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Biomedical subjects

Takashi Mashimo

Publications and source records attributed to Takashi Mashimo.

At least 55 records · Page 3Linked to original sources

Intrahospital transport of critically ill patients using ventilator with patient-triggering function.

OBJECTIVE: To compare a new transport ventilator to manual ventilation in terms of maintaining the respiratory and hemodynamic levels of critically ill patients. DESIGN: Prospective, randomized, single-center study. SETTING: ICU in a university hospital. PATIENTS: A total of 16 patients (22 transports) who were spontaneously breathing and required ventilatory assistance on excursions from the ICU. METHODS: For each transport, the patient was randomly assigned to receive either manual ventilation (group M) or mechanical ventilation (group V). For transports in group V, the ventilators were set the same as in the ICU. Respiratory and hemodynamic variables were measured 30 min before transport (T(0)), on arrival at the site of procedure (T(1)), on return to the ICU (T(2)), and 30 min after return the ICU (T(3)). RESULTS: After transport, five patients in group M showed a significant deterioration in PaO(2)/fraction of inspired oxygen ratio, while one patient in group V showed deterioration (p = 0.056). The mean (+/- SD) respiratory rate in group M at T(2) (32 +/- 9 breaths/min) was significantly higher (p < 0.001) than at T(0) (19 +/- 6 breaths/min) and also was higher (p < 0.01) than in group V at T(2) (19 +/- 6 breaths/min). The mean tidal volume and positive end-expiratory pressure in group M at T(2) showed significantly larger variation (p < 0.05 and p < 0.001, respectively) than in group V. CONCLUSIONS: The transport ventilator that was recently approved by the US Food and Drug Administration reliably provides more stable ventilatory support than does manual ventilation. Generally, the use of this transport ventilator for intrahospital transport is preferable to manual ventilation.

Critical Illness↗

Spontaneously breathing lung model comparison of work of breathing between automatic tube compensation and pressure support.

INTRODUCTION: Automatic tube compensation (ATC), a new ventilation mode that compensates for the work of breathing imposed by endotracheal tube resistance, recently became commercially available. METHODS: We conducted a laboratory study with a lung model and a Nellcor Puritan Bennett 840 ventilator to compare ATC and pressure-support ventilation (PSV). A bellows-in-a-box lung model simulated spontaneous breathing with the following settings: respiratory rate 10 breaths/min, inspiratory time 1.0 s, peak inspiratory flow 60 L/min without connecting to the ventilator and endotracheal tube (ETT). At each ETT size (5, 6, 7, 8 and 9 mm inner diameter) 100% ATC was compared with pressure support (PS) of 0, 2, 4, 6, 8, and 10 cm H(2)O at positive end-expiratory pressure (PEEP) of 0 and 5 cm H(2)O. The negative deflection (PI) of the "alveolar" pressure (ie, pressure inside the bellows, P(alv)) and the delay time were measured. The PI and total pressure-time product (PTP(tot)) integrated from P(alv) were analyzed. PTP(tot) was subdivided into PTP(trig) (the PTP from the beginning of inspiration to the minimum P(alv)) and PTP(supp) (the PTP from the minimum P(alv) to the return to baseline P(alv)). RESULTS: At PEEP of 0 cm H(2)O: with ETTs of 5, 6, and 7 mm the PI values with ATC corresponded to PS of 0-4 cm H(2)O; with the 8-mm ETT the PI values corresponded to PS of 0 cm H(2)O; with the 9-mm ETT the PI values corresponded to PS of 0-2 cm H(2)O. At PEEP of 5 cm H(2)O, with all ETT sizes the PI values corresponded to PS of 0 cm H(2)O. PTP(tot) and PTP(supp) of ATC corresponded to: PS of 2-4 cm H(2)O with the 5-mm ETT; PS of 2 cm H(2)O with the 6-mm ETT; PS of 0-2 cm H(2)O with the 7-mm ETT; and PS of 0 cm H(2)O with the 8- and 9-mm ETTs, at PEEP of 0 cm H(2)O. PEEP of 5 cm H(2)O was not tested for PTP. PTP(trig) with ATC showed comparable or greater values with each size of ETT. CONCLUSIONS: ATC with a Nellcor Puritan Bennett 840 ventilator provided inspiratory ventilatory support corresponding to PS of <or= 4 cm H(2)O, depending on ETT size, which was not enough to compensate for the work of breathing imposed by the ETT.

Humans↗

Intravenous anesthetic, propofol inhibits invasion of cancer cells.

Intravenous anesthetic, propofol (2,6-diisopropylphenol), is extensively used for general anesthesia without knowing the effects on cancer. We found here that clinically relevant concentrations of propofol (1-5 microg/ml) decreased the invasion ability of human cancer cells (HeLa, HT1080, HOS and RPMI-7951). In the HeLa cells treated with propofol, formation of actin stress fibers as well as focal adhesion were inhibited, and propofol had little effect on the invasion ability of the HeLa cells with active Rho A (Val(14)-Rho A). In addition, continuous infusion of propofol inhibited pulmonary metastasis of murine osteosarcoma (LM 8) cells in mice. These results suggest that propofol inhibits the invasion ability of cancer cells by modulating Rho A and this agent might be an ideal anesthetic for cancer surgery.

Actins↗

Nicorandil prevents epinephrine-induced arrhythmias in halothane-anesthetized rats by nitric oxide-dependent mechanism.

The effect of opening ATP-sensitive K(+) channels on the genesis of arrhythmias is still controversial. We investigated the effect of nicorandil, an ATP-sensitive K(+) channel opener, on the genesis of halothane-epinephrine arrhythmias in rats. We also clarified the involvement of nitric oxide in the effect of nicorandil. Furthermore, we studied the effect of levcromakalim, another ATP-sensitive K(+) channel opener, for comparison. Nicorandil and levcromakalim significantly increased the arrhythmogenic thresholds of epinephrine in a dose-dependent manner. On the other hand, nitroprusside, a potent vasodilator (5.0 micro g/kg per min), did not exert antiarrhythmic action significantly. Both glibenclamide (non-specific ATP-sensitive K(+) channel blocker) and 5-hydroxydecanoate (mitochondrial ATP-sensitive K(+) channel blocker) inhibited the antiarrhythmic action of nicorandil. Although pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, did not modulate the genesis of halothane-epinephrine arrhythmias in the absence of nicorandil, it completely abolished the antiarrhythmic action of nicorandil, but not the effect of levcromakalim. We concluded that nicorandil dose-dependently inhibited halothane-epinephrine arrhythmias through mitochondrial ATP-sensitive K(+) channels and nitric oxide is required for the antiarrhythmic effect of nicorandil.

Anesthetics, Inhalation↗

The effects of dexmedetomidine on the ventilatory response to hypercapnia in rabbits.

OBJECTIVE: Dexmedetomidine is a highly selective alpha(2)-adrenergic agonist that can reduce anesthetic requirements. This study, to assess its effect on respiration, examined the effects of various doses of dexmedetomidine (1, 10, 30 and 50 microg/kg) on the respiratory response to carbon dioxide (CO(2)) breathing in rabbits. DESIGN: Randomized prospective study. SETTING: Animal laboratory at a university school of medicine. INTERVENTION: From 28 animals, four groups of seven were randomly assigned to receive different doses of dexmedetomidine (groups D1, D10, D30 and D50). Under inhalation of sevoflurane, each animal was tracheostomized and intubated with a 4 mm internal diameter (i.d.) endotracheal tube. MEASUREMENTS AND RESULTS: After end-tidal sevoflurane concentration had decreased below 0.03% and during quiet breathing (QB); respiratory rate (RR), tidal volume (V(T)) and inspiratory time (T(I)) were measured, from which minute ventilation (MV) and mean inspiratory flow (V(T)/T(I)) were calculated. After these measurements had been completed, each animal breathed the balloon gas (5% CO(2) and 95% O(2)) until the end-tidal CO(2) (ETCO(2)) reached 10%. The respiratory measurements were repeated during the latter period. After the collection of these data, dexmedetomidine was infused intravenously and the same measurements were repeated 15 and 45 min after dexmedetomidine infusion. The slope of the ventilatory response to hypercapnia in D50 was significantly higher compared with D30 animals. In the range 1-30 microg/kg, during both QB and at 10% ETCO(2), MV was decreased in a dose-dependent manner. Dexmedetomidine depressed both V(T) and RR during QB and at 10% ETCO(2). CONCLUSION: Dexmedetomidine depressed resting ventilation and the respiratory response to CO(2), but it did not induce profound hypoxemia or hypercapnia in rabbits.

Adrenergic alpha-Agonists↗

Hypothermia and thiopentone sodium: individual and combined neuroprotective effects on cortical cultures exposed to prolonged hypoxic episodes.

Because there are many conflicting reports on cerebroprotective effects of hypothermia and barbiturates, we examined the degree of neuroprotection at defined temperatures (normothermia, 37 degrees C; mild hypothermia, 32 degrees C; deep hypothermia, 22 degrees C; and profound hypothermia, 17 degrees C) and various concentrations (low, 4 microM; moderate, 40 microM; and high, 400 & microM) of thiopentone sodium (TPS), alone and in combination in cortical cultures exposed to prolonged hypoxia (24-48 hr). The survival rate of embryonic day (E)16 Wistar rat cortical neurons was evaluated on photomicrographs before and after experiments. During the 24-hr hypoxic period, the survival rate of neurons was maximal with combinations of mild hypothermia with 40 microM (91.6 +/- 0.7%) and 400 microM TPS (90.8 +/- 0.7%) or deep hypothermia combined with all concentrations of TPS (4 microM, 90.6 +/- 1.0%; 40 microM, 91.4 +/- 0.8%; 400 microM, 91.8 +/- 1.2%). During 48 hr hypoxia, the highest survival rate was seen with the combination of deep hypothermia and either 40 microM (90.9 +/- 0.6%) or 400 microM (91.1 +/- 1.4%) TPS. In the presence of profound hypothermia in combination with all concentrations of TPS, the survival rate was significantly reduced (P< 0.01) compared to combined application of either mild or deep hypothermia with TPS. In summary, maximal neuroprotection was attained with hypothermia and TPS in combination rather than applied individually, during prolonged hypoxic episodes (24- 48 hr). During a 24-hr hypoxic period, both mild and deep hypothermia combined with a clinically relevant concentration of TPS (40 microM) offered the highest neuroprotection. Only deep hypothermia provided maximal neuroprotection when combined with 40 microM TPS, during 48-hr hypoxia. Combination of profound hypothermia and TPS did not confer considerable neuroprotection during long lasting hypoxia.

Animals↗

Epinephrine inhibits invasion of oral squamous carcinoma cells by modulating intracellular cAMP.

In oral and maxillofacial surgery, epinephrine is routinely used for cancer resection and it is important to clarify the effects of this agent on cancer. We found here that the clinically relevant concentrations of epinephrine (10, 50 and 100 microg/ml) decreased the invasion ability of oral squamous carcinoma (Sa3) cells. In the Sa3 cells treated with epinephrine (10, 50 and 100 microg/ml), migration, morphological changes and formation of actin stress fibers were inhibited and intracellular cyclic adenosine monophosphate (cAMP) increased significantly. These findings suggest that epinephrine inhibits the invasion of cancer cells by modulating intracellular cAMP and that clinicians could use epinephrine effectively for the surgical resection of the cancer.

Actins↗

Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF).

Although the mechanism is unknown, infiltration anesthetics are believed to have membrane-stabilizing action. We report here that such a most commonly used anesthetic, lidocaine, effectively inhibited the invasive ability of human cancer (HT1080, HOS, and RPMI-7951) cells at concentrations used in surgical operations (5-20 mM). Ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF) from the cell surface plays an important role in invasion by HT1080 cells. Lidocaine reduced the invasion ability of these cells by partly inhibiting the shedding of HB-EGF from the cell surface and modulation of intracellular Ca2+ concentration contributed to this action. The anesthetic action of lidocaine (sodium channel blocking ability) did not contribute to this anti-invasive action. In addition, lidocaine (5-30 mM), infiltrated around the inoculation site, inhibited pulmonary metastases of murine osteosarcoma (LM 8) cells in vivo. These data point to previously unrecognized beneficial actions of lidocaine and suggest that lidocaine might be an ideal infiltration anesthetic for surgical cancer operations.

Anesthetics, Local↗

Validity of gastric intramucosal pH (pHi) for circulatory evaluation in pediatric patients.

OBJECTIVE: To determine if the measurement of gastric intramucosal pH (pHi) is useful for evaluation of circulatory status of critically ill pediatric patients. DESIGN: Prospective clinical study. SETTING: General intensive care unit in a university hospital. PATIENTS: Seven pediatric patients (mean age: 2 y.o.); six post-cardiac surgery, one receiving barbiturate therapy. INTERVENTIONS: Tonometric catheters were placed via nasogastric approach. pHi was measured after confirmation of the catheter position by X-ray. MEASUREMENTS AND MAIN RESULTS: Saturation of venous blood oxygen (SvO2), arterial keton body ratio (AKBR), serum lactate level and pHi were evaluated simultaneously. No patients survived with pHi below 7.22; pHi above 7.11 significantly correlated with SvO2 values (r = 0.814, p < 0.001); pHi below 7.11 did not show any significant correlation with SvO2. Whereas SvO2 values of under 40% were distributed in the pHi range from 7.11 to 7.19, pHi below 7.11 occurred when SvO2 values were more than 40%. AKBR and serum lactate level did not correlate with pHi. CONCLUSION: pHi can be a useful parameter for evaluating the circulatory status of critically ill pediatric patients; it allows reliable evaluation of splanchnic and peripheral perfusion.

Child↗

The beta-lactam antibiotics, penicillin-G and cefoselis have different mechanisms and sites of action at GABA(A) receptors.

The action of the beta-lactam antibiotics, penicillin-G (PCG) and cefoselis (CFSL) on GABA(A) receptors (GABA(A)-R) was investigated using the two-electrode voltage clamp technique and Xenopus oocyte expressed murine GABA(A)-R. Murine GABA(A)-Rs were expressed in Xenopus oocytes by injecting cRNA that encoded for each subunit (alpha1, beta2, and gamma2) and the effects of PCG and CFSL on the alpha1beta2gamma2s subunit receptors were examined using two-electrode voltage clamp. Using the alpha1beta2gamma2s GABA(A)-R, PCG and CFSL inhibited GABA-induced currents in a concentration-dependent manner, with IC(50)s of 557.1+/-125.4 and 185.0+/-26.6 microM, respectively. The inhibitory action of PCG on GABA-induced currents was non-competitive whereas that of CFSL was competitive. Mutation of tyrosine to phenylalanine at position 256 in the beta2 subunit (beta2(Y256F)), which is reported to abolish the inhibitory effect of picrotoxin, drastically reduced the potency of PCG (IC(50)=28.4+/-1.42 mM) for the alpha1beta2(Y256F)gamma2s receptor without changing the IC(50) of CFSL (189+/-26.6 microM). These electrophysiological data indicate that PCG and CFSL inhibit GABA(A)-R in a different manner, with PCG acting non-competitively and CFSL competitively. The mutational study indicates that PCG might act on an identical or nearby site to that of picrotoxin in the channel pore of the GABA(A)-R.

Animals↗

The diverse actions of volatile and gaseous anesthetics on human-cloned 5-hydroxytryptamine3 receptors expressed in Xenopus oocytes.

BACKGROUND: General anesthetics can modulate the 5-hydroxytryptamine type 3 (5-HT3) receptor, which may be involved in processes mediating nausea and vomiting, and peripheral nociception. The effects of the new volatile anesthetic sevoflurane and the gaseous anesthetics nitrous oxide (N2O) and xenon (Xe) on the 5-HT3 receptor have not been well-characterized. METHODS: Homomeric human-cloned 5-HT3A receptors were expressed in Xenopus oocytes. The effects of halothane, isoflurane, sevoflurane, N2O, and Xe on 5-HT-induced currents were studied using a two-electrode, voltage clamping technique. RESULTS: Halothane (1%) and isoflurane (1%) potentiated 1 mum 5-HT-induced currents to 182 +/- 12 and 117 +/- 2%, respectively. In contrast, sevoflurane (1%), N2O (70%), and Xe (70%) inhibited 5-HT-induced currents to 76 +/- 1, 77 +/- 4, and 34 +/- 4%, respectively. The inhibitory effects were noncompetitive for sevoflurane and competitive for N2O and Xe. None of these inhibitory effects showed voltage dependency. CONCLUSION: Inhalational general anesthetics produce diverse effects on the 5-HT3 receptor. Both halothane and isoflurane enhanced 5-HT3 receptor function in a concentration-dependent manner, which is consistent with previous studies. Sevoflurane inhibited the 5-HT3 receptor noncompetitively, whereas N2O and Xe inhibited the 5-HT3 receptor competitively, suggesting the inhibitory mechanism of sevoflurane might be different from those of N2O and Xe.

Algorithms↗

Changes of electroencephalographic bicoherence during isoflurane anesthesia combined with epidural anesthesia.

BACKGROUND: The authors previously reported that, during isoflurane anesthesia, electroencephalographic bicoherence values changed in a fairly restricted region of frequency versus frequency space. The aim of the current study was to clarify the relation between electroencephalographic bicoherence and the isoflurane concentration. METHODS: Thirty elective abdominal surgery patients (male and female, aged 34-77 yr, American Society of Anesthesiologists physical status I-II) were enrolled. After electroencephalogram recording with patients in an awake state, anesthesia was induced with 3 mg/kg thiopental and maintained with oxygen and isoflurane. Continuous epidural anesthesia with 80-100 mg/kg 1% lidocaine was also administered. Using software they developed, the authors continuously recorded the FP1-A1 lead of the electroencephalographic signal and expired isoflurane concentration to an IBM-PC compatible computer. After confirming the steady state of each isoflurane (end-tidal concentration at 0.3, 0.5, 0.7, 0.9, 1.1, 1.3, and 1.5%), electroencephalographic bicoherence values were calculated. RESULTS: In a light anesthetic state, electroencephalographic bicoherence values were low (generally < or = 15.0%). At increased concentrations of isoflurane, two peaks of electroencephalographic bicoherence emerged along the diagonal line (f1=f2). The peak emerged at around 4.0 Hz and grew higher as isoflurane concentration increased until it reached a plateau (43.8 +/- 3.5%, mean +/- SD) at isoflurane 0.9%. The other peak, at about 10.0 Hz, also became significantly higher and reached a plateau (32.6 +/- 9.2%) at isoflurane 0.9%; at isoflurane 1.3%, however, this peak slightly decreased. CONCLUSION: Changes in the height of two electroencephalographic bicoherence peaks correlated well with isoflurane concentration.

Adult↗

[Postoperative management in single-lung transplantation for lymphangioleiomyomatosis].

A 35-yr-old woman presented with dyspnea has been diagnosed as having lymphangioleiomyomatosis (LAM). Despite treatment with estrogen, her pulmonary function deteriorated progressively. In January 2001, a left single-lung transplantation was performed on her from a cadaveric donor. On admission to the ICU after the transplantation, arterial blood gas analysis showed a severe respiratory acidosis. A double-lumen endotracheal tube (ETT) was replaced by a single-lumen ETT for a better suctioning of secretion. Gas exchange improved after the replacement of ETT and suctioning of secretion by bronchoscopy. Five hours after the admission to the ICU, the breath sound decreased over the right thorax. The chest X-ray showed right pneumothorax, and a chest tube was inserted. The patient was weaned from mechanical ventilation gradually and extubated on the 6th ICU day. The patient was discharged from ICU to the general ward on the 9th ICU day without pneumonia and other complications. The development of pneumothorax in the recipient lung should be kept in mind during the perioperative period of lung transplantation for LAM.

Adult↗

[Application of bispectral index (BIS) monitoring to anesthetic management of posterior spinal fusion in a patient with Duchenne muscular dystrophy].

A 12-year-old boy with Duchenne muscular dystrophy underwent posterior spinal fusion for progressive scoliosis. Preoperative evaluation was focused on respiratory function as well as cardiac function, which revealed markedly reduced respiratory reserve (FVC 0.77 l, %FVC 25.9%, FEV1.0 0.48 l, %FEV1.0 62%) and well-preserved biventricular function. A possible association between malignant hyperthermia and Duchenne muscular dystrophy has been documented. Thus anesthesia was administered without triggering agents. Propofol and fentanyl were used for induction and maintenance of anesthesia, and the patient was ventilated with O2-nitrous oxide mixture. The anesthesia machine, prepared by using a disposable circuit and fresh CO2-absorbent and disconnecting the vaporizers, was flushed with O2 at a rate of 10 l.min-1 for 20 minutes before use. A small dose of vecuronium was administered while monitoring the train-of-four ratio. The bispectral index (BIS) was utilized to optimize the depth of anesthesia so that the wake-up test could be performed promptly on surgeon's request while avoiding the intraoperative awareness. The BIS was helpful in continuously assessing the wakening process. BIS increased from 40's to 80's in 15 minutes after discontinuation of propofol and nitrous oxide during the test. The patient was kept under close observation postoperatively without any sign of malignant hyperthermia.

Anesthesia, General↗

In vitro antagonism of recombinant ligand-gated ion-channel receptors by stereospecific enantiomers of bupivacaine.

BACKGROUND AND OBJECTIVES: Bupivacaine is a racemic mixture of S(-)- and R(+)-enantiomers. Both isomers have similar potency as local anesthetics, but the S(-)-enantiomer produces less central nervous system and cardiovascular toxicity. Local anesthetic-induced convulsion is likely to be associated with not only sodium channel but also ligand-gated ion channel. The present study investigates the direct effects of the stereoenantiomers of bupivacaine on 4 recombinant ligand-gated ion-channel receptors. METHODS: The antagonist activities of the S(-)- and R(+)-enantiomers of bupivacaine were tested at the nicotinic acetylcholine, N-methyl-d-aspartate (NMDA), gamma-aminobutyric acid(A) (GABA(A)), and 5-hydroxytryptamine(3A) (5-HT(3A)) receptors expressed in Xenopus oocytes using a 2-voltage clamp technique. RESULTS: Racemic bupivacaine and its 2 enantiomers all antagonized the 4 receptors in a concentration-dependent manner. Potencies at nicotinic acetylcholine, NMDA, and 5-HT(3A) receptors were similar. At GABA(A) receptors, the potency of R(+)-bupivacaine was less than racemic bupivacaine or levobupivacaine. CONCLUSIONS: Comparison of the antagonist potencies with local concentrations obtained in clinical use suggests that bupivacaine and its enantiomers are likely to produce extensive inhibition at the nicotinic acetylcholine, NMDA, and 5-HT(3A) receptors but a much weaker and probably not clinically relevant effect at the GABA(A) receptor. It is possible that direct effects at these receptors may contribute, at least in part, to the spinal and epidural anesthesia induced by these compounds. It is unlikely, however, that the difference of the toxicity in bupivacaine enantiomers is because of the stereoselectivities of bupivacaine at ligand-gated ion-channel receptors studied.

Anesthetics, Local↗