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Biomedical subjects

F Kosaka

Publications and source records attributed to F Kosaka.

At least 19 recordsLinked to original sources

Albumin-binding superoxide dismutase with a prolonged half-life reduces reperfusion brain injury.

To test the possible involvement of superoxide radicals in the pathogenesis of reperfusion injury, we synthesized a superoxide dismutase (SOD) derivative [poly(styrene-co-maleic acid) butyl ester (SM) covalently linked to SOD] that circulates bound to albumin, has a prolonged in vivo half-life, and accumulates in pH-decreased tissues. The protective effects of SM-SOD on regional cerebral blood flow, intracranial pressure, cardiac index, vascular permeability, and neurological outcome were investigated using a model of global brain ischemia in dogs. Intra-arterial injection of SM-SOD (10 mg/kg) just before reperfusion increased reactive hyperemia (SM-SOD, 160 +/- 36 ml.100 g-1.min-1, means +/- SD, n = 6; control, 100 +/- 34 ml.100 g-1.min-1, n = 6, P = 0.015), ameliorated delayed hypoperfusion (7 h after ischemia: SM-SOD, 40 +/- 14 ml.100 g-1.min-1; control 17 +/- 6 ml.100 g-1.min-1, P = 0.003), vascular permeability, and neurological outcome without affecting the cardiac index. These results indicate that superoxide radicals and/or their metabolite(s) might play a critical role in the pathogenesis of reperfusion injury in the brain.

Animals↗

Effectiveness of pressure support ventilation for mechanical ventilatory support in patients with status asthmaticus.

We compared the effects of pressure support ventilation (PSV) with those of assist control ventilation (ACV) on breathing patterns and blood gas exchange in six patients with status asthmaticus. Both PSV and ACV delivered adequate minute ventilation (PSV: 7.5 +/- 1.4 l/min/m2, ACV: 7.3 +/- 1.3 l/min/m2) to correct respiratory acidosis (pH = 7.33 +/- 0.12 during both PSV and ACV) and prevent hypoxia. Peak airway pressure during PSV was significantly lower with the same tidal volume than that during ACV (PSV: 30 +/- 10 cmH2O (2.9 +/- 1.0 kPa), ACV: 50 +/- 13 cmH2O (4.9 +/- 1.3 kPa)). The lower airway pressure during PSV was due to persistent inspiratory muscle activity. The oxygen cost of breathing estimated by oxygen consumption was equivalent in both modes. We conclude that PSV is effective in supplying tidal volumes adequate to improve hypercarbia at markedly lower airway pressures than ACV.

Adolescent↗

Bacterial endotoxin-induced expression of metallothionein genes in rat brain, as revealed by in situ hybridization.

In order to clarify acute-phase response in brain, we investigated induction of metallothionein (MT) genes by administrating an endotoxin (lipopolysaccharide) in rat intraperitoneum. We performed in situ hybridization on the serial brain sections to identify the cells expressing the MT genes in acute-phase. After endotoxin administration, transcripts of MT genes were detected in the arachnoideal, ependymal cells and glial cells around the Purkinje cells of the cerebellum, while no significant induction of the MT genes by zinc ion was observed in brain. These results suggest that the acute-phase response occurs specifically in at least these 3 non-neuronal cells.

Acute-Phase Proteins↗

Frequency- and length-dependent tension development in rat heart muscles exposed to isoflurane and halothane.

Using 22 isolated rat ventricular muscle preparations, we investigated whether or not the increase in preload and/or contraction frequency may counteract the negative inotropy of both isoflurane (2.0%) and halothane (1.0%). Increases in preload from 94% of Lmax (the length where muscles produce the maximal tension) to Lmax did not alter significantly the percent decrements in tension development caused by either isoflurane or halothane. The increases in contraction frequency from 0.1 to 0.6 Hz augmented the depressant effect of isoflurane significantly ( P < 0.001), while the depressant effect of halothane was not altered at these contraction frequencies. Small but significant counteraction occurred in the depressant effects of halothane at 0.8 and 1.6 Hz ( P = 0.002). These changes in intracellular mechanism(s), resulted from the increase in contraction frequency, interacted with the two anesthetics on tension development, while these may not be the case for the increase in preload.

Journal Article↗

Pretreatment with d-tubocurarine, vecuronium, and pancuronium attenuates succinylcholine-induced increases in plasma norepinephrine concentrations in humans.

We studied in patients the effect of d-tubocurarine, which has sympathetic ganglion blocking action, on succinylcholine-induced increases in plasma levels of catecholamines, and compared it with the effects of vecuronium and pancuronium, which have little sympathetic ganglion blocking action. Thirty-two patients were divided into five groups: seven were given 3 mL saline; seven received 1 mg/kg succinylcholine; and six, seven, and five patients were given 0.08 mg/kg d-tubocurarine, 0.01 mg/kg vecuronium, and 0.01 mg/kg pancuronium, respectively, all of which were injected 5 min before 1 mg/kg succinylcholine. Succinylcholine alone significantly increased plasma norepinephrine concentrations, systolic blood pressure, and heart rate from 187 +/- 39 pg/mL (mean +/- SEM), 93 +/- 2 mm Hg, and 77 +/- 4 beats/min to 429 +/- 61 pg/mL, 120 +/- 7 mm Hg, and 102 +/- 6 beats/min, respectively, with onset of fasciculations. Pretreatment with d-tubocurarine, vecuronium, and pancuronium significantly and equally attenuated both the fasciculations and the cardiovascular responses to succinylcholine. These results suggest that the sympathetic ganglion blocking action of neuromuscular relaxants when given before succinylcholine is not an important factor in attenuation of succinylcholine-induced increases in plasma levels of catecholamines.

Adult↗

[Is airway occlusion pressure useful to predict successful weaning from mechanical ventilation in patients with acute respiratory failure?].

The purpose of this study was to evaluate whether airway occlusion pressure (P0.1) would be a useful predictor for successful weaning in mechanically ventilated patients with acute respiratory failure. We studied 23 marginal weaning candidates. Fourteen patients were able to be weaned from the ventilator, and 9 patients were not able to be weaned. P0.1 and other respiratory parameters were measured just prior to weaning and at the end of weaning or at the time of discontinuation of weaning. The mean value of P0.1 in the failed group was higher than that in the successful group both before and after weaning periods. However, P0.1 varied widely among patients and did not separate the failure group from the success group because of overlap between the two. There were significant differences between the two groups of the conventional weaning parameters, such as respiratory rate, minute ventilation, PaO2, and oxygen equivalent. We conclude that P0.1 is helpful to predict successful weaning. However, it can not be used as a single parameter for weaning because of the wide variations of absolute values among patients with acute respiratory failure.

Acute Disease↗

Synergistic and additive induction of metallothionein in Chang liver cells. A possible mechanism of marked induction of metallothionein by stress.

We have studied metallothionein (MT) induction by three primary inducers; a heavy metal, a glucocorticoid and a cytokine, and by the combinations of these inducers in the cultured cells. MT-protein was synergistically induced by either a cytokine or a heavy metal with a glucocorticoid hormone and was additively induced by the combination of a cytokine and a heavy metal, but MT-mRNA levels were not completely correlated with MT-protein levels. These results suggest that posttranscriptional regulation may be involved in the synergistic induction of MT-protein. We propose a possible mechanism in which marked MT induction by stress in vivo is dependent on the combined effect of two or more inducers, because marked MT induction is not seen by an injection of a plausible dose of either a glucocorticoid hormone or a cytokine in vivo.

Blotting, Northern↗

Histological changes of neuronal damage in vegetative dogs induced by 18 minutes of complete global brain ischemia: two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells.

We have developed a functional vegetative model by an 18-min clamping of the ascending aorta combined with a bypass formation between the aorta to right atrium and the aorta to femoral vein. Complete global brain ischemia (CGBI) induced for 18 min with this model provided the following distinct advantages: cardiopulmonary functions were well preserved during postischemic recirculation, and all dogs survived without serious extracerebral complications. Neuronal damage in vegetative dog induced by an 18-min CGBI was studied by light and electron microscopy. The Purkinje cells and the hippocampal CA1 pyramidal cells showing clumping of nuclear chromatin and slightly increased stainability were observed after CGBI without recirculation. All these neurons showed transient increased stainability with microvacuolation 15 min after recirculation. Over 50% of these neurons showed virtually normal features 1 h after recirculation. Damage to these neurons progressed again slowly up to 6 h after recirculation. However, all these neurons had disintegrated 2-3 days after recirculation. A decrease in synaptic vesicles was observed in many presynaptic terminals in the molecular layers of the cerebellum after CGBI without recirculation. These changes in the presynaptic terminals progressed 15 min after recirculation. These results indicated that the damage to the Purkinje cells and the CA1 pyramidal cells induced by CGBI consisted of two phases, and that the change in the early phase was reversible. We speculate that the damage to the Purkinje cells in the early stage is related to the decrease of the synaptic vesicles in the presynaptic terminals.

Animals↗

Neuromuscular effects of respiratory and metabolic acid-base changes in vitro with and without nondepolarizing muscle relaxants.

The effects of metabolic (bicarbonate, [HCO3]) and respiratory (carbon dioxide, PCO2) acid-base changes on indirectly elicited twitch tension with and without nondepolarizing neuromuscular blocking agents were compared in a rat phrenic nerve-hemidiaphragm preparation. Ionized calcium [Ca2+] and magnesium [Mg2+] concentrations in the modified Krebs' solution were measured and kept constant. Likewise, twitch was altered when pH changes were produced by altering either PCO2 or [HCO3]. Decreasing pH either by increasing PCO2 or by decreasing [HCO3] significantly decreased (P less than 0.01) twitch, by 9.5 +/- 0.6 (SEM, n = 8) and 10.6 +/- 1.5%, respectively. Increasing pH by decreasing PCO2 or by increasing [HCO3] significantly increased (P less than 0.01) twitch, by 5.6 +/- 0.9 and 7.9 +/- 0.6%, respectively. After a partial depression of twitch by nondepolarizing neuromuscular blocking agents, the effects of PCO2 and [HCO3] changes were again assessed. Decreasing pH by increasing PCO2 or by decreasing [HCO3] intensified d-tubocurarine (dTc) (28.2 +/- 1.6 and 32.0 +/- 2.9%, respectively) and vecuronium (23.0 +/- 1.4 and 36.8 +/- 3.2%, respectively) block, whereas it reversed metocurine (1.2 +/- 2.2% NS and 2.9 +/- 1.3%, respectively) and pancuronium (8.3 +/- 1.5 and 11.5 +/- 3.0%, respectively) block. Conversely, increasing pH by decreasing PCO2 or by increasing [HCO3] antagonised dTc (12.8 +/- 2.2 and 13.6 +/- 1.8%, respectively) and vecuronium (25.3 +/- 1.7 and 25.0 +/- 3.0%, respectively) block, whereas it potentiated metocurine (4.2 +/- 0.6 and 8.0 +/- 1.1%, respectively) and pancuronium (11.0 +/- 1.2 and 17.5 +/- 2.0%, respectively) block. Except where indicated, all changes in block described above were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Imbalance↗

Efficacy of flow-by during continuous positive airway pressure ventilation.

We investigated clinically the differences in respiratory work of patients imposed by three modes of one ventilator: the flow-by system, the demand valve system, and the pressure support system. Inspiratory work using flow-by and pressure support systems was reduced sufficiently when compared to the demand valve system. Moreover, fluctuation of the airway pressure was minimal with the flow-by mode. These results suggest that the flow-by mode is beneficial to patients breathing spontaneously with continuous positive airway pressure.

Aged↗

Interaction of sevoflurane, isoflurane, enflurane and halothane with non-depolarizing muscle relaxants and their prejunctional effects at the neuromuscular junction.

The interaction of four inhalational anesthetics (sevoflurane, isoflurane, enflurane and halothane) with pancuronium and vecuronium and also their prejunctional actions at the neuromuscular junction were quantitatively studied using rat phrenic nerve-hemidiaphragm preparations. To investigate the prejunctional effects of inhalational anesthetics, a train-of-four ratio (T4/T1) and the tetanus ratio (the ratio of the final response to the initial response during tetanus) were evaluated. All four inhalational anesthetics markedly potentiated the neuromuscular blockade of twitch response caused by either pancuronium or vecuronium with halothane and enflurane being the most potent both on a % concentration basis and on a MAC (minimum alveolar concentration) basis. Although none of the four inhalational anesthetics had any effects on the T4/T1 ratio, they produced variable effects on the tetanus ratio. Sevoflurane had little effect on the tetanus ratio, whereas 1 and 2% isoflurane and 1, 2 and 3% enflurane increased the tetanus ratio and 5% halothane and 5% enflurane significantly reduced the tetanus ratio. Halothane and enflurane had the most potent depressant action of the four inhalational anesthetics both on the % concentration basis and on the MAC basis. These results indicate that the main site of action of inhalational anesthetics is a postjunctional site at the neuromuscular junction and that they do not seem to act on prejunctional sites at the concentrations used in clinical situations.

Anesthetics↗

[The effect of pressure support ventilation on breathing patterns and the work of breathing].

We assessed breathing patterns during pressure support ventilation (PSV) and its relationship with the work of breathing in 10 postoperative patients. With increasing levels of pressure support, minute ventilation and tidal volume increased with a decrease in respiratory frequency. Increased minute ventilation was achieved by increased mean inspiratory flow. Duty cycle, however, decreased with PSV. This decrease might allow the diaphragm a longer rest period between contractions, which might decrease the risk of diaphragmatic fatigue. Furthermore, PSV reduced the inspiratory work added by a ventilator to near zero. Oxygen consumption was also decreased with PSV. We conclude that PSV improved the breathing patterns and minimized the work of breathing spontaneously via a ventilator.

Adult↗

Involvement of transforming growth factor-alpha secreted by macrophages in metallothionein induction by endotoxin.

The mechanism of metallothionein (MT) induction of the liver by endotoxin, which is mediated by a factor secreted by endotoxin-stimulated macrophages, was studied in vitro. MT induction of the liver cells by the endotoxin-stimulated macrophage conditioned medium was inhibited by a monoclonal antiepidermal growth factor (EGF) / transforming growth factor-alpha (TGF-alpha) receptor antibody, which acts as an antagonist of EGF and TGF-alpha. MT was induced by the substance, which was adsorbed by polyclonal antibody to TGF-alpha, but not by a monoclonal antibody to EGF, in the conditioned medium of endotoxin-stimulated macrophages. These results suggest that TGF-alpha secreted by macrophages is involved in MT induction by endotoxin.

Animals↗

Comparison of pressure support ventilation and assist control ventilation in patients with acute respiratory failure.

We compared the effects of pressure support ventilation (PSV) with those of assist control ventilation (ACV) on the breathing pattern, work of breathing and blood gas exchange in 8 patients with acute respiratory failure. During ACV, the tidal volume was set at 10 ml/kg, and the inspiratory flow was set at 50 to 70 l/min. During PSV, the pressure support level selected was 27 +/- 5 cm H2O to make the breathing pattern regular. Tidal volume was significantly higher (908 +/- 179 ml vs. 633 +/- 96 ml) during PSV than during ACV at a lower peak airway pressure. Respiratory frequency was lower (15 +/- 4 breaths/min vs. 24 +/- 5 breaths/min) during PSV than during ACV, associated with a lower duty cycle, which improved synchrony between the patient and the ventilator. The oxygen cost of breathing, an estimate based on the inspiratory work added by a ventilator and the oxygen consumption, did not change significantly. PaO2 was significantly higher during PSV than during ACV. We conclude that PSV using high levels of pressure support can improve the breathing pattern and oxygenation and fully sustain the patient's ventilation while matching his inspiratory efforts.

Adult↗

Effect of pressure support ventilation on breathing patterns and respiratory work.

We assessed the effect of pressure support ventilation (PSV) on breathing patterns and the work of breathing in 10 postoperative patients. Minute ventilation (VE) increased by 8% with 5 cm H2O PSV and 10% with 10 cm H2O PSV compared to 0 cm H2O PSV. The increase in VE was achieved by increased mean inspiratory flow (24% with 5 cm H2O PSV and 67% with 10 cm H2O PSV) and a decrease in duty cycle (13% with 5 cm H2O PSV and 39% with 10 cm H2O PSV). The decrease in duty cycle along with a decrease in respiratory frequency allowed a greater expiratory time including a rest period for the respiratory muscles, which might minimize the risk of muscle fatigue. Furthermore, the inspiratory work added by the ventilator was near zero with 5 cm H2O PSV and 10 cm H2O PSV. Oxygen consumption also decreased significantly with 5 cm H2O PSV. We conclude that PSV improves the breathing patterns and minimizes the work of breathing spontaneously via a ventilator.

Adult↗

Elevation in metallothionein messenger RNA in rat tissues after exposure to X-irradiation.

Metallothionein (MT) mRNA levels in tissues were measured in rats following whole-body X-irradiation (2 and 20 Gy). When compared with control rats, the elevation in MT mRNA levels of liver, kidney, and thymus was observed in irradiated rats at 9 or 72 hr after irradiation. However, the elevation in MT mRNA levels was not observed in brain, spleen, lung, heart, and testis. When compared with other tissues, testicular MT mRNA levels in control rats were extremely high, and treatment with X-irradiation produced a slight decrease of testicular MT mRNA levels. Time-course experiments indicated that hepatic and renal MT mRNA reached a maximum at 6 hr after irradiation. In low-dose (2 Gy) irradiated rat, these values were returned to control values by 4 days after irradiation. However, in high-dose (20 Gy) irradiated rat, the values were not decreased to control values. These data indicate that treatment with X-irradiation produces an elevation in MT mRNA in rat tissues.

Animals↗

Influence of suxamethonium on the action of subsequently administered vecuronium or pancuronium.

The effects of suxamethonium were studied on the onset time and duration of action of vecuronium or pancuronium in 45 adult patients anaesthetized with halothane and nitrous oxide. After an intubating dose of suxamethonium, the force of the evoked twitch returned to a value greater than control. The onset of the reduction in force produced by subsequent administration of vecuronium or pancuronium was faster and recovery slower. This potentiating effect of suxamethonium persisted for at least 2 h.

Adolescent↗