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Biomedical subjects

K Sumikawa

Publications and source records attributed to K Sumikawa.

At least 91 records · Page 5Linked to original sources
PubMed1996

Effects of sevoflurane with and without nitrous oxide on human cerebral circulation. Transcranial Doppler study.

BACKGROUND: This study was designed to evaluate the effects of sevoflurane with and without nitrous oxide on human middle cerebral artery (MCA) flow velocity, cerebrovascular carbon dioxide reactivity, and autoregulation compared with the awake state using transcranial Doppler ultrasonography. METHODS: In 14 patients, the time-mean middle cerebral artery flow velocity (Vmca) was measured when the end-tidal carbon dioxide level was approximately 30, 40, and 50 mmHg under the following conditions: (1) awake; (2) with 2% (1.2 MAC) sevoflurane; and (3) with 1.2 MAC sevoflurane-60% nitrous oxide. In six other patients, the cerebrovascular autoregulation during anesthesia was determined using intravenous phenylephrine to increase blood pressure. RESULTS: Sevoflurane (1.2 MAC) significantly decreased Vmca compared with the awake value at each level of end-tidal carbon dioxide, whereas 1.2 MAC sevoflurane-60% nitrous oxide did not exert significant influence. The Vmca in normocapnic patients decreased from 69 cm/s to 55 cm/s with 1.2 MAC sevoflurane and then increased to 70 cm/s when nitrous oxide was added. Sevoflurane (1.2 MAC) with and without 60% nitrous oxide had a negligible effect on cerebrovascular carbon dioxide reactivity. A phenylephrine-induced increase of mean arterial pressure did not influence Vmca during anesthesia. CONCLUSIONS: Sevoflurane (1.2 MAC) reduced Vmca compared with the awake condition, whereas the addition of nitrous oxide caused Vmca to increase toward the values obtained in the awake condition. The cerebrovascular carbon dioxide reactivity and autoregulation were well maintained during 1.2 MAC sevoflurane with and without 60% nitrous oxide.

Adult↗
PubMed1996

Adrenoceptor mechanism involved in thiopental-induced potentiation of halothane-epinephrine arrhythmias in dogs.

Although thiopental is known to potentiate halothane-epinephrine arrhythmias, the precise mechanism of this potentiation is obscure. The authors investigated the comparative role of alpha 1 and beta adrenergic actions in the thiopental-induced potentiation of halothane-epinephrine arrhythmias in dogs. Adult mongrel dogs were anesthetized with halothane alone (1.3%) or thiopental (20 mg kg-1) plus halothane and monitored continuously for systemic arterial pressures and for premature ventricular contractions. The arrhythmogenic doses of phenylephrine and isoproterenol were determined during the two anesthetic methods and the effect of thiopental on the arrhythmogenic action of alpha 1 and beta agonists was examined. Thiopental failed to exert a significant potentiation of arrhythmogenic effect of phenylephrine or isoproterenol, when these agents were administered separately. On the other hand, the potentiation of arrhythmogenicity by thiopental was remarkable in the case of combined administration of both the agonists, that is, thiopental enhanced the synergistic interaction between phenylephrine and isoproterenol for inducing arrhythmias during halothane anesthesia. In addition, the potentiation was more prominent when a low dose of isoproterenol and a high dose of phenylephrine was combined than that when a high dose of isoproterenol and a low dose of phenylephrine was given in combination. The results indicate that thiopental significantly potentiates the arrhythmogenic interaction of alpha 1 and beta adrenergic agonists administered concurrently, although individual potentiation of these agonists is not significant.

Anesthetics↗
PubMed1995

Direct action of 4-beta-phorbol-12,13-dibutyrate (PDBu) on nicotinic acetylcholine receptor channel independent of protein kinase C activation.

Torpedo acetylcholine receptor (AChR) has a protein kinase C (PKC) phosphorylation site, which modulates channel properties, on the alpha and delta subunit. The effect of a potent PKC activator, PDBu on AChR expressed into Xenopus oocytes was examined by whole cell voltage clamp recordings. The pretreatment with 4-beta-PDBu reversely accelerated desensitization of ACh-elicited membrane currents and the same effect was shown by co-application of 4-beta-PDBu and ACh without pre-incubation. Treatment with the inactive stereoisomer of phorbol ester, 4-alpha-PDBu also demonstrated an acceleration of desensitization. Furthermore, 4-beta-PDBu enhanced the rate of desensitization in mutant AChR deleting PKC phosphorylation sites on the alpha and delta subunit. These results indicate that phorbol ester directly acts on the AChR channel independent of PKC activation.

Animals↗
PubMed1995

Phosphatidylinositol responses are involved in the vascular effects of thiamylal and fentanyl.

Although thiobarbiturates potentiate, and fentanyl attenuates peripheral vasoconstriction, the intracellular mechanism involved in this phenomenon is not clear. Because smooth muscle contraction induced by alpha 1-adrenoceptor agonists is mediated by the phosphatidylinositol (PI) response, this study was carried out to clarify if thiamylal and fentanyl affect the norepinephrine-induced PI response in rat aortic slices. Rat aortic slices were incubated in Krebs-Henseleit solution containing 5 mM LiCl, [3H]myo-inositol, and varying concentrations of thiamylal or fentanyl. The Pl response was stimulated by 0.9 microM (ED50) norepinephrine (NE). The [3H]inositol monophosphate (IP1) was separated from [3H]myo-inositol by column chromatography and counted with a liquid scintillation counter. The basal IP1 accumulation was not affected by thiamylal and fentanyl. Norepinephrine-induced IP1 accumulation was potentiated by thiamylal at concentrations of 10 microM and 100 microM. Norepinephrine-induced IP1 accumulation was attenuated by 1 microM and 10 microM fentanyl. The results suggest that thiamylal stimulates the NE-induced PI response, which potentiates the vasoconstriction, and fentanyl attenuates NE-induced PI response, which would attenuate the vasoconstriction.

Anesthetics, Intravenous↗
PubMed1995

A sodium- and energy-dependent glucose transporter with similarities to SGLT1-2 is expressed in bovine cortical vessels.

In order to investigate glucose transport at the blood-brain barrier (BBB), glucose transport properties were studied pharmacologically with a novel model system of inverted bovine brain cortical arteries. These vessels displayed glucose transport characteristics of facilitative glucose transporters (GLUT1-5) and of sodium- and energy-dependent glucose transporters (SGLT1-2). So far, glucose transport in the central nervous system (CNS) has only been shown to be achieved by facilitative transporters, in particular by GLUT1 at the blood-brain barrier and in glial cells and by GLUT3 in a subset of neurons. We report here that a SGLT-like transporter might partake in glucose transport at the bovine BBB, as indicated by immunocytochemical analysis and by Western immunoblot analysis of cultured bovine brain endothelial cells. A RNA protection assay revealed the presence of a SGLT-like gene fragment in rabbit cortex.

Animals↗
PubMed1995

A comparison of coronary hemodynamics during isoflurane and sevoflurane anesthesia in dogs.

We studied the effects of sevoflurane and isoflurane on coronary hemodynamics in relation to myocardial oxygen supply and demand. Dogs were anesthetized with pentobarbital and fentanyl and received isoflurane or sevoflurane. An electromagnetic flow probe and a pair of piezoelectric crystals were placed on the left circumflex coronary artery (CX) to measure CX flow and diameter. The dogs were randomly assigned to receive isoflurane or sevoflurane at a dose of 0.75 and 1.5 minimum alveolar anesthetic concentration (MAC). The CX diameter decreased in parallel with the decrease in mean arterial pressure during both anesthetics. The CX blood flow decreased in parallel with the decrease in myocardial oxygen consumption (MVo2) during sevoflurane, whereas it did not change in spite of the decrease in MVO2 during isoflurane. The CX vascular resistance decreased significantly during isoflurane but not during sevoflurane. Moreover, the myocardial oxygen extraction ratio (Mo2exr) decreased at 0.75 and 1.5 MAC isoflurane and at 1.5 MAC sevoflurane, and the decrease in Mo2exr was significantly greater during isoflurane than during sevoflurane. The results suggest that sevoflurane is a less potent coronary arteriolar dilator than isoflurane, and that neither sevoflurane or isoflurane has a direct effect on the diameter of large coronary arteries.

Anesthesia↗
PubMed1995

Carbachol, norepinephrine, and hypocapnia stimulate phosphatidylinositol turnover in rat tracheal slices.

BACKGROUND: The intracellular mechanisms involved in the alpha-adrenoceptor- or hyperventilation-induced bronchoconstriction remain unknown. Because there is a direct relationship between phosphatidylinositol (PI) metabolism and airway smooth muscle contraction induced by muscarinic agonists, the authors examined the effects of carbachol (CCh), norepinephrine (NE), and hypocapnia on PI turnover in the airway smooth muscle. METHODS: Rat tracheal slices were incubated in Krebs-Henseleit solution containing LiCl and [3H]myo-inositol in the presence of NE, CCh, or neither. The PCO2 in the solution was 36 +/- 3 mmHg (normocapnia), 19 +/- 2 mmHg (moderate hypocapnia), or 5 +/- 2 mmHg (severe hypocapnia), respectively. [3H]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter. RESULTS: Basal IP1 formed was greater at severe hypocapnia than at normocapnia. Norepinephrine- and CCh-induced IP1 formation were also greater at hypocapnia than at normocapnia. CONCLUSIONS: These results indicate that CCh, NE, and hypocapnia stimulate PI turnover in the airway smooth muscle, which would cause bronchoconstriction, and hypocapnia also augments NE- and CCh-induced PI turnover, which could cause worsening of exercise-induced asthma and vagotonic asthma, respectively.

Animals↗
PubMed1995

Role of the vagus nerve in the antidysrhythmic effect of dexmedetomidine on halothane/epinephrine dysrhythmias in dogs.

BACKGROUND: Dexmedetomidine, an alpha 2-adrenergic agonist, can prevent the genesis of halothane/epinephrine dysrhythmias through the central nervous system. Because stimulation of alpha 2 adrenoceptors in the central nervous system enhances vagal neural activity and vagal stimulation is known to inhibit digitalis-induced dysrhythmias, dexmedetomidine may exert the antidysrhythmic property through vagal stimulation. To address this hypothesis, the effect of dexmedetomidine in vagotomized dogs was examined and compared with that in intact dogs. In addition, the effect of vagotomy on the antidysrhythmic action of doxazosin, an alpha 1 antagonist, was studied. METHODS: Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and premature ventricular contractions. Animals were divided into two groups receiving bilateral vagotomy or sham operation. The dysrhythmia threshold was expressed by the dysrhythmogenic dose of epinephrine, defined as the smallest dose producing four or more premature ventricular contractions within a 15-s period, and plasma concentration of epinephrine at the time when the dysrhythmogenic dose was reached. The threshold was determined in the presence of dexmedetomidine (a selective alpha 2 agonist that crosses the blood-brain barrier) and doxazosin (a selective alpha 1 antagonist that does not penetrate the blood-brain barrier) in the two groups. In addition, the effect of dexmedetomidine in the presence of atropine methylnitrate instead of vagotomy was examined. RESULTS: Vagotomy did not affect the basal vulnerability to halothane/epinephrine dysrhythmias significantly. Although dexmedetomidine dose-dependently prevented the genesis of the dysrhythmias in intact dogs, the beneficial effect of dexmedetomidine was abolished in both the vagotomized and the atropine-treated dogs. On the other hand, vagotomy did not change the antidysrhythmic property of doxazosin. CONCLUSIONS: The vagus nerve plays an important role in the prevention of halothane/epinephrine dysrhythmias by dexmedetomidine in dogs. However, resting vagal tone neither modulates the onset of halothane/epinephrine dysrhythmias nor affects the antidysrhythmic action of doxazosin.

Adrenergic alpha-Agonists↗
PubMed1994

Tunicamycin alters channel gating characteristics of junctional and extrajunctional acetylcholine receptors expressed in Xenopus oocytes.

The acute effects of tunicamycin on mouse junctional and extrajunctional acetylcholine receptors (AChRs) expressed in Xenopus oocytes, distinct from its ability to block N-glycosylation of the protein, was examined at the single channel level. Tunicamycin reduced the frequency of ACh-activated single channel openings and prolonged the mean channel open times of AChRs in a dose-dependent manner, without affecting inward conductances. Continuous application of ACh to both junctional and extrajunctional AChR channels very slowly decreased the number of channel opening events, and tunicamycin accelerated this process. These results suggest that tunicamycin alters channel gating kinetics and accelerates transition towards a desensitized state.

Animals↗
PubMed1994

A cAMP-dependent Ca2+ signalling pathway at the endplate provided by the gamma to epsilon subunit switch in ACh receptors.

During development of neuromuscular junctions there is a switch in the expression of acetylcholine receptors (AChR) from an embryonic form (gamma-AChR) to an adult form (epsilon-AChR). Studies with gamma- and epsilon-AChRs expressed in Xenopus oocytes showed that the gamma to epsilon subunit switch accelerates rates of desensitization and increases Ca2+ permeability. Site-directed mutagenesis of the gamma and epsilon subunits suggests that these changes are regulated by cAMP-dependent phosphorylation on the epsilon subunit. These results suggest that the gamma to epsilon subunit switch could provide for a cAMP-dependent Ca2+ signalling pathway at the endplate.

Acetylcholine↗
PubMed1994

The amino acid residues 1-128 in the alpha subunit of the nicotinic acetylcholine receptor contain assembly signals.

Expression of nicotinic acetylcholine receptor (AChR) involves complex processes including assembly of different receptor subunits into hetero-oligomers. To identify the minimal N-terminal region involved in AChR subunit association, we used a dominant negative assay. Co-expression of fragments of the alpha subunit, containing the N-terminal extracellular domain and transmembrane domain 1 (TM 1), with the parental AChR subunits in Xenopus oocytes blocked functional expression of the receptor. In contrast, co-expression of N-terminal extracellular fragments without TM1 failed to inhibit functional expression of AChRs, but altered the functional properties of co-expressed parental AChRs. Furthermore, when these alpha subunit fragments were co-expressed with the beta, gamma, and delta subunits, they were co-immunoprecipitated with a mixture of beta, gamma, and delta subunit specific antibodies. These results suggest that 'assembly signals' are confined to a local structure in the N-terminal extracellular domain. Our findings also indicate that an assembly step may be a target for genetic intervention not only to block the expression of functional receptors, but also to alter the function of the receptor.

Amino Acids↗
PubMed1994

Differential interactions of gentamicin with mouse junctional and extrajunctional ACh receptors expressed in Xenopus oocytes.

The nicotinic acetylcholine receptors (AChRs) from Torpedo electric organ and mouse muscles when expressed in Xenopus oocytes desensitize with different time courses. Initially, the role of cAMP-dependent phosphorylation on the gamma subunits in the different desensitization rates was investigated by expressing normal and mutant AChRs in the oocytes cultured in the presence of gentamicin. Mutant Torpedo AChRs lacking the potential cAMP-dependent phosphorylation sites in the gamma subunit appear to desensitize like normal Torpedo AChRs. Similarly, mutant mouse extrajunctional AChRs containing a newly created phosphorylation site in the gamma subunit appeared to desensitize like normal mouse AChRs, which lack the potential cAMP-dependent phosphorylation site in the gamma subunit. These results suggest that different rates of desensitization between the Torpedo and muscle extrajunctional AChRs are not attributable to differential cAMP-dependent phosphorylation of these AChRs. Subsequently, to determine whether gentamicin used in culturing oocytes differentially interacts with muscle junctional and extrajunctional AChRs, we analyzed rates of current decay following different gentamicin treatments. Both chronic and acute treatment with gentamicin profoundly accelerated the decay of whole-cell currents mediated by both types of AChR. The effect of prolonged gentamicin treatment on junctional AChRs was long lasting when compared to treatment on extrajunctional AChRs. Although the two types of AChR still desensitize differently in the absence of gentamicin, these results suggest that the characteristic desensitization of junctional and extrajunctional AChRs observed previously is largely due to differential interactions of gentamicin with the two types of AChR.

Acetylcholine↗
PubMed1994

Effects of intravenous anesthetics on phosphatidylinositol turnover in rat cerebral cortical prisms.

Noradrenergic pathways in the brain have been thought to be related to the site of anesthetic action. Norepinephrine (NE) in the central nervous system stimulates phosphatidylinositol (PI) turnover through alpha 1-adrenergic receptors. The present study was designed to examine the effects of intravenous anesthetics on NE-induced PI turnover in rat cerebral cortical prisms. NE-induced inositol monophosphate (IP1) formation was inhibited by droperidol (dose for 50% inhibition [ID50], 0.0258 +/- 0.00023 microM [mean +/- SE]), fentanyl (2.36 +/- 0.0017), diazepam (201 +/- 2.12), and thiamylal (231 +/- 1.94) in a dose-dependent manner, but was not affected by ketamine. Naloxone or flumazenil did not attenuate the inhibitory effect of fentanyl or diazepam on NE-induced IP1 formation. The results suggest that these effects on the PI turnover in the cortex may be related to their pharmacologic properties including the anesthetic action.

Anesthetics, Intravenous↗
PubMed1994

Decrease in vecuronium infusion dose requirements by nicardipine in humans.

This study was designed to analyze quantitatively the interaction of nicardipine with vecuronium using a constant infusion technique. Forty-seven patients undergoing elective otolaryngeal surgery were anesthetized with isoflurane (1% end-tidal) and nitrous oxide (67%). Patients were randomly assigned to receive one of four doses of nicardipine (0, 1, 2, and 3 micrograms.kg-1.min-1). Vecuronium infusion dose requirement was determined as a constant infusion rate which maintained 90% depression of control twitch tension. Nicardipine significantly decreased the vecuronium requirement in a dose-dependent manner, i.e., the vecuronium doses were 0.70 +/- 0.03, 0.55 +/- 0.04, 0.42 +/- 0.04, and 0.37 +/- 0.05 micrograms.kg-1.min-1 at nicardipine doses of 0, 1, 2, and 3 micrograms.kg-1.min-1, respectively. Nicardipine also reduced both the plasma concentration of vecuronium to maintain the 90% depression and the total plasma clearance of vecuronium. The reversal of the vecuronium effect with neostigmine was not influenced by nicardipine. The results indicate that the vecuronium infusion dose requirements are reduced as much as 53% by a clinical dose of nicardipine.

Adult↗
PubMed1993

Changes in erythrocyte membrane phospholipid composition induced by physical training and physical exercise.

The effects were investigated of physical training and exercise on lipids of the erythrocyte membrane of healthy students. Membrane cholesterol and phospholipids were analysed simultaneously by thin-layer chromatography with a flame ionization detector and the fatty acid composition was determined by gas chromatography. Physically trained students had similar physical characteristics to control students but a significantly higher aerobic capacity, estimated as the maximal oxygen uptake and anaerobic threshold. Of the phospholipids examined, only the content of membrane phosphatidylserine was significantly lower in the trained group. Fatty acid analysis showed that the amount of docosahexaenoic acid in membrane phosphatidylserine was lower in the trained group. There was no significant difference between the fatty acid compositions of membrane phosphatidylcholine in the two groups. Maximal exercise decreased membrane phosphatidylserine in the control group but not in the trained group. It also significantly decreased the relative amounts of unsaturated fatty acids in both phosphatidylcholine and phosphatidylserine in the untrained group. Maximal oxygen uptake was negatively correlated with the amount of erythrocyte membrane phosphatidylserine. These results would indicate that both physical training and acute exercise decrease phosphatidylserine and polyunsaturated fatty acids in erythrocyte membranes, possibly due to lipid peroxidation, suggesting limited enhancement of erythrocyte defense mechanisms in adaptation to chronic oxidative stress.

Adult↗
PubMed1993

Role of imidazoline-preferring receptors in the genesis of epinephrine-induced arrhythmias in halothane-anesthetized dogs.

BACKGROUND: Drugs with a central alpha 2-adrenergic action can increase the threshold for halothane-epinephrine-induced arrhythmias. Recently, imidazoline-preferring receptors were shown to play a significant role in the hypotensive effect of alpha 2-adrenergic agonists containing an imidazole ring in their structure. To address the question of whether the antiarrhythmic property of the alpha 2-adrenergic agonists was caused by activation of alpha 2-adrenoceptors or imidazoline-preferring receptors in the central nervous system, the effect of an imidazoline (atipamezole) and a nonimidazoline (L-659,066 and yohimbine) alpha 2-adrenergic antagonist were examined as etiologic factors in the genesis of halothane-epinephrine-induced arrhythmias in dogs. METHODS: Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and for premature ventricular contractions. The arrhythmogenic dose (AD) of epinephrine, defined as the smallest dose producing four or more premature ventricular contractions within a 15-s period, was determined in the presence of atipamezole (an imidazoline compound that acrosses the blood-brain barrier), L-659,066 (a nonimidazoline compound that does not penetrate the blood-brain barrier), and yohimbine (a nonimidazoline compound that passes the blood-brain barrier). These drugs were administered either intravenously or into the cisterna magna to assess the site of action for changes in responsiveness. RESULTS: Intravenous atipamezole decreased the AD of epinephrine in the dose-dependent fashion. However, neither L-659,066 nor yohimbine, administered peripherally, decreased the AD of epinephrine. Central administration of atipamezole also decreased the AD of epinephrine, while L-659,066, even if administered centrally, did not affect the AD of epinephrine in the presence of halothane. CONCLUSIONS: Because the imidazoline ring-containing alpha 2-adrenergic antagonist (atipamezole) potentiated the halothane-epinephrine-induced arrhythmias and the nonimidazole alpha 2-adrenergic antagonist (L-659,066 and yohimbine) did not, it is possible that the imidazoline-preferring, rather than the alpha 2-adrenergic, receptor is responsible for the antiarrhythmic property of alpha 2-adrenergic agonists.

Adrenergic alpha-Antagonists↗
PubMed1993

Comparative efficacy of antiarrhythmic agents in preventing halothane-epinephrine arrhythmias in rats.

BACKGROUND: Because the relative efficacy of antiarrhythmic agents on halothane-epinephrine arrhythmias has not been well characterized, this study was undertaken to comparatively evaluate the antiarrhythmic action of Na(+)-, K(+)- and Ca(2+)-channel blockers on epinephrine-induced ventricular arrhythmias during halothane anesthesia in rats. METHODS: Rats were anesthetized at random with either halothane (1.5%), isoflurane (2.0%), or pentobarbital (50 mg/kg intraperitoneally), and the lungs were mechanically ventilated with oxygen. The rats were studied in three consecutive protocols. Protocol I determined the arrhythmogenic thresholds of epinephrine during the three types of anesthesia in 33 rats. Protocol II determined the arrhythmogenic thresholds of epinephrine during halothane anesthesia in 64 rats receiving saline (control) or one of five antiarrhythmic agents. Protocol III measured the duration of epinephrine-induced arrhythmias during halothane anesthesia in 42 rats receiving saline (control) or one of five antiarrhythmic agents. RESULTS: In protocol I, the arrhythmogenic doses of epinephrine during halothane, isoflurane, or pentobarbital anesthesia were 1.7 +/- 3.2, 11.1 +/- 0.6, and 39.0 +/- 3.9 micrograms/kg, respectively, and the corresponding plasma concentrations were 4.3 +/- 0.8, 103.7 +/- 9.2, and 246.7 +/- 28.9 ng/ml, respectively. In protocol II, the arrhythmogenic doses were similar in rats receiving saline and in those receiving lidocaine. The arrhythmogenic doses in rats receiving verapamil, flecainide (Na(+)- and K(+)-channel blocker), E-4031 (K(+)-channel blocker), or amiodarone(K(+)-channel blocker with Na(+)-, Ca(2+)-, and beta-blocking activity) increased significantly, i.e., 4.2, 4.2, 5.5, and 31.7 times control (P < 0.01). In protocol III, lidocaine had no effect on the duration of arrhythmias. Flecainide, E-4031, and verapamil markedly reduced the duration of arrhythmias induced by epinephrine, 8 micrograms/kg intravenously (P < 0.01), whereas only amiodarone markedly reduced the duration of arrhythmias induced by epinephrine, 16 micrograms/kg intravenously (P < 0.01). CONCLUSIONS: It was concluded that agents with K(+)-channel blocking properties were the most effective in preventing halothane-epinephrine arrhythmias in rats.

Amiodarone↗