked by a weak tap applied to the biceps femoris tendon or stimulation of the common peroneal nerve (CPN) was compared in 17 healthy human subjects. The H-reflex was strongly depressed for a period lasting up to 300-400 ms (depression to 48 +/- 23%, mean +/- SD, of control at a conditioning test interval of 70 ms) by the biceps femoris tendon tap. In contrast, the short-latency soleus stretch reflex elicited by a quick passive dorsiflexion of the ankle joint was not depressed. The soleus T-reflex elicited by an Achilles tendon tap was only weakly depressed (92 +/- 8%). The H-reflex was also significantly more depressed than the T-reflex at long intervals (>15 ms) after stimulation of CPN (H-reflex 63 +/- 14%, T-reflex 91 +/- 13%; P < 0. 01). However, the short-latency (2 ms) disynaptic reciprocal Ia inhibition evoked by stimulation of CPN was equally strong for H- and T-reflexes (H-reflex 72 +/- 10%, T-reflex 67 +/- 13%; P = 0.07). Peaks in the poststimulus time histogram (PSTH) of the discharge probability of single soleus motor units (n = 53) elicited by an Achilles tendon tap had a longer duration than peaks evoked by electrical stimulation of the tibial nerve (on average 5.0 ms as compared with 2.7 ms). All parts of the electrically evoked peaks were depressed by the conditioning biceps femoris tendon tap (average depression to 55 +/- 27% of control; P < 0.001). A similar depression was observed for the initial 2 ms of the peaks evoked by the Achilles tendon tap (69 +/- 48%; P < 0.001), but the last 2 ms were not depressed. Conditioning stimulation of the CPN at long intervals (>15 ms) also depressed all parts of the electrically evoked PSTH peaks (n = 34; average 65%; P < 0.001) but had only a significant effect on the initial 2 ms of the peaks evoked by the Achilles tendon tap (85%; P < 0.001). We suggest that the different sensitivity of mechanically and electrically evoked reflexes to presynaptic inhibition is caused by a difference in the shape and composition of the excitatory postsynaptic potentials underlying the two reflexes. This difference may be explained by a different composition and/or temporal dispersion of the afferent volleys evoked by electrical and mechanical stimuli. We conclude that it is not straightforward to predict the modulation of stretch reflexes based on observations of H-reflex modulation.     

Isoflurane- and halothane-mediated dilation of distal bronchi in the rat depends on the epithelium

BACKGROUND: Respiratory epithelium releases substance(s) that can modulate bronchoconstriction in response to constrictive agonists and enhance bronchodilation in response to certain bronchodilators. The hypothesis that the bronchodilatory effect of isoflurane and halothane depends on the epithelium was tested in rat distal bronchial segments. METHODS: Wistar rat bronchial segments of the fourth order (diameter approximately 100 microns) were dissected. After preconstriction with 5-hydroxytryptamine, each bronchial segment was exposed to increasing concentrations of 0% to 3% isoflurane or 0% to 3% halothane under four conditions: after epithelial rubbing, after pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine, after pretreatment with the cyclooxygenase inhibitor indomethacin, or with no preintervention (control). Changes in bronchial diameter were monitored using an in vitro video detection system. RESULTS: Both isoflurane and halothane produced concentration-dependent bronchodilation (P < 0.001 for either anesthetic; 40% +/- 11% [mean +/- SD] dilation for 3% isoflurane and 57% +/- 10% dilation for 3% halothane). For both anesthetics, bronchodilation was significantly but incompletely attenuated by epithelial rubbing (12% +/- 7% dilation for 3% isoflurane [P < 0.01] and 31% +/- 10% dilation for 3% halothane [P < 0.01]), by pretreatment with indomethacin (20% +/- 8% dilation for 3% isoflurane [P < 0.02] and 21% +/- 9% dilation for 3% halothane [P < 0.001]), or by L-NNA (9% +/- 7% dilation for 3% isoflurane [P < 0.005] and 39% +/- 12% dilation for 3% halothane [P < 0.05]). Epithelial rubbing did not impair nitroprusside-associated bronchodilation. CONCLUSIONS: Isoflurane- and halothane-mediated bronchodilation depends at least partially on the epithelium and may involve both a prostanoid and nitric oxide in distal rat bronchi.     

Median nerve somatosensory evoked potentials during isoflurane anaesthesia

PURPOSE: The effect of isoflurane on the subcortical P14 component of the median nerve somatosensory evoked potential (SEP) is poorly known. We studied whether the P14 wave from the upper brainstem, recorded with a nasopharyngeal electrode, was attenuated at the isoflurane-induced EEG burst-suppression level. We also compared the effect of isoflurane on the P14, cervical N13 and cortical N20, N35 and N6, components. METHODS: Seventeen elective patients were anaesthetized with isoflurane. Somatosensory evoked potentials were recorded prior to anaesthesia, at 0.5 MAC and 1 MAC end-tidal isoflurane as well as at the level when EEG was in burst-suppression (mean 1.9 vol% end-tidal isoflurane). RESULTS: Isoflurane had varying effects on the subcortical components of median SEP. The amplitude of nasopharyngeal P14 was stable, but the mean latency increased from 14.4 +/- 1.2 msec at 0.5 MAC to 15.2 +/- 1.1 msec at burst-suppression level (P < 0.05). In contrast, the N13 neck response amplitude was attenuated from 3.3 +/- 0.6 microV to 2.6 +/- 0.5 microV (P < 0.005) without latency changes. The latency of the cortical N20 wave was increased from 19.7 +/- 1.1 msec at awake to 24.4 +/- 1.6 msec at burst-suppression level (P < 0.0001) and amplitude was reduced from 3.3 +/- 1.1 microV to 1.3 +/- 0.6 microV (P < 0.0001). The later cortical components were attenuated even during 0.5 MAC isoflurane and were not recordable during EEG burst-suppression. CONCLUSION: We conclude that P14 can reliably be recorded with nasopharyngeal electrodes during isoflurane anaesthesia, even during EEG burst-suppression, when the N20 wave is attenuated. In contrast, the middle-latency SEP components are sensitive to isoflurane anaesthesia.     

Acetazolamide reduces peripheral afferent transmission in humans

Carbonic anhydrase has been localized in skeletal muscle and nerve, thus, inhibition with acetazolamide (ACZ) may alter nerve and/or muscle function in healthy humans. ACZ (3 oral doses 14, 8, and 2 h prior to testing) reduced isometric force (37%) and peak to peak electromyographic (EMG) amplitude (1.38 mV to 0.83 mV), while increasing EMG latency associated with a unilateral Achilles tendon-tap. Reflex recovery profiles, following a contralateral conditioning tap, were similar in both placebo and ACZ experiments. ACZ led to significant changes in Hmax/Mmax ratio (52.19/14.42 to 45.73/15.65) and H-reflex latency (34.18 +/- 2.54 ms to 35.24 +/- 2.74 ms). Motor nerve conduction velocity and maximal voluntary isometric torque (knee extensors) were unaltered by ACZ. These data suggest that inhibition of the tendon-tap reflex and associated isometric force, following ACZ, is related to impairment of synaptic integrity between la fibers of the muscle spindle and the alpha motor neuron and not impairment of the muscle spindle or force-generating capacity.     

Return to work after laparoscopic cholecystectomy

Hoffmann's reflex or H-reflex (HR) is an electrically elicited reflex that measures excitability of motoneurons and shares some physiologic properties with the deep tendon reflex. Children with tendon hyperreflexia due to cerebral palsy usually have higher amplitude HRs. Nitrous oxide (N2O) depresses the HR in patients with normal spinal reflexes, although the effect of N2O in conditions with hyperreflexia such as cerebral palsy is not known. We propose to determine the effect of N2O on the amplitude of the HR under general anesthesia in children with hyperreflexia due to cerebral palsy. We studied eight children undergoing selective dorsal rhizotomy (SDR) for the relief of spasticity. The maximum amplitudes of the HR (HRmax) and direct motor response (MRmax) were routinely evoked under the following anesthetic conditions: 1) sufentanil and 66% N2O/33% oxygen; and 2) sufentanil and 100% oxygen. The HRmax amplitude was significantly lower when N2O was part of the inspired gas mixture. The differences between the no N2O and the 66% N2O groups were significant. The MRmax did not change significantly. Abnormal spinal reflexes seen in spastic diplegia can be abolished by inhaled N2O. This finding also suggests that N2O-induced depression of spinal reflexes should be a consideration during physiologic monitoring of the spinal cord under general anesthesia.     

Transduction of cultured oligodendrocytes from normal and twitcher mice by a retroviral vector containing human galactocerebrosidase (GALC) cDNA

We examined in mice the effect of chronic diazepam treatment on the sensitivity to isoflurane, and that of repeated isoflurane exposure on the sensitivity to diazepam. Mice were divided into four groups: group 1, treated with diazepam, 10 mg/kg i.p. twice daily; group 2, vehicle-treated controls; group 3, exposed to 3% isoflurane for 25 min twice daily; and group 4, untreated controls. After 14 days the effect of the treatment was assessed. Twenty-four hours after the last 10 mg/kg diazepam treatment, groups 1 and 2 received diazepam, 5 mg/kg i.p., and were subjected to the horizontal wire test (HWT). All control mice but only 10% of the diazepam-treated mice failed the HWT. Groups 1 and 2 were then exposed to increasing concentrations of isoflurane. Diazepam-treated mice (group 1) lost the HWT at 0.7+/-0.7%, compared with 0.6+/-0.1% in controls (group 2) (P<0.001); the ED50 was 0.75% vs. 0.65%. Group 1 mice lost the righting reflex at 0.94+/-0.07% isoflurane vs. 0.87+/-0.06% in group 2 (P<0.01); the ED50 was 0.93% vs. 0.82%. Recovery time was 175+/-161 s in group 1 vs. 343+/-275 s in group 2 (P<0.02). Twenty-four hours after the last of the repeated exposures to isoflurane, we examined the responses of groups 3 and 4 to increasing concentrations of isoflurane. Mice in group 3 lost the righting reflex at 1.0+/-0.06% isoflurane vs. 0.9+/-0.04% in controls (group 4) (P<0.001); the ED50 was 0.96% vs. 0.85%. Recovery time was 113+/-124 s vs. 208+/-126 s in groups 3 and 4 (P<0.09). Diazepam, 3 mg/kg i.p. administered to groups 3 and 4, caused loss of the HWT reflex in 33% of group 3 mice and in 82% of controls (group 4) (P<0.001). It appears that prolonged exposure to both diazepam and isoflurane caused reduced sensitivity to each drug separately, as well as to the other drug. This finding may strengthen the theory that inhalational anesthetics may act via the same mechanism as the benzodiazepines.     

Inhibition by taurine of the inwardly rectifying K+ current in guinea pig ventricular cardiomyocytes

Effects of taurine on the inwardly rectifying K+ current (IK1) in isolated guinea pig ventricular cardiomyocytes were examined using patch voltage-clamp methods. All experiments were performed at 36 degrees C. Taurine (10-20 mM) increased the action potential duration, but failed to affect the resting potential. Holding potential was maintained at -30 mV. The current was activated with an inwardly going rectification, and was completely blocked by Ba2+ (2 mM). Taurine inhibited IK1 at - 120 mV by 28.3+/-1.1% (n=6, P < 0.05) at 10 mM and by 36.0+/-2.1% (n=6, P < 0.01) at 20 mM. The reversal potential was shifted in the hyperpolarizing direction by 3.7+/-0.6 mV (n=6) at 20 mM. In inside-out patch-clamp experiments, the amplitude of unitary channels was -2.7+/-0.3 pA (n=21) at -90 mV. Symmetrical high-K+ (150 mM) solutions in both bath and pipette were used. The channel conductance was 32+/-2 pS (n=9). Taurine did not affect channel conductance, but markedly decreased the open probability at - 120 mV of channel by 21.5+/-2.4% (n=8, P < 0.01) at 10 mM, and by 56.7+/-3.8% (n=8, P < 0.001) at 20 mM. These responses were almost reversible. These results suggest that taurine directly modulates the open probability of the inwardly rectifying K+ current, resulting in regulation of the functions of heart cells.     

Pelviureteral inhibitory reflex and ureteropelvic excitatory reflex: role of the two reflexes in regulation of urine flow from the renal pelvis to the ureter

The mechanism by which the ureteropelvic junction (UPJ) regulates the passage of urine from the renal pelvis to the ureter, and prevents urinary backflow from the the ureter to the renal pelvis, is not completely understood. The current communication studies this mechanism in 18 dogs. With the dogs under anesthesia, nephrostomy was done through which two catheters (one pressure and one balloon-tipped) were introduced into the UPJ and the renal pelvis, respectively. Renal pelvis distension with a balloon filled with 1 ml of saline effected a rise of renal pelvic pressure from a mean basal pressure of 4.8 +/- 1.2 cm H2O to 6.9 +/- 2.3 cm H2O (P < 0.05). The basal UPJ pressure of 12.6 +/- 2.7 cm H2O showed no significant change with 1 ml distention of the renal pelvic balloon (P > 0.05). Renal pelvic distension with 2, 3, and 4 ml caused a significant rise of renal pelvic pressure to 8.4 +/- 2.7 (P < 0.05), 10.6 +/- 2.2 (P < 0.01), and 11.8 +/- 1.9 (P < 0.01) cm H2O, respectively, and a significant drop of UPJ pressure to 4.8 +/- 1.2, 4.7 +/- 1.1, and 4.6 +/- 1.2 cm H2O (P < 0.01), respectively. Ureteric distension with a balloon filled with 0.5 ml of saline significantly raised the ureteric pressure from a mean basal value of 4.3 +/- 1.4 cm H2O to 14.7 +/- 3.3 cm H2O (P < 0.01) and the UPJ pressure to a mean of 20.8 +/- 3.8 (P < 0.05). Ureteric distension with 1 and 1.5 ml of saline led to an elevation of ureteric and UPJ pressure which was not significantly different from that observed with distension with 0.5 ml (P > 0.05). In contrast, the UPJ showed no significant pressure change upon distension of the locally anesthetized renal pelvis or ureter, respectively. Likewise, the locally anesthetized UPJ exhibited no significant pressure response to renal pelvic or ureteric distension. The study demonstrates that urine might have to accumulate in the renal pelvis up to a certain volume and pressure so as to effect UPJ opening, which occurs at its maximum irrespective of the distending volume. UPJ opening upon renal pelvic distension postulates a reflex relationship which we call "pelviureteral inhibitory reflex." This reflex is believed to regulate the passage of urine from the renal pelvis to the ureter. Ureteric distension closes the UPJ; we call this reflex action the "ureteropelvic excitatory reflex" as it seems to prevent reflux of urine through the UPJ and thus protects the kidney. The concept that the UPJ acts as a physiologic sphincter is put forward.     

Effects of isoflurane on in vivo release of acetylcholine in the rat cerebral cortex and striatum

BACKGROUND: Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose-effect relationship of isoflurane on the in vivo release of ACh in rat brains. METHODS: Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique. RESULTS: In the cortex, the ACh release decreased to 30.8+/-10.1 (mean+/-SEM), 10.2+/-4.1, and 8.1+/-2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3+/-4.4, 49.2+/-4.2, and 40.7+/-4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8+/-4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3+/-13.3, and 68.2+/-5.4%, respectively. CONCLUSION: The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part one of the mechanisms of anesthesia.     

Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and intravenous anesthesia

The potency and time course of action of rocuronium were studied in patients anesthetized with 66% nitrous oxide in oxygen and 1.5 minimum alveolar anesthetic concentration of sevoflurane or isoflurane, or a propofol infusion. Potency was estimated by using the single-bolus technique. Neuromuscular block was measured by stimulation of the ulnar nerve and by recording the force of contraction of the adductor pollicis muscle. The mean (95% confidence limits) of the 50% and 95% effective doses were estimated tobe 142 (129-157) and 265 (233-301) microg/ kg, 165 (146-187) and 324 (265-396) microg/kg, and 183 (163-207) and 398 (316-502) microg/kg during sevoflurane, isoflurane, and propofol anesthesia, respectively (P < 0.05 for sevoflurane versus propofol). The mean +/- SD times to onset of maximal block after rocuronium 0.6 mg/kg were 0.96 +/- 0.16, 0.90 +/- 0.16, and 1.02 +/- 0.15 min during sevoflurane, isoflurane, and propofol anesthesia, respectively. The respective times to recovery of the first response in the train-of-four (TOF) stimulation (T1) to 25% and 90% were 45 +/- 13.1 and 83 +/- 29.3 min, 35 +/- 6.1 and 56 +/- 15.9 min, and 35 +/- 9.2 and 55 +/- 19.4 min. The times to recovery of the TOF ratio to 0.8 were 103 +/- 30.7, 69 +/- 20.4, and 62 +/- 21.1 min, and the 25%-75% recovery indices were 26 +/- 11.7, 12 +/- 5.0, and 14 +/- 6.9 min, respectively. There were no differences among groups in the times for onset of action or to recovery of T1 to 25%. However, the times for recovery of T1 to 90%, TOF ratio to 0.8, and recovery index in the sevoflurane group were all significantly longer compared with the other two groups (P < 0.05, < 0.01, and < 0.01, respectively). We conclude that the effects of rocuronium, especially duration of action, are significantly enhanced during sevoflurane compared with isoflurane and propofol anesthesia. IMPLICATIONS: In routine clinical use, the effects of rocuronium are enhanced by sevoflurane, in comparison with isoflurane and propofol anesthesia, and the recovery is slower. Particular attention should be paid to monitoring of neuromuscular block during sevoflurane anesthesia.     

H-reflex and F-wave potentials in leg and arm muscles

The systematic analyses of secondary muscle potentials of H-reflex and F-wave type were done in multicentric study. The examinations were carried out in healthy volunteers with 9 muscles analysed on the legs and 9 on the lower arms and hands. The H-reflex potential was found regularly in thigh muscles (vastus medialis 100%, biceps femoris 97%, semitendinosus 93%). Less frequently but still with high incidence it appeared in posterior lower leg muscles (soleus 93%, caput mediale gastrocnemii 73%). In anterior tibial muscle and extensor digitorum brevis it did not appear at all. Only exceptionally it was found in short peroneal muscle (3%) and occasionally, only on proximal nerve stimulation, in flexor hallucis brevis. The similar distribution pattern was found in lower arm and hand muscles with analysis on both sides. In flexor digitorum superficialis (73-70%) and flexor carpi radialis (73-57%) the percentage of H-potential muscles was the highest, in flexor carpi ulnaris (47-40%) lesser but still remarkable. Brachioradialis (37-30%) and extensor digitorum communis (27-27%) percentage decreased further. The even more distal, pronator quadratus (21-20%) and abuctor digiti minimi (17-17%) presented as muscles with low incidence of H-reflex positivity. In extensor indicis proprius (3%) the lowest H-potential incidence was found and in opponens pollicis no H-potential at all. F-waves if evaluated as "F-frequency" follow the similar distribution pattern. The lowest "F-frequency" was found on the legs in anterior tibial, short peroneal and extensor digitorum brevis muscles. In the last one more than one half of stimuli failed to evoke the F-potential. Those are the muscles in which H-potentials almost never appeared. The highest "F-frequency" was recorded in thigh, posterior lower leg muscle and flexor hallucis brevis. Some of the examinees displayed in almost all examined muscles H-potential (6 of 30), the others (9 of 30) had it in neither one or in a single muscle. It looks like as if a kind of H-reflex or F-wave individuals exist. If the H- or F-potentials distribution pattern got projected on the homunculus in quadrupedal position the following idea appears. The thigh muscles, the plantar flexors of the feet and hand and finger flexors are first of all tonic muscles mostly involved in standing or holding. The extensors of the foot/toes, respectively of hand/fingers interrupt phasically the sustained action of standing by lifting the foot/hand from the ground. The muscles with mostly tonic function produce much H-reflexes, transitional forms or at least F-wave with high "F-frequency". Is that a kind of phylogenetical remnants, better developed in the motorically less differentiated legs? Have the H-reflex muscles if compared with F-wave muscles different motor units structure? Have they different motoneurons, with different liability to produce recurrent discharges?     

Autoregulation of human inner ear blood flow during middle ear surgery with propofol or isoflurane anesthesia during controlled hypotension

We used controlled hypotension to obtain a bloodless cavity during middle ear surgery under an optical microscope. No previous study has assessed the effect of controlled hypotension on inner ear blood flow (IEF) autoregulation in humans receiving propofol or isoflurane anesthesia. In the present study, the IEF autoregulation was determined using laser Doppler flowmetry in combination with transient evoked otoacoustic emissions (TEOAEs) during controlled hypotension with sodium nitroprusside in 20 patients randomly anesthetized with propofol or isoflurane. A coefficient of IEF autoregulation (Ga) was determined during controlled hypotension, with a Ga value ranging between 0 (no autoregulation) and 1 (perfect autoregulation). During controlled hypotension with propofol, IEF remained stable (1%+/-6%; P > 0.05) but decreased by 25%+/-8% with isoflurane (P < 0.05). The Ga was higher during propofol anesthesia (0.62+/-0.03) than during isoflurane anesthesia (0.22+/-0.03; P < 0.0001). Under propofol anesthesia, there were individual relationships between TEOAE amplitude and change in IEF in four patients. Such a correlation was not observed under isoflurane anesthesia. These results suggest that human IEF is autoregulated in response to decreased systemic pressure. Furthermore, isoflurane has a greater propensity to decrease cochlear autoregulation and function than propofol. IMPLICATIONS: The present study shows that inner ear blood flow is autoregulated under propofol, but not isoflurane, anesthesia during controlled hypotension in humans during middle ear surgery. Further studies are needed to explore the postoperative auditory functional consequences of the choice of the anesthetic drug used in middle ear surgery.     

Changes in vitamin E concentration after surgery and anesthesia

The aim of this randomized study was to examine changes in vitamin E concentration in female subjects (age 30-60, ASA I) after cholecystectomy and halothane (N = 16) or isoflurane (N = 16) anaesthesia. Vitamin E concentration was measured two days before, and then one, five and twenty-four hours and four days after surgery. High-pressure liquid chromatography was used for its determination. Simultaneously activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) were determined. Statistical analysis: ANOVA, Tukay HSD test. The research has been accepted by the Drugs Committee of the Karlovac County Hospital. Preoperative vitamin E concentrations in the halothane group were 8.69 +/- 2.35 micrograms/L, median 8.67 micrograms/L and in the isoflurane group 9.43 +/- 2.4 micrograms/L, median 9.08 micrograms/L. Statistically lower vitamin E concentrations compared with preoperative values were noted one hour (P < 0.05), 5 hours (P < 0.01), 24 hours (P < 0.01), as well as 4 days (P < 0.01) after the operation. The lowest vitamin E concentrations were noted 24 hours after the operation with statistically insignificantly higher values in the isoflurane group (halothane group 5.98 +/- 2.08 micrograms/L, isoflurane group 6.58 +/- 1.51 micrograms/L). Analyzing enzyme (ALT, AST and GGT) pre- and postoperative values, no statistically significant differences between the investigated groups and during the time were observed. Statistically significant differences were found between individual measurement times, with no statistical significance of the differences between the halothane and isoflurane groups. It seems that neither the difference in halothane and isoflurane biotransformation nor their distinct effect on perfusion of some organs are the determining factors in post-operative changes in vitamin E concentration.     

Cerebral blood flow velocity in relation to cerebral blood flow, cerebral metabolic rate for oxygen, and electroencephalogram analysis during isoflurane anesthesia in dogs

The purpose of this study was to correlate changes in cerebral blood flow velocity (Vmean) with cerebral blood flow (CBF) during isoflurane anesthesia in dogs. The relation between cerebral oxygen consumption (CMRO2) and electroencephalogram (EEG) analysis also was investigated. Blood flow velocity was measured in the middle cerebral artery using a pulsed transcranial Doppler (TCD). CBF was measured with radioactive microspheres. EEG was measured over both hemispheres and median EEG frequency (median frequency) was calculated after fast Fourier transformation. Baseline anesthesia was maintained with 50% nitrous oxide in oxygen and 50 micrograms.kg-1 x h-1 fentanyl. Animals of Group I (control, n = 6) were not given isoflurane. Data were recorded at baseline, and at 30, 60, and 90 min. There was no significant change in any variable over time. In Group II (n = 7), data were recorded at baseline and at 1%, 2%, and 3% end-tidal isoflurane. Mean arterial pressure was maintained at baseline levels by phenylephrine infusion. CBF increased from 70.8 +/- 10.6 mL.100g-1 x min-1 at baseline to 146.1 +/- 36.9 mL.100 g-1 x min-1 with 3% isoflurane (P < 0.01). Vmean increased from 38.3 +/- 6.7 cm/s to 65.6 +/- 9.7 cm/s (P < 0.01). The correlation between relative changes in CBF and Vmean was r = 0.94 (P < 0.01). With 1% isoflurane the EEG shifted to slow-wave, high-voltage activity, and median frequency decreased from 5.9 +/- 0.7 Hz to 1.4 +/- 0.4 Hz (P < 0.05). Median frequency was not decreased further during 2% and 3% isoflurane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of differential delivery of isoflurane to head and torso on lumbar dorsal horn activity

BACKGROUND: The spinal cord appears to be the site where anesthetic agents prevent movement in response to noxious stimuli. When isoflurane is differentially delivered to the head and torso (with low torso concentrations), cranial anesthetic requirements increase compared with systemic administration. The aim of the current study was to test the hypothesis that isoflurane action in the brain has descending influences on spinal cord dorsal horn neurons. A secondary aim was to determine the association, if any, of high cranial concentrations of isoflurane (>6%) with dorsal horn activity. METHODS: Ten goats were anesthetized with isoflurane and the carotid arteries and jugular veins isolated and cannulated for cerebral bypass. A laminectomy was performed for recording from single lumbar dorsal horn neurons with hind limb mechanical receptive fields (one cell per goat). A standard noxious mechanical stimulus was applied to the dew claw or hoof bulb during a control period with end-tidal isoflurane at 1.3% and during bypass with the following head/torso isoflurane concentrations: 1.3%/1.3%, 3.2%/1.3%, 9.4%/1.3%, 1.3%/0.2%, 3.0%/0.2% and 8.8%/0.3%. RESULTS: When torso isoflurane concentration was 1.3%, increasing cranial isoflurane concentration to 3% or 9% had no significant effect on the activity of dorsal horn units. When torso isoflurane was 0.2-0.3%, spontaneous activity increased; however, at these torso concentrations, evoked responses were significantly decreased (-60%) only when cranial isoflurane concentration was increased to 9%. CONCLUSIONS: Isoflurane action in the brain had an inhibitory effect on dorsal horn activity with the combination of supraclinical cranial and low torso concentrations.