Continuous PECS II block for postoperative analgesia in patients undergoing transapical transcatheter aortic valve implantation.

It has been reported that PECS II block can alleviate postoperative pain following transapical transcatheter aortic valve implantation (TA-TAVI). However, the effectiveness of continuous PECS II block with catheterization has not yet been reported on the postoperative pain in patients undergoing TA-TAVI. We experienced two cases of TA-TAVI who received PECS II block with catheterization to manage postoperative pain. In the first case, a bolus injection for intraoperative pain and subsequent catheterization were performed before the implantation. However, the patient developed severe pain postoperatively in spite of the continuous block due to displacement of the catheter. In the second case, a bolus injection and the catheterization for the continuous block were performed before and after the implantation, respectively, which provided high-quality pain control. Continuous PECS II block may be useful to control perioperative pain associated with TA-TAVI. The insertion of the catheter after the implantation could be useful to avoid its displacement during the surgery.

Comparison of tracheal diameter measured by chest x-ray and by computed tomography.

Assessments of tracheal diameter (TD) are important to select proper endotracheal tubes. Previous studies have used X-ray and physical indices to estimate tracheal diameter but these may not reflect the actual TD. We compared TD measured by X-ray (TD-XP) and by computer tomography (TD-CT) in 200 patients. Also, we analyzed correlation of TD-CT with physical indices such as age, height, weight, and BMI. TD-XP and TD-CT were significantly correlated (male: n = 55, P = .0146; female: n = 91, P = .001). TD-XP was 0.4 mm wider in male and 1.0 mm wider in female than TD-CT. However, correlation coefficients of TD-XP and TD-CT are very weak (male: r = 0.36; female: r = 0.653). TD-CT did not correlate with age, height, weight, or BMI. Our findings suggest that correlations of TD-XP and TD are statistically significant but not clinically significant. Physical indices are not useful to estimate TD.

Effect of JM-1232(-), a new sedative on central respiratory activity in newborn rats.

JM-1232(-), a newly manufactured isoindole derivative, shows sedative effect at a lower concentration compared with propofol. In the present study, we analyzed the response of the central respiratory activity to JM-1232(-). The brainstem-spinal cord of a newborn rat was isolated and was continuously superfused with oxygenated artificial cerebrospinal fluid (ACSF). Rhythmic inspiratory burst activity was recorded from C4 spinal ventral root using a glass suction electrode. We measured C4 burst rate and amplitude of integrated C4 activity. After obtaining a control recording, the preparation was superfused with ACSF containing JM-1232(-) at 10, 100 or 500 microM for 10 min. The application of both 10 and 100 microM JM-1232(-) did not decrease C4 burst rate significantly. However, 500 microM JM-1232(-) reduced C4 burst rate. On the contrary, C4 burst amplitude was not affected by the application of JM-1232(-) for 10 min at any concentrations. In conclusion, JM-1232(-) at a low concentration (but presumably higher than hypnotic dose), did not depress the central respiratory activity, whereas at a high concentration depression was seen.

Caffeine reversal of opioid-evoked and endogenous inspiratory depression in perinatal rat en bloc medullas and slices.

Caffeine counters endogenous or drug-evoked depression of breathing in (preterm) infants. Despite its common clinical use, little is known on central nervous mechanisms of its stimulatory respiratory action. We show that millimolar concentrations of caffeine are needed in perinatal rat en bloc medullas and medullary slices for stimulation of fictive inspiratory rhythms that were either endogenously slow in fetuses or depressed by prostagandins or opioids. Findings suggests that caffeine blocks phospodiesterase-4 thus raising cAMP in rhythmogenic pre-Bötzinger complex (preBötC) networks and/or cells driving the inspiratory preBötC.

Neural mechanisms of sevoflurane-induced respiratory depression in newborn rats.

BACKGROUND: Sevoflurane-induced respiratory depression has been reported to be due to the action on medullary respiratory and phrenic motor neurons. These results were obtained from extracellular recordings of the neurons. Here, the authors made intracellular recordings of respiratory neurons and analyzed their membrane properties during sevoflurane application. Furthermore, they clarified the role of gamma-aminobutyric acid type A receptors in sevoflurane-induced respiratory depression. METHODS: In the isolated brainstem-spinal cord of newborn rat, the authors recorded the C4 nerve burst as an index of inspiratory activity. The preparation was superfused with a solution containing sevoflurane alone or sevoflurane plus the gamma-aminobutyric acid type A receptor antagonist picrotoxin or bicuculline. Neuronal activities were also recorded using patch clamp techniques. RESULTS: Sevoflurane decreased C4 burst rate and amplitude. Separate perfusion of sevoflurane to the medulla and to the spinal cord decreased C4 burst rate and amplitude, respectively. Both picrotoxin and bicuculline attenuated the reduction of C4 burst rate. Sevoflurane reduced both intraburst firing frequency and membrane resistance of respiratory neurons except for inspiratory neurons. CONCLUSION: Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Bötzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Bötzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. gamma-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.

CO2-sensitivity of GABAergic neurons in the ventral medullary surface of GAD67-GFP knock-in neonatal mice.

We investigated the CO2 responsiveness of GABAergic neurons in the ventral medullary surface (VMS), a putative chemoreceptive area using a 67-kDa isoform of GABA-synthesizing enzyme (GAD67)-green fluorescence protein (GFP) knock-in neonatal mouse, in which GFP is specifically expressed in GABAergic neurons. The slice was prepared by transversely sectioning at the level of the rostral rootlet of the XII nerve and the rostral end of the inferior olive in mock cerebrospinal fluid (CSF). Each medullary slice was continuously superfused with hypocapnic CSF. GFP-positive neurons in the VMS were selected by using fluorescent optics and their membrane potentials and firing activities were analyzed with a perforated patch recording technique. Thereafter, superfusion was changed from hypocapnic to hypercapnic CSF. In 4 out of 8 GABAergic neurons in the VMS, perfusion with hypercapnic CSF induced more than a 20% decrease in the discharge frequency and hyperpolarized the neurons. The remaining 4 GFP-positive neurons were CO2-insensitive. GABAergic neurons in the VMS have chemosensitivity. Inhibition of chemosensitive GABAergic neural activity in the VMS may induce increases in respiratory output in response to hypercapnia.

[Anesthetic management of a patient with Mulvihill-Smith syndrome].

Mulvihill-Smith syndrome is a rare disease that belongs to progeroid syndromes. This syndrome is characterized by a senile face with an underdeveloped lower half, short stature, microcephaly, multiple pigmented nevi, immunodeficiency, hearing loss, and high-pitched voice. We report anesthetic management of a 27-year-old woman, 138 cm and 27 kg, with this syndrome, who underwent removal of mandibular cyst, partial resection of tongue and keratoplasty. Anesthesia was induced with fentanyl, propofol and vecuronium. There was difficulty in maintaining adequate ventilation with a face mask for children, and we used a mask for infants. Her Cormack grade was rated 3 but her trachea could be intubated assisted by BURP procedure. Anesthesia was maintained with sevoflurane, nitrous oxide and oxygen supplemented with fentanyl. The changes of blood pressure during anesthesia were extraordinary, suggesting the presence of advanced arteriosclerosis. The postoperative course was uneventful, with stable hemodynamics, and the patient was discharged from the hospital on 9th postoperative day. Anesthesia for Mulvihill-Smith syndrome should be performed with caution for the potential risk of difficult airway and unstable hemodynamics.

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit.

Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease) can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C02. In the other experiment, apneic threshold PaC02 was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit.

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease) can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2). In the other experiment, apneic threshold PaC0(2) was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit.

Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats.

Nicotine exposure is a risk factor in several breathing disorders Nicotinic acetylcholine receptors (nAChRs) exist in the ventrolateral medulla, an important site for respiratory control. We examined the effects of nicotinic acetylcholine neurotransmission on central respiratory control by addition of a nAChR agonist or one of various antagonists into superfusion medium in the isolated brainstem-spinal cord from neonatal rats. Ventral C4 neuronal activity was monitored as central respiratory output, and activities of respiratory neurons in the ventrolateral medulla were recorded in whole-cell configuration. RJR-2403 (0.1-10 mM), alpha4beta2 nAChR agonist induced dose-dependent increases in respiratory frequency. Non-selective nAChR antagonist mecamylamine (0.1-100 mM), alpha4beta2 antagonist dihydro-beta-erythroidine (0.1-100 mM), alpha7 antagonist methyllycaconitine (0.1-100 mM), and a-bungarotoxin (0.01-10 mM) all induced dose-dependent reductions in C4 respiratory rate. We next examined effects of 20 mM dihydro-beta-erythroidine and 20mM methyllycaconitine on respiratory neurons. Dihydro-beta-erythroidine induces hyperpolarization and decreases intraburst firing frequency of inspiratory and preinspiratory neurons. In contrast, methyllycaconitine has no effect on the membrane potential of inspiratory neurons, but does decrease their intraburst firing frequency while inducing hyperpolarization and decreasing intraburst firing frequency in preinspiratory neurons. These findings indicate that alpha4beta2 nAChR is involved in both inspiratory and preinspiratory neurons, whereas alpha7 nAChR functions only in preinspiratory neurons to modulate C4 respiratory rate.

Electrophysiological and morphological characteristics of GABAergic respiratory neurons in the mouse pre-Bötzinger complex.

The characteristics of GABAergic neurons involved in respiratory control have not been fully understood because identification of GABAergic neurons has so far been difficult in living tissues. In the present in vitro study, we succeeded in analysing the electrophysiological as well as morphological characteristics of GABAergic neurons in the pre-Bötzinger complex. We used 67-kDa isoform of glutamic acid decarboxylase-green fluorescence protein (GAD67-GFP) (Delta neo) knock-in (GAD67(GFP/+)) mice, which enabled us to identify GABAergic neurons in living tissues. We prepared medullary transverse slices that contained the pre-Bötzinger complex from these neonatal mice. The fluorescence intensity of the pre-Bötzinger complex region was relatively high among areas of the ventral medulla. Activities of GFP-positive neurons in the pre-Bötzinger complex were recorded in a perforated whole-cell patch-clamp mode. Six of 32 GFP-positive neurons were respiratory and the remaining 26 neurons were non-respiratory; the respiratory neurons were exclusively inspiratory, receiving excitatory post-synaptic potentials during the inspiratory phase. In addition, six inspiratory and one expiratory neuron of 30 GFP-negative neurons were recorded in the pre-Bötzinger complex. GFP-positive inspiratory neurons showed high membrane resistance and mild adaptation of spike frequency in response to depolarizing current pulses. GFP-positive inspiratory neurons had bipolar, triangular or crescent-shaped somata and GFP-negative inspiratory neurons had multipolar-shaped somata. The somata of GFP-positive inspiratory neurons were smaller than those of GFP-negative inspiratory neurons. We suggest that GABAergic inhibition not by expiratory neurons but by inspiratory neurons that have particular electrophysiological and morphological properties is involved in the respiratory neuronal network of the pre-Bötzinger complex.

Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats

Nicotine exposure is a risk factor in several breathing disorders Nicotinic acetylcholine receptors (nAChRs) exist in the ventrolateral medulla, an important site for respiratory control. We examined the effects of nicotinic acetylcholine neurotransmission on central respiratory control by addition of a nAChR agonist or one of various antagonists into superfusion medium in the isolated brainstem-spinal cord from neonatal rats. Ventral C4 neuronal activity was monitored as central respiratory output, and activities of respiratory neurons in the ventrolateral medulla were recorded in whole-cell configuration. RJR-2403 (0.1-10mM), a4b2 nAChR agonist induced dose-dependent increases in respiratory frequency. Non-selective nAChR antagonist mecamylamine (0.1-100mM), a4b2 antagonist dihydro-b-erythroidine (0.1-100mM), a7 antagonist methyllycaconitine (0.1-100mM), and a-bungarotoxin (0.01-10mM) all induced dose-dependent reductions in C4 respiratory rate. We next examined effects of 20mM dihydro-b-erythroidine and 20mM methyllycaconitine on respiratory neurons. Dihydro-b-erythroidine induces hyperpolarization and decreases intraburst firing frequency of inspiratory and preinspiratory neurons. In contrast, methyllycaconitine has no effect on the membrane potential of inspiratory neurons, but does decrease their intraburst firing frequency while inducing hyperpolarization and decreasing intraburst firing frequency in preinspiratory neurons. These findings indicate that a4b2 nAChR is involved in both inspiratory and preinspiratory neurons, whereas a7 nAChR functions only in preinspiratory neurons to modulate C4 respiratory rate.