Kazumi Takaishi

Molecular mechanisms of the inhibitory effects of clonidine on vascular adenosine triphosphate-sensitive potassium channels.

BACKGROUND: We investigated the effects of the imidazoline-derived &agr;2-adrenoceptor agonist clonidine on vascular adenosine triphosphate–sensitive potassium (KATP) channel activity in rat vascular smooth muscle cells and recombinant vascular KATP channels transiently expressed in COS-7 cells. METHODS: Using the patch-clamp method, we investigated the effects of clonidine on the following: (1) native vascular KATP channels; (2) recombinant KATP channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits; (3) SUR-deficient channels derived from a truncated isoform of the Kir6.2 subunit (Kir6.2&Dgr;C36 channels); and (4) mutant Kir6.2&Dgr;C36 channels with diminished sensitivity to ATP (Kir6.2&Dgr;C36-K185Q channels). RESULTS: Clonidine (≥3 × 10−8 M) inhibited native KATP channel activity in cell-attached configurations with a half-maximal inhibitory concentration value of 1.21 × 10−6 M and in inside-out configurations with a half-maximal inhibitory concentration value of 0.89 × 10−6 M. With similar potency, clonidine (10−6 or 10−3 M) also inhibited the activities of various recombinant SUR/Kir6.0 KATP channels, the Kir6.2&Dgr;C36 channel, and the Kir6.2&Dgr;C36-K185Q channel. CONCLUSIONS: Clinically relevant concentrations of clonidine inhibit KATP channel activity in vascular smooth muscle cells. This inhibition seems to be the result of its effect on the Kir6.0 subunit and not on the SUR subunit.

Local anesthetics inhibit nitric oxide production and L-arginine uptake in cultured bovine aortic endothelial cells.

Previous studies have shown that local anesthetics have various effects on nitric oxide (NO) production, but the mechanisms remain unclear. The purpose of this study was to evaluate the effects of local anesthetics on NO production and 2-amino-5-guanidinopentanoic acid (l-arginine) uptake in one cell line. Cultured bovine aortic endothelial cells (BAEC) were stimulated with bradykinin and/or acetylcholine to activate endothelial NO synthase (NOS). BAEC were also incubated with interleukin-1β and lipopolysaccharide to stimulate inducible NOS. NO production was measured with the rapid spectrophotometric method, and l-arginine uptake was measured with high performance liquid chromatography. To assess the effects of local anesthetics, NO production and l-arginine uptake were measured in the presence or absence of procaine or lidocaine. NO was produced in BAEC stimulated with bradykinin and acetylcholine or interleukin-1β and lipopolysaccharide, but NO production was not affected by the addition of superoxide dismutase. In the cells stimulated with bradykinin and acetylcholine, 10 μM each of procaine and lidocaine significantly inhibited NO production by 35% and 20%, respectively. In the cells incubated with interleukin-1ß and lipopolysaccharide, the same quantities of procaine and lidocaine significantly inhibited NO production by 15% and 10%, respectively. Both procaine and lidocaine significantly suppressed l-arginine uptake in BAEC stimulated with either bradykinin/acetylcholine or interleukin-1β/lipopolysaccharide. It is suggested that inhibitory effects of procaine and lidocaine on NO production are partially due to suppression of l-arginine uptake.

Impact of newly developed, next-generation artificial endocrine pancreas.

BACKGROUND Recent studies have shown that strict perioperative blood glucose management may reduce mortality and morbidity in critically ill adult patients. The purpose of this study was to assess the accuracy and efficacy of the intraoperative application of a newly developed, next-generation artificial endocrine pancreas (STG-55, Nikkiso Co., Ltd., Tokyo, Japan). METHODS Twenty patients scheduled to undergo surgery were enrolled in this study. The STG-55 is designed to be more user-friendly than its conventional counterpart (STG-22) while maintaining the latters fundamental functions, such as a closed-loop system using algorithms for insulin and glucose infusion. After anesthetic induction, a 20G intravenous catheter was inserted into a peripheral forearm vein and connected to a continuous blood glucose monitor. The resultant 105 scores for paired blood glucose values were compared by Bland-Altman analysis. RESULTS Stable blood glucose values were maintained automatically, and there were no complications related to use of the STG-55. A close correlation (r=0.96) was observed between continuous glucose measurements using the STG-55 and conventional intermittent glucose measurements. The difficulty of manipulation using this system was decreased by improved preparation procedures. CONCLUSION The glycemic control system using the STG-55 could provide an alternative way to achieve effective and safe perioperative glycemic control.

Increase in prominence of electrocardiographic J waves after a single dose of propofol in a patient with early ventricular repolarisation.

J waves appear on an electrocardiogram as an elevation of the J point in the terminal portion of the QRS complex. J waves are often benign, but may be associated with malignant ventricular arrhythmias. In some cases, such problems appear to have been precipitated by propofol infusions. We observed a sudden increase in J waves and profound hypotension following a single intravenous dose of propofol in an 84‐year‐old woman with early repolarisation in the inferior ventricular wall. When early repolarisation (as shown by electrocardiographic J waves) is observed in the inferior ventricular wall pre‐operatively, patients should be carefully monitored. Myocardial ischaemia and the use of drugs that might worsen J waves should be avoided.

Nasotracheal intubation through pharyngeal flap after pharyngeal flap construction

A 24-year-old woman provided her written consent to publish the details of her case. She had undergonemultiple surgeries including pharyngeal flap construction for bilateral cleft lip and palate. All previous operationswere performed under general anesthesia by oral intubation. In the present procedure, sagittal split ramus osteotomy under general anesthesia with nasotracheal intubation was planned. We obtained the three-dimensional morphological structure of the pharyngeal flap (Fig. 1). The measurements of the cross-section at the narrowest were 5.1 × 12.8 mm for the left orifice and 3.2 × 13.2 mm for the right. Endoscopic observation revealed displacement of the nasal septum to the right and bony swelling of the left inferior concha and ridge. The fiberscope could be moved forward straight from the right nasal cavity to the right orifice, but not be advanced straight from the left nasal cavity to the left orifice. On the day of the operation, atropine 0.25 mg was administered intravenously. A tracheal tube (inner diameter: ID 7 mm) was inserted orally after the induction of anesthesia with remifentanil, propofol, and rocuronium. We inserted a cotton swab impregnated with 1% lidocaine containing adrenalin (1:33,000 dilution) into nasal cavities. After removing the swab, a bronchofiberscope (Olympus, MAF TYPE TM, Japan, outer diameter: OD 5.2 mm) was inserted into the right nasal cavity, and it was moved towards the right orifice of the pharyngeal flap. However, it was difficult to smoothly manipulate the fiberscope due to the narrowed right nasalmeatus.We judged that an endotracheal tube should be inserted through the left nasal cavity. We carefully inserted a nasal airway (ID 7 mm) with 1% lidocaine containing adrenalin from the left nasal cavity up to a point 2 cm short of reaching the pharyngeal flap, and we removed the airway. We then inserted a reinforced endotracheal tube (Parker Flex-Tip® PFRP, ID 6 mm, OD 8.4 mm), in which a bronchial fiberscope was inserted beforehand, up to the point 2 cm short of the pharyngeal flap. We attempted to lead the bronchofiberscope to the left orifice, but, the angle between the left nasal meatus and left orifice was too sharp to advance the fiberscope. Therefore, we led the fiberscope to the right orifice. Using the bronchofiberscope as a guide, we introduced the tracheal tube to the hypopharynx. We inserted the tracheal tube into the trachea using a Macintosh laryngoscope immediately after pulling out the oral tube. At the end of the operation, no abnormalities were confirmed to exist in the pharyngeal flap and the surrounding tissues. We could remove the tracheal tube without resistance after the patient emerged from general anesthesia. Pharyngeal flap construction is an operation to correct velopharyngeal insufficiency. The space between the pharyngeal flap

The unique action of nicorandil on cerebral circulation

Kotoda et al. [1] demonstrated that the intraperitoneal 1 mg/ kg nicorandil without affecting systemic hemodynamics causes the increase in cerebral blood flow (CBF), which is canceled by either an ATP-sensitive K+ channel (KATP) antagonist glibenclamide or a non-selective nitric oxide synthase inhibitor NG-nitro-l-arginine (l-NAME). They concluded that nicorandil produces the enhancement in CBF, which is probably induced via both the nitric oxide pathway and KATPs [1]. We would like to add several discussions regarding the conclusion. First, the systemic administration of l-NAME causes the reduction of CBF at the range of − 20 to − 40%, which is mediated by the nitric oxide synthase inhibition [2]. The CBF possibly remains unchanged within the baseline in the animals exposed to the systemic l-NAME, which results in the CBF reduction, in combination with the vasodilation induced by nicorandil. Therefore, there seems no evidence to conclude that nicorandil increases CBF via the enhanced levels of nitric oxide since Kotoda et al. [1] did not examine the effect of l-NAME alone on the naïve CBF and that of the nitric oxide inhibitor in combination with glibenclamide on increased CBF by nicorandil. On the other hand, the activation of nitric oxide synthase might be possible by the application of a KATP opener in the artery of rodents [3]. Second, whether nicorandil produces cerebral arterial dilation via KATPs is still unclear in animals. Indeed, the agent does not induce dilation of rat anterior cerebellar artery [4], and it causes relaxation via nitric oxide pathway, but not KATP activation, in the canine basilar artery [5]. Therefore, the CBF enhancement by nicorandil is most likely to be mediated by mechanisms such as the increased cardiac output resulting from systemic vasodilation other than that originated from vasorelaxation in the brain. Collectively, we would like to await the additional study to verify the role of nicorandil in the cerebral circulation.

Successful treatment of mixed (mainly cancer) pain by tramadol preparations

The patient, a 70-year-old Japanese woman diagnosed with parotid gland cancer, underwent wide excision and reconstruction (facial nerve ablation, nerve transposition). At 1 month after the surgery, she was brought to our hospitals pain medicine department because her postoperative pain and cancer-related pain were poorly controlled. She had already been prescribed a tramadol (37.5 mg)/acetaminophen (325 mg) combination tablet (5 tablets/day). However, in addition to the continuous pain in her face and lower limbs, she was troubled by a trigeminal neuralgia-like prominence ache. Because this pain could not be controlled by an increase to eight combination tablets per day, we switched her medication to a tramadol capsule. At 11 months post-surgery, we then switched her medication to an orally disintegrating tramadol tablet to improve medication adherence of the drug. From 14 months post-surgery, the patient also used a sustained-release tramadol preparation, and she was then able to sleep well. Her current regimen is an orally disintegrating sustained-release tablet combination (total 300 mg tramadol) per day, and she achieved sufficient pain relief. Because tramadol is not classified as a medical narcotic drug, it widely available and was shown here to be extremely useful for the treatment of our patients mixed (mainly cancer) pain. J. Med. Invest. 64: 311-312, August, 2017.

Cuffed Oropharyngeal Airway for Difficult Airway Management

Difficulties with airway management are often caused by anatomic abnormalities due to previous oral surgery. We performed general anesthesia for a patient who had undergone several operations such as hemisection of the mandible and reconstructive surgery with a deltopectoralis flap, resulting in severe maxillofacial deformation. This made it impossible to ventilate with a face mask and to intubate in the normal way. An attempt at oral awake intubation using fiberoptic bronchoscopy was unsuccessful because of severe anatomical abnormality of the neck. We therefore decided to perform retrograde intubation and selected the cuffed oropharyngeal airway (COPA) for airway management. We inserted the COPA, not through the patients mouth but through the abnormal oropharyngeal space. Retrograde nasal intubation was accomplished with controlled ventilation through the COPA, which proved to be very useful for this difficult airway management during tracheal intubation even though the method was unusual.