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Biomedical subjects

Katsuya Mikawa

Publications and source records attributed to Katsuya Mikawa.

At least 19 recordsLinked to original sources
PubMed2006

Effects of sivelestat, a new elastase inhibitor, on IL-8 and MCP-1 production from stimulated human alveolar epithelial type II cells.

PURPOSE: The alveolar epithelial cell type II (AEC-II) is itself able to amplify lung inflammation by producing inflammatory cytokines and chemokines, leading to the activation and recruitment of phagocytes. Sivelestat, a new neutrophil elastase inhibitor, has been shown to attenuate acute lung injury in animal experiments. In the current study, we assessed the effects of sivelestat on the production of chemokines from cultured A549 cells, a human AEC-II-like cell line. METHODS: A549 cells were stimulated with endotoxin or tumor necrosis factor-alpha in the presence of sivelestat (1-100 microg x ml(-1)). Culture supernatant levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay. The expression of IL-8 and MCP-1 mRNAs in stimulated A549 cells in the presence of sivelestat (100 microg x ml(-1)) was quantified by real-time polymerase chain reaction. RESULTS: Sivelestat, at 100 microg x ml(-1) reduced the accumulation of IL-8 and MCP-1 in the culture medium. The high dose of sivelestat significantly inhibited the expression of IL-8 mRNA in A549 cells. The drug also decreased MCP-1 mRNA expression, although not significantly. CONCLUSION: These data suggest that a high dose of sivelestat regulates the production of IL-8 and MCP-1 in AEC-II.

Cells, Cultured↗
PubMed2006

Oral clonidine premedication reduces minimum alveolar concentration of sevoflurane for laryngeal mask airway insertion in children.

BACKGROUND: Sevoflurane is widely employed for inhalational induction in children. Clonidine deepens volatile anesthetics and reduces several types of MAC of sevoflurane. Laryngeal mask airway is a useful device for pediatric anesthesia. The aim of the current study was to determine whether oral clonidine premedication can reduce MAC of sevoflurane for an LMA insertion in children. METHODS: Fifty-six ASA physical status I patients (3-11 years) scheduled for general anesthesia were randomly divided into two groups of 28 patients each. One group (clonidine group) received clonidine 4 microg x kg(-1) approximately 100 min before anesthesia, and the other (control) group did not. Anesthesia was induced with sevoflurane. Each concentration of sevoflurane, at which an LMA insertion was attempted, was predetermined according to the modification of Dixon's up-and-down method with 0.25% as a step size and held constant for at least 20 min before the trial. All responses ('movement' or 'no movement') to an LMA insertion were assessed. RESULTS: Minimum alveolar concentration values of sevoflurane for an LMA insertion were lower in the clonidine group (1.31% +/- 0.18% [mean +/- sd]) than in the control group (2.00% +/- 0.16%). Logistic regression analysis revealed that sevoflurane EC95 values were 1.79% and 2.49% in the clonidine and control groups, respectively. CONCLUSIONS: Oral clonidine premedication reduced the MAC (EC50) and EC95 values of sevoflurane for LMA insertion by 38% and 28%, respectively.

Administration, Oral↗
PubMed2005

Attenuation of acute lung injury with propofol in endotoxemia.

Endotoxin causes acute lung injury (ALI) through many mediators of inflammatory and immune responses. Propofol is an antiinflammatory and immunosuppressive drug. We conducted this study to evaluate whether propofol attenuates ALI associated with endotoxemia. Thirty-two anesthetized rabbits were randomly divided into four groups (n = 8 each). ALI was induced by IV endotoxin 5 mg/kg over 30 min in 3 groups. In 2 of the ALI groups, IV administration of propofol (2 or 5 mg/kg as a bolus followed by continuous infusion at 4 or 15 mg x kg(-1) x h(-1)) was started 15 min before endotoxin. The other ALI group received soybean-oil emulsion. The nonlung injury control group received infusion of both vehicles. The lungs were mechanically ventilated with 40% oxygen for 6 h after endotoxin. Hemodynamics did not differ among groups. The large dose of propofol attenuated lung leukosequestration, pulmonary edema (as assessed by lung wet/dry weight ratio), and pulmonary hyperpermeability (as assessed by albumin levels in bronchoalveolar lavage fluid) and resulted in better oxygenation, lung mechanics, and histological change. The small dose of propofol failed to do so. Our findings suggest that a large dose of propofol successfully mitigates physiological, biochemical, and histological deterioration in ALI in endotoxemia.

Animals↗
PubMed2005

The efficacy of fluorocarbon, surfactant, and their combination for improving acute lung injury induced by intratracheal acidified infant formula.

We conducted the current study to compare the efficacy of partial liquid ventilation (PLV), pulmonary surfactant (PSF), and their combination in ameliorating the acidified infant-formula-induced acute lung injury (ALI). In the Part I study, 42 rabbits receiving volume-controlled ventilation with positive end-expiratory pressure 10 cm H(2)O were randomly divided into 6 groups (groups noninjuryI, gas ventilation [GVi], PLVi, PSFi, PLVi-->PSFi, and PSFi-->PLVi). ALI was induced by intratracheal acidified infant formula (2 mL/kg, pH 1.8). Group GVi received neither PLV nor PSF therapy. Groups PLV and PSF received intratracheal fluorocarbon 15 mL/kg or surfactant 100 mg/kg, respectively, 30 min after acidified infant formula. Groups PLVi-->PSFi and PSFi-->PLVi received both treatments at 30-min intervals. In Part II, 42 rabbits (in 6 groups) undergoing pressure-controlled ventilation received the same drug therapies as in Part I. The lungs were excised to assess biochemical and histological damage 150 min after induction of ALI. In Parts I and II, PSF, fluorocarbon, and their combination attenuated lung leukosequestration and edema and superoxide production of neutrophils, consequently improving oxygenation, lung mechanics, and pathological changes. Independent of ventilation mode, PSF followed by fluorocarbon provided the most beneficial effects and fluorocarbon followed by PSF produced the least efficacy.

Acids↗
PubMed2005

[Anesthetic management for Cesarean section in a patient with left ventricular noncompaction].

Left ventricular noncompaction (LVNC) is a rare disease characterized by heart failure, arrhythmia, and embolic events. We report anesthetic management of a pregnant woman with LVNC. At 24 weeks gestation of the first pregnancy, the patient was scheduled for Cesarean section. Preoperatively the patient had symptomatic heart failure, and was anesthetized with propofol and fentanyl aiming at stable intraoperative hemodynamics. About 2 years later, the patient also underwent cesarean section under spinal anesthesia at 34 weeks gestation of the second pregnancy, because her cardiac function was almost normal and she was not receiving anticoagulant therapy. Both perioperative courses were uneventful. Careful preoperative assessment and close anesthetic planning are necessary.

Adult↗
PubMed2004

Efficacy of partial liquid ventilation in improving acute lung injury induced by intratracheal acidified infant formula: determination of optimal dose and positive end-expiratory pressure level.

OBJECTIVES: Partial liquid ventilation with fluorocarbon was successfully used for acute lung injury induced by oleic acid or lung lavage. Positive end-expiratory pressure (PEEP) during partial liquid ventilation enhances the efficacy of fluorocarbon. The aim of the current study was to assess whether partial liquid ventilation can repair lung damage induced by intratracheal acidified infant formula and to determine the optimal fluorocarbon dose and PEEP level. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SETTING AND SUBJECTS: Seventy-six male anesthetized rabbits. INTERVENTIONS: For study 1, acute lung injury was induced by intratracheal acidified infant formula in four groups. Next, three groups received 10, 15, or 20 mL/kg fluorocarbon, and the fourth group was conventionally gas ventilated. For study 2, acute lung injury was induced in five groups. One group was gas ventilated at a PEEP of 5 cm H2O, whereas the other four groups received fluorocarbon (15 mL/kg) and were assigned to one of four PEEP levels (5, 7.5, 10, or 12.5 cm H2O). The lungs were ventilated with 100% oxygen for 4 hrs after acute lung injury. MEASUREMENTS AND MAIN RESULTS: In study 1, fluorocarbon at doses of 15 and 20 mL/kg attenuated lung leukosequestration and edema and superoxide production of neutrophils, resulting in similar improvements in oxygenation, lung mechanics, and pathologic changes. The highest fluorocarbon dose caused mortality from pneumothorax. In study 2, the combination of PEEP with partial liquid ventilation improved gas exchange, lung compliance, pulmonary edema, and histologically observed damage. The beneficial effects of PEEP at 10 and 12.5 cm H2O were similar. Adverse side effects of 12.5 cm H2O PEEP included pneumothorax and hemodynamic instability. CONCLUSIONS: The combination of fluorocarbon and PEEP improved the physiologic, biochemical, and histologic lung injury induced by acidified infant formula. The beneficial effects of partial liquid ventilation are due, in part, to inhibition of pulmonary neutrophil accumulation and activation with fluorocarbon. The optimal fluorocarbon dose and PEEP level in our model were 15 mL/kg and 10 cm H2O, respectively.

Analysis of Variance↗
PubMed2004

Oral clonidine does not change ventilatory response to carbon dioxide in sevoflurane-anesthetized children.

BACKGROUND: Clonidine is a useful premedicant for pediatric anesthesia. The drug has potential for ventilatory depression. The aim of the current study was to determine the effects of clonidine premedication on the ventilatory response to hypercapnia during sevoflurane anesthesia using the carbon dioxide (CO(2)) steady state method. METHODS: Sixty children (3-13 yr) were assigned to receive clonidine 4 microg x kg(-1) or placebo. Anesthesia was maintained with spontaneous breathing and 2% sevoflurane. Minute ventilation (VE), respiratory rate (RR), endtidal CO(2) pressure (P(ECO(2)), and arterial hemoglobin oxygen saturation (SpO2) were measured with a facemask tightly fitted before and during 7% CO(2) inhalation. RESULTS: Compared with placebo, oral clonidine failed to reduce VE volume before CO(2) loading under general anesthesia with 2% sevoflurane. Inhalation of CO(2) increased VE. Oral clonidine did not attenuate the increase in VE induced by hypercapnic challenge under sevoflurane anesthesia. There were no differences in RR, P(ECO(2), or SpO2 between the placebo and clonidine groups before and during CO(2) loading. CONCLUSION: These data suggest that oral clonidine is a suitable premedication for sevoflurane anesthesia under spontaneous breathing conditions in children.

Administration, Oral↗
PubMed2004

Intratracheal application of recombinant surfactant protein-C surfactant to rabbits attenuates acute lung injury induced by intratracheal acidified infant formula.

UNLABELLED: Our aim in the current study was to determine whether recombinant surfactant protein-C (rSP-C) surfactant improves acute lung injury (ALI) induced by intratracheal acidified milk products. Twenty-eight rabbits were randomly divided into four groups. ALI was induced with intratracheal acidified infant formula (0.8 mL/kg, pH 1.8) in 3 groups. The control group received intratracheal acidified saline. Therapy groups received 1 of 2 doses of intratracheal rSP-C surfactant (0.5 or 2 SP-C mg/kg) 30 min after the acidified infant formula. The lungs were ventilated with 100% oxygen for 4 h after induction of ALI. Acidified infant formula dramatically reduced oxygenation and lung compliance, and increased resistance. Both doses of rSP-C improved the variables [mean PaO(2) (mm Hg) and compliance (mL/cm H(2)O) at 4 h: 61 and 0.4 for infant formula, 162 and 1.0 for small-dose rSP-C, and 152 and 1.2 for large-dose rSP-C, respectively; P < 0.05]. Pulmonary leukosequestration and edema, and severe morphological changes were attenuated by rSP-C treatment (ALI score: 14, 7, 7 in infant formula, small-dose rSP-C, and large-dose rSP-C; P < 0.05). The efficacy was similar for the two doses of rSP-C. These findings suggest that intratracheal administration of rSP-C ameliorates ALI induced by aspiration of acidified milk products. IMPLICATIONS: Small or large doses of recombinant surfactant protein-C surfactant given 30 min after intratracheal acidified infant formula attenuated physiological, biochemical, and morphological lung damage.

Airway Resistance↗
PubMed2003

The effects of enflurane, isoflurane, and intravenous anesthetics on rat diaphragmatic function and fatigability.

UNLABELLED: We examined the effect of isoflurane, enflurane, midazolam, ketamine, propofol, and thiopental on diaphragmatic functions under unfatigued and fatigued conditions in 228 rat isolated muscle strips. Diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to one of the anesthetics at clinically relevant plasma concentrations, and at 10 and 100 times this concentration, or at 1, 2, and 3 minimum alveolar anesthetic concentration (MAC). Isoflurane, midazolam, ketamine, propofol, and thiopental did not induce a direct inotropic or lusitropic effect under unfatigued and fatigued conditions. Enflurane did not change contraction or relaxation in fresh isolated diaphragm, but enflurane at 2-3 MAC enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. These effects were greater at 3 MAC than at 2 MAC. Our findings suggest that the reduction of diaphragm function previously reported in in vivo experiments using propofol, midazolam, and isoflurane is not related to a direct effect on intrinsic diaphragmatic contractility. Our results also indicate that large concentrations of enflurane may impair the diaphragmatic function at sites other than excitation-contraction coupling. IMPLICATIONS: Enflurane did not change contraction or relaxation in fresh isolated rat diaphragm, but enhanced diaphragmatic fatigability itself and fatigue-induced impairment of twitch characteristics and tetanic tensions. Isoflurane, midazolam, ketamine, propofol, and thiopental had no direct effects on diaphragmatic functions under unfatigued and fatigued conditions. Isoflurane and these i.v. anesthetics may be advantageous over enflurane to anesthetize and/or sedate patients who are predisposed to diaphragmatic fatigue.

Anesthetics, Inhalation↗
PubMed2003

ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits.

UNLABELLED: Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) expressed in the lung is thought to play a crucial role in the pathogenesis of endotoxin-induced acute lung injury (ALI). In this two-part study, we determined whether ONO-1714, a new selective iNOS inhibitor, attenuates endotoxin-induced ALI in rabbits. For Part I of the study, a control group received IV saline and ALI was induced by IV infusion of endotoxin 5 mg/kg over 30 min in 4 groups. Three groups received either 0.1, 0.03, or 0.01 mg/kg of ONO-1714 10 min before the start of endotoxin and the fourth group received saline. For Part II of the study, ALI was induced by endotoxin infusion in all 6 groups. One group was treated with saline. The other 5 groups received ONO-1714 0.1 mg/kg at various timings (10 min before or 1, 2, 3, or 4 h after ALI induction). The lungs were mechanically ventilated with 40% oxygen for 6 h after induction of ALI. In Part I, pretreatment with 0.1 mg/kg ONO-1714 mitigated endotoxin-induced ALI. In Part II, early posttreatment (within 2 h after the insult) with ONO-1714 was as effective as pretreatment in improving oxygenation, lung mechanics, lung leukosequestration, pulmonary edema, and histological change. However, lung damage was not improved in rabbits receiving the drug 3 or 4 h after endotoxin. These data suggest that the current study is a basis for future clinical trials to elucidate whether ONO-1714 can be a promising therapeutic approach in patients with acute respiratory distress syndrome induced by endotoxin/sepsis. IMPLICATIONS: An excess of nitric oxide is thought to play a crucial role in the pathogenesis of acute organ injury in endotoxemia. Early posttreatment with ONO-1714, a nitric oxide synthase inhibitor, attenuated physiological, biochemical, and pathological changes in endotoxin-induced acute lung injury in rabbits.

Airway Resistance↗
PubMed2002

Accuracy of visual estimation of body height and weight in supine paediatric patients.

BACKGROUND: When it is impossible to measure the weight and height of paediatric patients, these are usually estimated. We undertook this study to see how accurate these estimates are in practice. METHODS: Five observers estimated body height and weight, and subsequently calculated body surface area, in 48 paediatric inpatients who were lying on surgical ward trolleys. RESULTS: Regression analysis of the data revealed that good correlations existed between estimated and actual body size in all the investigators. However, we found large percentage errors in estimation for infants and younger children with small physical size, and a variation in scatter distribution of estimation errors among the five investigators. CONCLUSIONS: These findings suggest the necessity to titrate drug doses for administration in this small paediatric population.

Adjuvants, Anesthesia↗
PubMed2002

The effects of intravenous anesthetics and lidocaine on proliferation of cultured type II pneumocytes and lung fibroblasts.

UNLABELLED: Type II pneumocytes synthesize surfactant and differentiate into type I pneumocytes to maintain the epithelium (1). Alveolar type II cell proliferation is required for reepithelization after acute lung injury (ALI) and is thought to minimize the subsequent fibrotic response (1). Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are among the most potent mitogen for type II epithelial cells, but not for fibroblasts in the lung (1). These growth factors attenuate several experimental ALI models by promoting epithelial repair (2,3). Thus, KGF and HGF may be a promising therapeutic approach to ALI. Critically ill patients with ALI often receive IV anesthetics or sedatives to facilitate mechanical ventilation. Furthermore, these patients sometimes undergo bronchoscopy under local anesthesia to obtain bronchoalveolar lavage fluid or to remove respiratory secretions. Several IV and local anesthetics inhibit proliferation of various cells including epithelium (4,5). If these anesthetics impede proliferation of type II pneumocytes, this suppressive effect may be a disadvantage for alveolar reepithelization in the course of recovery from ALI. In this study, we examined the effects of midazolam, propofol, ketamine, thiopental, and lidocaine on proliferation of type II alveolar epithelial cells using in vitro culture system. Because fibroblast proliferation is a key event in late phase of ALI, inhibition of this fibroproliferation is probably beneficial. Thus, we further determined whether these anesthetics could regulate proliferation of lung fibroblasts. In the current study, rolipram was used as a positive control. In our previous preliminary experiment, we found that rolipram, a phosphodiesterase inhibitor type IV, augments spontaneous or KGF-/HGF-promoted type II cell proliferation (6). IMPLICATIONS: Midazolam, ketamine, thiopental, propofol, or lidocaine did not inhibit proliferation of cultured rat type II pneumocytes. Our findings suggest that these anesthetics do not impede alveolar reepithelization after acute lung injury.

Anesthetics, Dissociative↗
PubMed2002

The efficacy of lafutidine in improving preoperative gastric fluid property: a comparison with ranitidine and rabeprazole.

IMPLICATIONS: Acid aspiration syndrome remains a potentially critical perioperative complication. We compared lafutidine, ranitidine, and rabeprazole for reduction of preoperative gastric fluid acidity and volume in elective surgery and found that these variables were minimized with a single morning dose of lafutidine 20 mg compared with ranitidine or rabeprazole. Preoperative oral lafutidine may be an alternative to ranitidine as a prophylaxis against aspiration pneumonia.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

Efficacy of clonidine for prevention of perioperative myocardial ischemia: a critical appraisal and meta-analysis of the literature.

BACKGROUND: There is a belief that clonidine may be effective in reducing perioperative myocardial ischemic events, although the results of several trials are conflicting. The aim of the current study was to provide a systematic review of randomized controlled trials that tested the efficacy of clonidine in this regard. METHODS: Data was collected from a MEDLINE search of English-language studies published from 1980 to 1999 and a manual search of bibliographies from retrieved articles. A total of 28 studies were assessed. According to the selection criteria (study design, population, intervention, and outcome) and a quality scoring system, seven studies were finally included in the meta-analysis. After homogeneity was established by Q value, the data were then combined using the fixed-effects model. The pooled odds ratio was calculated. A subgroup analysis based on the types of surgery and administration route was also performed to qualify the results. The results were expressed as odds ratio and 95% confidence interval. RESULTS: Heterogeneity of outcome data was negative in the trials. The pooled odds ratio was 0.49 (95% confidence interval 0.34-0.71). In the subgroup analysis, clonidine reduced the incidence of myocardial ischemia in patients undergoing cardiac and noncardiac surgery. Rates of bradycardia were similar in clonidine and placebo groups. CONCLUSION: The meta-analysis suggests that perioperative clonidine reduces cardiac ischemic episodes in patients with known, or at risk of, coronary arterial disease without increasing the incidence of bradycardia. Therefore, these findings strongly justify planning and execution of a definitive study seeking the benefits of clonidine.

Adrenergic alpha-Agonists↗
PubMed2002

Clonidine in paediatric anaesthesia.

PURPOSE OF REVIEW: This review aims to summarize results of recently published studies concerning clonidine application in paediatric anaesthesia, to analyse trends in these studies, and to discuss perspectives of the perioperative use of clonidine for children. RECENT FINDINGS: Reassessment of clonidine premedication has revealed that oral clonidine is inferior to midazolam for preoperative sedation. Oral or intravenous clonidine has been successfully used for the prevention of sevoflurane-induced agitation during emergence from anaesthesia. Peripheral injection or caudal (epidural) administration of clonidine prolonged the duration and enhanced the quality of postoperative analgesia by local anaesthetics without severe side effects. However, some negative results concerning potentiation of postoperative analgesia with clonidine have been reported. SUMMARY: Clonidine may be less favored than midazolam as premedication for children because of inferior clonidine-induced sedation. Additional comparative studies are required, however, to confirm this finding. On the other hand, clonidine-induced analgesia may well be useful and find wide application in paediatric anaesthesia. Prospective multicentre trials using a larger number of patients will be needed to verify the usefulness of caudal clonidine for postoperative pain relief. Prophylactic use of clonidine against sevoflurane-induced agitation may represent a new and promising application. Assessment of the efficacy of clonidine in potentiating regional anaesthesia/analgesia by local anaesthetics in children also needs more investigation. Moreover, it may be worthwhile to try new successful applications demonstrated in adults for paediatric anaesthesia.

Journal Article↗