Anesthetic management of airway stent placement by rigid bronchoscopy with superior laryngeal nerve block while preserving spontaneous breathing: A case report.

Key Clinical Message: The combination of superior laryngeal nerve block can reduce the respiratory depression that occurs during management under total intravenous anesthesia. Abstract: Anesthetic management of endobronchial stent placement by rigid bronchoscopy requires the maintenance of spontaneous breathing while suppressing upper airway reflexes. The combination of superior laryngeal nerve block (SLNB) can reduce the respiratory depression that occurs during management under total intravenous anesthesia. The patient was diagnosed as having lung cancer with invasion into the right middle bronchus and stenosis of the right main bronchus on chest computed tomography, and emergency airway stent placement was performed. Sedation was initiated with propofol and dexmedetomidine, and ultrasound-guided SLNB was performed after local anesthetic spraying into the oral cavity and trachea. Bucking was minimally controlled during insertion of the rigid bronchoscope. The patient's intraoperative hemodynamics remained stable, and there were no hypoxic events. SLNB can provide the suppression of the upper airway reflex while minimizing effects on spontaneous breathing, and may be useful for achieving balanced anesthesia during rigid bronchoscopy.

Influence of p-glycoprotein on brain Bcl-2 family proteins and cytokines in transient cerebral ischemia.

OBJECTIVES: P-glycoprotein (P-gp), produced by the multidrug resistance (mdr1a) gene, is present in vascular endothelial cells, astrocytes, and microglia in the brain. We previously reported that P-gp aggravated cerebral infarct. Therefore, modulation of the function of P-gp is important for the treatment of brain ischemia. Here, we examined how P-gp exacerbates ischemic damage in the brain. METHODS: Experiments were performed using mdr1a knockout (KO) mice and wild-type mice. Mice of both groups were subjected to transient focal ischemia and Bcl-2 family proteins, p-glycoprotein and cytokines were measured. RESULTS: At 48 h after reperfusion, the expression of Bcl-2 protein in the brains of mdr1a KO mice was significantly greater compared with that of wild-type mice. The expression of brain Bax protein in mdr1a KO mice was significantly lower compared with that of wild-type mice. At 6 h after reperfusion, the expression of plasma IL-6 in mdr1a KO mice was significantly lower compared with that of wild-type mice. CONCLUSION: These results indicate that P-gp derived from the mdr1a gene has pro-apoptotic functions mediated through Bcl family proteins and increased IL-6, which exacerbates ischemic damage in the brain. In summary, the inhibition of P-gp function is an effective strategy to protect against brain damage caused by ischemic damage.

Edaravone and cyclosporine A as neuroprotective agents for acute ischemic stroke.

It is well known that acute ischemic stroke (AIS) and subsequent reperfusion produce lethal levels of reactive oxygen species (ROS) in neuronal cells, which are generated in mitochondria. Mitochondrial ROS production is a self-amplifying process, termed "ROS-induced ROS release". Furthermore, the mitochondrial permeability transition pore (MPTP) is deeply involved in this process, and its opening could cause cell death. Edaravone, a free radical scavenger, is the only neuroprotective agent for AIS used in Japan. It captures and reduces excessive ROS, preventing brain damage. Cyclosporine A (CsA), an immunosuppressive agent, is a potential neuroprotective agent for AIS. It has been investigated that CsA prevents cellular death by suppressing MPTP opening. In this report, we will outline the actions of edaravone and CsA as neuroprotective agents in AIS, focusing on their relationship with ROS and MPTP.

Co-administration of Cyclosporin A and Ondansetron decreases transient local cerebral ischemic injury in the mouse.

OBJECTIVES: Several studies indicate that cyclosporin A has a protective effect against brain infarction. In this study, we aimed to determine if co-administration of cyclosporin A and ondansetron could reduce damage caused by cerebral ischemia. METHODS: ICR (Charles River Laboratories) mice were subjected to transient focal cerebral ischemia and divided into 4 groups (O, V, C, and Mix). Immediately after reperfusion, each ligand was administered intravenously through the external jugular vein. Group V animals received 0.9% saline alone, group O animals received 0.1 mg/kg ondansetron solution, group C animals received 10 mg/kg cyclosporin A solution, and group Mix received 0.1 mg/kg ondansetron solution and 10 mg/kg cyclosporin A solution. RESULTS: Our results showed that the volume of brain infarction induced by middle cerebral artery occlusion in group Mix was significantly smaller than that seen in group V. Forty-eight hours after ischemia, the neurological scores of rats from group Mix significantly improved when compared to group V. CONCLUSION: Overall, our study showed that a combination of cyclosporin A and ondansetron may be a practical clinical method to treat brain infarction. However, further studies are required to investigate the cerebroprotective mechanism of action, the possible side effects of co-administration of these drugs, and the ability of these ligands to cross the blood brain barrier.

Repetitive cerebral blood flow measurements using laser speckle imaging in a transient cerebral ischemic mouse model.

Using laser speckle imaging (LSI), which can visualize quadratic distribution of blood flow, we measured blood flow changes in transient cerebral ischemic mice, and compared these results with data obtained using laser Doppler flowmetry (LDF). In addition, we examined the relationship between ischemic damage and blood flow change. ICR mice (n = 22) were subjected to transient middle cerebral artery occlusion using a 6-0 monofilament under general anesthesia. LSI was performed before -ischemia, during ischemia, and 30 min, 3 h, 24 h, 7 days, and 28 days after ischemia. LDF was monitored continuously from pre-ischemia to 10 min after ischemia commenced. The level of cerebral blood flow (CBF) measured by LSI was less than that using LDF. LSI was able to measure CBF quantitatively and repeatedly. Blood flow -measurements using LSI revealed that recovery of cerebral cortical blood flow after ischemia in mice without cortical infarction was earlier than that seen in mice with cortical infarction. This study indicates that LSI is a -useful technique for analyzing the relationship between -tissue damage and cerebral blood flow change following cerebral ischemia.

[Use of Airwayscope with pediatric intlock in a patient with first and second branchial arch syndrome].

First and second branchial arch syndrome is a congenital anomaly of craniofacial dysplasia involving organs derived from the second branchial arch. The main characteristics are microtia and mandibular hypoplasia. A 6-year-old boy was scheduled for adenoidectomy and bilateral myringotomy and tube placement. Slow induction was performed with oxygen, nitrous oxide, and sevoflurane. No difficulties were encountered during mask ventilation, and rocuronium was administered intravenously. His epiglottis was not visible during laryngoscopy. Therefore, we used the Airwayscope (AWS). His glottis was visible after application of cricold pressure from the left side. However, we could not closely conform his epiglottis to the mark on the AWS. Therefore, we passed a fiberoptic bronchoscope through a tracheal tube and placed it in the AWS. We attempted to intubate the trachea, but could not guide the bronchoscope to his glottis. We then attempted to pull the tracheal tube to improve the mobility of the bronchoscope. Control of the bronchoscope consequently became easy We successfully guided it to his glottis and performed tracheal intubation. His condition was stable during the procedure. In conclusion, we safely performed tracheal intubation in a patient with first and second branchial arch syndrome using the AWS and a fiberoptic bronchoscope.

Effects of different types of anesthetic agents on cellular protein kinase C-γ dynamics in mouse brain.

BACKGROUND/AIMS: Although protein kinase C-γ (PKC-γ) is a target for the effects of volatile anesthetics, the molecular mechanisms of the kinase function during their action remain unclear. We examined the effects of different types of anesthetics on PKC-γ knockout mice. Furthermore, we investigated the dynamics of the kinase in brain cells obtained from mice anesthetized with these anesthetics. METHODS: We measured the required times for loss of righting reflex (rtfLORR) after administration of isoflurane, sevoflurane, or propofol on PKC-γ knockout mice and compared the times with those of wild-type mice. We also used immunoblotting to investigate the intracellular distribution of PKC-γ and phosphorylated PKC-γ (p-PKC-γ) in brain cell fractions obtained from wild-type mice during the loss of righting reflex induced by these anesthetics. RESULTS: Isoflurane (2.6%) and sevoflurane (3.4%) used at twice the minimum alveolar concentration significantly prolonged the rtfLORRs in PKC-γ knockout mice compared to those in wild-type mice. On the other hand, no significant difference was observed between knockout and wild-type mice treated with propofol (200 mg/kg). Examination of the cellular fractions isolated from volatile anesthetic-treated mouse brains showed that PKC-γ was significantly decreased in the synaptic membrane fraction (P2), whereas p-PKC-γ was significantly increased in P2. There was no significant change in the supernatant fraction (S). In propofol-treated mice, PKC-γ and p-PKC-γ showed no significant changes in P2 or S. CONCLUSION: Our results provide new evidence to support the possibility of the involvement of PKC-γ in the actions of volatile anesthetics.

Reduction of brain infarction induced by a transient brain ischemia in mdr1a knockout mice.

In order to evaluate the functional role of P-glycoprotein (P-gp) in cerebral ischemia, both multidrug resistance 1a knockout (KO) mice and wild-type mice were subjected to transient focal ischemia under a constant body and brain temperature about 37 degrees C. The results showed that the volume of brain infarction induced by middle cerebral artery occlusion in KO mice was significantly smaller than that seen in wild-type mice, although there were no significant differences in cerebral blood flow, physiological data and on anatomical analysis of cerebrovasculature between both groups. We suggest that multidrug resistance 1a P-gp plays a role for adjusting the expressions of endogenous neuronal cell modulating substances, such as cytokines, neuronal peptides, and others, in the brain, which is consistent with a previous paper (Bobrov et al. Neurosci Lett 24: 6-11, 2008).

Isoflurane inhibits protein kinase Cgamma and calcium/calmodulin dependent protein kinase ii-alpha translocation to synaptic membranes in ischemic mice brains.

Volatile anesthetics isoflurane possibly improves the ischemic brain injury. However, its molecular actions are still unclear. In ischemia, protein kinase C (PKC)gamma and calcium/calmodulin dependent protein kinase II (CaMKII)-alpha are persistently translocated from cytosol to cell membranes, and diminish these translocation suggested to be neuroprotective. We thus tested a hypothesis that isoflurane inhibits PKCgamma and CaMKII-alpha translocation after ischemic brain insults. C57Bl/6J male mice were made to inhale 1 or 2 MAC isoflurane, after which 3 or 5 min cerebral ischemia was induced by decapitation. The sampled cerebrum cortex was then homogenized and centrifuged into crude synaptosomal fractions (P2), cytosolic fractions (S3), and particulate fractions (P3). CaMKII-alpha and PKCgamma levels of these fractions were analyzed by immunoblotting. PKCgamma and CaMKII-alpha are translocated to synaptic membrane from cytosol by cerebral ischemia, although isoflurane significantly inhibited such translocation. These results may explain in part the cellular and molecular mechanisms of neuroprotective effects of isoflurane.

[Neuroprotective effects of novel derivatives of vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide in two brain ischemic models on mice].

BACKGROUND: Vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP), are members of a VIP/secretin/glucagon family. These peptides were demonstrated to possess the neuroprotective properties. However, these peptides are not suited to be developed as a medicine for brain ischemia because of their susceptibilities to endopeptidases. METHODS: We examined the effects of IK 312548 (IK), VIP derivative, and Ac-PACAP, PACAP derivative, on the 10 min two-vessel occlusion (2 VO) model in C 57 BL/6 N mice lacking a part of the posterior communicating artery, and the 30 min middle cerebral artery occlusion (MCAO) model in ICR mice. A 10 ml x kg(-1) dose of each derivative (final concentration; 1 fmol x kg(-1) and 100 pmol x kg(-1)) was injected intraperitoneally (i.p.) to each animal just after the preparation of brain ischemia. RESULTS: In 2 VO experiments, the number of neuronal cells in hippocampus was significantly reduced. However IK and Ac-PACAP treatments inhibited such reductions of neuronal cells in a dose-dependent manner. Particularly, between 1 pmol x kg(-1) and 100 pmol x kg(-) IK, and also between 10 fmol x kg(-1) and 1 pmol x kg(-1) Ac-PACAP significantly protected neuronal cell loss. In MCAO experiments, more than 60% of hemisphere was damaged. By treatment of IK (1-100 pmol x kg(-1)) and Ac-PACAP (1 fmol-1 pmol x kg(-1)), the range of brain damage decreased in a dose-dependent manner. CONCLUSIONS: Ac-PACAP and IK after the brain ischemia could pass the blood-brain barrier and protect brain cell damage.

Neuroprotective and neurotoxic effects of cyclosporine A on transient focal ischemia in mdr1a knockout mice.

The proper dose of cyclosporine A as a neuroprotective agent was investigated using the middle cerebral artery occlusion model of mdr1a knockout mice. After a 30-min occlusion period, reperfusion was performed and the vehicle or cyclosporine A (1 mg/kg or 10 mg/kg x 2) was intraperitoneally administered to each animal model group. Forty eight hours after reperfusion, infarction volume in the 1 mg/kg cyclosporine A group was significantly less than that seen in the vehicle group, although, in the high dose cyclosporine A group, infarction volumes were significantly higher than those seen in the vehicle group. These results demonstrate that cyclosporine A shows not only anti-ischemic effects, but also neurotoxic effects depending on the dosage penetrating into the brain.