Junichiro Kotani

Sevoflurane enhances ethanol-induced cardiac preconditioning through modulation of protein kinase C, mitochondrial KATP channels, and nitric oxide synthase, in guinea pig hearts.

BACKGROUND:Volatile anesthetics and regular ethanol consumption induce cardioprotection mimicking ischemic preconditioning. We investigated whether sevoflurane enhances ethanol preconditioning and whether inhibition of protein kinase C (PKC) and mitochondrial KATP channels attenuated this enhanced cardioprotection. The effects of regular ethanol consumption on expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase were determined. METHODS:Isolated perfused guinea pig hearts underwent 30-min global ischemia and 120-min reperfusion (Control: CTL). The ethanol group (EtOH) received 2.5% ethanol in their drinking water for 6 wk. Anesthetic preconditioning was elicited by 10-min exposure to sevoflurane (1 minimum alveolar anesthetic concentration; 2%) in ethanol (EtOH + SEVO) or nonethanol (SEVO) hearts. PKC and mitochondrial KATP channels were inhibited with chelerythrine and 5-hydroxydecanoate pretreatment, respectively. Contractile recovery was assessed by monitoring of left ventricular developed and end-diastolic pressures. Infarct size was determined by triphenyltetrazolium chloride staining. Expression of iNOS and eNOS were determined by Western blot analysis. RESULTS:After ischemia-reperfusion, hearts from the EtOH, sevoflurane (SEVO), and EtOH + SEVO groups had higher left ventricular developed pressure and lower left ventricular end-diastolic pressure compared with CTL. Infarct size was reduced in EtOH and SEVO hearts compared with CTL (27% and 23% vs 45%, respectively, P < 0.001). Sevoflurane further reduced infarct size in EtOH hearts (27% vs 15%, P < 0.001). Chelerythrine and 5-hydroxydecanoate abolished cardioprotection in both SEVO and EtOH cardioprotected hearts. iNOS expression was reduced and eNOS expression was increased in EtOH hearts. CONCLUSIONS:Sevoflurane enhances cardiac preconditioning induced by regular EtOH consumption. This effect is mediated in part by modulation of PKC and mitochondrial KATP channels, and possibly by altered modulation of NOS expression.

Direct evidence for inhibition of mitochondrial permeability transition pore opening by sevoflurane preconditioning in cardiomyocytes: comparison with cyclosporine A.

To assess whether sevoflurane preconditioning is associated with inhibition of mitochondrial permeability transition pore (MPTP), the effects of sevoflurane were compared with those of cyclosporine A, a known inhibitor of MPTP opening. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (control). Sevoflurane preconditioning was elicited by administration of 2% sevoflurane for 10 min with 10 min washout before ischemia (sevoflurane). A preconditioning-like cardioprotection was also induced by administering cyclosporine A (0.2 μM) for 15 min, starting 5 min before ischemia and for 10 min after the onset of reperfusion (cyclosporine A). Left ventricular developed and end-diastolic pressures, coronary flow and infarct size were measured. Expressions of Akt and glycogen synthase kinase 3β (GSK3β), known mediators of inhibition of MPTP opening, were determined by Western blot analysis. GSK3β inhibition was achieved with LY294002. The effects of sevoflurane and cyclosporine A on calcium-induced MPTP opening in isolated calcein-loaded mitochondria were assessed. After ischemia-reperfusion, sevoflurane and cyclosporine A had higher left ventricular developed pressure. Infarct size was significantly reduced in sevoflurane and cyclosporine A vs. control. This was abolished by LY294002 in sevoflurane, but not in cyclosporine A. Akt and GSK3β phosphorylation after reperfusion were significantly increased in sevoflurane and cyclosporine A. Ca²⁺-induced reduction in calcein fluorescence was significantly attenuated in sevoflurane and cyclosporine A. Preconditioning agents, sevoflurane and cyclosporine A increase the threshold of calcium-induced MPTP opening to a similar extent. This effect by sevoflurane, but not cyclosporine A is at least partially mediated by GSK3β inactivation.

The Parker Flex-Tip tube for nasotracheal intubation: the influence on nasal mucosal trauma.

We tested our hypothesis that use of the Parker Flex‐Tip™ tracheal tube could reduce the incidence of nasal mucosal trauma during nasotracheal intubation when compared with a conventional tip tracheal tube. One hundred and two patients, who were scheduled for elective oral surgery in which nasotracheal intubation was indicated to optimise the surgical approach, were recruited into this study. Either a Flex‐Tip tracheal tube or a conventional tip tracheal tube was chosen randomly for each nasotracheal intubation. The incidence of epistaxis using the Flex‐Tip tracheal tube (6 (11.8%)) was significantly lower than that with the conventional tip tracheal tube (18 (35.3%); p = 0.009). Nasal pain due to intubation, rated on a 100‐mm visual analogue scale, was less intense with the Flex‐Tip tracheal tube (median, (10th–90th percentile) 19 (12–28) mm compared with the conventional tip tracheal tube (30 (22–35) mm; p < 0.001). The Flex‐Tip tracheal tube thus appeared to reduce the incidence of nasal mucosal trauma during nasotracheal intubation and the incidence of post‐intubation nasal pain, compared with the conventional tip tracheal tube.

The influence of head and neck position on ventilation with the i-gel airway in paralysed, anaesthetised patients.

Context and objective We hypothesised that head and neck position could affect the effectiveness of ventilation with the i-gel airway. To test this hypothesis, we investigated the influence of different head and neck positions on oropharyngeal sealing pressures and ventilation scores during ventilation with i-gel. Methods A single, experienced supraglottic airway device user inserted the i-gel in 20 paralysed, anaesthetised patients who were scheduled for oral surgery. Oropharyngeal leak pressures and ventilation scores were measured with the head and neck in the neutral position, flexed, extended or rotated to the right. Ventilation was scored from 0 to 3 based on three criteria (no leakage with an airway pressure of 15 cmH2O, bilateral chest excursion and a square wave capnogram; each item scoring 0 or 1 point). Results Compared with the neutral position (25.8 ± 5.2 cmH2O), oropharyngeal leak pressure was significantly higher with flexion (28.5 ± 3.4 cmH2O, P = 0.015) and lower with extension (23.0 ± 4.2 cmH2O, P = 0.015), but similar with rotation (26.7 ± 5.1 cmH2O, P = 0.667). Flexion of the head and neck [2 (1–3)] adversely affected the ventilation score compared with the neutral position [3 (2–3), P = 0.004]. Conclusion Effective ventilation with an i-gel can be performed in patients in whom the head and neck is extended or rotated, whereas flexion of the head and neck adversely affects ventilation. Clinically, flexion of the head and neck should be avoided during ventilation with the i-gel.

Aprotinin Abolishes Sevoflurane Postconditioning by Inhibiting Nitric Oxide Production and Phosphorylation of Protein Kinase C-δ and Glycogen Synthase Kinase 3β

Background:It remains controversial whether aprotinin use during cardiac surgery is cardioprotective or detrimental. In contrast, volatile anesthetics may offer cardioprotection perioperatively. Increased nitric oxide, protein kinase C activation, and glycogen synthase kinase 3β inhibition play a role in sevoflurane-induced cardioprotection. The authors investigated whether aprotinin affects sevoflurane postconditioning. Methods:Isolated guinea pig hearts underwent 30 min of global ischemia and 120 min of reperfusion (control [CTL]). Postconditioning was elicited with sevoflurane (2%) for 2 min at reperfusion onset (POST). Aprotinin (250 kallikrein inhibitor units/ml) was administered for 5 min at reperfusion onset (POST + APRO and CTL + APRO). In additional experiments, both sevoflurane and aprotinin were given before ischemia and throughout the reperfusion period (SEVO + APRO (throughout)) to mimic clinical conditions. Left ventricular developed and end-diastolic pressures and infarct size were measured. Western blot analysis determined phosphorylated protein kinase C-&dgr;, protein kinase C-&dgr;, Akt, and glycogen synthase kinase 3β expression. Nitric oxide production during reperfusion was measured by nitric oxide sensor. Results:After ischemia–reperfusion, POST had significantly higher left ventricular developed (56 ± 11 vs. 26 ± 8 mmHg [mean ± SD]) and lower end-diastolic pressures (20 ± 9 vs. 47 ± 15 mmHg) and reduced infarct size (15 ± 3% vs. 41 ± 10%) versus CTL. Aprotinin abolished these improvements. Expressions of phospho-Akt (activated), phospho–protein kinase C-&dgr; (activated), and phospho–glycogen synthase kinase 3β (inhibited) were significantly increased in POST. Aprotinin attenuated these increased expressions. Nitric oxide production after reperfusion was higher in POST than in CTL, but not in POST + APRO. Conclusions:Aprotinin abolishes sevoflurane postconditioning, associated with inhibited phosphorylation of Akt, protein kinase C-&dgr;, and glycogen synthase kinase 3β and reduced nitric oxide production.

Epistaxis During Nasotracheal Intubation: A Comparison of Nostril Sides

PURPOSE It is commonly believed that for preventing epistaxis during nasotracheal intubation (NTI), the right nostril should be used. However, there is no real evidence as to which nostril should be used. In this study, we tested our hypothesis that epistaxis during NTI is more frequent and severe using the left nostril rather than the right, provided that patency appears equal on both sides of the nose. PATIENTS AND METHODS A total of 54 patients who were scheduled for elective oral surgery, in which NTI was indicated to optimize the surgical approach, were recruited into this study. The nostril used for NTI was chosen randomly. RESULTS Epistaxis occurred significantly more frequently (44.4%) when the left nostril was used for NTI than when the right nostril was used (11.1%; P = .014). Although there were no statistical differences in the incidence of mild epistaxis between the 2 nostrils (P = .467), severe epistaxis was significant more frequent with the left (22.2%) than with the right nostril (0.0%; P < .023). CONCLUSIONS Our data show that epistaxis during NTI is more frequent and severe with the left nostril than the right. Hence, when deciding which nostril to use for NTI, the right nostril should be used if patency appears equal on both sides of the nose.

Increased expression of interleukin-18 in the trigeminal spinal subnucleus caudalis after inferior alveolar nerve injury in the rat

Interleukin-18 (IL-18) is an important regulator of innate and immune responses, and is known to be expressed in various types of cells and upregulated in pathological conditions including tissue injury and inflammation, suggesting it has both proinflammatory and compensatory roles. Here we show that IL-18 was increased in microglia in the trigeminal spinal subnucleus caudalis (Vc) after peripheral nerve injury. We used a trigeminal neuropathic pain model in which the withdrawal threshold of maxillary whisker pad skin was significantly decreased after inferior alveolar nerve transection, and observed a striking increase in IL-18 expression in the Vc around the obex area from 3d and continued until 14d after nerve injury. The IL-18 labeled cells were largely colocalized with Iba1, suggesting this upregulation occurred in hyperactive microglia. We also found that the IL-18 induction coexisted with phosphorylated p38 MAPK, indicating a possible role of p38 in the regulation of IL-18. Our findings are the first report that injury of trigeminal nerve induced IL-18 upregulation in activated microglia in the Vc, suggesting a possible role of IL-18 in orofacial neuropathic pain.

Hypersensitivity reaction probably induced by sugammadex

We report here an intellectually compromised 7-year-old boy with cerebral palsy who developed a hypersensitivity reaction several minutes after the administration of sugammadex for subsequent extubation. He developed signs of upper airway stenosis and decreased oxygen saturation, as well as wheals on his neck, chest, and both upper extremities. He was successfully treated with immediate administration of adrenaline and hydrocortisone. A hypersensitivity reaction to sugammadex was suspected on the basis of the patients clinical course.

Acute memory phase of sevoflurane preconditioning is associated with sustained translocation of protein kinase C-α and ε, but not δ, in isolated guinea pig hearts

Background and objective Anaesthetic preconditioning (APC) exerts cardioprotective effects by reducing infarct size and improving recovery of contractile function after ischaemia–reperfusion. The interval between brief exposure to volatile anaesthetic and sustained ischaemia, the acute memory phase, is dependent on intracellular signalling mediating this cardioprotection. Intramyocyte translocation of protein kinase C (PKC) is known to be a key mediator in APC. We examined the relationship between the time frame of the acute memory phase of sevoflurane preconditioning and intramyocyte translocation of PKC-α, δ and ϵ to the particulate fraction. Methods Isolated perfused guinea pig hearts were subjected to 30 min ischaemia and 120 min reperfusion. APC was elicited with one minimum alveolar concentration sevoflurane for 10 min. Washout times of 10, 30, 60 and 90 min were studied. Contractile recovery was assessed by monitoring left ventricular developed pressures. Infarct size was determined by triphenyltetrazolium chloride staining. Translocation of PKC was examined by western blot analysis. Results After ischaemia–reperfusion, left ventricular developed pressure recovered to a greater degree with APC compared with control for washout times of 10 and 30 min, but not 60 and 90 min. Similarly, infarct size was reduced for washout times of 10 and 30 min, but not 60 and 90 min. Sustained translocation of PKC-α and ϵ, but not δ, was associated with the time frame of the acute memory phase. Conclusion The acute memory phase of sevoflurane preconditioning is limited to less than 60 min. Sustained translocation of PKC-α and ϵ, but not δ, correlates with this acute memory phase of sevoflurane preconditioning.

Effect of cerebral venous congestion on the pressure-volume index in the evaluation of intracranial pressure dynamics.

&NA; Translocation of cerebrospinal fluid (CSF) between the intracranial and spinal subarachnoid space was blocked by ligating the cervical spinal core in eight cats under pentobarbital and nitrous oxide anesthesia, and the effects of cerebral venous congestion on the pressure‐volume index (PVI), a measure relating the change in intracranial volume, and the logarithm of intracranial pressure (ICP) were evaluated. The changes in the volume‐pressure response (VPR), a measure of intracranial elastance, were calculated simultaneously. Cerebral venous congestion was induced by lowering the head relative to the level of the heart by tilting the trunk of the animals to 20° below horizontal. The presence of venous congestion was confirmed by an increase in the sagittal sinus pressure (SSP). The body position was shifted from horizontal prone (H1 group) to head‐down tilt (D1 group) in four animals (group 1) and from headdown tilt (D2 group) to horizontal prone (H2 group) in the other four animals (group 2), and PVI and VPR were determined in each group. The changes in ICP and SSP with change of body position in group 1 were not significantly different from those in group 2, with both pressures changing by 7‐8 mm Hg. PVI showed no significant differences between the H1 group and H2 group or between the D1 group and D2 group. The mean (±SEM) PVI for all measurements in the head‐down tilt position (D1 and D2 groups) was significantly higher (0.50 ± 0.02 ml; p < 0.01) than in the horizontal position (H1 and H2 groups; 0.35 ± 0.02 ml). In contrast, VPR showed a positive linear relationship with ICP in both the horizontal and head‐down tilt positions. These results show that, when ICP is increased due to cerebral venous congestion, VPR correctly indicates increased intracranial elastance; however, PVI paradoxically indicates an increase in the pressure‐buffering ability as ICP is increased. The authors conclude that PVI is greatly affected by the cerebral venous volume and must be interpreted cautiously.