To investigate the effect of ketamine on endotoxin modulation of inositol 1,4,5-triphosphate (IP3) formation in cardiomyocytes.
A prospective observational cell culture study.
A research laboratory ...in the University of Hirosaki School of Medicine.
Neonatal rat cardiomyocytes.
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).
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.
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+.
We investigated inflammatory cytokine response in chronic depressed patients during abdominal surgery. Twenty-five major depressed patients (Group D) and twenty-five patients (Group C) as the control ...were studied. Plasma interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-α) concentrations were measured before and at 15 min after induction of anesthesia, the end of surgery, 24h and 3 days after the operation. Plasma IL-6 concentrations in Group D at the end of the operation and 24h after surgery were significantly lower than those of Group C. The plasma IL-6 concentration (87.1±55.3pg/ml) of patients scoring more than 18 points in the Hamilton depression-rating score at the end of the operation was significantly higher than 57.5±76.7pg/ml of patients scoring less than 18 points. Plasma IL-8 concentration (6.1±3.2pg/ml) in Group D at the end of the operation was significantly lower than 8.7±4.2pg/ml of Group C. We conclude that plasma IL-6 and IL-8 response to surgical trauma is inhibited in chronic depressed patients. The IL-6 response to surgical trauma is depending on the clinical state of depression.
To investigate whether epidural analgesia with local anesthetics affects postoperative confusion in schizophrenic patients or the relationships between cortisol or interleukin-6 (IL-6) and ...postoperative confusion.
Prospective, randomized study.
Hakodate Watanabe Hospital and Hirosaki National Hospital.
105 patients who were scheduled to undergo abdominal surgery with general anesthesia.
The schizophrenic patients were randomly divided into two groups: patients in Group A received epidural anesthesia and patients in Group B did not receive epidural anesthesia.
Postoperative confusion during the first 48 hours after the end of operation occurred in 7 of 33 patients (21%) in Group A and 10 of 33 patients (30%) in Group B. There were no significant differences in the frequency of postoperative confusion between Groups A and B. Plasma cortisol concentrations in schizophrenic patients in Group A were significantly lower 15 minutes after incision and the end of surgery than those levels of patients in Group B; however, there was no significant difference between groups in plasma cortisol concentrations after anesthesia. Plasma IL-6 concentrations (51.7 ± 22.0 and 31.4 ± 8.2 pg mL-1) in patients with postoperative confusion at the end of surgery and 24 hours after surgery were significantly higher than those levels (34.4 ± 16.2 and 16.9 ± 7.7 pg mL-1) in patients without postoperative confusion.
Epidural anesthesia does not significantly decrease the frequency of postoperative confusion in schizophrenic patients. Plasma IL-6 concentrations at the end of the operation and 24 hours after surgery in schizophrenic patients with postoperative confusion were significantly higher than those concentrations in patients without postoperative confusion.
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.
To investigate postoperative pain and current perception thresholds in chronic depression in patients who are treated with antidepressants.
Prospective, randomized study.
Hakodate Watanabe Hospital ...and Hirosaki National Hospital.
30 patients with major depression and 30 control patients who underwent abdominal surgery with general anesthesia.
Postoperative pain scores via visual analog scale (0-100), current perception thresholds at 5, 250, and 2000 Hz.
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.
The degree of postoperative pain in depressed patients who take antidepressants depends on their depressive state.
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.
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.
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.
