Inhibitory action of hydrogen sulfide on esophageal striated muscle motility in rats.

Hydrogen sulfide (H2S) is recognized as a gaseous transmitter and has many functions including regulation of gastrointestinal motility. The aim of the present study was to clarify the effects of H2S on the motility of esophageal striated muscle in rats. An isolated segment of the rat esophagus was placed in an organ bath and mechanical responses were recorded using a force transducer. Electrical stimulation of the vagus nerve evoked contractile response in the esophageal segment. The vagally mediated contraction was inhibited by application of an H2S donor. The H2S donor did not affect the contraction induced by electrical field stimulation, which can excite the striated muscle directly, not via vagus nerves. These results show that H2S has an inhibitory effect on esophageal motility not by directly attenuating striated muscle contractility but by blocking vagal motor nerve activity and/or neuromuscular transmissions. The inhibitory actions of H2S were not affected by pretreatment with the transient receptor potential vanniloid-1 blocker, transient receptor potential ankyrin-1 blocker, nitric oxide synthase inhibitor, blockers of potassium channels, and ganglionic blocker. RT-PCR and Western blot analysis revealed the expression of H2S-producing enzymes in esophageal tissue, whereas application of inhibitors of H2S-producing enzymes did not change vagally evoked contractions in the esophageal striated muscle. These findings suggest that H2S, which might be produced in the esophageal tissue endogenously, can regulate the motor activity of esophageal striated muscle via a novel inhibitory neural pathway.

Does the capsaicin-sensitive local neural circuit constitutively regulate vagally evoked esophageal striated muscle contraction in rats?

To determine whether a capsaicin-sensitive local neural circuit constitutively modulates vagal neuromuscular transmission in the esophageal striated muscle or whether the neural circuit operates in a stimulus-dependent manner, we compared the motility of esophageal preparations isolated from intact rats with those in which capsaicin-sensitive neurons had been destroyed. Electrical stimulation of the vagus nerve trunk evoked contractile responses in the esophagus isolated from a capsaicin-treated rat in a manner similar to those in the esophagus from a control rat. No obvious differences were observed in the inhibitory effects of D-tubocurarine on intact and capsaicin-treated rat esophageal motility. Destruction of the capsaicin-sensitive neurons did not significantly affect latency, time to peak and duration of a vagally evoked twitch-like contraction. These findings indicate that the capsaicin-sensitive neural circuit does not operate constitutively but rather is activated in response to an applied stimulus.

Actions of probiotics on trinitrobenzenesulfonic acid-induced colitis in rats.

We investigated the actions of probiotics, Streptococcus faecalis 129 BIO 3B (SF3B), in a trinitrobenzenesulfonic acid- (TNBS-) induced colitis model in rats. After TNBS was administered into the colons of rats for induction of colitis, the rats were divided into two groups: one group was given a control diet and the other group was given a diet containing SF3B for 14 days. There were no apparent differences in body weight, diarrhea period, macroscopic colitis score, and colonic weight/length ratio between the control group and SF3B group, suggesting that induction of colitis was not prevented by SF3B. Next, we investigated whether SF3B-containing diet intake affects the restoration of enteric neurotransmissions being damaged during induction of colitis by TNBS using isolated colonic preparations. Recovery of the nitrergic component was greater in the SF3B group than in the control group. A compensatory appearance of nontachykininergic and noncholinergic excitatory components was less in the SF3B group than in the control group. In conclusion, the present study suggests that SF3B-containing diet intake can partially prevent disruptions of enteric neurotransmissions induced after onset of TNBS-induced colitis, suggesting that SF3B has therapeutic potential.

[Technical Tips for Spinal Anesthesia].

Spinal anesthesia is a standard technique for all anesthesiologists and surgeons. This review deals with basic knowledge and tips for spinal anesthesia in an empirical manner. It is important to understand practical knowledge about specific character of each local anesthetic, spread patterns of the anesthetics in the subarachnoid space and relation between anesthesia level and puncture site. This review also introduces tips for subarachnoid puncture and divided administration method of isobaric local anesthetic solution based on the literature. Anesthesiologists and surgeons have to recognize that it is necessary to take enough time to perform precious and optimal spinal anesthesia.

Functional roles of capsaicin-sensitive intrinsic neural circuit in the regulation of esophageal peristalsis in rats: in vivo studies using a novel method.

A well-developed myenteric plexus exists in the esophagus composed of striated muscle layers, but its functional role in controlling peristaltic movements remains to be clarified. The purpose of this study was to clarify the role of a local neural reflex consisting of capsaicin-sensitive primary afferent neurons and intrinsic neurons in esophageal peristalsis. We firstly devised a method to measure peristaltic movement of esophagus in vivo in rats. Rats were anesthetized with urethane, and esophageal intraluminal pressure and propelled intraluminal liquid volume were recorded. In the experimental system, an intraluminal pressure stimulus evoked periodic changes in intraluminal pressure of the esophagus, which were consistently accompanied by intraluminal liquid propulsion. Bilateral vagotomy abolished changes in intraluminal pressure as well as liquid propulsion. These results indicate that the novel method is appropriate for inducing peristalsis in the esophagus composed of striated muscles. Then, by using the method, we examined functional roles of the local reflex in esophageal peristalsis. For that purpose, we used rats in which capsaicin-sensitive neurons had been destroyed. The esophagus of capsaicin-treated rats showed a multiphasic rise in intraluminal pressure, which may due to noncoordinated contractions of esophageal muscles, whereas a monophasic response was observed in the intact rat esophagus. In addition, destruction of capsaicin-sensitive neurons increased the propelled liquid volume and lowered the pressure threshold for initiating peristalsis. These results suggest that the local neural reflex consisting of capsaicin-sensitive neurons and intrinsic neurons contributes to coordination of peristalsis and suppresses mechanosensory function of vagal afferents in the esophagus.

Inhibitory actions of a local neural reflex on propulsive activity of the esophageal striated muscle portion in rats.

The aim of the present study was to clarify functional roles of a local neural reflex in propulsive activity of the rat esophageal striated muscle. Firstly, we established a method for measuring the volume of fluid expelled from an isolated esophageal segment to evaluate propulsive activity. Electrical stimulation to vagus nerves induced propulsion of intraluminal solution in the esophageal segment. The vagally evoked propulsion was abolished in the presence of d-tubocurarine. Next, this quantitative method was applied to examine the functional roles of intrinsic nerves in the esophagus. Capsaicin, a stimulant of primary afferents, inhibited the vagally mediated propulsion. A nitric oxide synthase inhibitor or a selective tachykinin NK(1) receptor antagonist significantly blocked the inhibitory effect of capsaicin. These findings suggest that the local neural reflex, which consists of tachykininergic and nitrergic neurons, might participate in modulation of propulsive activity in the striated muscle portion of the rat esophagus.

Neural regulation of esophageal striated muscle in the house musk shrew (Suncus murinus).

In the present study, we characterized the neural regulation of esophageal striated muscle in Suncus murinus (a house musk shrew; "suncus" used as a laboratory name), which was compared with that in the rat. The tunica muscularis consists of striated muscle in the suncus esophagus. An isolated segment of the suncus esophagus was placed in an organ bath and the contractile responses were recorded using a force transducer. Electrical stimulations to vagus nerves induced contractile responses in the esophageal segment. Treatment with α-bungarotoxin, a blocker of nicotinic acetylcholine receptors, blocked the vagally mediated contractions of the suncus esophagus. D-tubocurarine and succinylcholine, typical antagonists of nicotinic acetylcholine receptors, also inhibited the suncus esophageal contractions, while higher concentrations of the agents were required rather than concentrations for producing an equivalent block in the rat. We used capsaicin, a stimulator of small-caliber afferent neurons, for activating the peripheral neural network. The reagent inhibited the vagally mediated twitch contractions of striated muscle in the suncus esophagus, which was reversed by pretreatment with a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester. Application of a nitric oxide donor, diethylamine NONOate diethylammonium salt, mimicked capsaicin-induced inhibition. The results suggest that motility of the suncus esophagus, which consists of striated muscles, is regulated by vagal cholinergic neurons. The local neural network including capsaicin-sensitive neurons and intrinsic nitrergic neurons can modify the vagally mediated motility in the suncus esophagus. In addition, nicotinic acetylcholine receptors of the suncus esophagus might be pharmacologically distinct from those of rodent esophagi.

Extract of grains of paradise and its active principle 6-paradol trigger thermogenesis of brown adipose tissue in rats.

Grains of paradise (GP) is a species of the ginger family, Zingiberaceae, extracts of which have a pungent, peppery taste due to an aromatic ketone, 6-paradol. The aim of this study was to explore the thermogenic effects of GP extracts and of 6-paradol. Efferent discharges from sympathetic nerves entering the interscapular brown adipose tissue were recorded. Intragastric injection of a GP extract or 6-paradol enhanced the efferent discharges of the sympathetic nerves in a dose-dependent manner. The enhanced nerve discharges were sustained for as long as 3h. The rats did not become desensitized to the stimulatory effects these compounds on sympathetic nerve activity. The tissue temperature of brown adipose tissue showed significant increase in rats injected with 6-paradol. These results demonstrate that GP extracts and 6-paradol activate thermogenesis in brown adipose tissue, and may open up new avenues for the regulation of weight loss and weight maintenance.

Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats.

Ginger (rhizome of Zingiber officinale Roscoe) is an herbal medicine for the treatment of gastrointestinal disorders including constipation and diarrhea. Zingerone is a likely active constituent responsible for the antidiarrheal activity of ginger. The current study was designed to characterize pharmacological actions of zingerone on colonic motility. To evaluate pharmacological effects of zingerone on colonic motility, we used isolated colonic segments from rats, in which mechanical responses were recorded in the longitudinal direction. In addition, we evaluated the effects on colonic motility in vivo by measuring intraluminal pressure changes and expelled fluid volume from the colon in anesthetized rats. Zingerone was applied to the lumen of the colon to allow the drug to access from the mucosal side. Zingerone inhibited spontaneous contractile movements in the isolated colonic segments in a dose-dependent manner. The inhibitory effects of zingerone on colonic movements were not affected by pretreatment with capsazepine, a typical antagonist of transient receptor potential vanilloid 1. In addition, tetrodotoxin, a blocker of voltage-dependent sodium channels on neurons, did not affect the suppression of colonic movements by zingerone, suggesting that zingerone acts on the smooth muscles directly. Zingerone also attenuated colonic motility in vivo without affecting blood pressure and heart rate. The effects were reversible and reproducible. Our findings suggest that zingerone can inhibit colonic motility via direct action on smooth muscles. Zingerone might exert beneficial therapeutic effects on hypermotility-induced diarrhea by abrogating excessive gastrointestinal motility.

Contractile properties of esophageal striated muscle: comparison with cardiac and skeletal muscles in rats.

The external muscle layer of the mammalian esophagus consists of striated muscles. We investigated the contractile properties of esophageal striated muscle by comparison with those of skeletal and cardiac muscles. Electrical field stimulation with single pulses evoked twitch-like contractile responses in esophageal muscle, similar to those in skeletal muscle in duration and similar to those in cardiac muscle in amplitude. The contractions of esophageal muscle were not affected by an inhibitor of gap junctions. Contractile responses induced by high potassium or caffeine in esophageal muscle were analogous to those in skeletal muscle. High-frequency stimulation induced a transient summation of contractions followed by sustained contractions with amplitudes similar to those of twitch-like contractions, although a large summation was observed in skeletal muscle. The results demonstrate that esophageal muscle has properties similar but not identical to those of skeletal muscle and that some specific properties may be beneficial for esophageal peristalsis.

The neural regulation of the mammalian esophageal motility and its implication for esophageal diseases.

In contrast to the tunica muscularis of the stomach, small intestine and large intestine, the external muscle layer of the mammalian esophagus contains not only smooth muscle but also striated muscle fibers. Although the swallowing pattern generator initiates the peristaltic movement via vagal preganglionic neurons that project to the myenteric ganglia in the smooth muscle esophagus, the progressing front of contraction is organized by a local reflex circuit composed by intrinsic neurons similarly to other gastrointestinal tracts. On the other hand, the peristalsis of the striated muscle esophagus is both initiated and organized by the swallowing pattern generator via vagal motor neurons that directly innervate the muscle fibers. The presence of a distinct ganglionated myenteric plexus in the striated muscle portion of the esophagus had been enigmatic and neglected in terms of peristaltic control for a long time. Recently, the regulatory roles of intrinsic neurons in the esophageal striated muscle have been clarified. It was reported that esophageal striated muscle receives dual innervation from both vagal motor fibers originating in the brainstem and varicose intrinsic nerve fibers originating in the myenteric plexus, which is called 'enteric co-innervation' of esophageal motor endplates. Moreover, a putative local neural reflex pathway that can control the motility of the striated muscle was identified in the rodent esophagus. This reflex circuit consists of primary afferent neurons and myenteric neurons, which can modulate the release of neurotransmitters from vagal motor neurons in the striated muscle esophagus. The pathogenesis of some esophageal disorders such as achalasia and gastroesophageal reflux disease might be involved in dysfunction of the neural networks including alterations of the myenteric neurons. These evidences indicate the physiological and pathological significance of intrinsic nervous system in the regulation of the esophageal motility. In addition, it is assumed that the components of intrinsic neurons might be therapeutic targets for several esophageal diseases.

Contractile responses induced by physalaemin, an analogue of substance P, in the rat esophagus.

We examined the effects of physalaemin, an agonist of tachykinin receptors, on mechanical responses in the rat esophagus to clarify possible regulatory roles of tachykinins in esophageal motility. Exogenous application of physalaemin caused tonic contractions in rat esophageal segments when tension was recorded in the longitudinal direction but not when tension was recorded in the circular direction. The physalaemin-evoked contractions were blocked by pretreatment with nifedipine, a blocker of L-type calcium channels in both striated and smooth muscle cells. However, tetrodotoxin, a blocker of voltage-dependent sodium channels in striated muscle cells and neurons, did not affect the physalaemin-induced contractions. These results indicate that physalaemin might induce contractile responses in longitudinal smooth muscle of the muscularis mucosa via direct actions on muscle cells but not on neurons. Although pretreatment with a tachykinin NK(1) receptor antagonist, N-acetyl-l-tryptophan 3,5-bis (trifluoromethyl) benzyl ester (L-732,138), did not significantly affect the physalaemin-evoked contractions in rat esophageal segments, a tachykinin NK(2) receptor antagonist, (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl) butyl] benzamide (SR48968), and a tachykinin NK(3) receptor antagonist, (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)-N-methylacetamide (SR142801), significantly inhibited the physalaemin-evoked contractions. These results suggest that tachykinins can activate longitudinal contraction of smooth muscle in the muscularis mucosa, mediated via tachykinin NK(2) and NK(3) receptors on muscle cells, in the rat esophagus.

[Caesarean section to prevent supine hypotension syndrome].

BACKGROUND: The objective of this study was to investigate the effects of posture after spinal anesthesia with 2% lidocaine and 0.5% isobaric bupivacaine in parturients undergoing caesarean section and to demonstrate our modified combined spinal epidural (CSE) method. METHODS: The patients in groups 2%lido (S) and (L) received 2 ml of 2% lidocaine and the patients in groups 0.5%bupi (S) and (L) received 1.6 ml of 0.5% isobaric bupivacaine. The two (S) groups were turned into the supine position after spinal injection and the two (L) groups were kept on their left side for 10 or 15 minutes before they turned supine. All the patients received an epidural injection of 6 ml of 2% lidocaine or 6 ml of 1% ropivacaine 16 minutes after spinal injection. RESULTS: There was a significant difference in the level of analgesia between the (S) groups and the (L) groups 10 minutes after spinal injection (P<0.05). The systolic blood pressures 10 minutes after spinal injection were significantly decreased than those before spinal injection in the (S)groups (P<0.05). CONCLUSIONS: Our modified CSE method can provide beneficial effects on full term pregnant women by preventing hypotension due to spinal anesthesia.

[Symmetrical bilateral epidural hematoma after head injury in the mid parietooccipital region: case report].

The authors presented a patient with acute symmetrical bilateral epidural hematomas, which are rare but life threatening. A 72-year-old male accidentally fell from the roof at a height of about 3 meters and hit his head against the ground. He was transferred to the emergency ward in our hospital. On admission, he was alert and had no neurological deficits. Skull X-ray film revealed a depressed fracture in the mid parietoocipital region and bilateral linear fractures extending from the parietal regions to the temporal regions. CT scan showed symmetrical bilateral epidural hematomas in the both parietotemporal regions. His consciousness deteriorated to be drowsiness about one hour after admission. An additional CT scan revealed enlargement of the both epidural hematomas and impending tentorial herniation. Therefore, an emergency operation was called for. For rapid decompression of the brain, bilateral craniotomies were carried out simultaneously by the two neurosurgeon-groups involved and bilateral epidural hematomas were also simultaneously removed. Injury of both of the middle meningeal arteries was revealed to be the cause of the bilateral epidural hematomas. Clinical course after operation was uneventful and the patient was discharged without any neurological deficit. Simultaneous bilateral craniotomies and removal of the epidural hematomas would have contributed to obtaining the good result in this patient.

Intra-arterial vasopressin injection for the treatment of massive bleeding from the external carotid artery after craniofacial trauma--technical note.

Vasopressin (0.8-1.0 IU), diluted with saline (10 IU vasopressin per 100 ml saline), was selectively injected into the external carotid artery (ECA) to control massive hemorrhage caused by inaccessible serious craniofacial injuries in two patients. This method produced remarkable angiographic vasoconstriction at the involved ECA branches and resulted in immediate hemostasis. Intra-arterial vasopressin injection is a useful option for the treatment of intractable traumatic hemorrhage from inaccessible ECA branches.

Intraoperative hemodynamic measurements of the vertebral artery and common carotid artery.

The hemodynamics in the vertebrobasilar artery (VBA) system were investigated in patients with vertebrobasilar insufficiency (VBI). Vertebral artery (VA) stump pressure and blood flows in the VA and common carotid artery (CCA) were intraoperatively measured in 45 patients who underwent surgical correction of the first segment of the VA (V1) for angiographic tortuosity, kinking, and/or stenosis manifesting as symptomatic VBI. The effects of changes in the systemic arterial blood pressure (SABP) induced by trimethaphan, phenylephrine, and cervical epidural anesthesia were also investigated. The VA stump pressure was 79.3 +/- 13.6 (mean +/- SD) mmHg and the ratio of the VA stump pressure to the SABP was 0.87 +/- 0.08. The baseline values were SABP 90.5 +/- 10.1 mmHg, VA blood flow 53.4 +/- 33.0 ml/min, and CCA blood flow 204.3 +/- 50.3 ml/min. During changes in the SABP, autoregulation of the blood flow in the VA appeared tighter than in the CCA. During cervical epidural anesthesia, blood flows in both the VA and CCA were significantly reduced in response to SABP reduction. This study demonstrated that the VBA system maintains excellent autoregulation with good collateral flows and cervical sympathetic nerve function. However, this autoregulatory capacity may be overwhelmed by unexpected occlusion of the VA due to postural changes associated with tortuosity, kinking, and/or stenosis of the V1 segment.

[Effect of propofol on sevoflurane agitation in children].

BACKGROUND: Sevoflurane may be associated with a high incidence of agitation during recovery from anesthesia in children. We tested the hypothesis that bolus administration of propofol after sevoflurane anesthesia would reduce the incidence of recovery agitation compared with sevoflurane anesthesia alone. METHODS: We conducted a randomized, double-blinded study in 90 children, 1-7 yr of age, undergoing short general anesthesia. They were divided into three groups; 2 mg.kg-1 propofol (group P2), 1 mg.kg-1 propofol (group P1) and intralipid 0.2 ml.kg-1 as control (group C). After sevoflurane induction and maintenance and 5 minutes before the end of operation, propofol or intralipid was administered. We compared the speed and quality of each recovery. We made a new scoring system for the assessment of agitation. Each child received a point from -4 to 10 with this system. RESULTS: Recovery score was similar among the three groups (group P2 had point 4, group P1, point 5, and group C point 4). Recovery time in group P2 was significantly longer than that in group C (about 6 minutes). CONCLUSIONS: Bolus administration of propofol after sevoflurane anesthesia prolonged recovery time, but did not inhibit sevoflurane agitation compared with sevoflurane anesthesia alone.

Usefulness of ultrasonologic examinations on microemboli and hemodynamics for the prevention of complications associated with carotid endarterectomy.

The purpose of this study was to investigate the correlation between plaque characteristics and microembolic signals using transcranial Doppler during endarterectomy. We also investigated successive changes of the pulsality index and average flow velocity in the ipsilateral middle cerebral artery. The subjects of the study were 28 patients who underwent carotid endarterectomy. Transcranial Doppler monitoring was performed before, during, and after carotid endarterectomy. Plaques were classified into 3 types by the brightness on B-mode ultrasonogram. In addition, extracted specimens were macroscopically examined to observe the presence of plaque ulcerations and intraplaque hemorrhages. The blood flow of the internal carotid artery in all cases was measured intraoperatively using an electromagnetic flow meter. The patients who had plaque ulcerations showed significantly more microembolic signals preoperatively than those who had intraplaque hemorrhage during an endarterectomy. Flow velocity in the ipsilateral middle cerebral artery increased immediately after the operation and reached its peak on the day after the operation. The pulsatility index reached its peak on the day of the operation, and remained at this point until 2 days after the operation. We conclude that (1) the patients who had intraplaque hemorrhage had a high risk for embolization of manipulation during dissection and carotid endarterectomy, and (2) systemic management, including that of blood pressure under transcranial Doppler monitoring, was necessary for at least 3 postoperative days in order to prevent hyperperfusion.

Good clinical course in infants with desmoplastic cerebral neuroepithelial tumor treated by surgery alone.

We investigated why surgery alone provides for a benign clinical course in patients with desmoplastic infantile ganglioglioma and astrocytoma (DIG/A). The clinical course of 4, less than six-month-old girls, surgically treated at our institutions, was evaluated retrospectively. All presented with the clinical symptom of increasing head circumference. CT and MRI scans revealed a solid tumor attached to the dura that was surrounded by large, multiple cysts, in fronto-temporo-parietal lobe. Gross total removal succeeded in all 4 cases because the solid components of the tumor were very firm in contrast to the soft adjacent brain tissue. Microscopically, the surgical specimens consisted almost entirely of dense fibrous connective tissue containing generally elongate cells with inconspicuous cytoplasm. Most of these cells were immunopositive for GFAP. There was no evidence of tumor cells in the cyst wall. In 3 cases, some small neurons were positive for neurofilament immunostain. A high proportion of undifferentiated small cells in a less demoplastic area far from the dura were immunopositive for MIB-1. All of the 4 patients have been free of recurrence for more than five years. In patients with DIG/A, there are 5 reasons for a good clinical course. [1] At surgery, the tumor margin is clearly discernible because of the difference between the solid tumor and the soft adjacent brain tissue. [2] The tumor is located in the superficial cerebral hemisphere. [3] Large, multiple cysts surround the tumor. [4] The growth point appears to be adjacent to the cysts. [5] The cyst walls are free of invading tumor cells.