Biomedical subjects

Akira Asada

Publications and source records attributed to Akira Asada.

29 records · Page 2Linked to original sources

PubMed2004

Pharmacokinetics and pharmacodynamics of olprinone after cardiac surgery.

BACKGROUND: Phosphodiesterase type III inhibitors are often delivered by continuous intravenous infusion without initial loading to prevent hypotension, i.e., by "slow induction". We evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of olprinone slow induction after open-heart surgery. METHODS: Olprinone was infused at a rate of 0.2 microg x kg(-1) x min(-1) in seven patients post operatively after elective cardiac surgery. Olprinone plasma concentration was determined by HPLC. PK parameters were calculated from concentrations at 90 and 180 minutes after start of infusion. PD data were analyzed by collected E(max) model using SAAMII PC programs. RESULTS: Systemic vascular resistance index initially decreased about 20 ng/mL and then cardiac index increased. Initially, a vasodilating effect occurs and then inotropic effect follows. Systemic hypotension may induced by the different EC50 between inotropic and vasodilating action. Moreover, much vasodilating effect will be observed with olprinone than with milrinone, based on our previous data. CONCLUSIONS: Olprinone slow induction is useful and safe for critically ill patients.

Aged↗

PubMed2003

The P-glycoprotein inhibitor quinidine decreases the threshold for bupivacaine-induced, but not lidocaine-induced, convulsions in rats.

PURPOSE: To examine whether inhibition of P-glycoprotein (P-gp) activity by quinidine affects the central nervous system toxicity of lidocaine and racemic bupivacaine (bupivacaine). METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10). Fifteen minutes following administration of 15 mg x kg(-1) of quinidine (QL and QB groups) or saline (L and B groups), lidocaine (L and QL groups, 4 mg x kg(-1) x min(-1)) or bupivacaine (B and QB groups, 1 mg x kg(-1) x min(-1)) was infused until convulsions occurred. Concentrations of lidocaine and its primary metabolite, monoethylglycinexylidide (MEGX) and bupivacaine in plasma and in the brain at the onset of convulsions were measured by high-performance liquid chromatography. RESULTS: There were no differences in the dose of lidocaine required to induce convulsions between the L and QL groups. There were no differences in the concentrations of total (L = 17.2 +/- 3.5, QL = 16.6 +/- 2.6 micro g x mL(-1)) or unbound lidocaine (L = 7.8 +/- 2.5, QL = 7.3 +/- 2.3 micro g x mL(-1)), total (L = 1.2 +/- 0.5, QL = 1.3 +/- 0.7 micro g x mL(-1)) or unbound MEGX (L = 0.9 +/- 0.5, QL = 0.8 +/- 0.4 micro g x mL(-1)) in plasma, total lidocaine or MEGX in the brain at the onset of convulsions between the L and QL groups. The dose of bupivacaine required to induce convulsions was comparable in the B and QB groups. At the onset of convulsions, plasma concentrations of both total (B = 4.9 +/- 1.1, QB = 4.0 +/- 0.6 micro g x mL(-1), P = 0.03) and unbound bupivacaine (B = 1.4 +/- 0.6, QB = 0.9 +/- 0.2 micro g x mL(-1), P = 0.02) were significantly lower in the QB group than in the B group. There were no differences in concentration of total bupivacaine in the brain between the B and QB groups. CONCLUSION: These results suggest that quinidine inhibited P-gp activity, resulting in increased brain/plasma concentration ratio of bupivacaine, but not of lidocaine, and decreased the threshold of plasma concentration for bupivacaine-induced convulsions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Anesthesia induction for a difficult intubation infant with a laryngeal cyst.

We report a case of difficult airway in a 37-day-old female with a laryngeal cyst during induction of general anesthesia. This case illustrates that upper airway obstruction can occur during induction of anesthesia with an unusual infantile aryepiglottic fold cyst. In this case, successful orotracheal intubation was achieved with spontaneous respiration, and preoperative information on orientation of the lesion assisted in positioning the patient to minimize the degree of dynamic obstruction.

Airway Obstruction↗

PubMed2003

Non-genomic modulation of dopamine release by bisphenol-A in PC12 cells.

An endocrine disruptor chemical, bisphenol-A (BPA), is reported to have several short-term actions in various tissues and/or cells; however, the mechanisms of these actions have not been fully elucidated. We investigated short-term actions evoked by BPA in pheochromocytoma PC12 cells. BPA elicited dopamine release in PC12 cells in a dose-dependent manner. A selective N-type calcium channel antagonist (omega-conotoxin GVIA) and a ryanodine receptor blocker (ryanodine) inhibited the BPA-induced dopamine release. The expression of ryanodine receptor mRNA was detected by RT-PCR in PC12 cells. Subsequently, in order to prove whether membrane receptors participate in BPA-evoked dopamine release, a guanine nucleotide-binding protein inhibitor [guanosine 5'-(beta-thio) diphosphate], cyclic AMP antagonist (Rp-cAMPS) or protein kinase A inhibitor (H7 or H89) was added to PC12 cells prior to BPA-treatment. All of these agents suppressed BPA-evoked dopamine release, indicating that multiple signaling pathways may be involved in BPA-evoked dopamine release in PC12 cells. In conclusion, we demonstrated that BPA induced dopamine release in a non-genomic manner through guanine nucleotide-binding protein and N-type calcium channels. These findings illustrate a novel function of BPA and suggest that exposure to BPA influences the function of dopaminergic neurons.

Animals↗

PubMed2003

Converting enzyme inhibitor temocaprilat prevents high glucose-mediated suppression of human aortic endothelial cell proliferation.

We examined the involvement of the oxidative stress in high glucose-induced suppression of human aortic endothelial cell proliferation. Chronic glucose treatment for 72 h concentration-dependently (5.6-22.2 mol/l) inhibited human coronary endothelial cell proliferation. Temocaprilat, an angiotensin-converting enzyme inhibitor, at 10 nmol/l to 1 micromol/l inhibited high glucose (22.2 mmol/l)-mediated suppression of human aortic endothelial cell proliferation. Temocaprilat at 1 micromol/l inhibited high glucose-induced membrane-bound protein kinase C activity in human aortic endothelial cells. The protein kinase C inhibitors calphostin C 100 nmol/l or chelerythrine 1 micromol/l inhibited high glucose-mediated suppression of human aortic endothelial cell proliferation. Chronic high glucose treatment for 72 h increased intracellular oxidative stress, directly measured by flow cytometry using carboxydichlorofluorescein diacetate bis-acetoxymethyl ester, and this increase was significantly suppressed by temocaprilat 10 nmol/l to 1 micromol/l. Bradykinin B2 receptor antagonist icatibant 100 nmol/l significantly reduced the action of temocaprilat; whereas bradykinin B1 receptor antagonist des-Arg9-Leu8-bradykinin 100 nmol/l had no effect. These findings suggest that high glucose inhibits human aortic endothelial cell proliferation and that the angiotensin-converting enzyme inhibitor temocaprilat inhibits high glucose-mediated suppression of human aortic endothelial cell proliferation, possibly through suppression of protein kinase C, bradykinin B2 receptors and oxidative stress.

Alkaloids↗

PubMed2003

Epidural clonidine suppresses the baroreceptor-sympathetic response depending on isoflurane concentrations in cats.

Epidural administration of clonidine induces hypotension and bradycardia secondary to decreased sympathetic nerve activity. In this study, we sought to elucidate the change in baroreflex response caused by epidural clonidine. Thirty-six cats were allocated to six groups (n = 6 each) and were given either thoracic epidural clonidine 4 micro g/kg or lidocaine 2 mg/kg during 0.5, 1.0, or 1.5 minimum alveolar anesthetic concentration (MAC) isoflurane anesthesia. Heart rate (HR), mean arterial blood pressure (MAP), and cardiac sympathetic nerve activity (CSNA) were measured. Depressor and pressor responses were induced by IV nitroprusside 10 micro g/kg and phenylephrine 10 micro g/kg, respectively. Baroreflex was evaluated by the change in both CSNA and HR relative to the peak change in MAP (deltaCSNA/deltaMAP and deltaHR/deltaMAP, respectively). These measurements were performed before and 30 min after epidural drug administration. Epidural clonidine and lidocaine decreased HR, MAP, and CSNA by similar extents. deltaCSNA/deltaMAP and deltaHR/deltaMAP for depressor response were suppressed with epidural lidocaine and clonidine in all groups but the clonidine 0.5 MAC isoflurane group (0.197 +/- 0.053 to 0.063 +/- 0.014 and 0.717 +/- 0.156 to 0.177 +/- 0.038, respectively, by epidural lidocaine [P < 0.05] but 0.221 +/- 0.028 to 0.164 +/- 0.041 and 0.721 +/- 0.177 to 0.945 +/- 0.239, respectively, by epidural clonidine during 0.5 MAC isoflurane). Those for pressor response were suppressed in all groups. We conclude that thoracic epidural clonidine suppresses baroreflex gain during isoflurane anesthesia >1.0 MAC but may offer certain advantages compared with epidural lidocaine during 0.5 MAC isoflurane by virtue of preserving baroreflex sensitivity when inadvertent hypotension occurs.

Acidosis↗

PubMed2002

Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite and concentrations of antioxidants in plasma.

BACKGROUND: Cigarette smoking is a well-known risk factor for the development of cardiovascular disease, yet the mechanism of action involved is not completely understood. Because cigarette smoke contains superoxide and other reactive oxygen species, it has been hypothesized that some of the adverse effects of smoking may result from oxidative damage to endothelial cells, which results in nitric oxide (NO) shortage. However, little information is available regarding the acute effects of smoking on plasma concentrations of NO and antioxidants. We measured the changes in the combined plasma concentrations of nitrate and nitrite as an index of NO concentration, as well as changes in concentrations of major serum antioxidants (ascorbic acid, cysteine, methionine, and uric acid) in smokers after smoking a single cigarette. METHODS AND RESULTS: A randomized crossover study of the effects of smoking a single cigarette was performed in 20 smokers. Smoking a sham cigarette induced no significant changes in all assayed parameters. However, smoking a single cigarette significantly decreased nitrate and nitrite plasma concentrations by 3.5 +/-1.2 and 3.4 +/- 1.1 micromol/L, compared with plasma concentrations at presmoking and sham smoking, respectively. The concentrations of ascorbic acid and other antioxidants were also significantly lower after smoking a single cigarette. These parameters returned to preexperimental levels 60 minutes after smoking cessation. CONCLUSION: The present findings indicate that smoking a single cigarette temporarily decreases nitrate, nitrite, and serum antioxidant concentrations in the plasma. These transient changes may partially contribute to coronary vasoconstriction, which is routinely observed after smoking.

Adult↗

PubMed2002

Antioxidant protection of propofol and its recycling in erythrocyte membranes.

alpha-Tocopherol is a potent antioxidant that effectively protects biological membranes against oxidative injury through coordination with ascorbic acid. Because propofol has a phenolic structure similar to that of alpha-tocopherol, this intravenous anesthetic may also have similar antioxidant activity. To test this hypothesis, the effect of propofol on oxidative injury of human erythrocytes was examined. Propofol inhibited oxidative hemolysis and cis-parinaric acid oxidation in erythrocyte membranes (ED(50) = 6 microM). Although ascorbic acid alone has no appreciable effect, the protective effect of propofol was enhanced by ascorbic acid. An electron spin resonance (ESR) study showed that propofol-derived radicals (g = 2.005) were continuously generated during the oxidation of erythrocyte membranes by an ascorbic acid-inhibitable mechanism. These and other results suggest that propofol interacts with ascorbic acid, thereby exhibiting potent antioxidant activity in and around membranes as does alpha-tocopherol. Kinetic analysis revealed that propofol increased the membrane fluidity of erythrocytes, thereby increasing their resistance to physical and hemodynamic stress. Further, a greater preservation of red blood cell counts was seen after surgery with propofol compared with conventional sevoflurane anesthesia. Thus, propofol may protect erythrocytes against both oxidative and physical stress, indicating its potential as an efficient and safe antioxidant.

Antioxidants↗

PubMed2002

[Accurate placement of central venous catheter--ECG-guided method vs patient height method].

Correct positioning of central venous catheters (CVC) is important. We compared the positioning of CVCs by ECG-monitoring via the guidewire and that by method using patient height. "Certofix" triple-lumen CVCs were inserted in 60 cardiac surgical patients via right internal jugular puncture. Of these, 30 were placed with ECG guidance via the guidewire (Group ECG), and 30 with reference to patient height (modified Pere's method) (Group H). The distance from CVC tip to the superior vena cava/right atrial junction (C-J distance) was measured by postoperative chest X-ray. There was no difference in height between the two groups. The depth of insertion of CVC and C-J distance (cm) were 15.1 +/- 0.3 and 3.6 +/- 2.0 in group H and 14.3 +/- 1.5 and 4.9 +/- 1.2 in group ECG, respectively, with no statistically significant differences between the two groups. In one case of group H, the catheter tip was placed in the right atrium. In group ECG, there was a significant correlation between height and the depth of insertion of CVC. In conclusion, ECG guidance via the guidewire is useful for avoiding CVC displacement.

Aged↗

PubMed2002

[Fentanyl administration during sevoflurane anesthesia suppresses spike waves from epileptic focus on electrocorticogram].

A 36-year-old man with intractable epileptic seizures underwent insertion of subdural electrodes on bilateral temporal lobes under air-oxygen-sevoflurane anesthesia. After the completion of the operation, we measured electrocorticogram at end-tidal sevoflurane concentration of 2.5%, 1.5%, and 1.5% with 0.1 mg intravenous fentanyl. When sevoflurane concentration was reduced to 1.5%, the incidence and voltage of the spike waves on electrocorticogram were reduced. When 0.1 mg fentanyl was intravenously administrated during 1.5% sevoflurane anesthesia, the frequency of the spike waves was further reduced. Caution should be taken when using sevoflurane-fentanyl anesthesia because this combination may interrupt identification of epileptic focus on intraoperative electrocorticogram.

Adjuvants, Anesthesia↗

PubMed2002

Dose-related attenuation of cardiac sympathetic nerve activity and intracardiac conduction with thoracic epidural clonidine in alpha-chloralose-anesthetized cats.

Epidural clonidine produces hypotension, bradycardia and sympatholysis. We studied the dose-effects of thoracic epidural and intravenous clonidine (1 to 8 microg/kg) on cardiac sympathetic nerve activity (CSNA), hemodynamics and intracardiac conduction in cats anesthetized with alpha-chloralose. Mean arterial pressure was decreased with epidural clonidine doses above 2 microg/kg, and to a greater extent with 4 microg/kg than 8 microg/kg. Sinus heart rate, Wenckebach atrial rate and CSNA were significantly decreased and corrected sinus node recovery time and Atrium-His interval were significantly prolonged with doses above 2 microg/kg. Vagotomy induced no significant change in these parameters. Thoracic epidural clonidine doses above 2 microg/kg caused a similar extent of sympatholysis. Less of CSNA decrease and hemodynamic changes by intravenous clonidine suggested that sympatholysis caused by epidural clonidine was primarily mediated by spinal mechanism, although hemodynamic changes were influenced by clonidine systemically redistributed from epidural space. Vagal facilitation played no role in suppression of the sinoatrial and AV nodal functions.

Anesthesia↗