Jung Un Lee

Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure

γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents (Itonic) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABAA receptors (GABAARs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of Itonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The Itonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced Itonic sensitivity to THIP argued for the decreased function of GABAAR δ subunits in HF, whereas similar Itonic sensitivity to benzodiazepines argued against the difference of γ2 subunit-containing GABAARs in SHAM and HF rats. HF Itonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal Itonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF Itonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABAARs function, the enhanced astroglial GABA uptake-induced attenuation of Itonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure.

Major role of GABAA-receptor mediated tonic inhibition in propofol suppression of supraoptic magnocellular neurons

Using slice patch clamp recording, we examined the effects of general anesthetic propofol (2,6-diisoprophlphenol) on dual modality of GABA(A) inhibition in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs): conventional quantal synaptic transmission (IPSCs, I(phasic)) and persistent tonic form of inhibitory current (I(tonic)). Propofol (10 μM) enhanced I(tonic) as shown by an inward shift in I(holding) (16.46±2.93 pA, n=27) and RMS increase (from 3.37±0.21 pA to 4.68±0.33 pA, n=27) in SON MNCs. Propofol also prolonged the decay time of IPSCs with decreased IPSCs frequency but no significant changes in IPSCs amplitude. Overall, propofol (1-10 μM) caused much smaller increase in mean I(phasic) than mean I(tonic) at all tested concentrations. In consistent with the enhancement of GABA(A) currents, propofol attenuated ongoing firing activities of SON MNCs by ∼65% of control. Selective inhibition of I(phasic) by a GABA(A) antagonist, gabazine (1 μM), failed to block the propofol suppression of the firing activities, while inhibition of I(tonic) and I(phasic) by bicuculline (20 μM) efficiently blocked the propofol-induced neurodepression in SON MNCs. Taken together, our results showed that propofol facilitated I(tonic) with marginal increase in mean I(phasic), and this could be a mechanism reducing the intrinsic SON MNCs excitability during propofol anesthesia.

Attenuated benzodiazepine-sensitive tonic GABAA currents of supraoptic magnocellular neuroendocrine cells in 24-h water-deprived rats.

In supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs), γ‐GABA, via activation of GABAA receptors (GABAARs), mediates persistent tonic inhibitory currents (Itonic), as well as conventional inhibitory postsynaptic currents (IPSCs, Iphasic). In the present study, we examined the functional significance of Itonic in SON MNCs challenged by 24‐h water deprivation (24WD). Although the main characteristics of spontaneous IPSCs were similar in 24WD compared to euhydrated (EU) rats, Itonic, measured by bicuculline (BIC)‐induced Iholding shifts, was significantly smaller in 24WD compared to EU rats (P < 0.05). Propofol and diazepam prolonged IPSC decay time to a similar extent in both groups but induced less Itonic in 24WD compared to EU rats, suggesting a selective decrease in GABAA receptors mediating Itonic over Iphasic in 24WD rats. THIP (4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol), a preferential δ subunit agonist, and L‐655,708, a GABAA receptor α5 subunit selective imidazobenzodiazepine, caused a significantly smaller inward and outward shift in Iholding, respectively, in 24WD compared to EU rats (P < 0.05 in both cases), suggesting an overall decrease in the α5 subunit‐containing GABAARs and the δ subunit‐containing receptors mediating Itonic in 24WD animals. Consistent with a decrease in 24WD Itonic, bath application of GABA induced significantly less inhibition of the neuronal firing activity in 24WD compared to EU SON MNCs (P < 0.05). Taken together, the results of the present study indicate a selective decrease in GABAARs functions mediating Itonic as opposed to those mediating Iphasic in SON MNCs, demonstrating the functional significance of Itonic with respect to increasing neuronal excitability and hormone secretion in 24WD rats.

Pain management in pediatric day surgery patients at The Maternal and Child Medical Research Center in Mongolia

Background Pediatric day surgery shortens the hospital stay, reduces the exposure of nosocomial infections and allows for active parental participation. But pain delays the recovery and it increases the morbidity, including nausea and vomiting, and the maladaptive behavioral changes. This study was conducted to compare the effect of rectally administered paracetamol or diclofenac combined with regional nerve block with the traditional pain control method. Methods Two hundred forty one randomly selected pediatric patients were allocated into two groups. The empirical pain relief group (the control group, n = 120) included the patients that received intravenous sulpyrin and/or meperidine postoperatively. The patients in the multimodal preemptive pain relief group (the study group, n = 121) received regional nerve blockade with 0.25% bupivacaine combined with preoperative rectally administered paracetamol 45 mg/kg or diclofenac 1 mg/kg 60 min before surgery for cases that were to undergo lower abdominal surgery. But only paracetamol or diclofenac was rectally administered preoperatively in the other surgical cases. Results The mean time in the recovery room for the study group was shorter than that for the control group. The postoperative pain was hurts even more in 16.7%, worst in 11.8%, a whole lot in 26.5% and no pain in 27.5% of the control group patients. But the pain was hurts little more only in 11%, a little bit in 10.0% and no pain in 88.9% of the study group patients. The average postoperative VAS score was 0.21 ± 0.6 in the study group and 8.36 ± 1.7 in the control group, respectively. Vomiting, nausea and fever were more frequently observed in the control group. Conclusions The pain intensity of the children who were treated with rectally administered paracetamol or diclofenac combined with regional nerve block before surgery was significantly decreased as compared to that of the children who were treated with the traditional method.

The optimal effect site concentration of remifentanil for tracheal intubation without muscle relaxant during inhalation anesthetic induction using sevoflurane in adult

BACKGROUND Sevoflurane has been shown to be suitable for inhalation induction of anesthesia in adults. The addition of remifentanil during sevoflurane induction allows for rapid and smooth tracheal intubation without muscle relaxant. The high concentration of remifentanil can result in improved conditions for tracheal intubation but also caused a cardiovascular instability. We tried to estimate optimal effect site concentration of remifentanil for tracheal intubation without muscle relaxants during inhalation anesthetic induction with 8 vol% sevoflurane and 50% N2O. METHODS One hundred five ASA I and II patients were randomly allocated to receive an effect site concentration of remifentanil 2, 4, or 6 ng/ml. Trachea was intubated without muscle relaxant after 3 minutes of inhalation induction with 8 vol% sevoflurane and 50% N2O. The intubating conditions for tracheal intubation were assessed and blood pressure and heart rate were recorded at the baseline, before intubation, just after intubation, 1, and 3 minute after intubation. RESULTS Tracheal intubation was successful in all patients. Clinically acceptable intubation conditions were 60%, 94%, and 100% in 2 ng/ml, 4 ng/ml, and 6 ng/ml group respectively. However, the number of patient who requested rescue medication for bradycardia in 6 ng/ml group was significantly higher than that in the other group (P < 0.05). CONCLUSIONS We concluded that 4 ng/ml effect site concentration of remifentanil is adequate concentration for tracheal intubation without muscle relaxants during inhalation induction using sevoflurane.