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Biomedical subjects

Akira Kudoh

Publications and source records attributed to Akira Kudoh.

16 recordsLinked to original sources

Ketamine inhibits endotoxin-induced inositol 1,4,5-triphosphate in rat ventricular cardiomyocytes.

OBJECTIVE: To investigate the effect of ketamine on endotoxin modulation of inositol 1,4,5-triphosphate (IP3) formation in cardiomyocytes. DESIGN: A prospective observational cell culture study. SETTING: A research laboratory in the University of Hirosaki School of Medicine. MATERIALS: Neonatal rat cardiomyocytes. INTERVENTION: We investigated bradykinin-induced IP3 production in the presence of lipopolysaccharide (LPS) and the effect of ketamine on the LPS modulation of IP3 formation. The LPS modulation of IP3 formation was measured in the presence of BM13177 (a thromboxane A2 (TXA2) receptor inhibitor) or GDPbetaS (a GTP-binding protein inhibitor). U46619 (a TXA2 agonist)-induced IP3 production was measured in the presence of ketamine, and the ketamine modulation of U46619-induced IP3 production was measured in the presence of W7 (a Ca2+ releasing agent) and verapamil (a Ca2+ channel blocker). RESULTS: One micromole ketamine significantly attenuated the LPS-induced IP3 production from 763.8+/-34.6 to 461.6+/-65.1 pmol mg protein(-1). Ten micromoles of BM13177 or 1 mM GDPbetaS significantly blocked LPS modulation of bradykinin-induced IP3 production from 786.0+/-33.8 to 218.6+/-21.6 and 226.8+/-25.4 pmol mg protein(-1). One micromole of ketamine significantly decreased U46619-induced IP3 production from 857.3+/-45.0 to 632.9+/-64.5 pmol mg(-1) protein. The ketamine inhibition of U46619-induced IP3 production was enhanced by W7 and inhibited by verapamil. CONCLUSION: Ketamine decreased LPS-induced IP3 formation and the ketamine inhibition was associated with inhibition of the TXA2-IP3 sequence. Inhibition of TXA2 by ketamine was associated with a decrease in intracellular Ca2+.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Chronic treatment with antidepressants decreases intraoperative core hypothermia.

UNLABELLED: We investigated temperature regulation during anesthesia and postoperative shivering in chronically depressed patients given antidepressant drugs. We studied 35 depressed patients and 35 control patients who underwent orthopedic surgery. Tympanic membrane temperatures 60, 75, and 90 min after induction in the depression group were significantly (P < 0.05) higher than those of the control group. There were no significant differences in mean skin temperature between the depression and the control groups. Eight of 35 patients in the depression group and 2 of 35 patients in the control group developed postanesthetic shivering. The incidence of shivering in the depression group was significantly more frequent than that in the control group (P = 0.04). The tympanic membrane temperature of the patients treated with clomipramine tended to be higher than that of the patients treated with maprotiline. In conclusion, intraoperative core hypothermia in chronically depressed patients was decreased. However, the incidence of shivering in depressed patients was significantly more frequent. IMPLICATIONS: Thermoregulation in chronically depressed patients is often altered. The alteration of body temperature is affected by depression itself and by antidepressants. General anesthesia has an influence on thermoregulatory control. However, temperature regulation during anesthesia in chronically depressed patients remains unclear.

Adult↗

Norepinephrine-induced inositol 1,4,5-trisphosphate formation in atrial myocytes is regulated by extracellular calcium, protein kinase C, and calmodulin.

We investigated whether alteration of extracellular and intracellular Ca2+ concentrations, protein kinase C, and calmodulin modulate norepinephrine (NE)-induced inositol 1,4,5-trisphosphate (IP3) formation in neonatal rat atrial myocytes. NE-induced IP3 production in atrial myocytes was stimulated by elevation of extracellular Ca2+ in a dose-dependent manner. However, TMB-8 (an intracellular calcium antagonist) and A23187 (an intracellular calcium agonist) did not significantly affect NE-induced IP3 production. PMA (a protein kinase C agonist) significantly decreased and staurosporine (a protein kinase C antagonist) significantly stimulated NE-induced IP3 production. W7 (a calmodulin antagonist) significantly increased the NE-induced IP3. In conclusion, elevation of extracellular Ca2+ concentrations affects NE-induced IP3 formation in atrial myocytes. Protein kinase C and calmodulin may control the IP3 response to NE by a negative feedback mechanism.

Animals↗

Antidepressant treatment for chronic depressed patients should not be discontinued prior to anesthesia.

PURPOSE: To investigate whether antidepressants administered to patients for chronic depression patients should be continued or discontinued before anesthesia. RESULTS: We studied 80 depressed patients who were scheduled to undergo orthopedic surgery under general anesthesia. The patients were divided randomly into two groups; patients in Group A (n=40) continued antidepressants before surgery and patients in Group B (n=40) discontinued antidepressants 72 hr before surgery. Two (5%) out of 40 patients in Group A and eight (20%) out of 40 patients in Group B had deterioration of depressive symptoms (P=0.04). Delirium or confusion during the perioperative course occurred in five patients (13%) in Group A and in 12 (30%) in Group B (P=0.05). There were no significant differences in incidence (5 vs 6%) of hypotension and arrhythmias during anesthesia between the two groups. CONCLUSION: Antidepressants administered to depressed patients should be continued before anesthesia. Discontinuation of antidepressants did not increase the incidence of hypotension and arrhythmias during anesthesia, but increased symptoms of depression and delirium or confusion.

Adult↗

Anesthesia with ketamine, propofol, and fentanyl decreases the frequency of postoperative psychosis emergence and confusion in schizophrenic patients.

STUDY OBJECTIVE: To investigate whether total IV anesthesia with ketamine, propofol, and fentanyl affects the frequency of postoperative psychosis emergence or confusion in schizophrenic patients. DESIGN: Prospective, controlled study. SETTING: Hirosaki National Hospital and Hakodate Watanabe Hospital. PATIENTS: 76 ASA physical status I and II schizophrenic patients taking chronic antipsychotic drugs and schedule for orthopedic surgery of extremities. INTERVENTIONS: In Group A (n = 38) patients, anesthesia was maintained with sevoflurane, nitrous oxide, and fentanyl. In Group B (n = 38) patients, anesthesia was maintained with ketamine, propofol, and fentanyl. MEASUREMENTS AND MAIN RESULTS: The frequency of psychosis emergence or confusion (54%) in Group A during the first 48 hours after surgery was significantly higher than the 30% figure in Group B. CONCLUSION: Ketamine, when combined with propofol and fentanyl, is an appropriate anesthetic drug for schizophrenic patients.

Adult↗

Increased postoperative pain scores in chronic depression patients who take antidepressants.

STUDY OBJECTIVE: To investigate postoperative pain and current perception thresholds in chronic depression in patients who are treated with antidepressants. DESIGN: Prospective, randomized study. SETTING: Hakodate Watanabe Hospital and Hirosaki National Hospital. PATIENTS: 30 patients with major depression and 30 control patients who underwent abdominal surgery with general anesthesia. INTERVENTIONS: Postoperative pain scores via visual analog scale (0-100), current perception thresholds at 5, 250, and 2000 Hz. MEASUREMENTS AND MAIN RESULTS: Postoperative pain scores of depressed patients at 8 and 16 hours after the end of anesthesia were 36.2 +/- 10.4 and 33.4 +/- 8.5, which were significantly higher than 25.2 +/- 9.3 and 22.7 +/- 8.5 scores of the control patients. Current perception thresholds at 5 Hz, 250 Hz, and 2000 Hz in depressed patients were 38.2 +/- 6.7, 76.1 +/- 11.3, and 190.8 +/- 19.2, respectively. There were no significant differences between the depressed patients and control patients in current perception thresholds at 5 Hz, 250 Hz, and 2000 Hz. We found that visual analog scale scores in depressed patients at 8 and 16 hours after the end of anesthesia correlated with the Hamilton Depression Scale scores before operation. CONCLUSIONS: The degree of postoperative pain in depressed patients who take antidepressants depends on their depressive state.

Abdomen↗

Ketamine suppresses norepinephrine-induced inositol 1,4,5-trisphosphate formation via pathways involving protein kinase C.

UNLABELLED: Inositol 1,4,5-trisphosphate (IP(3)) is not only involved in the physiologic regulation of excitation-contraction coupling, but could also play a role in cardiac pathophysiology. We investigated the mechanism of ketamine modulation of norepinephrine (NE)-induced IP(3) formation in neonatal rat cardiomyocytes. Ketamine 1 and 10 microM significantly decreased the IP(3) response to 1 microM NE by 27% and 43%, respectively. One micromolar TMB-8 (an intracellular calcium antagonist) produced 42% more decreases in IP(3) production than produced by ketamine alone. One hundred micromolar anthranilic acid (a phospholipase A(2) inhibitor) significantly decreased NE (1 microM)-induced IP(3) formation, and the inhibition was further enhanced by ketamine. Ten micromolar U 73122 (a phospholipase C inhibitor) did not significantly affect NE-induced IP(3) in the presence or absence of ketamine. One micromolar ketamine significantly inhibited staurosporine (a nonselective protein kinase C antagonist)-, bisindolylmaleimide (a selective protein kinase C antagonist)-, and wortmannin (a phosphatidylinositide 3-kinase antagonist)-stimulated IP(3) formation. In conclusion, ketamine suppresses NE-induced IP(3) production, and the inhibition is caused through pathways including protein kinase C and a decrease in intracellular Ca(2+) concentrations. IMPLICATIONS: Ketamine inhibits norepinephrine-induced inositol 1,4,5-triphosphate formation in a dose-dependent manner via pathways that involve protein kinase C and a decrease in intracellular Ca(2+) concentrations.

Anesthetics, Dissociative↗

Small-dose ketamine improves the postoperative state of depressed patients.

UNLABELLED: We investigated whether ketamine is suitable for depressed patients who had undergone orthopedic surgery. We studied 70 patients with major depression and 25 patients as the control (Group C). The depressed patients were divided randomly into two groups; patients in Group A (n = 35) were induced with propofol, fentanyl, and ketamine and patients in Group B (n = 35) were induced with propofol and fentanyl, and all patients were maintained with 1.5%-2.0% isoflurane plus nitrous oxide. The mean Hamilton Depression Rating (HDR) score was 12.7 +/- 5.4 for Group A and 12.3 +/- 6.0 for Group B 2 days before surgery and 9.9 +/- 4.1 for Group A and 14.4 +/- 3.8 for Group B 1 day after surgery. The HDR score in Group A 1 day after surgery was significantly (P < 0.05) lower than that in Group B. The HDR score in Group C was 4.2 +/- 1.7 2 days before surgery and 4.8 +/- 1.6 1 day after surgery. Depressed mood, suicidal tendencies, somatic anxiety, and hypochondriasis significantly decreased in Group A as compared with Group B. Postoperative pain scores in Group A at 8 and 16 h after the end of anesthesia were 26.6 +/- 8.7 and 24.9 +/- 8.2, respectively, which were significantly (P < 0.05) lower than 34.3 +/- 12.0 and 31.1 +/- 8.8 in Group B. In conclusion, small-dose ketamine improved the postoperative depressive state and relieved postoperative pain in depressed patients. IMPLICATIONS: NMDA receptor antagonists are reported to be effective for improving depression. It remains unclear whether ketamine, which is an NMDA receptor antagonist, postoperatively affects the psychological state in depressed patients. We investigated the effect of 1.0 mg/kg of ketamine on postoperative outcomes in depressed patients.

Adult↗

Sevoflurane increases glucose transport in skeletal muscle cells.

UNLABELLED: Sevoflurane activates phospholipase C and protein kinase C, leading to an increase in intracellular Ca(2+) concentration, which modulates glucose transport. We studied in vitro the effect of sevoflurane on the uptake of 2-deoxyglucose in rat skeletal muscle cells and the mechanism that modulates the glucose transport. Sevoflurane 0.8, 1.2, and 2.0 mM significantly increased glucose uptake from 13.1 +/- 1.2 pmol. h(-1). mg protein(-1) to 22.6 +/- 1.4, 32.1 +/- 1.8, and 37.4 +/-2.7 pmol. h(-1). mg protein(-1), respectively. Tyrphostin A-23 (a highly selective tyrosine kinase inhibitor) 1 and 10 nM significantly decreased the sevoflurane-stimulated glucose uptake from 32.1 +/- 1.8 to 25.8 +/- 1.1 and 15.2 +/- 1.7 pmol. h(-1). mg protein(-1), respectively. Genistein (a selective tyrosine kinase inhibitor) 1 and 10 nM also significantly decreased the sevoflurane- stimulated glucose uptake from 32.1 +/- 1.8 to 25.7 +/- 1.5 and 15.2 +/- 1.4 pmol. h(-1). mg protein(-1), respectively. The sevoflurane-stimulated glucose uptake was decreased by 100 nM and 1 microM TMB-8 (an intracellular Ca(2+) antagonist), from 32.1 +/- 1.8 pmol. h(-1). mg protein(-1) to 25.6 +/- 3.3 and 20.3 +/- 1.6 pmol. h(-1). mg protein(-1), respectively. Staurosporine (a protein kinase C antagonist) 100 nM significantly decreased sevoflurane-stimulated glucose uptake to 26.1 +/- 1.5 pmol. h(-1). mg protein(-1). We conclude that sevoflurane increases glucose uptake in skeletal muscle cells and that the sevoflurane-stimulated glucose uptake was associated with tyrosine kinase, protein kinase C, and intracellular Ca(2+). IMPLICATIONS: Sevoflurane anesthesia has an inhibitory effect on insulin secretion. Glucose concentrations in plasma do not significantly change during sevoflurane anesthesia. Plasma glucose concentrations are affected by intracellular glucose metabolism. However, glucose transport into cells during sevoflurane anesthesia remains unclear.

Anesthetics, Inhalation↗

Insulin potentiates bradykinin-induced inositol 1,4,5-triphosphate in neonatal rat cardiomyocytes.

This study investigated whether cross-talk between insulin and the bradykinin receptor exists to modulate bradykinin-induced increase in inositol 1,4,5-triphosphate (IP3) in neonatal rat cardiomyocytes. Treatment of the cultures with 1, 2, and 20 nM of insulin for 90 min before adding bradykinin increased the IP3 response to the same bradykinin dose to 372.0 +/- 17.8, 413.7 +/- 17.7, and 457.3 +/- 18.2 pmol/mg protein, respectively. Tyrphostine A23 and genistein (tyrosine kinase inhibitors) decreased the bradykinin (10 nM)-induced IP3 production potentiated by 2 nM insulin from 400.7 +/- 19.4 pmol/mg protein to 297.3 +/- 42.4 and 314.3 +/- 37.5 pmol/mg protein, respectively. Administration of 100 nM N-(6-aminohexyl)-5-chloro-naphthalenesulfonamide (W7, a calmodulin antagonist) significantly increased the bradykinin (10 nM)-induced IP3 production from 311.7 +/- 13.0 pmol/mg protein in the absence of insulin to 457.8 +/- 19.9, 578.2 +/- 25.9, and 665.2 +/- 16.0 pmol/mg protein in the presence of 1, 2, and 20 nM insulin, respectively. These results demonstrate that cross-talk between the insulin receptor and the bradykinin signaling system may exist in neonatal rat cardiomyocytes. Tyrosine kinase appears to play an important role in the cross-talking. Calmodulin controls the IP3 response to bradykinin by a negative feedback mechanism.

Animals↗

Atrial natriuretic peptide increases glucose uptake during hypoxia in cardiomyocytes.

The action of atrial natriuretic peptide on glucose uptake during hypoxia was investigated in neonatal cardiomyocytes. When the cultures were exposed to 100 n and 1 and 10 micro M of atrial natriuretic peptide for 60 min, hypoxia-induced glucose uptake significantly increased from 20.4 +/- 1.2 to 28.2 +/- 3.1, 31.6 +/- 2.7, and 30.1 +/- 2.8 pmol/h/mg protein, respectively, although atrial natriuretic peptide alone did not significantly affect the basal glucose uptake in normoxic condition. The atrial natriuretic peptide-stimulated glucose uptake during hypoxia was significantly decreased by 100 n of genistein and tyrphostin A-23 (a tyrosine kinase inhibitor) from 31.6 +/- 2.7 to 22.8 +/- 2.4 and 23.8 +/- 2.7 pmol/h/mg protein. U73122 100 n, which is a phospholipase C antagonist, significantly inhibited the atrial natriuretic peptide-induced glucose uptake under hypoxic conditions from 31.6 +/- 2.7 to 13.6 +/- 1.9 pmol/h/mg protein. However, the atrial natriuretic peptide-induced glucose uptake did not involve elevation of intracellular Ca and phosphatidylinositol (PI)3 kinase. It was concluded that the atrial natriuretic peptide-stimulated glucose uptake during hypoxia acts through a phospholipase C-tyrosine kinase pathway.

Animals↗

Schizophrenic patients who develop postoperative confusion have an increased norepinephrine and cortisol response to surgery.

The purpose of this study was to investigate the relationship between postoperative confusion and the plasma norepinephrine (NE), adrenocorticotropin (ACTH) or cortisol response to surgery in schizophrenic patients. We studied 50 schizophrenic patients and 35 control patients who underwent orthopedic surgery and perioperatively measured plasma NE, ACTH and cortisol levels. Postoperative confusion during 72 h after the end of the operation occurred in 14 of 50 schizophrenic patients (28%) and in 2 of 35 control patients (6%). Plasma NE levels 15 min after skin incision, the next day, the second day and the third day after operation in schizophrenic patients with postoperative confusion (668.0 +/- 59.2, 522.0 +/- 96.5, 463.2 +/- 71.2 and 398.9 +/- 56.2 pg/ml, respectively) were significantly higher than those in schizophrenic patients without confusion (524.1 +/- 62.6, 342.4 +/- 38.6, 311.2 +/- 58.3 and 314.1 +/- 77.1 pg/ml, respectively). Plasma cortisol levels 15 min after the skin incision and the next and second days after operation in schizophrenic patients with postoperative confusion (23.6 +/- 3.2, 21.1 +/- 4.3 and 19.9 +/- 4.4 microg/dl, respectively) were significantly higher than those in schizophrenic patients without confusion (15.2 +/- 4.5, 14.3 +/- 5.1 and 13.8 +/- 3.8 microg/dl, respectively). In conclusion, the occurrence of postoperative confusion in schizophrenic patients is associated with an increase in plasma norepinephrine and cortisol levels during and after surgery.

Adrenocorticotropic Hormone↗

Cortisol response to surgery and postoperative confusion in depressed patients under general anesthesia with fentanyl.

The purpose of this study was to investigate the relationship between postoperative confusion and plasma cortisol response to surgery in depressed patients. We studied 80 depressed patients and 40 control patients who had undergone orthopedic surgery and perioperatively measured plasma cortisol and adrenocorticotropin levels. Postoperative confusion in the first 3 postoperative days occurred in 5 (13%) depressed patients given fentanyl during anesthesia, 13 (33%) patients without fentanyl and 1 (3%) control patients. Plasma cortisol concentration (19.7 +/- 6.9 and 19.2 +/- 8.0 microg dl(-1)) 15 min after skin incision and 60 min after the end of surgery in depressed patients with fentanyl was significantly lower than that (24.2 +/- 7.2 and 23.5 +/- 8.1 microg dl(-1)) of depressed patients without fentanyl. Plasma cortisol levels during and after surgery in depressed patients with postoperative confusion were higher than those of depressed patients without postoperative confusion. We conclude that the occurrence of postoperative confusion in depressed patients is associated with an increase in plasma cortisol levels during and after surgery. The incidence of postoperative confusion in depressed patients with fentanyl was significantly lower than that of depressed patients without fentanyl.

Adrenocorticotropic Hormone↗

[A successfully treated case of aspiration pneumonia with adult respiratory distress syndrome and shock].

Right hip replacement was scheduled for a 74-year-old man who was treated with morphine for cancer pain. As the patient developed dyspnea and hypoxia after anesthesia, he was intubated and kept under mechanical ventilation. A diagnosis of aspiration pneumonia with adult respiratory distress syndrome was made based on the detection of gall obtained from the endotracheal tube. A chest X-ray showed pulmonary edema. He was treated with positive pressure ventilation and inotropic support. As he developed severe shock 10 hours after the intubation, he was treated with 20 mg.kg-1 of methylprednisolone for 3 days. The steroid therapy was successful and he was extubated on the 6th postoperative day and was discharged from the ICU on the 7th postoperative day. High-dose pulse methylprednisolone therapy resulted in a remarkable clinical improvement. Corticosteroids rescue treatment is effective for such a severe case of aspiration pneumonia with shock when the treatment is done in the early phase of the pneumonia.

Aged↗