Biomedical subjects

Kazuyoshi Hirota

Publications and source records attributed to Kazuyoshi Hirota.

30 records · Page 2Linked to original sources

PubMed2003

Lack of an interaction between orexinergic and opioid/nociceptinergic systems in rat cerebrocortical slices.

We have recently reported that orexins (OXs) selectively evoke norepinephrine release from rat cerebrocortical slices. In the present study, we have examined orexin-opioid interactions in OXA (100 nM) and K(+) (40 mM)-evoked norepinephrine release. OXA-evoked norepinephrine release was reversed approximately 90% by SB-334867 (OX(1)-receptor antagonist) (10 microM) but not naloxone (10 microM). [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) (DOP-agonist) and nociceptin/orphanin-FQ (N/OFQ) also failed to affect OXA-evoked release. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) (MOP-agonist) and spiradoline (KOP-agonist) significantly reduced OXA-evoked release with the concentration producing 50% of the maximal inhibition (EC(50)) [maximal inhibition (E(max))] of 3.2 microM [41.8%] and 4.3 microM [54.9%] respectively. The effects of DAMGO and spiradoline were naloxone (10 microM)-insensitive. In contrast, naloxone significantly antagonized the inhibitory effects of DAMGO and spiradoline on K(+)-evoked release. We conclude that opioid receptors (DOP and KOP) are involved in K(+) but not OXA-evoked release. Moreover, we have failed to demonstrate an interaction between orexinergic and opioid/N/OFQ-ergic systems in this system.

Amino Acid Sequence↗

PubMed2003

Effects of nociceptin/orphanin FQ receptor ligands on blood pressure, heart rate, and plasma catecholamine concentrations in guinea pigs.

Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide receptor (NOP) and has been shown previously to produce bradycardia and hypotension in rodents. In this study we have measured the effects of intravenous N/OFQ, and the NOP antagonists [Nphe(1)]N/OFQ(1-13)-NH(2) ([Nphe(1)]) and [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101) on cardiovascular parameters and plasma catecholamine concentrations. Female Hartley guinea pigs were anesthetized with pentobarbital and ventilated artificially. MAP and HR were measured via a femoral arterial catheter and ECG, respectively. Plasma catecholamine concentrations were measured by HPLC. Animals received saline, N/OFQ (0.25, 1.25, 6.25 and 25 nmol cumulatively at 10-min intervals), [Nphe(1)] (600 nmol) and UFP-101 (60 nmol) i.v. in various combinations. After establishing a stable baseline, MAP and HR measurements and blood sampling were performed at the beginning and 3 min following each drug administration. N/OFQ significantly decreased MAP, HR and the plasma noradrenaline concentrations in a dose dependent manner (maximally by 29.1+/-1.8%, 13.8+/-0.8% and 46.6+/-7.8%, respectively) To the contrary, N/OFQ tended to increase plasma adrenaline concentration but did not affect plasma dopamine concentrations. There was a significant correlation between percent change in MAP (0.69, P<0.01) or HR (0.84, P<0.01) and that in plasma noradrenaline. [Nphe(1)], but not UFP-101, alone significantly decreased MAP. [Nphe(1)] partially antagonized N/OFQ-induced hypotension, bradycardia and the decrease in plasma concentration of noradrenaline. UFP-101 fully prevented the effects of N/OFQ in this model. In conclusion, the present study shows that intravenous N/OFQ, via NOP receptors, elicits hypotension and bradycardia also in the anaesthetized guinea pig and that the decrease in MAP and HR are positively correlated with the decrease in the plasma noradrenaline level.

Animals↗

PubMed2003

Coronary flow reserve correlates left ventricular diastolic dysfunction in patients with dilated cardiomyopathy.

The relationship between altered coronary circulation and left ventricular (LV) function in dilated cardiomyopathy (DCM) remains unclear. We used the Doppler guidewire and transthoracic echo Doppler in 24 DCM patients to investigate the relationship between coronary flow reserve (CFR) and LV systolic/diastolic function, trying to predict diastolic dysfunction and evaluate DCM severity with CFR. CFR correlated better with the deceleration time (DT) of the E-wave and the ratio of E-wave peak value to that of the A-wave (E/A) than with LV ejection fraction (EF). The optimal CFR cutoff value for predicting the restrictive pattern of transmitral flow velocity (DT = 120 msec) was 2.6 (sensitivity 91%, specificity 100%). Dividing patients into two groups around the CFR = 2.6 cutoff, differences in DT and E/A between groups were more prominent than those for EF. CFR correlates better with LV diastolic than systolic function and may be useful for predicting diastolic dysfunction in DCM patients.

Adult↗

PubMed2003

The effects of local and intravenous anesthetics on recombinant rat VR1 vanilloid receptors.

UNLABELLED: Capsaicin, acting at the vanilloid 1 receptor (VR1), may potentiate local anesthetic activity, and as a ligand-gated ion channel of the transient receptor potential family, may also be a target for IV general anesthetics. We have examined whether local (lidocaine, prilocaine, and procaine 0.1-10 mM; 10 mM represents 0.25%-0.27% wt/vol) or IV anesthetics (propofol 10 micro M, thiopental 100 micro M, and ketamine 100 micro M) interact with recombinant rat VR1 expressed in human embryonic kidney (HEK293) cells (VR1-HEK293). We have assessed receptor interaction functionally by monitoring intracellular Ca(2+) ([Ca(2+)](i)) in Fura2-loaded cells at 37 degrees C. The addition of capsaicin (60 nM) produced a time-dependent biphasic increase in [Ca(2+)](i) amounting to 50-100 nM above than basal, which was inhibited by capsazepine 10 micro M and was absent in wild type HEK293 cells. Lidocaine and prilocaine alone (e.g., at 10 mM) significantly increased [Ca(2+)](i) by 67 +/- 6 nM and 33 +/- 7 nM, respectively, and concentration-dependently inhibited the capsaicin response. The effects of procaine were obscured by anesthetic-induced quenching of Fura2. In wild type HEK293 cells, lidocaine (10 mM) alone produced a small increase in [Ca(2+)](i). All IV anesthetics failed to modify capsaicin-increased [Ca(2+)](i). In conclusion, the present data suggest that local but not IV general anesthetics interact with recombinant rat VR1 receptors with the former anesthetics having antagonistic activity. IMPLICATIONS: Vanilloid receptors (VR1) are activated by capsaicin, the pain-producing component of hot chili peppers. We suggest that local (but not IV general) anesthetics may have inhibitory actions on this receptor.

Anesthetics, Intravenous↗

PubMed2003

[Obstruction of an reinforced endotracheal tube due to dissection of internal tube wall during total intravenous anesthesia].

We report here a case of obstruction of an reinforced endotracheal tube during laryngomicrosurgery under total intravenous anesthesia. In this case, we used a 6.0 mm ID reinforced endotracheal tube that had been used previously for other patients and sterilized two times by ethylene oxide gas. During the operation, the peak airway pressure increased gradually and eventually reached to 35 cmH2O. After the exchange of the endotracheal tube, ventilation was improved immediately. The endotracheal tube was occluded by dissection of internal wall. Several cases of reinforced tube obstruction have already been reported and in most of these cases the obstruction was related to their repeated use and nitrous oxide anesthesia. However, the present case showed that dissection of reinforced endotracheal tube could also occur during general anesthesia without using nitrous oxide. We should bear in mind that repeated use of reinforced endotracheal tube could induce a critical airway obstruction.

Airway Obstruction↗

PubMed2002

Inhibitory effects of intravenous anaesthetic agents on K(+)-evoked glutamate release from rat cerebrocortical slices. Involvement of voltage-sensitive Ca(2+) channels and GABA(A) receptors.

It is widely accepted that most general anaesthetic agents depress the central nervous system (CNS) by potentiation or activation of the GABA(A) receptor-mediated Cl(-) conductance. These agents also reportedly inhibit voltage-sensitive Ca(2+) channels (VSCCs), thus depressing excitatory transmission in the CNS. However, in this regard there are few functional data at the level of neurotransmitter release. In this study we examined the effects of VSCC antagonists and a range of intravenous anaesthetic agents on K(+)(40 mM)-evoked glutamate release from rat cerebrocortical slices in the absence and presence of the GABA(A) receptor antagonist bicuculline (100 microM). We employed both selective and non-selective VSCC antagonists, the anaesthetic barbiturates thiopental, pentobarbital and phenobarbital, the non-anaesthetic barbiturate barbituric acid, the non-barbiturate anaesthetics alphaxalone, propofol and ketamine and the GABA(A) receptor agonist, muscimol. Glutamate released into the incubation medium was determined by a glutamate dehydrogenase-coupled assay. Omega-agatoxin IV(A) (P-type VSCC), omega-conotoxin MVII(C) (P/Q-type VSCC) and Cd(2+) (non-selective) essentially abolished glutamate release whilst nifedipine (L-type VSCC) and omega-conotoxin GVI(A) (N-type VSCC) reduced release by less than 30%. The concentrations producing 50% of the maximum inhibition (IC(50)) for thiopental, pentobarbital, phenobarbital, alphaxalone, propofol and ketamine were (in microM) 8.3, 22, 112, 6.3, 83 and 120, respectively. Barbituric acid produced a small (about 20%) inhibition. With the exception of ketamine, the IC(50) values for these anaesthetic agents were increased threefold by bicuculline (100 microM). In addition, muscimol significantly inhibited release by 26% with an IC(50) of 1.1 microM. In summary, a range of anaesthetic agents at clinically achievable concentrations inhibit glutamate release and this inhibition of release appears to be due mainly to direct inhibition of P/Q-type VSCCs, although activation of the GABA(A) receptor plays a role in this response.

Anesthetics, Intravenous↗

PubMed2002

Alpha-2 adrenoceptor activity affects propofol-induced sleep time.

UNLABELLED: alpha(2) Adrenoceptor activity is involved in the mechanism of anesthesia. Clonidine, a alpha(2) adrenoceptor agonist, and yohimbine, a alpha(2) adrenoceptor antagonist, increase and decrease barbiturate-induced sleep times. In this study, we examined the effects of these drugs on propofol-induced sleep time. One-hundred-eighteen male Wistar rats weighing 320-400 g were used. Rats received saline, yohimbine (1, 0.1, or 0 mg/kg), or clonidine (300, 30, 3, or 0 microg/kg) intraperitoneally followed by 60 mg/kg of propofol in various combinations. In two series of experiments, either sleep time or prefrontal cortex norepinephrine release (microdialysis) was measured. One milligram/kilogram of yohimbine decreased propofol-induced sleep time to approximately 70% of control, and this was accompanied by an increase in perfusate norepinephrine of approximately 240% of control. Clonidine increased sleep time approximately 260% (300 microg/kg) and approximately 170% (30 microg/kg), and this was accompanied by a decrease (approximately 60% in both doses) in perfusate norepinephrine. In the present study, we show that the alpha(2) antagonist, yohimbine, decreased and the alpha(2) agonist, clonidine, increased propofol-induced sleep times. These changes were essentially mirrored in both groups by changes in norepinephrine release in the prefrontal cortex. IMPLICATIONS: Central alpha(2) adrenoceptor is thought to be involved in several IV anesthetics-induced sleep. In this study, activation of the receptor increased the propofol-induced sleep time, whereas its inhibition decreased the sleep time. The results provide further evidence that the alpha(2) receptor is a good tool to elucidate the mechanism of anesthetics-induced sleep.

Anesthetics, Intravenous↗

PubMed2002

Quantification and comparison of pulmonary emboli formation after pneumatic tourniquet release in patients undergoing reconstruction of anterior cruciate ligament and total knee arthroplasty.

UNLABELLED: The amount of emboli formed (percentage of total emboli area to the right atrial area [%Ae]) after tourniquet release in invasive procedures of the medullary cavity is empirically much larger than that in noninvasive procedures, even if the tourniquet duration is similar. Thus, we compared %Ae between arthroscopic reconstruction of the anterior cruciate ligament (ACL, n = 20) and total knee arthroplasty (TKA, n = 20). The right atrium was continuously monitored by transesophageal echocardiography to assess %Ae. Peak %Ae +/- SD (ACL, 4.1% +/- 3.4%; TKA, 20.7% +/- 16.7%) appeared 30-40 s after tourniquet release in both groups. However, %Ae in the TKA group was always larger than the peak %Ae in the ACL group. In addition, although the ET(CO(2)) significantly increased after tourniquet release in both groups, increase of ET(CO(2)) (1.1% +/- 0.3%) in the ACL group was significantly larger than that in the TKA group (0.5% +/- 0.2%). An increase in ET(CO(2)) was inversely proportional to peak %Ae (P < 0.01; r = 0.703). Therefore, the present data suggest that the risk of acute pulmonary embolism after tourniquet release may be more frequent during TKA than ACL. IMPLICATIONS: We compared emboli formation after tourniquet release in patients undergoing arthroscopic reconstruction of the anterior cruciate ligament (ACL, n = 20) and total knee arthroplasty (TKA, n = 20) using transesophageal echocardiography. The present data suggest that the risk of acute pulmonary embolism after tourniquet release could be more frequent during TKA than ACL.

Acute Disease↗

PubMed2002

Interaction of intravenous anesthetics with recombinant human M1-M3 muscarinic receptors expressed in chinese hamster ovary cells.

UNLABELLED: Previous reports suggest that the effects of propofol, ketamine, and thiopental on airway tone may be because of modulation of parasympathetic activity. We examined if these anesthetics interact with recombinant human M1-M3 muscarinic receptors expressed in Chinese hamster ovary cells (CHO-M1, M2, and M3) using the displacement of 0.4 nM of l-[N-methyl-(3)H]scopolamine methyl chloride([(3)H]NMS). In addition, functional studies were performed by fluorometrically monitoring methacholine (1 mM) stimulated intracellular Ca(2+) ([Ca(2+)](i)) responses. Ketamine concentration dependently displaced [(3)H]NMS binding to CHO-M1, M2, and M3 cells with affinity, pK(i) (mean K(i)) values of 4.34 +/- 0.14 (45 micro M), 3.53 +/- 0.10 (294 micro M), and 3.61 +/- 0.02 (246 micro M), respectively. The effects at M1 were in the clinical range. Ketamine did not affect either basal or methacholine stimulated increase in [Ca(2+)](i) in CHO-M1 cells. Thiopental significantly displaced [(3)H]NMS binding to M3 (pKi [mean Ki] = 4.12 +/- 0.06 [75 micro M]) but not M1 or M2 receptors. Thiopental (10(-5)-10(-3) M) concentration dependently inhibited methacholine stimulated increase in [Ca(2+)](i) in CHO-M3 cells. Propofol and barbituric acid did not interact with any muscarinic receptor subtype. We suggest that at the level of [Ca(2+)](I), thiopental may possess M3 antagonist activity, whereas there are no functional consequences of the interaction of ketamine with the M1 receptor. IMPLICATIONS: In this study using recombinant human M1-M3 muscarinic receptors, we show that for agonist-stimulated increases in intracellular Ca(2+) thiopental acts as a M3 antagonist.

Anesthetics, Intravenous↗

PubMed2002

[Can adenosine triphosphate induce maximal hyperemic response in patients with impaired coronary microcirculation?: comparison of hyperemic response to adenosine triphosphate administered by intravenous and by intracoronary injection using Doppler guide wire].

OBJECTIVES: This study compared the hyperemic responses to adenosine triphosphate (ATP) administered by intravenous and by intracoronary injection in patients with impaired coronary microcirculation. METHODS: The hyperemic responses to intravenous and intracoronary administration of ATP in 107 patients (mean age 63 +/- 10 years, 77 males, 30 females) with impaired coronary circulation [including myocardial infarction (n = 68), cardiomyopath (n = 20) and diabetes mellitus (n = 11)] were compared by measurement of coronary flow reserve (CFR) using the Doppler guide wire. Patients with chest pain syndrome were used as the normal controls. The coronary blood flow velocity was measured at rest and during peak hyperemic responses to intravenous infusion (150 micrograms/kg/min) and intracoronary infusion of ATP (50 micrograms in the left coronary artery, 25 micrograms in the right coronary artery). The CFR was calculated as the ratio of averaged peak velocity during hyperemia to baseline averaged peak velocity. RESULTS: The CFR after intravenous administration of ATP (CFRi.v.) was well correlated with CFR by intracoronary administration of ATP(CFRic) (r = 0.77, p < 0.001). However, the CFRi.v. was also inversely correlated with the ratio of CFRic to CFRiv (CFRic/i.v.) (r = -0.36, p < 0.001). There were no relationships between the changes of hemodynamic parameters(blood pressure and heart rate) induced by ATP and CFRic/i.v. A lower CFRi.v. of less than 2.0 provided significantly greater CFRic/i.v. than that of CFRiv greater than 2.0. CONCLUSIONS: The maximal hyperemic response of coronary artery was not always induced by conventional intravenous administration of ATP, especially in patients with lower CFR than 2.0. High dose of intravenous ATP and/or intracoronary ATP should be administered in patients with lower CFR to attain maximum hyperemia in the impaired coronary circulation.

Adenosine Triphosphate↗

PubMed2002

[Evaluation of coronary flow reserve using Doppler guide wire in patients with ampulla cardiomyopathy: three case reports].

Coronary flow velocity recordings were obtained in three patients with ampulla (Takotsubo) cardiomyopathy using Doppler guide wire. Immediately after admission, coronary angiography demonstrated no significant stenosis and normal coronary flow in the epicardial coronary artery. Left ventriculography showed abnormal wall motion of the left ventricle mimicking ampulla shape in all patients. The coronary flow velocity pattern was normal, but coronary flow reserve of the left anterior descending coronary artery was decreased by adenosine administration in all patients. The coronary flow reserve in the left circumflex and right coronary artery also decreased. Cardiac catheterization was performed during the follow-up period in two patients. Left ventriculography revealed almost normal wall motion of the left ventricle. The coronary flow reserve normalized in one patient.

Aged↗

PubMed2002

[A clinical study of total intravenous anesthesia by using mainly propofol, fentanyl and ketamine--with special reference to its safety based on 26,079 cases].

During a period of five years from January 1996 through December 2000 total intravenous anesthesia with mainly propofol, fentanyl and ketamine was administered to 26,079 patients including cardiac and neurosurgical patients at the University of Hirosaki Hospital and five other affiliated hospitals. The patients studied ranged from 1 year 8 months to 93 years in age, 9.2 kg to 135.0 kg in body weight and from 18 min to 22 hours 50 min in anesthetic time. With adequate monitoring, fentanyl 1-2 micrograms.kg-1 was given at first, then total-dose of ketamine 1 mg.kg-1 and propofol 1-2 mg.kg-1 were administered for the induction of anesthesia in adult patients. A total dose of fentanyl 3-15 micrograms.kg-1 was given combined with propofol 5-10 mg.kg-1 and ketamine 0.3-1.0 mg.kg.h-1. In craniotomy patients, ketamine was excluded. For pediatric patients, sevoflurane anesthesia was employed to establish i.v. route, and intravenous agents were given almost same as in the same manner as in adult patients. None of them developed either cardiac arrest or severe cardiovascular insufficiencies due to anesthesia alone. Their postoperative hepatic and renal functions evaluated by various biochemical indices and urine output were adequately maintained during anesthesia and for a week postoperatively. They were followed up to 3 months postoperatively only to fail to detect any adverse events related directly to this method of anesthesia. These data suggest that total intravenous anesthesia with propofol, fentanyl and ketamine has a very wide margin of safety.

Adolescent↗