Haruhisa Fukayama

The different effects of intravenous propofol and midazolam sedation on hemodynamic and heart rate variability.

Heart rate (HR) and arterial blood pressure (BP) changes have been reported during conscious sedation with propofol and midazolam. One potential mechanism to explain these changes is that propofol and midazolam affect HR and BP via changes in the cardiac autonomic nervous system. Two specific hypotheses were tested by HR variability analysis: 1) propofol induces predominance of parasympathetic activity, leading to decreased HR and BP, and 2) midazolam induces predominance of sympathetic activity, leading to increased HR and decreased BP. Thirty dental patients were included in a prospective, randomized study. HR, BP, low frequency (LF), high frequency (HF), and entropy were monitored during the awake, sedation, and recovery periods and depth of sedation was assessed using the Observer’s Assessment of Alertness/Sedation score. Propofol induced a significant decrease in total power (503 ± 209 ms2/Hz versus 162 ± 92 ms2/Hz) and LF/HF ratio (2.5 ± 1.2 versus 1.0 ± 0.4), despite the absence of any change in HR during the sedation period compared with baseline. Midazolam decreased normalized HF (34 ± 10% versus 10 ± 4%) but did not significantly change LF/HF ratio (2.3 ± 1.1 versus 2.2 ± 1.4) and increased HR in the sedation period. Compared with baseline, propofol was associated with a significant increase in normalized HF in the recovery period (34 ± 11% versus 44 ± 12%) and a significant decrease in HR, whereas midazolam was associated with an increase in LF/HF ratio (2.3 ± 1.1 versus 3.7 ± 1.8) with no change in HR. These results indicated a dominant parasympathetic effect of propofol and a dominant sympathetic effect of midazolam in both periods. These results should be considered during conscious sedation, especially in patients at risk of cardiovascular complications.

Heterogeneous electrophysiological and morphological properties of neurons in the mouse medial amygdala in vitro

Neurons in the medial nucleus of the amygdala (MeA) play a key role in the innate maternal, reproductive, defensive, and social behaviors. However, it is unclear how activation of the vomeronasal system leads to the behavioral outputs that are associated with pheromones. Here, we characterized the electrophysiological and morphological properties of MeA neurons using whole-cell recordings in mice slice preparations. Biocytin labeling revealed that MeA neurons possessed bipolar to multipolar cell bodies and dendritic fields covering projection areas from the accessory olfactory bulb. In 70% of recorded MeA neurons, monosynaptic excitatory postsynaptic currents (EPSCs) were evoked from the accessory olfactory bulb afferent in which the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate component was dominant and was rarely followed by the N-methyl-d-aspartic acid component. Norepinephrine increased the frequency of spontaneous inhibitory postsynaptic currents in some neurons, whereas α-methyl-5-hydroxytryptamine increased spontaneous EPSCs in other neurons. Morphologically and physiologically, heterogeneous MeA neurons appear likely to produce multiplex outputs of instinctive behaviors.

Acute NK1 receptor antagonist administration affects reward incentive anticipation processing in healthy volunteers

The primary brain structures of reward processing are mainly situated in the mid-brain dopamine system. The nucleus accumbens (NAc) receives dopaminergic projections from the ventral tegmental area and works as a key brain region for the positive incentive value of rewards. Because neurokinin-1 (NK₁) receptor, the cognate receptor for substance P (SP), is highly expressed in the NAc, we hypothesized that the SP/NK₁ receptor system might play a role in positive reward processing in the NAc in humans. Therefore, we conducted a functional MRI (fMRI) study to assess the effects of an NK₁ receptor antagonist on human reward processing through a monetary incentive delay task that is known to elicit robust activation in the NAc especially during gain anticipation. Eighteen healthy adults participated in two series of an fMRI study, taking either a placebo or the NK₁ receptor antagonist aprepitant. Behavioural measurements revealed that there was no significant difference in reaction time, hit rate, or self-reported effort for incentive cues between the placebo and aprepitant treatments. fMRI showed significant decrease in blood oxygenation-level-dependent signals in the NAc during gain anticipation with the aprepitant treatment compared to the placebo treatment. These results suggest that SP/NK₁ receptor system is involved in processing of positive incentive anticipation and plays a role in accentuating positive valence in association with the primary dopaminergic pathways in the reward circuit.

Modafinil augments brain activation associated with reward anticipation in the nucleus accumbens

RationaleThe nucleus accumbens (NAc) works as a key brain structure of the reward system, in which reward-related neural activity is well correlated with dopamine release from mesolimbic dopaminergic neurons.ObjectivesSince modafinil can modulate dopaminergic transmission through re-uptake inhibition of dopamine, we investigated whether modafinil affects the reward-related brain activity in the NAc in healthy subjects.MethodsTwenty healthy participants underwent two series of functional magnetic resonance imaging while performing monetary incentive delay task in which they were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money, under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD) activation signals during gain and loss anticipations were analyzed in the NAc as an a priori region of interest as well as the whole brain.ResultsModafinil significantly changed subjective feelings toward positive ones. The activation of BOLD signals was observed during gain anticipation under the placebo and modafinil conditions in the left and bilateral NAc, respectively. The modafinil condition showed significantly higher BOLD signal change at the highest gain (+¥500) cue compared to the placebo condition.ConclusionsThe present study showed that modafinil affects reward processing in the NAc in healthy subjects through enhancing more positive anticipation, and it may provide a basis for the use of this drug for treating anhedonia observed in psychiatric disorders.

Postoperative hyperthermia of unknown origin treated with dantrolene sodium.

An 11-year-old girl was scheduled for alveolar cleft bone grafting with an iliac bone under general anesthesia. Anesthesia was performed with 70% nitrous oxide, 30% oxygen, and propofol. On the first and second postoperative day, persistent hyperthermia was observed. Because the administration of diclofenac sodium had not been effective for the hyperthermia, dantrolene sodium was given. Her body temperature gradually dropped and returned to normal level on the fifth postoperative day. The hyperthermia in the present case might have been caused by a rapidly elevated muscle metabolism in response to pain and stress after the propofol anesthesia. The oral administration of dantrolene sodium successfully lowered the patients high body temperature.

Trigeminal neuralgia: differences in magnetic resonance imaging characteristics of neurovascular compression between symptomatic and asymptomatic nerves

OBJECTIVES Neurovascular compression (NVC) of the trigeminal nerve is the primary cause of trigeminal neuralgia (TN) but is known to occur in both symptomatic and asymptomatic nerves. The purposes of this study were to evaluate the relationship between the magnetic resonance imaging (MRI) findings regarding the site of NVC and the manifestation of TN symptoms. METHODS In 147 patients with unilateral TN, the presence or absence of NVC was evaluated on MRI in both symptomatic and asymptomatic nerves. In cases with NVC, the shortest distance from the trigeminal nerve root to the responsible vessel was measured. RESULTS The mean distance from the trigeminal nerve root to the site of NVC in asymptomatic nerves (3.85 ± 2.69 mm) was significantly greater than that in symptomatic nerves (0.94 ± 1.27 mm). When the distance was 3 mm or less, the rate of the manifestation of TN symptoms was 83.1% (103/124). On the other hand, it was only 19.6% (9/46) in cases with a distance of greater than 3 mm. CONCLUSIONS Whether or not NVC of the trigeminal nerve was symptomatic was closely related to the distance from the trigeminal nerve root to the responsible blood vessel.

Modafinil enhances alerting-related brain activity in attention networks

RationaleModafinil is a wake-promoting agent and has been reported to be effective in improving attention in patients with attentional disturbance. However, neural substrates underlying the modafinil effects on attention are not fully understood.ObjectivesWe employed a functional magnetic resonance imaging (fMRI) study with the attention network test (ANT) task in healthy adults and examined which networks of attention are mainly affected by modafinil and which neural substrates are responsible for the drug effects.MethodsWe used a randomized placebo-controlled within-subjects cross-over design. Twenty-three healthy adults participated in two series of an fMRI study, taking either a placebo or modafinil. The participants performed the ANT task, which is designed to measure three distinct attentional networks, alerting, orienting, and executive control, during the fMRI scanning. The effects of modafinil on behavioral performance and regional brain activity were analyzed.ResultsWe found that modafinil enhanced alerting performance and showed greater alerting network activity in the left middle and inferior occipital gyri as compared with the placebo. The brain activations in the occipital regions were positively correlated with alerting performance.ConclusionsModafinil enhanced alerting performance and increased activation in the occipital lobe in the alerting network possibly relevant to noradrenergic activity during the ANT task. The present study may provide a rationale for the treatment of patients with distinct symptoms of impaired attention.

Risk Factors With Intravenous Sedation for Patients With Disabilities

The purpose of this study was to identify the risk factors associated with low peripheral oxygen saturation (SpO2) and delayed recovery of dental patients with disabilities after intravenous sedation. A total of 1213 patients with disabilities were retrospectively investigated with respect to demographic parameters and sedation conditions. Multivariate logistic analyses were conducted for patients with an SpO2 <90% and a recovery period of >60 minutes to identify the risk factors for poor sedation conditions. A significant odds ratio related to decreased SpO2 was observed for age, sex, midazolam and propofol levels, concurrent use of nitrous oxide, cerebral palsy, Down syndrome, and mental retardation. The most problematic patients were those diagnosed with Down syndrome (odds ratio, 3.003-7.978; 95% confidence interval; P < .001). Decision tree analysis showed an increased risk of decreased SpO2 in males with Down syndrome or after administration of >0.493 mg/kg propofol in combination with midazolam. An increased risk of delayed awakening was seen in patients aged less than 21 years and in males administered >0.032 mg/kg of midazolam. Intravenous sedation for dental patients with disabilities, particularly those with cerebral palsy, Down syndrome, or mental retardation, increases the risk of decreased SpO2. In addition, delayed recovery is expected after midazolam administration.

The effect of alternating current iontophoresis on rats with the chronic constriction injury to the infraorbital nerve.

This study aimed to examine the effect of AC iontophoresis on rats with the chronic constriction injury (CCI) to the infraorbital nerve by animal experiments. CCI model rats were divided into four groups, namely, rats that received general anesthesia for 60 min except AC IOP (CCI: n = 5), AC IOP with 0.9% physiological saline for 60 min (CCI + saline AC IOP: n = 5), AC IOP with 4% lidocaine hydrochloride for 60 min (CCI + lidocaine AC IOP: n = 5), and attachment of two electrodes soaked with 4% lidocaine hydrochloride to the facial skin for 60 min (CCI + attach lidocaine: n = 5). In the CCI + lidocaine AC IOP group, an elevated withdrawal threshold was observed after AC IOP, and the duration of efficacy was longer compared with that in the CCI + saline AC IOP and CCI + attached lidocaine groups. A significant decrease in the number of Fos-like immunoreactive (LI) cells was observed in the CCI + lidocaine AC IOP group compared with that in the CCI group. These findings suggest that the effect of CCI + lidocaine AC IOP group may be caused by active permeation of lidocaine into the facial skin and electrical stimulation of the trigeminal nucleus.

The relation between the duty cycle and anesthetic effect in lidocaine iontophoresis using alternating current.

We assessed the effect of the duty cycle on the anesthetic effect during lidocaine alternating current (AC) iontophoresis. A solution of 2% lidocaine was delivered to the medial antecubital skin for 20 minutes using AC iontophoresis with a duty cycle of 60%, 70%, or 80%. The von Frey test was then performed to evaluate the anesthetic effect. In the groups treated with a duty cycle of 80% or 70% the touch thresholds (TT) were significantly elevated from 0 minutes to 30 minutes and from 0 minutes to 20 minutes. TT were significantly elevated at 0 minutes in the group treated with a 60% duty cycle. The anesthetic effect was significantly enhanced in a duty cycle‐dependent manner.