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Yoshitsugu Yamada

Publications and source records attributed to Yoshitsugu Yamada.

At least 19 recordsLinked to original sources

Age and sex-related differences in dose-dependent hemodynamic response to landiolol hydrochloride during general anesthesia.

OBJECTIVE: Landiolol hydrochloride is a new ultra-short-acting beta(1)-adrenergic receptor blocking agent that is used for patients with tachycardia during general anesthesia. The hemodynamic response to a beta-adrenergic receptor blocking agent is generally dependent on the subject. In the present investigation we investigated the effects of age and sex on the hemodynamic response to different doses of landiolol. METHODS: Following a persistence of tachycardia for more than 1 min, landiolol was infused at 0.03125, 0.0625 and 0.125 mg kg(-1) min(-1) for 1 min followed by 0.01, 0.02 and 0.04 mg kg(-1)min(-1) for 10 min in groups L, M and H, respectively. Heart rate (HR), systolic (sBP) and diastolic blood pressure (dBP) were recorded each minute during the procedure. The respective changes were evaluated using logistic analysis with the equation Y(t) = p + (q - p)/[1 + exp {4m/(q - p))(k - t)}], where p, q, m and k indicate the upper asymptote, lower asymptote, maximum slope and time at the maximum slope. RESULTS: Parameters q and k for HR in group H were smaller than those in group L, whereas the parameters for sBP and dBP were unchanged among the three groups. Parameter q for HR in group H decreased with age of the patient. There was no significant difference in the landiolol-induced change in HR between males and females. CONCLUSION: The hemodynamic response to landiolol is reliably modeled by the logistic function, especially in terms of HR. Landiolol causes a rapid and dose-dependent decrease in HR, whereas landiolol-induced changes in sBP and dBP are independent of dose. The landiolol-induced decrease in HR becomes larger with aging, but shows no sex difference. The logistic model may be useful for studying hemodynamic responses to landiolol based on age and sex differences, and may allow development of an improved monitoring system. IMPLICATION STATEMENT: The logistic function reliably represents the hemodynamic responses to landiolol. Landiolol reduces HR rapidly and in a dose-dependent manner whereas landiolol-induced changes in sBP and dBP are independent of dose. A larger decrease in HR is caused by landiolol in elderly patients, but there is no sex difference in the landiolol-induced change in HR.

Adrenergic beta-Antagonists↗

A1 adenosine receptor-mediated modulation of neuronal ATP-sensitive K channels in rat substantia nigra.

ATP-sensitive K (K(ATP)) channels, widely expressed in cytoplasmic membranes of neurons, couple cell metabolism to excitability. They are considered to play important roles in controlling seizure activity during hypoxia and in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity. It is known that adenosine augments the opening of cardiac surface K(ATP) channels by reducing the sensitivity of these channels to ATP blockade. We investigated whether a similar modulation occurs in neuronal channels. Whole cell voltage-clamp recordings were made using rat midbrain slices to record the membrane current and conductance in principal neurons of the substantia nigra pars compacta (SNc). When the pipette solution contained 1 mM ATP, the membrane current at -60 mV and cellular conductance remained stable for at least 15 min. When slices were treated with (-)-N(6)-2-phenylisopropyl adenosine (R-PIA), a selective agonist for A(1) adenosine receptors, in the same condition, the outward current developed slowly to the amplitude of 109.9+/-26.6 pA, and conductance increased to 229+/-50% of the baseline. These changes were strongly inhibited by 200 microM tolbutamide, a K(ATP) channel blocker, suggesting that opening of K(ATP) channels mediated these changes. Pretreatment with 8-cyclopentyltheophylline (CPT), a selective A(1) adenosine receptor antagonist, abolished the outward current and conductance increases. Treatment of adenosine resulted in the similar changes sensitive to tolbutamide. These changes were abolished by CPT. These results suggest that activation of A(1) adenosine receptors promotes the opening of K(ATP) channels in principal neurons of the SNc by removing the blockade by ATP.

Adenosine↗

High tidal volume ventilation induces lung injury after hepatic ischemia-reperfusion.

Ischemia-reperfusion not only damages the affected organ but also leads to remote organ injuries. Hepatic inflow interruption usually occurs during hepatic surgery. To investigate the influence of liver ischemia-reperfusion on lung injury and to determine the contribution of tidal volume settings on liver ischemia-reperfusion-induced lung injury, we studied anesthetized and mechanically ventilated rats in which the hepatic inflow was transiently interrupted twice for 15 min. Two tidal volumes, 6 ml/kg as a low tidal volume (IR-LT) and 24 ml/kg as a high tidal volume (IR-HT), were assessed after liver ischemia-reperfusion, as well as after a sham operation, 6 ml/kg (NC-LT) and 24 ml/kg (NC-HT). Both the IR-HT and IR-LT groups had a gradual decline in the systemic blood pressure and a significant increase in plasma TNF-alpha concentrations. Of the four groups, only the IR-HT group developed lung injury, as assessed by an increase in the lung wet-to-dry weight ratio, the presence of significant histopathological changes, such as perivascular edema and intravascular leukocyte aggregation, and an increase in the bronchoalveolar lavage fluid TNF-alpha concentration. Furthermore, only in the IR-HT group was airway pressure increased significantly during the 6-h reperfusion period. These findings suggest that liver ischemia-reperfusion caused systemic inflammation and that lung injury is triggered when high tidal volume ventilation follows liver ischemia-reperfusion.

Animals↗

Pre-anesthetic evaluation can play a crucial role in the determination of airway management in a child with oropharyngeal tumor.

We experienced a case of a huge hemangioma occupying the oropharyngeal space in an 11-year-old child. Although urgent surgical tracheostomy under local anesthesia was suggested initially, medical interview and findings of computerized tomography and fiberoptic laryngoscopy revealed that the airway of the patient was relatively stable when she was in the semi-left decubitus position. General anesthetic induction would have had potential risks of airway obstruction. Thus, after placing the patient in the semi-left decubutus position, we chose semi-awake induction to secure the airway. With a small dose of fentanyl, we accomplished orotracheal intubation. In this report, we discuss the importance of referring to an airway management algorithm when encountering a difficult airway.

Airway Obstruction↗

[Acute popliteal arterial occlusion during extracorporeal circulation].

A 79-year-old man underwent aortic arch replacement for thoracic aortic aneurysm. He had a history of smoking, coronary stenting for ischemic heart disease and replacement with artificial blood vessel for abdominal aortic aneurysm. Anesthesia was induced and maintained with midazolam, fentanyl, sevoflurane, and vecuronium. A 20 gage catheter was placed in the right radial artery and a 22 gage catheter in the left posterior tibial artery. Total circulatory arrest under profound hypothermia and retrograde cerebral perfusion were performed using extracorporeal circulation. After finishing anastomosis with artificial blood vessel, he was weaned from extracorporeal circulation. The pressure in the left posterior tibial artery was maintained at 15 mmHg, although the blood pressure in the right radial artery increased gradually. Then, the pressure in the left femoral artery in the operative field was the same as the pressure in the right radial artery. Therefore, we suspected the arterial line occlusion of the left posterior tibial artery. After the operation, we found the left leg and foot pale and cold with no pulsation on the left popliteal, dorsal pedis, and posterior tibial arteries. Further, acute left popliteal arterial occlusion was assessed by means of Doppler and left lower extremity angiography. We immediately performed the balloon-catheter embolectomy. However, as he developed compartment syndrome on the left lower limb due to reperfusion injury postoperatively, fascitomy was performed. On the 58th postoperative day, he was discharged from our hospital. Measurement by Doppler is useful for the early diagnosis of the lower leg arterial occlusion.

Aged↗

Time to change diagnostic criteria of ARDS: towards the disease entity-based subgrouping.

Because of high mortality and morbidity, acute respiratory distress syndrome (ARDS) continues to be one of the clinical challenges for intensivists. The diagnostic criteria for ARDS published by the American-European consensus conference were over simplified and made it possible to conduct large-scale randomized controlled trails (RCTs). Thus, many RCTs have been conducted in attempts to evaluate new treatment modalities, but many have reported negative results, in part because this definition was too broad to be used as diagnostic criteria. Pulmonary ARDS and extrapulmonary ARDS differ in terms of their morbidity and mortality with the presence of organ failure being an important risk factor for mortality in ARDS patients. The Classification of ARDS into several subgroups, which take the underlying disease into account, might limit the number of patients enrolled in an RCT. Where as this subgroup classification would enable selection of a homogeneous population of ARDS patients and may be a key to conducting more focused RCTs and, therefore, having more reliable results.

Humans↗

Expiratory asynchrony.

Expiratory asynchrony is a universal phenomenon, and expiratory synchrony occurs only by chance. Expiratory asynchrony exists in all breath modes and has a significant impact on the patient's work of breathing and the weaning process. Advancements in ventilator designs and basic physiologic science could lead to the improvement of the expiratory asynchrony.

Exhalation↗

Practical range of effective dose for Cre recombinase-expressing recombinant adenovirus without cell toxicity in mammalian cells.

The site-specific recombinase Cre is valuable for regulation of gene expression not only in vitro but also in vivo. We previously reported that replication-deficient recombinant adenovirus (rAd) expressing Cre can mediate efficient and strict regulation in 100% of cultured cells. Recently, the constitutive-expression of Cre using retrovirus or lentivirus vector reportedly inhibited cell-growth, but the effect of transient Cre expression have not yet been examined. Here we showed that an excess amount of Cre produced from Cre-expressing rAd caused a deleterious effect in cells even when Cre was transiently expressed. We used three rAds carrying promoters with different activities: the SV40 early promoter (AxSVENCre), the SR alpha promoter (AxSRCre) and the CAG promoter (AxCANCre). Cell toxicity was clearly caused by Cre itself and was distinguishable from that caused by rAd virions when the cytopathic effects of these rAds were compared with that of a control virus lacking the Cre expression unit. Cre toxicity was strongly correlated with the expression level of Cre. Importantly, AxSRCre and AxCANCre gave a 60-fold range of effective MOIs ("effective range") sufficient for gene activation without causing cell toxicity from either the rAd particles or Cre itself, while AxSVENCre failed to give such a range because the expression level of Cre was too low. When Cre was tagged with a nuclear localization signal (NLS), not only its activity but also Cre toxicity was increased fourfold, and the effective range was unchanged. Therefore, AxSRNCre might be more useful to control cell toxicity from the rAd virions than AxSRCre. Cre-induced cell toxicity can be avoided by pre-examining the "effective range" using the purpose cell lines before starting experiments utilizing the experiment of Cre-expressing rAd.

Adenoviridae↗

PKC-independent inhibition of neuronal nicotinic acetylcholine receptors by diacylglycerol.

Diacylglycerol modulates cell functions primarily through activation of protein kinase C (PKC). In a previous study, however, we found that a diacylglycerol analogue, 1-oleoyl-2-acetylglycerol (OAG), accelerated desensitization of neuronal nicotinic acetylcholine receptors (nAchRs) independently of PKC activation in PC12 cells. In the present study, we investigated whether other analogues and endogenous diacylglycerol exert similar effects on neuronal nAchRs and characterized the modulation by diacylglycerol. We measured the nicotine-induced whole-cell current in the absence and presence of diacylglycerol analogues in PC12 cells. We also investigated the effects of a blockade of metabolic pathways of diacylglycerol by inhibiting diacylglycerol lipase and kinase. We found that all four diacylglycerol analogues studied promoted desensitization and depressed the nondesensitized component of the nicotine-induced current. These effects seemed independent of PKC activation because they were not antagonized by the PKC inhibitors staurosporine or bisindolylmaleimide I; one analogue that lacks the PKC-stimulating action was also effective. The effects of diacylglycerol analogues were not antagonized by high doses of nicotine and were independent of the membrane potential. Similar modulatory effects were observed by treatment with RHC80267, a blocker of diacylglycerol lipase, and R59949, an inhibitor of diacylglycerol kinase, in the presence of staurosporine. These results suggest that diacylglycerol, both exogenously applied and endogenously produced, modulates neuronal nAchRs independently of PKC activation in PC12 cells; further, these effects seemed consistent with a noncompetitive and voltage-independent block. They raised the possibility that PKC-independent inhibition of neuronal nAchRs by diacylglycerol may be a novel modulatory process.

Animals↗

Effect of lung-protective ventilation on severe Pseudomonas aeruginosa pneumonia and sepsis in rats.

Pneumonia caused by Pseudomonas aeruginosa carries a high rate of morbidity and mortality. A lung-protective strategy using low tidal volume (V(T)) ventilation for acute lung injury improves patient outcomes. The goal of this study was to determine whether low V(T) ventilation has similar utility in severe P. aeruginosa infection. A cytotoxic P. aeruginosa strain, PA103, was instilled into the left lung of rats anesthetized with pentobarbital. The lung-protective effect of low V(T) (6 ml/kg) with or without high positive end-expiratory pressure (PEEP, 10 or 3 cmH(2)O) was then compared with high V(T) with low PEEP ventilation (V(T) 12 ml/kg, PEEP 3 cmH(2)O). Severe lung injury and septic shock was induced. Although ventilatory mode had little effect on the involved lung or septic physiology, injury to noninvolved regions was attenuated by low V(T) ventilation as indicated by the wet-to-dry weight ratio (W/D; 6.13 +/- 0.78 vs. 3.78 +/- 0.26, respectively) and confirmed by histopathological examinations. High PEEP did not yield a significant protective effect (W/D, 4.03 +/- 0.32) but, rather, caused overdistension of noninvolved lungs. Bronchoalveolar lavage revealed higher concentrations of TNF-alpha in the fluid of noninvolved lung undergoing high V(T) ventilation compared with those animals receiving low V(T). We conclude that low V(T) ventilation is protective in noninvolved regions and that the application of high PEEP attenuated the beneficial effects of low V(T) ventilation, at least short term. Furthermore, low V(T) ventilation cannot protect the involved lung, and high PEEP did not significantly alter lung injury over a short time course.

Animals↗

Effects of isoflurane and ketamine on ATP-sensitive K channels in rat substantia nigra.

Whole cell recordings were made using midbrain slices to examine the effects of two different anaesthetics on ATP-sensitive K (K(ATP)) channels in principle neurons of rat substantia nigra pars compacta. When neurons were dialyzed with an ATP-free pipette solution during perfusion with a glucose-free external solution, a hyperpolarization and an outward current developed slowly in a tolbutamide-inhibitable manner. The volatile anaesthetic 3% isoflurane slightly depolarised the neurons in the presence of ATP in the pipette solution and glucose in the external solution, but it did not affect the hyperpolarization or outward current in response to omission of ATP and glucose. Ketamine, an intravenous anaesthetic, did not change the membrane potential when ATP and glucose were included; however, it reversibly inhibited the hyperpolarization and outward current induced by intracellular ATP depletion in a dose-dependent manner. These effects of ketamine were not mimicked by AP-5, an NMDA receptor antagonist, or indatraline, an inhibitor of catecholamine uptake. These findings suggest that these anaesthetics have no stimulatory action on K(ATP) channels in these neurons when intracellular ATP is preserved and that ketamine but not isoflurane inhibits K(ATP) channels when the channels were activated by low intracellular ATP.

Adenosine Triphosphate↗

Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan: clinical and immunological findings.

We produced lethally irradiated retrovirally GM-CSF-transduced autologous renal tumor cell vaccines (GVAX) from six Japanese patients with stage IV renal cell cancer (RCC). Four patients received GVAX ranging from 1.4 x 10(8) to 3.7 x 10(8) cells on 6-17 occasions. Throughout a total of 48 vaccinations, there were no severe adverse events. After vaccination, DTH skin tests became positive to autologous RCC (auto-RCC) in all patients. The vaccination sites showed significant infiltration by CD4(+) T cells, eosinophils, and HLA-DR-positive cells. The kinetic analyses of cellular immune responses using peripheral blood lymphocytes revealed an enhanced proliferative response against auto-RCC in four patients, and cytotoxicity against auto-RCC was augmented in three patients. T cell receptor beta-chain analysis revealed oligoclonal expansion of T cells in the peripheral blood, skin biopsy specimens from DTH sites, and tumors. Western blot analysis demonstrated the induction of a humoral immune response against auto-RCC. Two of the four patients are currently alive 58 and 40 months after the initial vaccination with low-dose interleukin-2. Our results suggest that GVAX substantially enhanced the antitumor cellular and humoral immune responses, which might have contributed to the relatively long survival times of our patients in the present study.

Aged↗

[Anesthetic management of a patient with olivopontocerebellar atrophy using heart rate variability (HRV)].

A 65-year-old woman with olivopontocerebellar atrophy (OPCA), manifested with cerebellar ataxia mainly, with coexisting impairment of the autonomic nervous system function, and extrapyramidal symptoms, was scheduled for cholecystectomy. With no premedication, anesthesia was induced with sevoflurane and maintained with 1-1.5% of sevoflurane and 66% of nitrous oxide mixed with oxygen. Heart rate variability (HRV) calculated from ECG was used for a monitor of the autonomic nervous system activity. Before the induction of anesthesia, severe reduction of the HRV parameters suggested that both her sympathetic and parasympathetic nervous activities might have been severely reduced. We considered that the patient might have postganglionic sympathetic nerve hypersensitivity against inotropic agents. When her blood pressure decreased temporarily after the induction of anesthesia, a bolus dose of ephedrine 1 mg wa given intravenously, which stimulated the sympathetic nervous system indirectly, and could increase her blood pressure. Hypotension during anesthesia in a patient with OPCA with severe autonomic nervous failure was successfully treated by a minimal dose of ephedrine.

Aged↗

[Analysis by computer simulation of double breathing during pressure support ventilation].

BACKGROUND: Pressure support ventilation (PSV) usually provides good patient-ventilator synchrony, but asynchrony is sometimes encountered. Double breathing is one form of asynchrony in which the ventilator assists two or more times during a single inspiration of the patient. METHODS: Double breathing was analyzed using a computer simulation. RESULTS: In an obstructive lung model, inspiratory support was terminated just after the beginning of the inspiration lasting until inspiratory effort triggering the ventilator again. One of the causes of this premature termination was that the compressed and consumed volume in the circuit created a high peak inspiratory flow setting. The other cause was oscillation of the airway pressure. Reducing the circuit volume, slowing the inspiratory rise time, or decreasing the termination criteria could prevent this phenomenon. In a restrictive lung model, the time-constant of the lung was so short that the inspiratory flow finished early and double breathing occurred. It was difficult to prevent this phenomenon by adjusting the circuit assembly or respiratory parameters. CONCLUSIONS: Double breathing during PSV was considered to be closely associated with obstructive or restrictive lung. If the problem arises and cannot be resolved by adjusting ventilatory parameters, the ventilatory mode must be changed.

Airway Resistance↗

High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis.

Deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mice results in pulmonary alveolar proteinosis (PAP) from impaired surfactant catabolism by alveolar macrophages (AMs). Recently, we have shown that neutralizing anti-GM-CSF autoantibodies develop specifically in patients with idiopathic pulmonary alveolar proteinosis (iPAP). Analogous to murine PAP models, it is plausible that the autoantibodies reduce GM-CSF activity, resulting in AM dysfunction and surfactant accumulation. To examine this hypothesis, we estimated the neutralizing activity of the autoantibodies in the lungs of patients and characterized their biologic properties. GM-CSF bioactivity was completely abrogated in the bronchoalveolar lavage fluid (BALF) of patients with iPAP but not in healthy subjects. Autoantibodies were present in the alveoli in high concentrations and colocalized with GM-CSF. They recognized human GM-CSF with high avidity (K(AV) = 20.0 +/- 7.5 pM) and high specificity, reacting with its superstructure and neutralizing GM-CSF activity to a level 4000 to 58 000 times the levels of GM-CSF normally present in the lung. Although target epitopes varied among patients, GM-CSF amino acids 78 to 94 were consistently recognized. Thus, autoantibodies bind GM-CSF with high specificity and high affinity, exist abundantly in the lung, and effectively block GM-CSF binding to its receptor, inhibiting AM differentiation and function. Our data strengthen the evidence associating anti-GM-CSF autoantibodies with the pathogenesis of this disease.

Adult↗

Spectral analyses of electroencephalography and heart rate variability during sleep in normal subjects.

We investigated the relationship between electroencephalogram (EEG) activity and autonomic nervous system function using spectral analyses of EEG and heart rate variability (HRV) in healthy subjects during sleep. Eleven subjects were enrolled in this study. From EEG, the spectral edge frequencies (SEFs including SEF50, SEF90 and SEF95) were calculated. From electrocardiogram (ECG), the spectral powers of low-frequency band (LF: 0.04-0.15 Hz), high-frequency band (HF: 0.15-0.4 Hz) and the ratio of LF to HF (LF/HF) were calculated. During sleep, each set of data was obtained as the average of a 5-min measurement. We found that SEFs and LF/HF or LF decreased simultaneously and periodically, suggesting simultaneous depression of EEG activity and relative sympathetic activity, and SEFs significantly correlated with LF/HF and LF in all subjects during sleep, but not with HF. The existence of a clear correlation of SEFs with LF or LF/HF may offer a simple approach to estimate the relationship between EEG activity and autonomic nervous system function during sleep.

Adult↗

Neural mechanism of propofol anesthesia in severe depression: a positron emission tomographic study.

BACKGROUND: The precise neural mechanisms of propofol anesthesia in humans are still unknown. The authors examined the acute effects of propofol on regional cerebral blood flow (rCBF) using positron emission tomography in patients with severe depression. METHODS: In six severely depressed patients (mean age, 55.0 yr) scheduled for electroconvulsive therapy, anesthetic levels were monitored by electroencephalography, and rCBF was serially quantified in the awake, sedated, and anesthetized states. The authors used high-resolution positron emission tomography with 15O-labeled water and statistical parametric mapping 99 for imaging and analysis of the data. RESULTS: Global cerebral blood flow showed sharp decreases from the awake level during the administration of propofol, decreasing 26.8% in the sedated state and 54.4% in the anesthetized state. Moreover, a dose effect was seen in both parietal cortices and the left lateral prefrontal region with larger regions of relative decrease in rCBF at higher propofol doses. At the higher dose, the values of rCBF in the pulvinar nucleus of the thalamus, the pontine tegmentum, and the cerebellar cortex were also affected. Meanwhile, there were few changes of relative rCBF in the basal frontal lobes during both sedated and anesthetized states. CONCLUSIONS: As in earlier studies using normal subjects, pronounced suppression in rCBF in the brain stem reticular formation, the thalamus, and the parietal association cortex occurred even in severely depressed patients. However, previously reported decreases in rCBF in the basal frontal lobe were absent in depressed patients.

Adult↗