The possible role of collateral sprouting in the functional restitution of corticospinal connections after spinal hemisection.

We investigated in monkeys whether the corticospinal fibers increase their connections with lumbosacral neurons after spinal hemisection, using the retrograde horseradish peroxidase (HRP) method. In three monkeys 3.5-38 months after spinal hemisection at the lower thoracic or upper lumbar cord, HRP was injected into the lumbosacral cord unilaterally on the hemisected side at a level caudal to the lesion. Control injections were performed in two intact monkeys and in two other monkeys immediately after hemisection. In all animals, corticospinal neurons in the precentral motor cortex were labeled bilaterally. However, in the chronically spinal hemisected monkeys, the number of the labeled neurons was significantly increased on the side ipsilateral to the lesion. These results suggest that corticospinal connections to lumbosacral motoneurons are newly formed on the side of spinal cord hemisection. This synapse formation may be due to collateral sprouting of intact corticospinal fibers, and it may underlie the mechanisms of motor recovery.

Localization of the spinal accessory motoneurons in the cervical cord in connection with the phrenic nucleus: an HRP study in cats.

The localization of the spinal accessory motoneurons (SAMNs) that innervate the accessory respiratory muscles, the sternocleidomastoid (SCM) and trapezius (TP) muscles, was identified in the cat using the horseradish peroxidase (HRP) method. In the cases of HRP bathing of the transected spinal accessory nerve (SAN), HRP-labeled motoneurons were observed ipsilaterally from the C1 to the rostral C6 segments of the spinal cord. Labeled neurons were located principally in the medial and central regions of the dorsomedial cell column of the ventral horn in the C1 segment, in the lateral region of the ventrolateral cell column in the C2-C4 segments, between the ventrolateral and ventromedial cell columns in the C5 segment and in the lateral region of the ventromedial cell column in the C6 segment. In the cases of HRP injection into either SCM or TP muscles, labeled SCM motoneurons were found in the C1-C3 segments of the spinal cord and labeled TP motoneurons were chiefly localized more caudally within the spinal accessory nucleus. The present study revealed that, in the C5 and C6 segments, the SAMNs have a very similar topographic localization to the phrenic nucleus in the ventral horn. This finding implicated the functional linkage of the SAMNs with the phrenic motoneurons in particular types of respiration.

Bupivacaine-induced convulsion is suppressed by MK-801.

BACKGROUND AND OBJECTIVES: Not only the facilitation of inhibitory synapses but also the suppression of excitatory synapses may be effective in treating convulsion induced by local anesthetics. The effects of MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, on bupivacaine-induced convulsion and hemodynamic changes were studied. METHODS: Cortex and hippocampal (A4; L5.5; H8) electroencephalogram (EEG), heart rate, and mean arterial pressure were measured in 21 cats anesthetized with urethane. Blood samples were obtained when cats demonstrated arrhythmias, convulsed, and became hypotensive. In the control group (n = 7), bupivacaine was continuously infused until a hypotensive state of 40 mm/Hg was reached. In the MK-801 pretreated group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously 15 minutes before the bupivacaine injection. In the MK-801 treatment group (n = 7), MK-801 (0.5 mg/kg) was injected intravenously at the appearance of convulsive EEG after the bupivacaine injection. RESULTS: Bupivacaine produced convulsion in the control group (17.1 +/- 2.4 microg/mL), but not in the MK-801 pretreated group. In the treatment group, convulsive EEG was suppressed gradually after injection of MK-801. The mean plasma bupivacaine concentrations (microg/mL) reaching arrhythmia and hypotension were 9.5 +/- 2.9 and 23.0 +/- 3.0, respectively, in the control group; 10.9 +/- 3.5 and 22.5 +/- 4.9, respectively, in the MK-801 pretreated group; and 7.5 +/- 1.6 and 21.0 +/- 3.0, respectively, in the MK-801 treatment groups. The mean arterial pressure and heart rate did not differ among the three groups. CONCLUSIONS: These results demonstrated that one mechanism of bupivacaine-induced convulsion is the excitatory neurotransmitter system in central nervous system and that MK-801 is effective in suppressing the convulsion without any effects on hemodynamics.

Effects of levobupivacaine, bupivacaine, and ropivacaine on tail-flick response and motor function in rats following epidural or intrathecal administration.

BACKGROUND AND OBJECTIVES: Commercially available bupivacaine is a racemic mixture of S (-)- and R(+)-enantiomers. Although the S(-)-enantiomers levobupivacaine and ropivacaine are less toxic to the cardiovascular and central nervous systems than bupivacaine, their relative efficacy has not been determined. This study directly compares the dose response of levobupivacaine, ropivacaine, and bupivacaine following epidural and intrathecal administration in the rat. METHODS: The time course of change in tail-flick latency and qualitative motor function was studied in rats following epidural or intrathecal administration of 0.25-0.75% levobupivacaine, ropivacaine, or bupivacaine in blinded, randomized fashion. RESULTS: Levobupivacaine and bupivacaine produced comparable and significantly enduring antinociceptive effects compared with ropivacaine at all test concentrations following both epidural and intrathecal administrations. Duration of motor block at lower local anesthetic concentrations (epidurally and intrathecally) was comparable with levobupivacaine and ropivacaine but significantly shorter than with bupivacaine. Epidural 0.75% levobupivacaine and bupivacaine showed more enduring motor block than ropivacaine. CONCLUSIONS: Levobupivacaine, given epidurally or intrathecally, produces longer lasting antinociceptive action than ropivacaine at equivalent concentrations and similar motor blocking effect at lower concentrations in both epidural and intrathecal administrations. Levobupivacaine-induced prolongation of the tail-flick latency is comparable to that of bupivacaine, as is motor blocking effect at higher concentrations. The possibility of significant differential block with levobupivacaine compared with bupivacaine warrants further study.

Spontaneous nasal oscillations in dog. A mucosal expression of the respiration-related activities of cervical sympathetic nerve.

We studied the respiratory oscillations of the nasal mucosa in dogs. Even after temporarily stopping the respirator, intranasal balloon pressure showed respiration-related oscillations (spontaneous nasal oscillations). These spontaneous oscillations were recorded in all 21 dogs. Spontaneous nasal oscillations were not abolished even after thoracotomy, vagotomy and vidian neurectomy. Only cervical sympathectomy could to a large extent abolish the spontaneous nasal oscillations. Furthermore, the spontaneous nasal oscillations were found to be synchronized with the respiration-related fluctuations of cervical sympathetic nerve activities. Rhythms of the spontaneous nasal oscillations were not dependent on the rates of artificial ventilation, but were closely related to the rates of spontaneous respiration before administering the muscle relaxant. On some occasions, we recognized remarkable differences in the height of waves of the spontaneous nasal oscillations between the sides of the body. On eight occasions in 5 dogs, reciprocal changes of the dominant side of bilateral spontaneous nasal oscillations were noted which might be an expression of the nasal cycle.

Respiration-related movements of the nose in dogs.

We studied the respiration-related movements of the canine nose by examining the respiratory oscillations of intranasal balloon pressure and EMG activities of the dilator nares in dogs. Under spontaneous respiration, balloon pressure decreased and EMG activities increased during the early inspiratory phase. These respiratory movements of the nose differed and changed reciprocally in strength between the two sides of the body spontaneously, after painful stimulation or intranasal histamine administration. When the muscle relaxant was administered and the respiration was controlled by the ventilation pump, the intranasal balloon pressure increased during the inspiratory phase. This phenomenon had a completely inverted pattern compared with that during spontaneous respiration. Furthermore, even when the ventilation pump was stopped, respiration-like spontaneous oscillations of the intranasal balloon pressure were recognized. These were abolished by sectioning of the ipsilateral cervical sympathetic nerve trunk. From these findings, the respiration-related movements of the nose were thought to be controlled not only by the cardiac output and the vagal nerve reflexes but also by respiratory activities in the nervous systems controlling the nose, which might be originated from the medullary respiratory centres.

Control of the nasal mucosa by the tonic activities of the autonomic nervous system in dogs.

We studied the effects of stimulation and acute denervation of the cervical sympathetic nerve and the vidian nerve on the nasal vascular tone, as measured by intranasal balloon pressure. Significant vasoconstriction was found during electrical stimulation of the cervical sympathetic nerve. When the cervical sympathetic nerve was sectioned, causing a transient vasoconstriction due to the stimulatory effect of the nerve injury, then significant vasodilation was found in 23 out of 30 experiments. Significant vasodilation during electrical stimulation of the vidian nerve and slight but significant vasoconstriction after sectioning of the vidian nerve were also found. In addition, we found spontaneous nerve discharges in the cervical sympathetic nerve trunks. These nerve discharges increased after stopping the respiratory pump. Differences in these sympathetic nerve discharges between the sides of the body were also recognized.

[The effects of pentazocine, diazepam and midazolam in patients to reduce the uncomfortable feeling during epidural block procedure].

The effects of pentazocine, diazepam and midazolam in 100 patients to reduce the uncomfortable feeling during epidural block procedure were studied. All patients (ASA I-II) were premedicated with intramuscular atropine sulfate 0.5 mg and hydroxyzine 50 mg. To relieve pain and anxiety during epidural block procedure, pentazocine (15 mg; 20 Cases or 30 mg; 20 Cases), diazepam (5 mg; 20 Cases) or midazolam (2.5 mg; 20 Cases) was given intravenously in the operating room before epidural procedure. After the epidural block, patients were anesthetized with nitrous oxide-oxygen-isoflurane or nitrous oxide-oxygen-sevoflurane. The following day, patients' self-assessments of pain during epidural block procedure were categorized as good and fair. The effects of drugs were compared between patients with im premedication only with patients with further iv administration. Patients with pentazocine 15 mg were similar to the patients given only im premedication. Pentazocine 30 mg and diazepam 5 mg tended to allay the patients' pain feeling. Midazolam 2.5 mg was effective producing anterograde amnesia and antianxiety effects. Small doses of midazolam were effective to relief patients' uncomfortable feeling.

[The effects of small dose midazolam in patients to reduce the uncomfortable feeling during epidural block procedure].

The effects of small dose midazolam to reduce the uncomfortable feeling during epidural block procedure were studied. All 160 patients (ASA I approximately II) were premedicated with intramuscular (I.M.) atropine sulfate 0.5 mg and hydroxyzine 50 mg. To relieve pain and anxiety during epidural block procedure, small dose midazolam (1 mg; 80 patients) was given intravenously in the operating room before epidural procedure. After epidural block, patients were anesthetized with nitrous oxide-oxygen-isoflurane or nitrous oxide-oxygen-sevoflurane. The following day, patient's self-assessments of pain during epidural block procedure were categorized as good and fair. Midazolam 1 mg was effective in the males (from 45% to 10%) and tended to allay patients' pain feeling in the females (from 40% to 23%). To investigate the uncomfortable feeling 1 further asked the patients whether epidural block procedure was more noxious than I.M. premedication or not. Noxious feeling was expressed in more I.M. premedicated patients (78%) than in epidural block procedure patients (48%). These results suggest that small dose midazolam is effective to relieve patients' uncomfortable feeling due to its sedative and antianxiety effects.

[The effects of cervical epidural anesthesia on epidural somatosensory evoked potentials and phrenic nerve activities].

We have investigated the effects of cervical epidural anesthesia on-phrenic nerve activity (PNA), and epidural somatosensory evoked potential (SSEP) elicited by stimulation of the radial nerve in pentobarbital anesthetized cats. PNA was suppressed significantly to 72% of control value 10 min after injection of 1% lidocaine and recovered to control value within 30 min. Following 2% lidocaine injection, PNA tended to be more suppressed than with 1% lidocaine to 57% and recovered to control value within 30 min. Peak latencies of P1, N1, P2, N2, and P3 before injection of 1% lidocaine were 1.05 (0.24), 1.20 (0.11), 1.51 (0.20), 1.56 (0.34), 2.71 (0.33) (msec (SD)), respectively. Though these latencies did not increase after injection of 1% lidocaine, injection of 2% lidocaine increased them significantly and these elevations continued for 120 min. The amplitude of N2 increased significantly after injection of 1% lidocaine and the amplitude of N2 and N2-P3 increased after injection of 2% lidocaine. These results indicate that 2% lidocaine blocked the sensory nerve and the effects continued much longer than the depression of PNA by cervical epidural anesthesia.

[The effects of intravenous lidocaine on the activity of medullary respiratory neurons in cats].

The effects of intravenous lidocaine on the activity of medullary respiratory neuron were studied in urethane anesthetized cats. Using a tungsten microelectrode, spikes from medullary inspiratory neurons were recorded around nucleus ambiguous. Lidocaine was administered using a constant-rate infusion pump until electrographic seizures appeared. The effect of lidocaine on the activity of respiratory neurons showed two types. In one type, consisting of 7 units out of 10, a sequence of changes was observed: the initial stage was represented by increased duration of the burst and decreased frequency of neural discharge; the second stage by desynchronization with mechanical lung inflation; the third stage by continuous activity and the forth stage by decreased spike activity and electrographic seizures. Blood concentration of the lidocaine was 9.6 +/- 3.5 micrograms.ml-1 at the second stage, 15.3 +/- 4.4 micrograms.ml-1 at the third stage, 26.6 +/- 4.1 micrograms.ml-1 at the fourth stage. In another type, consisting of 3 units out of 10, following administration of lidocaine the number of spikes showed only a concentration related depression. Blood concentration of the lidocaine was 6.9 +/- 2.7 micrograms.ml-1 when the spikes disappeared. These results indicate that intravenous lidocaine influences the respiratory rhythm and produces the respiratory depression working in the central nervous system.

[A comparative study of the depressive effects of halothane and isoflurane on medullary respiratory neurons in cats].

The depressive effects of halothane (H) and isoflurane (I) on the same respiratory neuron were studied in cats. Using a tungsten microelectrode, activities of medullary inspiratory neurons were recorded around nucleus ambiguus. The number of spikes (Spike) of each respiratory cycle and inter-spike interval (ISI) were measured. At 1 MAC, in 9 units out of 11, Spike was significantly fewer with I than with H. In 2 units out of 11, Spike was not significantly different between H and I. These results indicate that each respiratory neuron shows different sensitivity to H and I at 1MAC concentration. With increasing depth of anesthesia, Spike showed a concentration-related depression. During the course of respiratory depression, the spikes were 75.9 (1MAC), 63.3 (1.5MAC), 48.0 (2MAC), 24.2 (2.5MAC), 5.0 (3MAC) with H, and 77.4 (0.5MAC), 51.9 (1MAC), 23.5 (1.5MAC) with I. These spikes were completely depressed at 3.5MAC in H and 2MAC in I. Both H and I increased ISI with increasing depth of anesthesia. The effects of H and I on the phrenic nerve discharges closely resembled their effects on the respiratory neurons. We conclude that the respiratory depression produced by I exceeds that produced by equal MAC of H.

[The effects of caffeine on the respiratory depression by morphine].

The effects of intravenous administration of caffeine on the discharge of the phrenic nerve were studied following vagotomy in 7 pentobarbital anesthetized mechanically ventilated rats. Morphine (0.4 mg.kg-1.min-1) was administered until the respiratory rate decreased to about half of the baseline respiratory rate. In those state, we first administered caffeine (20 mg.kg-1), intravenously and then administered naloxone (0.02 mg) intravenously. The increase of inspiratory time from 0.49 +/- 0.16 to 2.01 +/- 0.47 s by morphine recovered to 0.86 +/- 0.38 s by caffeine and 0.50 +/- 0.22 s by naloxone. Expiratory time did not change during each drug administration. The decrease of respiratory rate from 46.6 +/- 5.9 to 20.6 +/- 4.1 breaths.min-1 by morphine recovered to 39.6 +/- 6.1 breaths.min-1 by caffeine and 47.6 +/- 4.6 breaths.min-1 by naloxone. Amplitude of integrated phrenic nerve discharge increased to 117 +/- 32% by caffeine and 156 +/- 39% by naloxone compared to the baseline. These results suggest that caffeine acts as a respiratory stimulant on the respiratory depression by morphine.

[The effects of flumazenil or bicuculline on the respiratory depression by morphine].

The effects of intravenous administration of flumazenil (n = 6) or bicuculline (n = 6) on the discharge of the phrenic nerve were studied following vagotomy in pentobarbital anesthetized mechanically ventilated rats. Morphine (0.4 mg.kg-1.min-1) was administrated until the respiratory rate decreased to about a half of the baseline respiratory rate. In this state, we first administered flumazenil (0.25 mg.kg-1) or bicuculline (0.4 mg.kg-1), intravenously and then administered naloxone (0.02 mg) intravenously in the two groups. The increase of inspiratory time from 0.7 +/- 0.1 to 2.0 +/- 0.5 s by morphine recovered to 0.8 +/- 0.2 s by bicuculline and to 0.6 +/- 0.1 s by naloxone. The increase of inspiratory time from 0.7 +/- 0.1 to 1.7 +/- 0.3 s by morphine, and to 2.1 +/- 0.5 s by flumazenil recovered to 0.6 +/- 0.1 s by naloxone. Expiratory time did not change during each drug administration in the two groups. The decrease of respiratory rate from 44 to 23 +/- 4 breaths.min-1 by morphine recovered to 37 +/- 5 breaths.min-1 by bicuculline and to 42 +/- 2 breaths.min-1 by naloxone. The decrease of respiratory rate from 45 +/- 3 to 22 +/- 6 breaths.min-1 by morphine, and to 18 +/- 4 breaths.min-1 by flumazenil recovered to 46 +/- 3 breaths.min-1 by naloxone. Amplitude of integrated phrenic nerve discharge increased to 125 +/- 42% by bicuculline and to 175 +/- 93% by naloxone compared to the baseline values. The decrease of amplitude to 54 +/- 18% by flumazenil recovered to 125 +/- 42% by naloxone. These results suggest that bicuculline not flumazenil antagonizes the respiratory depression of morphine by increasing the respiratory rate and respiratory movement.

[Effects of intravenous lidocaine administration on auditory brainstem response].

The effect of lidocaine on the auditory brainstem response (ABR) was investigated in 14 neurologically normal patients. Lidocaine 1.5 mg.kg-1.min-1 was injected intravenously over a 5 min period immediately followed by a continuous infusion of lidocaine 60 micrograms.kg-1.min-1. The seven peak latencies (waves I-VII) and amplitudes (waves I-VII) of the ABR were recorded before and 7-8 min after lidocaine infusion. Peak latencies of waves IV, V, VI, VII increased after epidural anesthesia compared with control values. Amplitudes of all waves were unchanged following intravenous lidocaine injection compared with control values. Interpeak latencies (I-II, II-III, III-IV, IV-V, V-VI, VI-VII), of every second peak (I-III, II-IV, III-V, IV-VI, V-VII), of every third peak except (III-VI, IV-VII) were unchanged compared with control values. Interpeak latencies of every fourth peak, of fifth peak increased after lidocaine injection compared with control values. The data obtained in this study with lidocaine injection were similar to the data after epidural anesthesia with lidocaine. One of the reason of the latency changes of ABR after epidural anesthesia was the systemic effect of lidocaine absorbed intravenously from the epidural space.

[Effect of epidural anesthesia on airway constriction induced with methacholine or capsaicin in cats].

The choice of epidural anesthesia for patients with bronchial asthma is controversial. We studied the effect of epidural anesthesia on airway constriction induced by methacholine or capsaicin in cats. Cats were anesthetized with pentobarbital and mechanically ventilated. Peak airway pressure and compliance, as well as cardiac sympathetic and vagal nerve activity were recorded. We sprayed 0.2% methacholine of 0.2% capsaicin into the trachea to produce airway constriction, and 15 min after drug spray we injected 2% lidocaine 1.0 ml into the epidural space. Methacholine increased peak airway pressure by 25% and decreased compliance by 26%. Capsaicin increased peak airway pressure 20% and decreased compliance 22%. After epidural anesthesia, cardiac sympathetic nerve activity decreased to 40% and 44%, vagal nerve activity decreased to 92% and 61% of control values in methacholine and capsaicin groups, respectively. However, here were no changes in the peak airway pressure and compliance in the two groups. These results suggest that epidural anesthesia, even if epidural anesthesia decrease sympathetic nerve activity, has no effect on the airway constriction induced with methacholine or capsaicin.

[The effects of thiamylal, ketamine and nicardipine on the hippocampal theta waves produced by cerebral ischemia in cats].

Spontaneous hippocampal electroencephalogram (EEG) was recorded in the pyramidal cell layer (PCL) and dentate gyrus (DG) during and after ischemia produced by bilateral clamping of the common carotid arteries in cats. Hippocampal theta waves, approximately 180 degree out of phase in PCL and DG, appeared within 4.3 +/- 2.3 seconds after the onset of bilateral carotid artery occlusion and continued for more than 60 minute. These hippocampal theta waves disappeared 34.2 +/- 10.2 seconds after 4 vessel occlusion. We could not find the clear difference between the two areas in the appearance and disappearance of the hippocampal theta waves. We further investigated the effects of thiamylal, ketamine and nicardipine on the hippocampal theta waves during bilateral carotid artery occlusion. Thiamylal changed the two hippocampal theta waves to a similar pattern of EEG, which has irregular slow and fast waves, in both PCL and DG. Ketamine changed the two theta waves to irregular complex pattern of fast and slow waves and spike activity, which is independent at two areas. Nicardipine, a Ca antagonist, changed the theta waves to irregular slow waves which were similar to the pattern of EEG observed before carotid artery occlusion. These results indicate that thiamylal, ketamine and nicardipine have different effects on the ischemia of hippocampus.

[Epidural anesthesia for patients with bronchial asthma].

The choice of epidural anesthesia for patients with bronchial asthma is controversial. We used epidural anesthesia during surgery in 16 cases of asthma. Epidural anesthesia produced by 1% or 2% lidocaine or mepivacaine without epinephrine did not induce asthmatic attack in any patients. After epidural block, general anesthesia was induced with midazolam and vecuronium and endotracheal tube was inserted in 9 patients. Asthmatic attack occurred in two patients. In one patient it occurred by the endotracheal intubation and in another patient during thyroidectomy under nitrous oxide - oxygen - sevoflurane anesthesia, although no attack was observed in 7 patients. Two patients were considered to be in severe state of bronchial asthma and they had been on steroid drug and inhalation therapy before surgery. Both patients recovered soon with antiasthmatic therapy. These results suggest that epidural anesthesia has little or no relevance to asthmatic attack.

[Analysis of inadvertent epidural injection of drugs].

We asked 31 anesthesiologists, who were on the Japanese Board of Anesthesiology, about inadvertent injection of drugs into the epidural space, and received answers from 28 (90%). Fifteen (54%) had an experience of inadvertent epidural injection, and five of them had two experiences. Injected drugs were ephedrine (6 times), a mixture of neostigmine and atropine (3), thiopental (2), etilefrine (2), vecuronium (1), suxamethonium (1), bicarbonate (1), midazolam (1), lactated Ringer's solution (1), nicardipine (1), and pentazocine (1). The inadvertent injection of thiopental or bicarbonate was noticed by back pain during injection. No treatment was added after the inadvertent injections, except a patient with an epidural steroid injection following thiopental. No neurological complications were found in any patients.

[Effects of lumbar or thoracic epidural anesthesia on median nerve somatosensory evoked potentials].

Somatosensory evoked potentials (SSEP) are used increasingly to monitor the integrity of neural pathways in anesthetized patients. To evaluate the influence of epidural anesthesia on the central nervous system, we studied the effects of lumbar or thoracic epidural anesthesia with lidocaine on the median nerve SSEP in 9 patients. The peak latencies (N1, P2, N2) and amplitudes (N1-P2, P2-N2) of the SSEP response over the sensory cortex were recorded before and 15 min after epidural anesthesia. The peak latencies of control and post epidural anesthesia of N1, P1, N2 were 19.2 +/- 1.7 msec, 19.6 +/- 1.6 msec (N1), 24.7 +/- 2.3 msec, 25.7 +/- 2.0 msec (P2), 32.8 +/- 2.8 msec and 34.6 +/- 2.5 msec (N2), respectively. The amplitude of control and post epidural anesthesia of N1-P2, P2-N2 were 4.5 +/- 2.9 microV, 5.9 +/- 6.6 microV (N1-P2), 4.4 +/- 3.2 microV and 5.6 +/- 5.2 microV (P2-N2), respectively. Peak latencies of all components (L1, P2, N2) increased after epidural anesthesia compared with control values. Amplitude of N1-P2 increased significantly following epidural anesthesia compared with control values. The data obtained in this study were contrary to the previous concept that anesthetic agents generally increase the latency of SSEP and decrease their amplitude.