Jun-ichi Satoh

Changes in concentrations of free propofol by modification of the solution

Because free propofol is thought to be responsible for pain on injection, we investigated the changes in concentrations of free propofol by modifying two kinds of propofol products in a medium- and long-chain triglyceride (MCT/LCT) emulsion and in an LCT emulsion. The techniques used in this study were 1) mixing 2% lidocaine (10:1), 2) mixing 5% dextrose in acetated Ringer’s solution to reduce pH (10:1), and 3) changing the temperature to 4°, 20°, and 36°C. The propofol preparations were dialyzed for 24 h, and the receptor medium was analyzed using high-performance liquid chromatography. The concentration of free propofol in propofol MCT/LCT was significantly smaller by 30% than that in propofol LCT. Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products, but the concentrations were reduced by a decrease in pH and by an increase in temperature. Because mixing lidocaine can induce instability in an emulsion of propofol and warming can rapidly induce microbial growth, injection of lidocaine before propofol administration is recommended to reduce the pain on injection. The concentrations of free propofol in propofol MCT/LCT were significantly smaller (by approximately 30%–45%) than those in propofol LCT during any situation in this study.

Desflurane induces airway contraction mainly by activating transient receptor potential A1 of sensory C-fibers

We previously reported that desflurane induced airway contraction via antidromic tachykinin release from sensory C-fibers. Here, we investigated the effect of desflurane on airway lung resistance (RL) using specific receptor antagonists in C-fibers. Young guinea pigs were anesthetized and their tracheas were cannulated with an endotracheal tube via a tracheotomy. A Fleisch pneumotachograph and a differential transducer were used to monitor respiratory flow rate, intrapleural pressure, and airway pressure, and RL was calculated and recorded. A transient receptor potential A1 (TRPA1) or a transient receptor potential V1 (TRPV1) selective antagonist of sensory C-fibers, i.e., HC030031 or BCTC, was administered before the exposure to desflurane. In an additional experiment, tachykinin receptor of airway smooth muscles was antagonized only by the neurokinin-2 receptor antagonist MEN-10376 before the exposure to desflurane. HC030031 completely inhibited both the first and the second contractile responses induced by desflurane, whereas BCTC had little effect. MEN-10376 also significantly and substantially diminished the contractile response. Desflurane contracts the airway in untreated guinea pigs mainly by activating irritant gas receptor TRPA1 of afferent C-fibers, resulting in the release of contractile tachykinins such as neurokinin A.

Desflurane but not sevoflurane can increase lung resistance via tachykinin pathways

BACKGROUND Although there is evidence that the volatile anaesthetic desflurane directly relaxes preconstricted airway smooth muscle in vitro, the anaesthetic increases the lung resistance in vivo. The constrictive mechanisms of desflurane are, however, still unknown. This study was conducted to clarify the increasing mechanisms of desflurane on lung resistance by examining the vagal nerve reflexes in guinea pigs. METHODS The effects of desflurane and sevoflurane on total lung resistance (R(L)) and dynamic lung compliance (C(Dyn)) were investigated in animals that were either untreated, pretreated with atropine or vagotomy, pretreated with the tachykinin receptor antagonists sendide or MEN-10376, or given chronic pretreatment with capsaicin. RESULTS Desflurane biphasically and dose-dependently increased R(L) (by 180% and 230% at the first and second peaks, respectively, at 2 minimum alveolar concentration) concomitant with a decrease in C(Dyn). However, sevoflurane had little effect on either R(L) or C(Dyn). Although vagotomy partially inhibited the first peak of R(L) by 30%, neither atropine nor vagotomy had any effect on the other respiratory responses to desflurane. Antagonization of tachykinin receptors of airway smooth muscles completely diminished the increase in R(L) induced by desflurane. Desflurane also had little effect on respiratory parameters after the capsaicin pretreatment, in which tachykinin containing afferent C-fibres was desensitized. CONCLUSIONS Desflurane but not sevoflurane increased R(L) concomitant with a decrease in C(Dyn) in guinea pigs. The increase in lung resistance by desflurane might be due to antidromic tachykinin release from afferent C-fibres but not acetylcholine release from parasympathetic efferent nerves.

Three-Dimensional Imaging of the Temporal Bone Using a Helical CT Scan and Its Application in Patients with Cochlear Implantation

Recent advanced techniques for the reconstruction of three-dimensional (3D) images allow further visual recognition of the fine structures of the temporal bone. We demonstrate the advantages of reconstruction 3D imaging in helical CT scans of the normal temporal bone and in patients who have received cochlear implants. After the temporal bone was scanned in the axial plane in the helical scan mode, the data were transferred to a workstation and 3D reconstruction was performed. The normal temporal bone structures were well recognized on these 3D images. The spatial relationship between the lymphatic space of the inner ear and the electrode array is visible. This method provides a detailed anatomy of the insertion of the electrodes into the cochlea and provides precise images of electrode routes by means of varying the angles of view on the computer display. Individual electrodes could not be distinguished. The information from 3D images may be useful not only for pre-but also postoperative investigations in cochlear implantation.

Middle Ear Imaging Using Virtual Endoscopy and Its Application in Patients with Ossicular Chain Anomaly

Virtual endoscopy (VE) is a recently developed technique to provide a realistic surface rendering of various organs, which can be applied to the use of three-dimensional (3D) studies of several lesions. However, its advantages in otological disease have not been well investigated. In this study, we evaluated the application of VE in patients with ossicular chain anomalies. Virtual middle ear endoscopy was a time-saving method, however, we needed the appropriate technical procedures of algorithm and reconstruction spacing to generate accurate 3D images of ossicles. We obtained virtual surgical views of middle ear structures and related anomalies, and confirmed by intraoperative findings that these images were mostly compatible with the actual lesions of ossicles. VE allowed an identification of the anatomy of the ossicles and adjacent structures simultaneously. The elements of the stapedial crura were clearly visualized with VE images in 93.3% of normal ears. Pathological ossicular chain findings such as malleus or incus fixation, dislocation and disruption, except footplate fixation were investigated successfully. One possible procedure, using alterable CT value in the obtained VE images on the monitor, is proposed for further detection of fine lesions of the ossicles. These observations suggest that virtual middle ear simulations accurately represent major intraoperative findings. This technique may have an important role in preoperative planning, surgical training, and/or postoperative evaluation in otology.

The usefulness of an earphone-type infrared tympanic thermometer for intraoperative core temperature monitoring.

BACKGROUND:In this study we sought to determine the usefulness of a novel earphone-type infrared tympanic thermometer (IRT) for core temperature monitoring during surgery. METHODS:Two groups of patients were studied under different surgical conditions. The first group consisted of 18 adult patients (ASA I or II) who had been scheduled for elective surgery under general anesthesia. Before induction of general anesthesia, an earphone-type IRT was inserted into either the left or right ear canal. Tympanic temperature was monitored and recorded along with both rectal and esophageal temperatures during anesthesia. The second group consisted of eight adult patients (ASA II or III) who had been scheduled for cardiac surgery with cardiopulmonary bypass. Similar to the first group, tympanic temperature was measured by the earphone-type IRT and recorded along with the rectal and esophageal temperatures during cooling and rewarming phases of cardiopulmonary bypass. RESULTS:Study 1—The average temperature (±2 sd) measured with the IRT was +0.08°C (±0.34°C) above the esophageal temperature, and that with the rectal temperature was +0.11°C (±0.55°C) above the esophageal temperature. Study 2—The average temperature (±2 sd) measured with the IRT was +0.72°C (±2.2°C) above the esophageal temperature during cooling and warming phases during cardiac surgery with cardiopulmonary bypass. CONCLUSIONS:The earphone-type IRT might be used in a clinical setting for reliable and continuous core temperature monitoring during an operation.

Beta-1 selective adrenergic antagonist landiolol and esmolol can be safely used in patients with airway hyperreactivity.

This study was undertaken to clarify the effects of esmolol and landiolol, beta-1 selective adrenergic antagonists, on hyperreactive airways in both ovalbumin-sensitized guinea pigs and asthmatic patients. In the animal study, asthma was induced by ovalbumin. After control acetylcholine responses for total pulmonary resistance (Raw) and dynamic lung compliance (Cdyn) were obtained, the animals received propranolol, esmolol, or landiolol, and the same protocol was again performed. Sixty inpatients with coronary risk factors and asthma were enrolled in the human study. Under propofol anesthesia, the patients received saline, esmolol, or landiolol. To assess intubation-induced bronchoconstriction, the presence of wheezing was determined. The dose-response curves of Raw and Cdyn to acetylcholine were significantly elevated and declined in the ovalbumin-sensitized model compared with those in the control group. Neither esmolol nor landiolol had any effect on the acetylcholine-induced response curve in these sensitized animals. However, propranolol significantly enhanced Raw and reduced Cdyn in this model. Tracheal intubation increased the incidence of wheezing in asthmatic patients. However, there was no significant difference in the incidence of wheezing among these groups. The ultra-short-acting beta-1 selective adrenergic antagonists esmolol and landiolol can be safely used perioperatively in patients with airway hyperreactivity.

Different Inhibitory Effects of Sevoflurane on Hyperreactive Airway Smooth Muscle Contractility in Ovalbumin-sensitized and Chronic Cigarette-smoking Guinea Pig Models

Background: The authors hypothesized that sevoflurane had different inhibitory effects on hyperreactive airway smooth muscle contractility in different types of hyperreactive airway models. Methods: The effects of sevoflurane on hyperreactive airways in ovalbumin-sensitized and chronic cigarette-smoking guinea pig models were investigated by measuring (1) total lung resistance, (2) smooth muscle tension and intracellular concentration of free Ca2+, (3) voltage-dependent Ca2+ channel activity, and (4) cyclic adenosine monophosphate levels. Results: Ovalbumin and muscarinic airway hyperreactivity was seen in ovalbumin-sensitized animals. Enlarged alveolar ducts/alveoli and lesser muscarinic hyperreactivity were observed in chronic cigarette-smoke animals. Although sevoflurane inhibited the acetylcholine-induced increase in total lung resistance in the control and ovalbumin-sensitized models, the anesthetic had a smaller effect in the chronic cigarette-smoking model. Similarly, in the chronic cigarette-smoking model, sevoflurane had a smaller inhibitory effect on carbachol-induced muscle contraction and increase in intracellular concentration of free Ca2+. Sevoflurane also had a smaller inhibitory effect on voltage-dependent Ca2+ channel activity in the chronic cigarette-smoking group than in the other two groups. The sevoflurane-induced increase in cyclic adenosine monophosphate that was seen in the control and ovalbumin-sensitized groups was significantly suppressed in the chronic cigarette-smoking group. Conclusions: Although sevoflurane potently inhibited airway contractility in control and ovalbumin-sensitized models, the anesthetic had a smaller effect in a chronic cigarette-smoking model. The different inhibitory effects of sevoflurane on airway contractility depend, at least in part, on different effects on voltage-dependent Ca2+ channel activity and cyclic adenosine monophosphate level.

Inhibitory effects of the alpha-2 adrenergic agonists clonidine and dexmedetomidine on enhanced airway tone in ovalbumin-sensitized guinea pigs

Background and objective: The alpha‐2 adrenergic agonists clonidine and dexmedetomidine are used as an antihypertensive and a sedative, respectively. The aim of this study was to determine the effects of these agonists on ovalbumin‐sensitized airway tone in guinea pigs. Methods: The animals were divided into two groups: control and sensitized. The sensitized group received ovalbumin intraperitoneally and was boosted by exposure to aerosolized ovalbumin. The effects of the alpha‐2 agonists were investigated by measuring (1) total lung resistance and (2) smooth muscle tension using a tracheal ring preparation. Results: In the control group, acetylcholine significantly increased total lung resistance in a dose‐dependent manner. In the sensitized animals, total lung resistance was significantly higher (by 95%) at 6 &mgr;g kg−1 acetylcholine than that in the control group. Both clonidine and dexmedetomidine had a slight but significant inhibitory effect on the response curve of lung resistance at higher concentrations of carbachol, a potent muscarinic receptor agonist. Similar to the data obtained in the control group, both clonidine and dexmedetomidine significantly decreased total lung resistance and the inhibitory effects of these alpha‐2 agonists on lung resistance were significantly distinguishable. Similar direct inhibitory effects of the alpha‐2 agonists on carbachol‐induced muscle contraction were observed in both the control and sensitized groups, the inhibitory effects in the sensitized group being significantly greater. Conclusion: Both clonidine and dexmedetomidine can relax the airway even in the hyper‐reactive state.

Effects of the Chinese herbal medicines Bupleuri radix, Ginseng radix, and Zingiberis rhizoma on lymphatic vessel activity in rats.

The aim of the present study was to determine the effects of the Chinese herbal medicines Bupleuri radix, Ginseng radix and Zingiberis rhizoma on spontaneous lymphatic vessel activity. The effect of each herbal medicine on in vivo lymphatic flow was examined by injection of dye into the femoral regions of rats after feeding with the herbal medicines. In an in vitro study, spontaneous changes in diameter of the rat thoracic duct were monitored, and each segment was exposed to each herbal medicine. In the in vivo study, 100% of the right iliac lymphatic node were positively stained in the herbal medicine group, whereas only 40% of the node were positively stained in the control group. In the in vitro study, Bupleuri radix and Ginseng radix increased the amplitude of spontaneous activity of lymphatic vessels in a concentration-dependent manner with or without L-NAME, an NO synthase inhibitor. The results indicated that the herbal medicines Bupleuri radix and Ginseng radix activated spontaneous lymphatic vasomotion and lymph flow, and the mechanisms of this effect seem to be independent of endothelial cells.