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Y R Kou

Publications and source records attributed to Y R Kou.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of high thoracic epidural anaesthesia on the peripheral airway reactivity in dogs.

BACKGROUND: It has been speculated that epidural anaesthesia may induce bronchoconstriction via the mechanism of a sympathetic blockade. However, this hypothesis has not been confirmed by any experimental evidence. Therefore, we investigated the effects of high thoracic epidural anaesthesia with neural sympathetic blockade on basal airway resistance and airway reactivity in response to bronchoconstrictive stimuli in a canine periphery lung model. METHODS: Acetylcholine (Ach, 8 microg kg[-1] i.v.) or histamine (His, 3 microg kg[-1] i.v.) was administered to 7 anaesthetized mongrel dogs before and after thoracic epidural anaesthesia. Successful neuronal sympathectomy was confirmed by nitroglycerin test. The changes of peripheral airway resistance (Rp), haemodynamics, cardiac output (CO), and the recovery time for Rp from peak returning to baseline in each challenge were studied. RESULTS: Thoracic epidural anaesthesia altered neither the baseline Rp nor the peak Rp evoked by Ach or His. However, the recovery time of the Rp was prolonged significantly after epidural anaesthesia (P<0.01) and correlated inversely with the CO in response to Ach or His challenge (Ach, r=0.542; His, r=0.651). CONCLUSIONS: Our results suggest that epidural anaesthesia with neural sympathetic blockade has no influence on the basal peripheral airway resistance; however, it prolongs the airway reactivity to Ach or His challenge, probably by the mechanism of reducing CO.

Acetylcholine↗
PubMed1998

Stimulation of vagal pulmonary C fibers by inhaled wood smoke in rats.

This study investigated the stimulation of vagal pulmonary C fibers (PCs) by wood smoke. We recorded impulses from PCs in 58 anesthetized, open-chest, and artificially ventilated rats and delivered 6 ml of wood smoke into the lungs. Within 1 or 2 s after the smoke delivery, an intense and nonphasic burst of discharge [delta = +7.4 +/- 0.7 (SE) impulses/s, n = 68] was evoked in 60 of the 68 PCs studied and lasted for 4-8 s. This immediate stimulation was usually followed by a delayed and more sustained increase in C-fiber activity (delta = +2.0 +/- 0.4 impulses/s). The overall stimulation was not influenced by removal of smoke particulates (n = 15) or by pretreatment with vehicle (n = 8) for dimethylthiourea (DMTU; a hydroxyl radical scavenger) or indomethacin (Indo; a cyclooxygenase inhibitor). The immediate-phase stimulation was not affected by pretreatment with Indo (n = 8) but was largely attenuated by pretreatment with DMTU (n = 12) or by a combined treatment with DMTU and Indo (DMTU + Indo; n = 8). Conversely, the delayed-phase stimulation was partially suppressed either by DMTU or by Indo but was totally abolished by DMTU + Indo. These results suggest that 1) the stimulation of PCs is linked to the gas phase of wood smoke and 2) hydroxyl radical, but not cyclooxygenase products, is involved in the immediate-phase stimulation, whereas both metabolites are responsible for evoking the delayed-phase stimulation.

Animals↗
PubMed1998

Inhibitory effect of inhaled wood smoke on the discharge of pulmonary stretch receptors in rats.

We investigated the inhibition of slowly adapting pulmonary stretch receptors (PSRs) by inhaled wood smoke. Impulses were recorded from PSRs in 68 anesthetized, open-chest, and artificially ventilated rats. Eighty-one of one hundred five PSRs were inhibited within one or two breaths when 6 ml of wood smoke were delivered into the lungs. As a group (n = 105), PSR activity significantly decreased from a baseline of 19.0 +/- 1.3 (SE) to a lowest level of 12.9 +/- 1.2 impulses/breath at the fourth or fifth breath after smoke delivery. This afferent inhibition usually persisted for 5-18 breaths. In contrast, smoke delivery did not affect transpulmonary pressure. Delivery of gas-phase smoke or a hypercapnic gas mixture containing CO2 at a concentration (15%) matching that in the smoke produced a nearly identical inhibition in the same PSRs (n = 10). This afferent inhibition was largely prevented by pretreatment with acetazolamide (an inhibitor of carbonic anhydrase; n = 10) but was not affected by pretreatment with the vehicle for acetazolamide (n = 8) or isoproterenol (a bronchodilator; n = 10). These results suggest that 1) an increase in H+ concentration resulting from hydration of CO2 in the smoke may be responsible for the inhibitory effect of wood smoke on the discharge of PSRs and 2) changes in lung mechanics are not the cause of this afferent inhibition.

Acetazolamide↗
PubMed1997

Possible effect of pneumoperitoneum on the spreading of colon cancer tumor cells.

PURPOSE: By using a murine hepatic metastatic model, we tried to investigate the possible influence of gas insufflation in colon cancer cells spreading from the portal system to the liver. METHODS: After transducing the human placental ALP gene into murine colon cancer cell line CT26, we successfully selected a clone of CT26/DAP that would yield a specific color following histochemical staining. Fifty mice were assigned into two groups, receiving either an intrasplenic injection of 10(6) CT26/DAP cells alone or the cells followed by intra-abdominal helium insufflation with the pressure of 15 cm H2O for ten minutes. Five mice in each group were used to observe their survival and the other mice were killed at four different time periods: 10 minutes, 24 hours, 48 hours, and 72 hours following cell injection. The livers and spleens were removed for histochemical staining. By counting the numbers of specific dark reddish spots of CT26/DAP cells, we could estimate the number of tumor cells on the hepatic surface. RESULTS: At the very beginning following tumor cell injection, we found a significantly greater number of tumor cells on the hepatic surface in mice with gas insufflation (6354 +/- 1072 vs. 2133 +/- 223, respectively; P = 0.012). But the difference of these two groups became smaller and smaller as time went by. The number of tumor cells on the hepatic surface would reach the lowest level at postoperative 48 hours, and the tumor foci then began to grow both in size and number. The above patterns of dynamic change in tumor cell distribution were similar in mice both with and without gas insufflation. Average survival was slightly shorter in mice with gas insufflation, but the difference was not statistically significant. CONCLUSION: Pneumoperitoneum caused by gas insufflation may increase tumor cell spread from the portal system to the liver at the very beginning stage; however, there was no significant difference in long-term survival between mice with and without gas insufflation in this murine animal model.

Adenocarcinoma↗
PubMed1997

Involvement of hydroxyl radical in the immediate ventilatory responses to inhaled wood smoke in rats.

Spontaneous inhalation of wood smoke (approximately 6 ml) via a tracheostomy immediately triggered either a slowing of respiration (SR, n = 51) or an augmented inspiration (AI, n = 32) in 83 anesthetized Sprague-Dawley rats studied. To investigate the involvement of hydroxyl radical (OH.) in evoking these immediate smoke-induced ventilatory responses, smoke challenges were repeated following intravenous infusion (0.05 ml/min for 20 min) of saline vehicle, dimethylthiourea (DMTU, 500 mg/kg), deferoxamine (DEF, 20 mg/kg), or iron-saturated DEF (DEF + Fe, 20 mg/kg). DMTU is a scavenger for OH.. DEF is an iron-chelator which prevents the formation of OH., whereas DEF saturated with iron results in the loss of its iron-chelating properties. In the vehicle group, both the SR (n = 8) and the AI (n = 7) were unaffected by the pretreatment. However, in the DMTU group, the SR (n = 23) was abolished in seven and attenuated in 16 rats, while the AI (n = 10) was eliminated in eight and unaffected in two rats. In the DEF group, the SR (n = 12) was abolished in three and attenuated in nine rats, while the AI (n = 8) was eliminated in six and unaffected in two rats. In contrast, in the DEF + Fe group, both the SR (n = 8) and the AI (n = 7) were not attenuated by the pretreatment. These results suggest that an increase in OH. burden following smoke inhalation is actively involved in evoking the acute irritant effects of wood smoke on breathing in rats.

Animals↗
PubMed1997

Mechanisms underlying stimulation of rapidly adapting receptors during pulmonary air embolism in dogs.

We investigated the mechanisms underlying stimulation of rapidly adapting receptors (RARs) during pulmonary air embolism (PAE). Impulses were recorded from RARs in 43 anesthetized, open-chest and artificially ventilated dogs. Forty one out of 56 RARs were stimulated by infusion of air into the right atrium (0.2 ml/kg per min for 10 min). As a group (n = 56), RAR activity increased from a baseline of 1.2 +/- 0.2 to a peak of 4.3 +/- 0.3 impulses/breath at 8-10 min after the onset of PAE induction. PAE also caused an increase in total lung resistance and a decrease in dynamic lung compliance. Studies were repeated in 33 RARs initially stimulated by PAE. In nine receptors, hyperinflation of the lungs performed at the termination of the second PAE induction largely reversed both the afferent and bronchomotor responses. Furthermore, the residual PAE-evoked activity subsequent to hyperinflation was almost eliminated by elevation in the heart position. In another 24 receptors, the responses of RARs to PAE were unaltered by pretreatment with saline (n = 8) or dimethylthiourea (a hydroxyl radical scavenger; n = 8), but was significantly attenuated by pretreatment with ibuprofen (a cyclooxygenase inhibitor: n = 8). These results suggest that: (1) the increased RAR activity following PAE is associated primarily with an increase in bronchomotor tone and secondarily with the mechanical action of the beating heart impacting on lung tissues; and (2) cyclooxygenase products may be involved in this sensory stimulation.

Afferent Pathways↗
PubMed1997

Mechanisms of stimulation of vagal pulmonary C fibers by pulmonary air embolism in dogs.

We investigated the involvement of the cyclooxygenase metabolites and hydroxyl radical (.OH) in the stimulation of vagal pulmonary C fibers (PCs) by pulmonary air embolism (PAE). Impulses were recorded from PCs in 51 anesthetized, open-chest, and artificially ventilated dogs. Fifty of 59 PCs were stimulated by infusion of air into the right atrium (0.2 ml.kg-1.min-1 for 10 min). As a group (n = 59), PC activity increased from a baseline of 0.4 +/- 0.1 to a peak of 1.7 +/- 0.2 impulses/s during the period from 1 min before to 2 min after the termination of PAE induction. In PCs initially stimulated by PAE induction, PAE was repeated after the intervening treatment (iv) with saline (n = 9), ibuprofen (a cyclooxygenase inhibitor; n = 11), or dimethylthiourea (a .OH scavenger; n = 12). The responses of PCs to PAE were not altered by saline vehicle but were abolished by ibuprofen and significantly attenuated by dimethylthiourea. Although hyperinflation of the lungs reversed the PAE-induced bronchomotor responses, it did not reverse the stimulation of PCs (n = 8). These results suggest that 1) cyclooxygenase products are necessary for the stimulation of PCs by PAE, whereas changes in lung mechanics are not, and 2) the functional importance of cyclooxygenase products may be mediated in part through the formation of .OH.

Animals↗
PubMed1997

Reflex apneic response evoked by laryngeal exposure to wood smoke in rats: neural and chemical mechanisms.

We investigated the neural and chemical mechanisms contributing to the immediate ventilatory responses to laryngeal exposure to wood smoke in anesthetized Sprague-Dawley rats. Five milliliters of wood smoke were delivered into a functionally isolated larynx at a constant flow rate of 1.4 ml/s while the animals breathed spontaneously. Within 1 s after exposure, laryngeal wood smoke consistently triggered an apnea in each of the 42 rats tested. The apneic duration reached 1,636.4 +/- 105.4 (SE) % (n = 42) of the baseline expiratory duration. This apneic response was not affected by denervation of recurrent laryngeal nerves (n = 6) or by removal of smoke particulates (n = 14), but it was totally eliminated by topical application of an anesthetic (n = 8; lidocaine hydrochloride, 8%) to the laryngeal mucosa or by sectioning of the superior laryngeal nerves (n = 42). Furthermore, laryngeal application of a hydroxyl radical scavenger (dimethylthiourea; 500 mg/ml; n = 8) greatly diminished or abolished the smoke-induced apneic response, but it did not affect the apneic response evoked by laryngeal exposure to air saturated with 6% ammonia. These results suggest that the immediate apneic response to laryngeal wood smoke is a reflex resulting from the stimulation of the superior laryngeal afferents by the gas phase of wood smoke and that the stimulation is mediated through a hydroxyl radical mechanism.

Ammonia↗
PubMed1996

Inhibitory influence of lung vagal C-fiber afferents on the delayed ventilatory response to inhaled wood smoke in rats.

We studied the influences of lung vagal afferents on the delayed ventilatory response to inhaled wood smoke in 35 Sprague-Dawley rats. Wood smoke (approximately 6 ml) was inhaled via tracheostomy when animals breathed spontaneously. Immediately after inhalation, wood smoke evoked a slowing of respiration or an augmented inspiration, followed by a delayed tachypnea. Owing to the increase in respiratory frequency, the delayed ventilatory response usually resulted in an increase in minute ventilation (VI). The smoke-induced increase in VI was elevated after perineural capsaicin treatment of both cervical vagi (PCT, n = 12), but was unaltered during cooling of both vagi to 6.7 degrees C (VGC, n = 9); PCT selectively blocked the conduction of unmyelinated C-fibers, whereas VGC differentially blocked the conduction of myelinated fibers. Furthermore, the smoke-induced increase in VI after PCT was unaffected by an additional application of VGC (n = 12), whereas it was magnified by an additional application of PCT during VGC (n = 9). This magnification was not changed after a subsequent bilateral vagotomy (n = 21). Removal of smoke particulates did not affect the increase in VI evoked by smoke inhalation (n = 14). These results suggest that 1) the smoke-induced delayed ventilatory response is restrained by the inhibitory input from lung vagal C-fibers, whereas it was not influenced by the input from irritant receptors and 2) the gas phase of wood smoke is responsible for eliciting this delayed ventilatory response.

Afferent Pathways↗
PubMed1995

Analysis of carotid chemoreceptor responses to substance P analogue in anaesthetized cats.

Analogues of Substance P (SP) have been shown to act as SP receptor antagonists in various physiological systems. We have previously shown that the carotid body sensory response to hypoxia could be attenuated by D-Pro2-D-Trp7,9-SP (DPDT-SP) and suggested that SP may be important for chemoreception. In the absence of detailed characterization of the antagonistic effects of DPDT-SP, the role of SP in carotid body chemoreception remains uncertain. The present study was undertaken to analyze the effects of DPDT-SP on carotid body activity in anaesthetized cats (n = 18). Intra-carotid infusion of DPDT-SP antagonized SP-induced chemoreceptor stimulation. 90% blockade of SP responses was obtained at infusion rates of 15 micrograms/kg per min of DPDT-SP for 15 min. By contrast, infusions of either saline (controls) or at doses below 10 micrograms/kg per min had no effect on SP responses. The doses that effectively antagonized SP excitation (i.e., 15 micrograms/kg per min) also blocked or markedly attenuated the chemoreceptor responses to hypoxia, without affecting the carotid body stimulation caused by nicotine. The effects of DPDT-SP were associated with significant reduction in baseline activity in normoxia. The antagonistic effects were reversible after terminating the infusion of DPDT-SP. Increasing the dose to 25 micrograms/kg per min, however, abolished the carotid body excitation by any of the stimuli tested (i.e., SP, hypoxia and nicotine), indicating that at higher doses DPDT-SP is non-selective. These results demonstrate that DPDT-SP given in adequate doses to block SP response also attenuates or abolishes the carotid body excitation by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Role of vagal afferents in the acute ventilatory responses to inhaled wood smoke in rats.

Spontaneous inhalation of wood smoke (approximately 6 ml) via tracheostomy immediately evoked either a slowing of respiration (SR) or an augmented inspiration (AI) in each of the 76 anesthetized Sprague-Dawley rats studied. The SR was abolished after perineural capsaicin treatment of both cervical vagi (PCT; n = 20) but persisted during cooling of both vagi to 6.7 degrees C (VGC, n = 12); PCT selectively blocked the conduction of unmyelinated C fibers, whereas VGC differentially blocked the conduction of myelinated fibers. In contrast, the AI was eliminated during VGC (n = 10) but was unaffected by PCT (n = 5). Furthermore, after the SR was abolished in rats with PCT, an AI became the dominant immediate response to inhaled wood smoke. Conversely, after the AI was eliminated in rats receiving VGC, a SR was instantly evoked by inhaled wood smoke. Removal of smoke particulates did not affect the SR (n = 17) but did prevent the AI in 5 of the 12 rats studied. These results suggest the following: 1) the SR is a reflex resulting from stimulation of bronchopulmonary C-fiber nerve endings by the gas-phase smoke; 2) the AI results from excitation of lung irritant receptors by the gas-phase and/or smoke particulates; and 3) in intact animals, both types of vagal bronchopulmonary afferents are probably activated by inhaled wood smoke.

Administration, Inhalation↗
PubMed1994

Inhibitory sympathetic action on the carotid body responses to sustained hypoxia.

The mammalian carotid bodies receive sympathetic innervation from the superior cervical ganglion. The purposes of the present study were: (1) to investigate whether sympathetic innervation influences the carotid body response to hypoxia, and, if so, (2) to determine the involvement of adrenoceptors in these influence. Chemo-sensory activity was recorded from clearly identifiable action potentials from the carotid sinus nerve in 20 anaesthetized, paralyzed and artificially ventilated cats. Chemoreceptor responses to sustained isocapnic hypoxia (30 min, duration) were compared before and after carotid body sympathectomy (n = 8 cats). In response to low PO2, chemoreceptor discharge increased during the first 10 min, and plateaued for the rest of the hypoxic challenge. After sympathectomy, chemoreceptor response in the initial 10 min was the same; whereas, the magnitude of the response in remaining 20 min was significantly greater than controls (P < 0.01). Systemic administration of SKF-86466, an alpha 2-adrenoceptor antagonist augmented the hypoxic response by 80% (n = 6 cats). In presence of alpha 2-antagonist, sympathectomy had no further effect on the hypoxic response. Administration of alpha 2-antagonist in sympathectomized carotid bodies potentiated the hypoxic response, but the magnitude of potentiation was less than with intact sympathetic innervation (34% vs 80%; P < 0.01; n = 6 cats). From these results, it is concluded that (1) sympathetic innervation exerts an inhibitory influence on chemoreceptor response to sustained hypoxia, and (2) this inhibitory influence is mediated at least in part by alpha 2-adrenoceptors. The inhibitory effects of sympathetic innervation could be of importance in the efferent regulation of the carotid body activity during sustained hypoxia.

Action Potentials↗
PubMed1994

Tachykinin antagonists in carotid body responses to hypoxia and substance P in the rat.

In the present study, we tested the hypothesis that substance P (SP) is an excitatory peptide to the rat carotid body and plays an important role in chemosensory excitation by hypoxia. Chemosensory discharge was recorded from the cut carotid sinus nerve in 19 anaesthetized, paralyzed and mechanically ventilated rats. Intracarotid administration of SP augmented the chemoreceptor activity in a dose-dependent manner. Maximal excitation was seen with 10 nmol SP. Carotid body stimulation by SP was independent of its effects on arterial blood pressure. The effect of SP antagonists, D-Pro2-D-Trp7,9-SP (DPDT-SP) or Spantide, on chemoreceptor responses to SP and hypoxia was examined in 12 rats. Close carotid body administration of either antagonist at doses of 40 micrograms.kg-1.min-1 elicited an augmentation followed by a progressive depression of baseline carotid body activity. SP antagonists significantly reduced peptide-induced carotid body stimulation and also markedly attenuated the chemoreceptor response to hypoxia. Systemic administration of sodium bicarbonate stimulated the carotid bodies, presumably by releasing CO2, and the bicarbonate-induced chemoreceptor stimulation was not affected by SP antagonists. From these results we conclude that in rats (a) SP stimulates the carotid bodies independently of its effects on arterial blood pressure, and (b) SP is associated with the chemosensory stimulation by hypoxia but not with other excitatory stimuli.

Action Potentials↗
PubMed1994

Reflex changes in breathing pattern evoked by inhalation of wood smoke in rats.

The acute ventilatory response to inhalation of wood smoke was studied in 58 anesthetized Sprague-Dawley rats. Wood smoke (approximately 6 ml) was inhaled spontaneously via a tracheal cannula. Within the first two breaths of smoke inhalation, either a slowing of respiration (SR) (n = 39) or an augmented inspiration (AI) (n = 19) was elicited consistently in each rat. The SR was primarily due to a prolongation of expiratory duration, whereas the AI was characterized by a two-step inspiratory flow leading to an exceedingly large tidal volume. Both initial responses, usually accompanied by bradycardia and hypotension, were reduced by inhaling smoke at a decreased concentration. After these initial responses, a delayed tachypnea developed and reached its peak 6-10 breaths after inhalation of smoke. Both the SR and AI were completely abolished by bilateral cervical vagotomy. In contrast, the delayed tachypneic response was not prevented by vagotomy but was significantly attenuated by denervation of peripheral chemoreceptors. We conclude that the initial responses to inhalation of several tidal breaths of wood smoke are mediated through vagal bronchopulmonary afferents, whereas the delayed tachypnea may involve nonvagal mechanisms that include a stimulation of peripheral chemoreceptors.

Animals↗
PubMed1992

Stimulatory effect of circulated nicotine on rapidly adapting receptors in canine lungs.

The objective of this study was to determine the effect of circulated nicotine on rapidly adapting receptors (RARs) in canine lungs. Afferent activities of RARs were studied with a single fiber recording technique in 10 anesthetized, open-chest and artificially ventilated dogs. Bolus injection of nicotine (10 micrograms/kg) into either right or left atrium did not activate the RARs in the first two breaths, but it consistently evoked a mild stimulatory effect beginning approximately 3-6 breaths after the injection, accompanied by a mild increase in tracheal pressure (Pt). There was no significant difference between the receptor responses to nicotine injected via these two different routes in either the peak discharge or the latency time. By contrast, nicotine delivered by cigarette smoke directly into the airways triggered an intense burst of activity upon the very first breath of smoke delivery. Taken together, these results suggest that the sensory endings of RARs are located near the surface of airway epithelium, more easily accessible from the luminal side of the airways. The delayed stimulation of RARs following the nicotine injection was probably activated by the bronchoconstrictive effect of nicotine.

Animals↗
PubMed1991

Role of alpha 2-adrenergic receptors in the carotid body response to isocapnic hypoxia.

Alpha-2 adrenergic receptors have been identified in numerous tissues containing norepinephrine. Carotid bodies are sensory organs that detect changes in partial pressure of arterial oxygen and contain substantial amounts of norepinephrine. However, neither the presence nor the functional significance of alpha 2-receptors in the carotid body is known. The purpose of the present study was two-fold: (1) to determine the alpha 2-receptor density in the carotid body and (2) to assess their participation in the chemoreceptor responses to hypoxia. Experiments were performed on 27 anesthetized, paralyzed and artificially ventilated cats. Alpha-2 receptor binding determined by [125I]p-iodoclonidine averaged 10 +/- 2 fmol/mg of protein (n = 18 carotid bodies). Intracarotid infusion of an alpha 2-agonist (guanabenz; 0.5, 1, and 5 micrograms/min for 5 min) caused a dose-dependent depression of the baseline activity and 5 micrograms/min reduced the magnitude of the chemoreceptor response to isocapnic hypoxia by 61% (n = 8). Systemic administration of an alpha 2-antagonist (SKF-86466, 0.5-2 mg/kg) prevented the effects of guanabenz on the chemoreceptor activity. Furthermore, alpha 2-antagonist (0.5-2 mg/kg, i.v.) alone significantly increased baseline discharge by 68% and potentiated the chemoreceptor response to isocapnic hypoxia by 46% (n = 10). These results demonstrate that (1) alpha 2-adrenergic receptors are present in the carotid body and (2) they exert an inhibitory influence on chemoreceptor response to hypoxia. It is suggested that norepinephrine may tune the carotid body responses to hypoxia in part by its action on alpha 2-receptors.

Action Potentials↗