Hiroshi Hanamoto

Anesthetic effects on susceptibility to cortical spreading depression.

Cortical spreading depression (CSD) is a transient neuronal and glial depolarization and disruption of membrane ionic gradients that propagates slowly across the cerebral cortex. Recent clinical and experimental evidence has implicated CSD in the pathophysiology of migraines and neuronal injury states. In the current study, we examined the influence of four different anesthetics (propofol, dexmedetomidine, isoflurane, pentobarbital) on CSD susceptibility in a KCl application animal model. We found that isoflurane and dexmedetomidine suppressed CSD frequency, and tended to reduce the CSD propagation speed. Our data suggest that these anesthetics may be therapeutically beneficial in preventing CSD in diverse neuronal injury states.

Influence of acute progressive hypoxia on cardiovascular variability in conscious spontaneously hypertensive rats

The purpose of this study is to examine the influence of acute progressive hypoxia on cardiovascular variability and striatal dopamine (DA) levels in conscious, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). After preparation for measurement, the inspired oxygen concentration of rats was decreased to 10% within 5 min (descent stage), maintained at 10% for 10 min (fixed stage), and then elevated back to 20% over 5 min (recovery stage). The systolic blood pressure (SBP) and heart rate (HR) variability at each stage was calculated to evaluate the autonomic nervous system response using the wavelet method. Striatal DA during each stage was measured using in vivo microdialysis. We found that SHR showed a more profound hemodynamic response to progressive hypoxia as compared to WKY. Cardiac parasympathetic activity in SHR was significantly inhibited by acute progressive hypoxia during all stages, as shown by the decrease in the high frequency band of HR variability (HR-HF), along with transient increase in sympathetic activity during the early hypoxic phase. This decrease in the HR-HF continued even when SBP was elevated. Striatal DA levels showed the transient similar elevation in both groups. These findings suggest that acute progressive hypoxic stress in SHR inhibits cardiac parasympathetic activity through reduction of baroreceptor reflex sensitivity, with potentially severe deleterious effects on circulation, in particular on HR and circulatory control. Furthermore, it is thought that the influence of acute progressive hypoxia on striatal DA levels is similar in SHR and WKY.

Autonomic and cardiovascular effects of pentobarbital anesthesia during trigeminal stimulation in cats

Stimulation of the trigeminal nerve can elicit various cardiovascular and autonomic responses; however, the effects of anesthesia with pentobarbital sodium on these responses are unclear. Pentobarbital sodium was infused intravenously at a nominal rate and the lingual nerve was electrically stimulated at each infusion rate. Increases in systolic blood pressure (SBP) and heart rate (HR) were evoked by lingual nerve stimulation at an infusion rate between 5 and 7 mg·kg−1·h−1. This response was associated with an increase in the low-frequency band of SBP variability (SBP-LF). As the infusion rate increased to 10 mg·kg−1·h−1 or more, decreases in SBP and HR were observed. This response was associated with the reduction of SBP-LF. In conclusion, lingual nerve stimulation has both sympathomimetic and sympathoinhibitory effects, depending on the depth of pentobarbital anesthesia. The reaction pattern seems to be closely related to the autonomic balance produced by pentobarbital anesthesia.

Hemodynamic and autonomic response to acute hemorrhage in streptozotocin-induced diabetic rats

BackgroundThe various autonomic control systems lead to characteristic changes in heart rate (HR) and blood pressure (BP) during acute hemorrhage. However, cardiovascular autonomic neuropathy due to diabetes mellitus may interfere with the normal compensation for hemorrhage.Materials and methodsA controlled graded bleeding (6 - 36% loss of estimated total blood volume: ETBV) was performed in streptozotocin-induced diabetic rats (STZ rats) under a conscious state. Hemodynamic and autonomic responses to acute hemorrhage were examined using analysis of BP-HR variability. The effects of dextran treatment after hemorrhage were also examined.ResultsA significant reduction in mean arterial pressure began at 12% ETBV loss in STZ rats and 18% in the control rats, respectively. When blood loss reached 18% of TEBV, the decrease in HR was prominent in STD rats due to the activation of a parasympathetic drive, as indicated by the increase in high frequency (HF; 0.75~3.0 Hz) power in HR variability, while in the control rats this response was not observed. The administration of dextran prevented the activation of the parasympathetic drive in STZ rats during hemorrhaging. In the control rats, the dextran treatment sustained the initial increase in HR with reduced HF power in HR variability.ConclusionSTZ rats showed different hemodynamic and autonomic responses to acute hemorrhage from the control rats. STZ rats were prone to develop bradycardiac hypotension characterized by marked parasympathetic activation during hemorrhaging. This finding suggests enhancement of the Bezold-Jarisch reflex in STZ rats. Dextran treatment to maintain a normovolemic hemorrhage state inhibits this reflex.

Influence of acute hypoxia combined with nitrous oxide on cardiovascular variability in conscious hypertensive rats

Anesthetics have been reported to depress autonomic nervous system (ANS) responses to hypoxia. The mechanisms by which cardiovascular variability responds to acute progressive hypoxia (APH) under nitrous oxide (N(2)O) inhalation, however, remain unclear. Additionally, the effect of hypertension on ANS responses in such cases has not been fully clarified. The present study examined the influence of APH (10% O(2)) under 60% N(2)O inhalation on cardiovascular variability in conscious, spontaneously hypertensive rats (SHR). Twenty-seven male SHR were randomly assigned to 3 treatment groups receiving N(2)O inhalation alone, APH stress alone or APH stress under N(2)O inhalation, using Wistar Kyoto rats (WKY) or non-N(2)O inhalation rats as controls. Systolic blood pressure (SBP) and heart rate (HR) variability were evaluated time-dependently using the wavelet method. While inhalation of N(2)O alone induced more powerful sympathomimetic actions in SHR than in WKY, circulatory and parasympathetic reactions were weaker. APH stress alone evoked significant inhibition of cardiac parasympathetic activity from immediately after exposure to hypoxic stress in SHR in contrast to WKY, facilitating tachycardia. This inhibition of parasympathetic activity in SHR continued without coupled changes in sympathetic activity. In SHR, APH under N(2)O inhalation decreased SBP and sympathetic activity more prominently and earlier than APH alone, and earlier than APH under N(2)O inhalation in WKY. Additionally, APH under N(2)O inhalation inhibited cardiac parasympathetic activity in SHR as compared to APH stress alone. In conclusion, APH under N(2)O inhalation in SHR potentially results in exacerbation of circulatory suppression from the earlier hypoxic phase, compared with non-N(2)O inhalation.

Which nostril should be used for nasotracheal intubation: the right or left? A randomized clinical trial

STUDY OBJECTIVE To determine which nostril is more suitable for nasotracheal intubation in patients with normal patency of both nostrils. DESIGN Prospective, randomized clinical trial. SETTING Operating room of a university medical center. PATIENTS 191 ASA physical status 1 and 2 patients scheduled for elective oral surgery requiring general anesthesia with nasotracheal intubation. INTERVENTIONS Patients were randomized to two groups to undergo nasotracheal intubation through the right nostril (Group R; n = 96) or the left nostril (n = 95). Standard traditional nasotracheal intubation was performed using the Macintosh laryngoscope. Tube rotation was attempted for alignment toward the glottis, and Magill forceps were then used to assist intubation, as necessary. MEASUREMENTS Epistaxis was inspected in the pharynx after the tube tip was passed through the nasal cavity and 15 minutes after nasotracheal intubation was completed. Intubation time was the interval between when the anesthesiologist opened the patients mouth with the cross finger maneuver and when the tube was connected to the anesthetic circuit after nasotracheal completion. MAIN RESULTS The frequency of epistaxis was significantly lower in Group R than Group L (P = 0.0006). Although there was no significant difference in nasal passage time between two groups, the intubation time in Group R (24.5 ± 9.4 sec) was shorter than in Group L (30.5 ± 15.6 sec; P = 0.0015). CONCLUSION Nasal intubation via the right nostril is more safely performed than with the left nostril. Because of less epistaxis and faster intubation.

Cough Reflex Under Intravenous Sedation During Dental Implant Surgery Is More Frequent During Procedures in the Maxillary Anterior Region

PURPOSE The present study was performed to evaluate the incidence of cough episodes and the association between cough episodes and patient-related and site-specific parameters during implant surgery when performed under intravenous sedation. MATERIALS AND METHODS One hundred forty-seven patients scheduled for dental implant surgeries under intravenous sedation were enrolled in this study. Heart rate, blood pressure, percutaneous oxygen saturation, and bispectral index were monitored. Sedation was induced intravenously by a bolus administration of midazolam and maintained by a continuous administration of propofol. Sedation level was adjusted to achieve scores of 3 to 4 on the Ramsay Sedation Scale. Surgical procedures were divided into 11 stages. Implant sites were labeled as right maxillary molar, maxillary anterior, left maxillary molar, right mandibular molar, mandibular anterior, and left mandibular molar sites. When coughing occurred, heart rate, blood pressure, percutaneous oxygen saturation, bispectral index, procedure being performed, and surgical site being stimulated were recorded. RESULTS One hundred seventy-two cough episodes were observed in 97 patients (66%). Cough episodes occurred during all stages of surgery but were substantially more frequent during preparation of the implant site. The incidence of cough episodes was significantly higher at the maxillary anterior site and lowest at the right mandibular molar areas. CONCLUSION These findings suggest that difficulties in swallowing and in the suction of intraoral fluids have variable effects at different surgical sites. Careful suction of intraoral water and an appropriate sedation level are required, especially in procedures in the maxillary anterior region.

Trigeminal nervous system sensitization by infraorbital nerve injury enhances responses in a migraine model

Background Although the peripheral and central sensitizations of trigeminal nervous system may be one of the important factors of migraine, the precise mechanism is not fully understood. In this study, we examined the influence of the sensitization of the second division of the trigeminal nerve (V2) by chronic constriction injury (CCI) of the infraorbital nerve (ION) on migraine headache, using the capsaicin-induced migraine model. Methods Male Sprague-Dawley rats were assigned to four groups: (a) sham surgery and topical-dural vehicle application (Sham + Vehicle) group, (b) CCI-ION and topical-dural vehicle application (CCI-ION + Vehicle) group, (c) sham surgery and topical-dural capsaicin application (Sham + Capsaicin) group, (d) CCI-ION and topical-dural capsaicin application (CCI-ION + Capsaicin) group. Behavioral testing and immunohistochemical staining were performed. Results In the behavioral test, the Sham + Capsaicin group showed significantly longer duration of immobilization and shorter duration of exploration compared with the Sham + Vehicle group, which is similar to clinical features of migraine patients. Moreover, CCI-ION enhanced these effects in the CCI-ION + Capsaicin group. Immunohistochemical staining for phospho-extracellular signal-related kinase (pERK) in the trigeminal ganglion (TG) containing first and second divisions of the trigeminal nerve and the trigeminocervical complex (TCC) revealed that pERK expression was significantly increased in the CCI-ION + Capsaicin group compared with the other groups. However, comparing between effects of the peripheral and central sensitizations (in the TG and TCC), from our results, peripheral sensitization would play a much less or not significant role. Conclusions These data demonstrate that the sensitization of V2 could influence the activation and the sensitization of the first division of the trigeminal nerve in the TCC, subsequently exacerbating pain sensation and pain-related behaviors. We have shown for the first time that the existence of the central sensitization of V2 can be an exacerbating factor for migraine related nociceptive thresholds/activation.

A Prospective, Randomized Controlled Trial of Conscious Sedation Using Propofol Combined With Inhaled Nitrous Oxide for Dental Treatment

PURPOSE Adverse reactions during propofol sedation include a decrease in arterial blood pressure, propofol-induced pain on injection, and airway complications. The purpose of this study was to investigate whether combined use of intravenous propofol and inhaled nitrous oxide could decrease the hypotensive and other adverse effects of propofol. PATIENTS AND METHODS We designed and implemented a prospective, randomized controlled trial. Patients undergoing dental procedures requiring intravenous sedation were randomly allocated to 2 groups: group P comprised those receiving sedation with propofol alone, and group N+P comprised those receiving sedation with 40% nitrous oxide inhalation and propofol. During the dental procedures, the sedation level was maintained at an Observers Assessment of Alertness/Sedation scale score of 4 by adjusting propofols target plasma concentration. Nitrous oxide inhalation was the predictor variable, whereas the hemodynamic changes, amount and concentration of propofol, and adverse events were the outcome variables. RESULTS Eighty-eight patients were successfully analyzed without any complications. The total amount of propofol was significantly less in group N+P (249.8 ± 121.7 mg) than in group P (310.3 ± 122.4 mg) (P = .022), and the mean concentration of propofol was significantly less in group N+P (1.81 ± 0.34 μg/mL) than in group P (2.05 ± 0.44 μg/mL) (P = .006). The mean blood pressure reduction in group N+P (11.0 ± 8.0 mm Hg) was significantly smaller than that in group P (15.8 ± 10.2 mm Hg) (P = .034). Pain associated with the propofol injection and memory of the procedure were less in group N+P (P = .011 and P = .048, respectively). Nitrous oxide did not affect respiratory conditions or recovery characteristics. CONCLUSIONS The results of this study suggest that nitrous oxide inhalation combined with propofol sedation attenuates the hypotensive effect and pain associated with propofol injections, along with potentiating the amnesic effect.

The effect of nitrous oxide inhalation on the hypotensive response to propofol: a randomized controlled trial

OBJECTIVE Decrease in arterial blood pressure is a prominent adverse reaction during propofol (Disoprivan; AstraZeneca K.K., Osaka, Japan) sedation. The purpose of this prospective randomized study was to explore the effects of nitrous oxide (N2O) on the hypotensive response during propofol sedation. STUDY DESIGN Twenty-six healthy volunteers received intravenous sedation with propofol alone (group P, n=13) or a combined technique using 20% N2O and propofol (group N+P, n=13). Propofol was administered by a target-controlled infusion system to attain and maintain a plasma propofol concentration of 1.5μg/mL. Hemodynamic and autonomic parameters were measured. RESULTS Mean arterial pressure decreased in both groups, the hypotensive response in group N+P being significantly smaller than in group P. Reduction in the low-frequency power of systolic blood pressure variability, indicative of sympathetic nervous activity, was also smaller in group N+P than in group P. CONCLUSIONS Addition of N2O to propofol sedation can attenuate the hypotensive effect of propofol.